Comparison of the influenza vaccination coverage among high-risk people between the online registration system and walk-in service system in Bangkok, Thailand.

Until recently, the Thai national program of seasonal influenza vaccination for high-risk people has been using a walk-in service system. However, in 2020, an online registration system was introduced in Bangkok to improve vaccine coverage. This study aimed to compare the coverage of influenza vaccination between the walk-in service and online registration systems. The study participants included 374,710 Thai individuals who obtained an influenza vaccination from the national program in the Bangkok health region in 2018 (n = 162,214) and in 2020 (n = 212,496). The registration systems that were examined were the walk-in service system in 2018 and the online registration system in 2020. The characteristics of vaccine recipients and the vaccine coverage in each risk group and health facility level were compared between the two systems. Coverage comparison in Bangkok between the years 2018 and 2020 showed an increase in coverage, particularly among individuals who had an influenza vaccination at health facilities of the primary level and in the elderly and obesity groups. The coverage among children was lowest among all high-risk groups. To improve coverage in Thailand, the online registration system should be introduced in all regions. Additionally, information about influenza vaccination for children should be disseminated to parents using handbooks or by word-of-mouth from healthcare workers.

Design and synthesis of 7-membered lactam fused hydroxypyridinones as potent metal binding pharmacophores (MBPs) for inhibiting influenza virus PAN endonuclease.

Since influenza virus RNA polymerase subunit PAN is a dinuclear Mn2+ dependent endonuclease, metal-binding pharmacophores (MBPs) with Mn2+ coordination has been elucidated as a promising strategy to develop PAN inhibitors for influenza treatment. However, few attentions have been paid to the relationship between the optimal arrangement of the donor atoms in MBPs and anti-influenza A virus (IAV) efficacy. Given that, the privileged hydroxypyridinones fusing a seven-membered lactam ring with diverse side chains, chiral centers or cyclic systems were designed and synthesized. A structure-activity relationship study resulted in a hit compound 16l (IC50 = 2.868 ± 0.063 µM against IAV polymerase), the seven-membered lactam ring of which was fused a pyrrolidine ring. Further optimization of the hydrophobic binding groups on 16l afforded a lead compound (R, S)-16s, which exhibited a 64-fold more potent inhibitory activity (IC50 = 0.045 ± 0.002 µM) toward IAV polymerase. Moreover, (R, S)-16s demonstrated a potent anti-IAV efficacy (EC50 = 0.134 ± 0.093 µM) and weak cytotoxicity (CC50 = 15.35 µM), indicating the high selectivity of (R, S)-16s. Although the lead compound (R, S)-16s exhibited a little weaker activity than baloxavir, these findings illustrated the utility of a metal coordination-based strategy in generating novel MBPs with potent anti-influenza activity.

Antiviral Effect of Ferula Plants and their Potential for Treatment of COVID-19: A Comprehensive Review.

Viral diseases have always been a threat to mankind throughout history, and many people have lost their lives due to the epidemic of these diseases. In recent years, despite the progress of science, we are still witnessing a pandemic of dangerous diseases such as COVID-19 all over the world, which can be a warning for humanity. Ferula is a genus of flowering plants commonly found in Central Asia, and its species have shown antiviral activity against a variety of viruses, including respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, hepatitis B, and coronaviruses. In this study, we intend to review the antiviral effects of Ferula plants, emphasizing the therapeutic potential of these plants in the treatment of COVID-19. Google, PubMed, Web of Science, and Scopus databases were searched to review the relevant literature on the antiviral effect of Ferula or its isolated compounds. The search was performed using the keywords Ferula, antiviral, Coronaviruses, respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, and hepatitis B. According to the reviewed articles and available scientific evidence, it was determined that the plants of this genus have strong antiviral effects. Also, clinical studies have shown that some species, such as Ferula assa-foetida, can be used effectively in the treatment of COVID-19. Ferula plants have inhibitory effects on various viruses, making them an attractive alternative to conventional antiviral agents. Therefore, these plants are a natural source of valuable compounds that can help us fight infectious diseases.

Highly pathogenic avian influenza A (H5N1) virus outbreak in Peru in 2022-2023.

Background: An epizootic of highly pathogenic avian influenza A (H5N1) has spread worldwide since 2022. Even though this virus has been extensively studied for many decades, little is known about its evolution in South America. Methods: Here, we describe the sequencing and characterization of 13 H5N1 genomes collected from wild birds, poultry, and wild mammals in Peru during the genomic surveillance of this outbreak. Results: The samples belonged to the highly pathogenic avian influenza (H5N1) 2.3.4.4b clade. Chilean and Peruvian samples clustered in the same group and therefore share a common ancestor. An analysis of the hemagglutinin and neuraminidase genes detected new mutations, some dependent upon the host type. Conclusions: The genomic surveillance of highly pathogenic avian influenza is necessary to promote the One Health policy and to overcome the new problems entailed by climate change, which may alter the habitats of resident and migratory birds.

Exploring the Lagged Correlation Between Baidu Index and Influenza-Like Illness - China, 2014-2019.

Introduction: This study investigated the lagged correlation between Baidu Index for influenza-related keywords and influenza-like illness percentage (ILI%) across regions in China. The aim is to establish a scientific foundation for utilizing Baidu Index as an early warning tool for influenza-like illness epidemics. Methods: In this study, data on ILI% and Baidu Index were collected from 30 provincial-level administrative divisions (PLADs) spanning April 2014 to March 2019. The Baidu Index was categorized into Overall Index, Ordinary Index, Prevention Index, Symptom Index, and Treatment Index based on search query themes. The lagged correlation between the Baidu Index and ILI% was examined through the cross-correlation function (CCF) method. Results: Correlating the Baidu Overall Index of 30 PLADs with ILI% revealed CCF values ranging from 0.46 to 0.86, with a median lag of 0.5 days. Subcategory analysis indicated that the Prevention Index and Symptom Index exhibited quicker responses to ILI%, with median lags of -9 and -0.5 days, respectively, compared to 0 and 3 days for the Ordinary and Treatment Indexes. The median lag days between the Baidu Index and the ILI% were earlier in the northern PLADs compared to the southern PLADs. Discussion: The Prevention and Symptom Indexes show promising predictive capabilities for influenza-like illness epidemics.

Detection of influenza A(H3N2) viruses with polymerase acidic subunit substitutions after and prior to baloxavir marboxil treatment during the 2022-2023 influenza season in Japan.

Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022-2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n=234), with a minor circulation of A(H1N1)pdm09 (n=10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23K/G, or I38M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6 to 100 %), a polymorphism and a mixture of PA/E23K/G, and I38M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7-14 years, with a median fever duration of 16.7 hours and a median symptom duration of 93.7 hours, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza.

Relative vaccine effectiveness of MF59®-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017-2020 influenza seasons.

OBJECTIVES: This study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions ("ED/IP") and for IP admissions alone pooled across the 2017-2020 influenza seasons. Exploratory individual season analyses were also performed. METHODS: This retrospective test-negative design study included US adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017-2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders. RESULTS: Pooled analyses over the 3 seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (-2.5% [-19.6, 12.2]) visits and admissions or IP admissions alone (-1.6% [-22.5, 15.7]). The exploratory individual season analyses also showed no significant differences. CONCLUSIONS: Evidence from the 2017-2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.

An in vitro antiviral evaluation of punicalagin toward influenza A virus.

Objective: Influenza complications are mild to serious, and can cause death in some cases. A great deal of attention has been paid in recent years to the development and use of new antiviral compounds to overcome drug resistance in certain strains of the influenza virus and treat the clinical implications. This study aimed to investigate the antiviral effect of punicalagin and its associated mechanism against influenza A (H1N1) virus in vitro. Materials and Methods: the ant-influenza activity of punicalagin was studied in Madin-Darby Canine Kidney (MDCK) cells using influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) using Hemagglutinin assay (HA) and 50% tissue culture infective dose (TCID50). Then, the inhibition of haemagglutination, virucidal activity, inhibitory effect at different times, replication of viral RNA and expression of viral genes were investigated. Results: Punicalagin could inhibit influenza virus infection with 50% inhibitory concentration (IC50) of 3.98 µg/ml and selectivity index (SI) value of 6.1. Punicalagin decreased virus titers with an inhibitory effect on virus hemagglutination (p<0.05). Punicalagin also inhibited viral adsorption. The results of virus RNA replication and viral mRNA (NS1 and HA) expression after treatment with punicalagin showed significant suppression of viral mRNA expression but no effect on replication of viral RNA. Conclusion: The results of the present study indicated that punicalagin was effective against influenza infection most probably via inhibition of haemagglutination activity and virus binding.

Do pregnant persons want influenza vaccines? Knowledge, attitudes, perceptions, and practices toward influenza vaccines in 8 low- and middle-income countries.

BACKGROUND: While vaccination is the most effective way to prevent influenza infection and adverse outcomes, and despite WHO recommendations to vaccinate pregnant persons, access to seasonal influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons about seasonal influenza vaccines to inform actions to improve vaccine uptake among this priority population. METHODS: We pooled individual-level data from cross-sectional surveys assessing pregnant persons' attitudes toward seasonal influenza vaccines in eight low- and middle-income countries during 2018-2019. The eight countries used a standard protocol and questionnaire to measure attitudes and intents toward influenza vaccination. We stratified by country-level (presence/absence of a national influenza vaccination program, country income group, geographic region) and individual-level factors. FINDINGS: Our analysis included 8,556 pregnant persons from eight low- and middle-income countries with and without seasonal influenza vaccination programs. Most pregnant persons (6,323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without influenza vaccination programs (2,383, 89%) than in those with such programs (3,940, 67%, p < 0.001). INTERPRETATION: Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs may be well-received by pregnant persons, leading to averted illness both in pregnant persons themselves and in their newborn babies. FUNDING: US Centers for Disease Control and Prevention.

Protection against the H1N1 influenza virus using self-assembled nanoparticles formed by lumazine synthase and bearing the M2e peptide.

There is an urgent need for influenza vaccines that offer broad cross-protection. The highly conserved ectodomain of the influenza matrix protein 2 (M2e) is a promising candidate; however, its low immunogenicity can be addressed. In this study, we developed influenza vaccines using the Lumazine synthase (LS) platform. The primary objective of this study was to determine the protective potential of M2e proteins expressed on Lumazine synthase (LS) nanoparticles. M2e-LS proteins, produced through the E. coli system, spontaneously assemble into nanoparticles. The study investigated the efficacy of the M2e-LS nanoparticle vaccine in mice. Mice immunized with M2e-LS nanoparticles exhibited significantly higher levels of intracellular cytokines than those receiving soluble M2e proteins. The M2e-LS protein exhibited robust immunogenicity and provided 100% protection against cross-clade influenza.

Death on the permafrost: Revisiting the 1918-20 influenza pandemic in Alaska using death certificates.

The 1918-20 influenza pandemic devastated Alaska's Indigenous populations. We report on quantitative analyses of pandemic deaths due to pneumonia and influenza (P&I) using information from Alaska death certificates dating between 1915 and 1921 (n=7,147). Goals include a reassessment of pandemic death numbers, analysis of P&I deaths beyond 1919, estimates of excess mortality patterns overall and by age using intercensal population estimates based on Alaska's demographic history, and comparisons between Alaska Native (AN) and non-AN residents. Results indicate that ANs experienced 83% of all P&I deaths and 87% of all-cause excess deaths during the pandemic. AN mortality was 8.1 times higher than non-AN mortality. Analyses also uncovered previously unknown mortality peaks in 1920. Both subpopulations showed characteristically high mortality of young adults, possibly due to imprinting with the 1889-90 pandemic virus, but their age-specific mortality patterns were different: non-AN mortality declined after age 25-29 and stayed relatively low for the elderly, while AN mortality increased after age 25-29, peaked at age 40-44, and remained high up to age 64. This suggests a relative lack of exposure to H1-type viruses pre-1889 among AN persons. In contrast, non-AN persons, often temporary residents, may have gained immunity before moving to Alaska.

RNA N6-methyladenosine methylation in influenza A virus infection.

Influenza A virus (IAV) is a negative-sense single-stranded RNA virus that causes acute lung injury and acute respiratory distress syndrome, posing a serious threat to both animal and human health. N6-methyladenosine (m6A), a prevalent and abundant post-transcriptional methylation of RNA in eukaryotes, plays a crucial regulatory role in IAV infection by altering viral RNA and cellular transcripts to affect viral infection and the host immune response. This review focuses on the molecular mechanisms underlying m6A modification and its regulatory function in the context of IAV infection and the host immune response. This will provide a better understanding of virus-host interactions and offer insights into potential anti-IAV strategies.

Evaluation of the cross-protection of the Vero cell-derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization.

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 105 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 µg/mL of carbopol971P and 50 µg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program.

The impact of the COVID-19 pandemic and the free vaccination policy on seasonal influenza vaccination uptake among older adults in Ningbo, Eastern China.

In 2020-21, during the COVID-19 pandemic, a free influenza vaccination program was initiated among the elderly residents in Ningbo, China. The impact of the COVID-19 pandemic and free vaccination policy on influenza vaccine uptake needs to be evaluated. The influenza vaccine uptake among individuals born before 31 December, 1962 from 2017-18 to 2022-23 season in Ningbo was analyzed. Multivariate logistic regressions were used to estimate the impact of the COVID-19 pandemic and free vaccination policy. Our analysis included an average of 1,856,565 individuals each year. Influenza vaccination coverage increased from 1.14% in 2017-18 to 33.41% in 2022-23. The vaccination coverage among the free policy target population was 50.03% in 2022-23. Multivariate analysis showed that free vaccination policy increased influenza vaccine uptake most (OR = 11.99, 95%CI: 11.87-12.11). The initial phase of the pandemic was associated with a positive effect on influenza vaccination (OR = 2.09, 95%CI: 2.07-2.12), but followed by a negative effect in the subsequent two seasons(2021-22: OR = 0.75, 95%CI: 0.73-0.76; 2022-23: OR = 0.40, 95%CI: 0.39-0.40). COVID-19 vaccination in the current season was a positive predictor of influenza vaccine uptake while not completing booster COVID-19 vaccination before was negative predictor in 2022-23. Having influenza vaccine history and having ILI medical history during the last season were also positive predictors of influenza vaccine uptake. Free vaccination policies have enhanced influenza vaccination coverage among elderly population. The COVID-19 pandemic plays different roles in different seasons. Our study highlights the need for how to implement free vaccination policies targeting vulnerable groups with low vaccination coverage.

Mortality in sea lions is associated with the introduction of the H5N1 clade 2.3.4.4b virus in Brazil October 2023: whole genome sequencing and phylogenetic analysis.

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.

HDL-based therapeutics: A promising frontier in combating viral and bacterial infections.

Low levels of high-density lipoprotein (HDL) and impaired HDL functionality have been consistently associated with increased susceptibility to infection and its serious consequences. This has been attributed to the critical role of HDL in maintaining cellular lipid homeostasis, which is essential for the proper functioning of immune and structural cells. HDL, a multifunctional particle, exerts pleiotropic effects in host defense against pathogens. It functions as a natural nanoparticle, capable of sequestering and neutralizing potentially harmful substances like bacterial lipopolysaccharides. HDL possesses antiviral activity, preventing viruses from entering or fusing with host cells, thereby halting their replication cycle. Understanding the complex relationship between HDL and the immune system may reveal innovative targets for developing new treatments to combat infectious diseases and improve patient outcomes. This review aims to emphasize the role of HDL in influencing the course of bacterial and viral infections and its and its therapeutic potential.

Genomic diversity and evolutionary dynamics of Influenza A viruses in Colombian swine: implications for one health surveillance and control.

Influenza A viruses (IAV) impose significant respiratory disease burdens in both swine and humans worldwide, with frequent human-to-swine transmission driving viral evolution in pigs and highlighting the risk at the animal-human interface. Therefore, a comprehensive One Health approach (interconnection among human, animal, and environmental health) is needed for IAV prevention, control, and response. Animal influenza genomic surveillance remains limited in many Latin American countries, including Colombia. To address this gap, we genetically characterized 170 swine specimens from Colombia (2011-2017). Whole genome sequencing revealed a predominance of pandemic-like H1N1 lineage, with a minority belonging to H3N2 and H1N2 human seasonal-like lineage and H1N1 early classical swine lineages. Significantly, we have identified reassortant and recombinant viruses (H3N2, H1N1) not previously reported in Colombia. This suggests a broad genotypic viral diversity, likely resulting from reassortment between classical endemic viruses and new introductions established in Colombia's swine population (e.g. the 2009 H1N1 pandemic). Our study highlights the importance of a One Health approach in disease control, particularly in an ecosystem where humans are a main source of IAV to swine populations, and emphasizes the need for continued surveillance and enhanced biosecurity measures. The co-circulation of multiple subtypes in regions with high swine density facilitates viral exchange, underscoring the importance of monitoring viral evolution to inform vaccine selection and public health policies locally and globally.

Characteristics and factors of repeated influenza vaccination among elderly individuals in Shanghai, China from 2020 to 2022.

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection.

Regulatory T cells (Tregs) play a crucial and complex role in balancing the immune response to viral infection. Primarily, they serve to regulate the immune response by limiting the expression of proinflammatory cytokines, reducing inflammation in infected tissue, and limiting virus-specific T cell responses. But excessive activity of Tregs can also be detrimental and hinder the ability to effectively clear viral infection, leading to prolonged disease and potential worsening of disease severity. Not much is known about the impact of Tregs during severe influenza. In the present study, we show that CD4+/CD25+FoxP3+ Tregs are strongly involved in disease progression during influenza A virus (IAV) infection in mice. By comparing sublethal with lethal dose infection in vivo, we found that not the viral load but an increased number of CD4+/CD25+FoxP3+ Tregs may impair the immune response by suppressing virus specific CD8+ T cells and favors disease progression. Moreover, the transfer of induced Tregs into mice with mild disease symptoms had a negative and prolonged effect on disease outcome, emphasizing their importance for pathogenesis. Furthermore, treatment with MEK-inhibitors resulted in a significant reduction of induced Tregs in vitro and in vivo and positively influenced the progression of the disease. Our results demonstrate that CD4+/CD25+FoxP3+ Tregs are involved in the pathogenesis of severe influenza and indicate the potential of the MEK-inhibitor zapnometinib to modulate CD4+/CD25+FoxP3+ Tregs. Thus, making MEK-inhibitors even more promising for the treatment of severe influenza virus infections.