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The role of sub-Saharan Africa in the global spread of influenza viruses remains unclear due to insufficient spatiotemporal sequence data. Here, we analyzed 222 codon-complete sequences of influenza A viruses (IAVs) sampled between 2011 and 2013 from five countries across sub-Saharan Africa (Kenya, Zambia, Mali, Gambia, and South Africa); these genomes were compared with 1209 contemporaneous global genomes using phylogeographical approaches. The spread of influenza in sub-Saharan Africa was characterized by (i) multiple introductions of IAVs into the region over consecutive influenza seasons, with viral importations originating from multiple global geographical regions, some of which persisted in circulation as intra-subtype reassortants for multiple seasons, (ii) virus transfer between sub-Saharan African countries, and (iii) virus export from sub-Saharan Africa to other geographical regions. Despite sparse data from influenza surveillance in sub-Saharan Africa, our findings support the notion that influenza viruses persist as temporally structured migrating metapopulations in which new virus strains can emerge in any geographical region, including in sub-Saharan Africa; these lineages may have been capable of dissemination to other continents through a globally migrating virus population. Further knowledge of the viral lineages that circulate within understudied sub-Saharan Africa regions is required to inform vaccination strategies in those regions.
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Virus de la Influenza A , Gripe Humana , Filogenia , Filogeografía , Virus Reordenados , Humanos , África del Sur del Sahara/epidemiología , Gripe Humana/epidemiología , Gripe Humana/virología , Virus de la Influenza A/genética , Virus Reordenados/genética , Genoma ViralRESUMEN
In this study, we describe the genetic characteristics of influenza A(H1N1)pdm09 strains detected in Myanmar from 2015 to 2019. Whole genomes from 60 A(H1N1)pdm09 virus isolates were amplified using real-time polymerase chain reaction and successfully sequenced using the Illumina iSeq100 platforms. Eight individual phylogenetic trees were retrieved for each segment along with those of the World Health Organization (WHO)-recommended Southern Hemisphere vaccine strains for the respective years. A(H1N1)pdm09 viruses from 2015 were found to belong to clade 6B, those from 2016 to 6B.1, 2017 to 6B.1A, and 2019 to 6B.1A.5a, and were genetically distinct from the Southern Hemisphere vaccine strains for the respective seasons, A/California/7/2009 and A/Michigan/45/2015. We observed one virus with intra-subtype reassortment, collected in the 2015 season. Importantly, three viruses possessed the H275Y substitution in the neuraminidase protein, appearing to be community-acquired without the prior administration of neuraminidase inhibitors. These viruses exhibited highly reduced susceptibility to oseltamivir and peramivir. This study demonstrates the importance of monitoring genetic variations in influenza viruses that will contribute to the selection of global influenza vaccines.
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Antivirales , Farmacorresistencia Viral , Genoma Viral , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Neuraminidasa , Oseltamivir , Filogenia , Secuenciación Completa del Genoma , Humanos , Mianmar/epidemiología , Gripe Humana/virología , Gripe Humana/epidemiología , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H1N1 del Virus de la Influenza A/clasificación , Farmacorresistencia Viral/genética , Oseltamivir/farmacología , Antivirales/farmacología , Antivirales/uso terapéutico , Neuraminidasa/genética , Pacientes Ambulatorios , Infecciones Comunitarias Adquiridas/virología , Infecciones Comunitarias Adquiridas/epidemiologíaRESUMEN
The unexpected emergence of oseltamivir-resistant A(H1N1) viruses in 2008 was facilitated in part by the establishment of permissive secondary neuraminidase (NA) substitutions that compensated for the fitness loss due to the NA-H275Y resistance substitution. These viruses were replaced in 2009 by oseltamivir-susceptible A(H1N1)pdm09 influenza viruses. Genetic analysis and screening of A(H1N1)pdm09 viruses circulating in Germany between 2009 and 2024 were conducted to identify any potentially synergistic or resistance-associated NA substitutions. Selected viruses were then subjected to further characterization in vitro. In the NA gene of circulating A(H1N1)pdm09 viruses, two secondary substitutions, NA-V241I and NA-N369K, were identified. These substitutions demonstrated a stable lineage in phylogenetic analysis since the 2010-2011 influenza season. The data indicate a slight increase in viral NA bearing two additional potentially synergistic substitutions, NA-I223V and NA-S247N, in the 2023-2024 season, which both result in a slight reduction in susceptibility to NA inhibitors. The accumulation of secondary synergistic substitutions in the NA of A(H1N1)pdm09 viruses increases the probability of the emergence of antiviral-resistant viruses. Therefore, it is crucial to closely monitor the evolution of circulating influenza viruses and to develop additional antiviral drugs against different target proteins.
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Antivirales , Farmacorresistencia Viral , Evolución Molecular , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Mutación , Neuraminidasa , Oseltamivir , Filogenia , Proteínas Virales , Neuraminidasa/genética , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/enzimología , Antivirales/farmacología , Farmacorresistencia Viral/genética , Humanos , Gripe Humana/virología , Proteínas Virales/genética , Proteínas Virales/metabolismo , Oseltamivir/farmacología , Alemania , Sustitución de Aminoácidos , Animales , PerrosRESUMEN
Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, ß = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, ß = -1.372, p = 0.045), and basophil counts (Baso, ß = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.
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Estudio de Asociación del Genoma Completo , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Análisis de la Aleatorización Mendeliana , Humanos , Gripe Humana/virología , Gripe Humana/genética , Gripe Humana/epidemiología , Subtipo H1N1 del Virus de la Influenza A/genética , Japón/epidemiología , Predisposición Genética a la Enfermedad , Índice de Severidad de la Enfermedad , Polimorfismo de Nucleótido Simple , Aspartato Aminotransferasas/sangre , LDL-Colesterol/sangre , Asia Oriental/epidemiología , Pueblo Asiatico/genética , Pueblos del Este de AsiaRESUMEN
Since May 2023, a novel combination of neuraminidase mutations, I223V + S247N, has been detected in influenza A(H1N1)pdm09 viruses collected in countries spanning 5 continents, mostly in Europe (67/101). The viruses belong to 2 phylogenetically distinct groups and display ≈13-fold reduced inhibition by oseltamivir while retaining normal susceptibility to other antiviral drugs.
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Antivirales , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Neuraminidasa , Oseltamivir , Filogenia , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Gripe Humana/virología , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Neuraminidasa/antagonistas & inhibidores , Neuraminidasa/genética , Farmacorresistencia Viral/genética , MutaciónRESUMEN
Influenza Like Illness (ILI) and Severe Acute Respiratory Infection (SARI) cases are more prone to Influenza and SARS-CoV-2 infection. Accordingly, we genetically characterized Influenza and SARS-CoV-2 in 633 ILI and SARI cases by rRT-PCR and WGS. ILI and SARI cases showed H1N1pdm09 prevalence of 20.9% and 23.2% respectively. 135 (21.3%) H1N1pdm09 and 23 (3.6%) H3N2 and 5 coinfection (0.78%) of H1N1pdm09 and SARS-CoV-2 were detected. Phylogenetic analysis revealed H1N1pdm09 resemblance to clade 6B.1A.5a.2 and their genetic relatedness to InfA/Perth/34/2020, InfA/Victoria/88/2020 and InfA/Victoria/2570/2019. Pan 24 HA and 26 NA nonsynonymous mutations and novel HA (G6D, Y7F, Y78H, P212L, G339R, T508K and S523T) and NA (S229A) mutations were observed. S74R, N129D, N156K, S162N, K163Q and S164T alter HA Cb and Sa antibody recognizing site. Similarly, M19T, V13T substitution and multiple mutations in transmembrane and NA head domain drive antigenic drift. SARS-CoV-2 strains genetically characterized to Omicron BA.2.75 lineage containing thirty nonsynonymous spike mutations exhibited enhanced virulence and transmission rates. Coinfection although detected very minimal, the mutational changes in H1N1pdm09 and SARS-CoV-2 virus infected individuals could alter antibody receptor binding sites, allowing the viruses to escape immune response resulting in better adaptability and transmission. Thus continuous genomic surveillance is required to tackle any future outbreak.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Filogenia , SARS-CoV-2 , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , SARS-CoV-2/genética , Gripe Humana/virología , Gripe Humana/epidemiología , COVID-19/virología , COVID-19/epidemiología , Adulto , Persona de Mediana Edad , Masculino , Femenino , Adolescente , Adulto Joven , Genoma Viral/genética , Anciano , Coinfección/virología , Coinfección/epidemiología , Niño , Preescolar , Síndrome Respiratorio Agudo Grave/virología , Síndrome Respiratorio Agudo Grave/epidemiología , Mutación , LactanteRESUMEN
The current influenza season started in Italy in October 2023, approaching the epidemic peak in late December (52nd week of the year). We aimed to explore the mid-term virologic surveillance data of the 2023/2024 influenza season (from 16 October 2023 to 7 January 2024) in Sicily, the fourth most populous Italian region. A test-negative design was used to estimate the effectiveness of seasonal influenza vaccine (VE) against A(H1N1)pdm09 virus, the predominant subtype in Sicily (96.2% of laboratory-confirmed influenza cases). Overall, 29.2% (n = 359/1230) of oropharyngeal swabs collected from patients with influenza-like illness (ILI) were positive for influenza. Among the laboratory-confirmed influenza cases, 12.5% (n = 45/359) were vaccinated against influenza, with higher prevalence of laboratory-confirmed diagnosis of influenza A among subjects vaccinated with quadrivalent inactivated standard dose (29.4%), live attenuated intranasal (25.1%), and quadrivalent inactivated high-dose (23.8%) influenza vaccines. Comparing influenza vaccination status for the 2023/2024 season among laboratory-confirmed influenza-positive and -negative samples, higher vaccination rates in influenza-negative samples (vs. positive) were observed in all age groups, except for 45-64 years old, regardless of sex and comorbidities. The overall adjusted VE (adj-VE) was 41.4% [95%CI: 10.5-61.6%], whereas the adj-VE was 37.9% [95%CI: -0.7-61.7%] among children 7 months-14 years old and 52.7% [95%CI: -38.0-83.8%] among the elderly (≥65 years old).
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BACKGROUND: Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic. METHODS: To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023. RESULTS: Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade. CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Niño , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Estudios Transversales , Deriva y Cambio Antigénico , Subtipo H3N2 del Virus de la Influenza A , COVID-19/epidemiología , PandemiasRESUMEN
Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized. A patient (age group 5-15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined. Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed. The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.
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Síndrome Hemolítico-Urémico , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , Preescolar , Niño , Adolescente , Células Epiteliales , Pulmón , Gripe Humana/epidemiologíaRESUMEN
Influenza virus is known to cause mild to severe respiratory infections and is also prone to genetic mutations. Of all the mutations, neuraminidase (NA) gene mutations are a matter of concern, as most approved antivirals target this protein. During the 2020 influenza season, an emergence of mutation in the NA gene, affecting the binding of the World Health Organization (WHO)-recommended probes to the specific site of the NA gene, was reported by our group. As a result of this mutation, the WHO-recommended allelic discrimination real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was unable to detect wild-type (H275) or mutant oseltamivir-resistant (Y275) strains of influenza A(H1N1)pmd09 viruses. In the current study, the WHO-recommended probes were redesigned according to the mutation in the probe binding site. Fifty undetermined samples (2020-2021) from the previous study were retested with the newly designed probes and found to be positive for H275 and/or Y275. The results obtained were similar to the Sanger sequencing results from the previous study, suggesting that the redesigned probes were efficient in discriminating between wild-type and mutant-type viruses. Furthermore, 133 samples from 2022, making a total of 183 samples (2020-2022), were tested using improved allelic discrimination real-time RT-PCR, and the overall prevalence rate of oseltamivir resistance in 2020-2022 was found to be 0.54%.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Mutación Missense , Proteínas Virales/genética , Farmacorresistencia Viral/genética , Mutación , Neuraminidasa/genéticaRESUMEN
The advent of influenza A (H1N1) drug-resistant strains led to the search quest for more potent inhibitors of the influenza A virus, especially in this devastating COVID-19 pandemic era. Hence, the present research utilized some molecular modelling strategies to unveil new camphor imine-based compounds as anti-influenza A (H1N1) pdm09 agents. The 2D-QSAR results revealed GFA-MLR (R2train = 0.9158, Q2=0.8475) and GFA-ANN (R2train = 0.9264, Q2=0.9238) models for the anti-influenza A (H1N1) pdm09 activity prediction which have passed the QSAR model acceptability thresholds. The results from the 3D-QSAR studies also revealed CoMFA (R2train =0.977, Q2=0.509) and CoMSIA_S (R2train =0.976, Q2=0.527) models for activity predictions. Based on the notable information derived from the 2D-QSAR, 3D-QSAR, and docking analysis, ten (10) new camphor imine-based compounds (22a-22j) were designed using the most active compound 22 as the template. Furthermore, the high predicted activity and binding scores of compound 22j were further justified by the high reactive sites shown in the electrostatic potential maps and other quantum chemical calculations. The MD simulation of 22j in the active site of the influenza hemagglutinin (HA) receptor confirmed the dynamic stability of the complex. Moreover, the appraisals of drug-likeness and ADMET properties of the proposed compounds showed zero violation of Lipinski's criteria with good pharmacokinetic profiles. Hence, the outcomes in this work recommend further in-depth in vivo and in-vitro investigations to validate these theoretical findings.Communicated by Ramaswamy H. Sarma.
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Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Humanos , Gripe Humana/tratamiento farmacológico , Alcanfor/farmacología , Alcanfor/química , Iminas/farmacología , Iminas/química , Pandemias , Relación Estructura-Actividad Cuantitativa , Anticuerpos , Simulación del Acoplamiento MolecularRESUMEN
ObjectiveTo investigate the mutation and genetic evolution of drug resistance gene of A（H1N1） pdm09 influenza pandemic strain in 2023 in Huzhou City， Zhejiang Province. MethodsRespiratory tract specimens from 2 influenza monitoring hospitals were collected forA（H1N1） pdm09 influenza virus nucleic acid detection. Positive specimens were inoculated with MDCK cells for influenza virus isolation and sequencing. DNA Star 7.1 software and Mega 4.0 software were used to analyze the neuraminidase （NA） enzyme active site and the amino acid sites related to drug resistance in M2 protein. ResultsNucleotide homology and amino acid homology of NA between the isolated and the vaccine strains were 98.87%‒99.22% and 98.94%‒99.36%， respectively. The nucleotide homology range of M gene was 99.07% to 99.85%， and the amino acid homology range was 99.02%‒99.94%. The isolates and vaccine strains belong to the evolutionary clades of 6B.1A.5a.2a. The amino acids at the key sites of the enzyme activity center of NA were still highly conserved， and the 9 key amino acid sites related to NA inhibitor resistance did not change， but some mutations occurred at the non-enzyme active sites in some popular strains. The 5 amino acid sites related to drug resistance of M2 protein were not replaced， but the 31st amino acid sites changed from serine to asparagine. ConclusionThe A（H1N1） pdm09 pandemic strain in Huzhou in 2023 has high homology with the 2023‒2024 vaccine strain recommended by WHO. All endemic strains are resistant to amantadines.
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We detected high titers of cross-reactive neuraminidase inhibition antibodies to influenza A(H5N1) virus clade 2.3.4.4b in 96.8% (61/63) of serum samples from healthy adults in Hong Kong in 2020. In contrast, antibodies at low titers were detected in 42% (21/50) of serum samples collected in 2009. Influenza A(H1N1)pdm09 and A(H5N1) titers were correlated.
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Subtipo H1N1 del Virus de la Influenza A , Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Gripe Humana , Adulto , Animales , Humanos , Neuraminidasa , Anticuerpos AntiviralesRESUMEN
Influenza virus can infect the vascular endothelium and cause endothelial dysfunction. Persons at higher risk for severe influenza are patients with acute and chronic cardiovascular disorders; however, the mechanism of influenza-induced cardiovascular system alteration remains not fully understood. The aim of the study was to assess the functional activity of mesenteric blood vessels of Wistar rats with premorbid acute cardiomyopathy infected with Influenza A(H1N1)pdm09 virus. For this, we determined (1) the vasomotor activity of mesenteric blood vessels of Wistar rats using wire myography, (2) the level of expression of three endothelial factors: endothelial nitric oxide synthase (eNOS), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) in the endothelium of mesenteric blood vessels using immunohistochemistry, and (3) the concentration of PAI-1 and tPA in the blood plasma using ELISA. Acute cardiomyopathy in animals was induced by doxorubicin (DOX) following infection with rat-adapted Influenza A(H1N1)pdm09 virus. The functional activity of mesenteric blood vessels was analyzed at 24 and 96 h post infection (hpi). Thus, the maximal response of mesenteric arteries to both vasoconstrictor and vasodilator at 24 and 96 hpi was significantly decreased compared with control. Expression of eNOS in the mesenteric vascular endothelium was modulated at 24 and 96 hpi. PAI-1 expression increased 3.47-fold at 96 hpi, while the concentration of PAI-1 in the blood plasma increased 6.43-fold at 24 hpi compared with control. The tPA concentration in plasma was also modulated at 24 hpi and 96 hpi. The obtained data indicate that influenza A(H1N1)pdm09 virus aggravates the course of premorbid acute cardiomyopathy in Wistar rats, causing pronounced dysregulation of endothelial factor expression and vasomotor activity impairment of mesenteric arteries.
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Cardiomiopatías , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Ratas , Animales , Humanos , Ratas Wistar , Activador de Tejido Plasminógeno , Inhibidor 1 de Activador PlasminogénicoRESUMEN
Influenza viruses can mutate genetically and cause a range of respiratory ailments. The H275Y mutation in the neuraminidase (NA) gene reduces the effectiveness of oseltamivir, a widely used drug for the treatment of Influenza A and B virus infection. The World Health Organization (WHO) recommends single-nucleotide polymorphism assays to detect this mutation. The present study aims to estimate the prevalence of H275Y mutation conferring oseltamivir resistance in Influenza A(H1N1)pdm09 virus among hospitalized patients from June 2014 to December 2021. Following the WHO protocol, allelic discrimination real-time RT-PCR was performed for 752 samples. Out of the 752 samples, 1 tested positive for Y275 gene mutation by allelic discrimination real-time RT-PCR. In samples of years 2020 and 2021, neither the H275 nor Y275 genotype was detected. Sequencing of the NA gene of all negative samples showed a mismatch between the NA sequence and the probes used in the allelic discrimination assay. Also, Y275 mutation was detected in only 1 sample from 2020. The prevalence of oseltamivir resistance was estimated as 0.27% among the Influenza A(H1N1)pdm09 patients during 2014-2021. The study highlights that the WHO-recommended probes for detecting H275Y mutation may not be useful to detect 2020 and 2021 circulating strains of Influenza A(H1N1)pdm09, emphasizing the need for continuous monitoring of mutations in the influenza virus.
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Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Humanos , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Antivirales/farmacología , Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Mutación Missense , Mutación , Virus de la Influenza A/genética , Neuraminidasa/genética , Farmacorresistencia Viral/genéticaRESUMEN
Community surveillance found the 2019-2020 A(H1N1)pdm09 predominant influenza season in Israel to be a high-intensity season with an early and steep morbidity peak. To further characterize disease severity in the 2019-2020 season, we analyzed a cohort of hospitalized patients with laboratory-confirmed influenza from this season (n = 636). Quantitative polymerase chain reaction was performed on clinical samples to detect the presence of influenza. Demographic, clinical, and laboratory data were retrieved via electronic health records and MDClone. Electronic health records were accessed to obtain data on intensive care unit patients, missing data and for data verification purposes. Univariate analysis was performed to compare demographic, comorbidity, and clinical characteristics across the three influenza strains. The A(H1N1)pdm09 predominant 2019-2020 influenza season in Israel was characterized by an early and steep morbidity peak, vaccine delays and shortages, and with the A(H3N2) and B/Victoria strains disproportionately targeting children and young adults, most probably due to reduced immunity to these strains. A greater proportion of children <5 years infected with A(H3N2) and B/Victoria developed severe influenza compared with those infected with A(H1N1)pdm09. Our study emphasizes the vulnerability of infants and young children in the face of rapidly evolving influenza strains and underscores the importance of influenza prevention measures in this population.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Niño , Lactante , Adulto Joven , Humanos , Preescolar , Gripe Humana/epidemiología , Subtipo H3N2 del Virus de la Influenza A , Estaciones del Año , Israel , Morbilidad , Virus de la Influenza BRESUMEN
@#Abstract: Objective To analysis the genetic evolution characteristics of hemagglutinin (HA) gene of influenza A(H1N1)pdm virus in Changsha City from 2016-2023, to understand the trend of the HA genetic evolution and the mutations of the amino acid. It provides a scientific basis for the prevention and control of influenza epidemics, as well as the screening of vaccines under the new situation. Methods The A(H1N1)pdm09 virus strains from Changsha City from 2016 to 2023 were isolated using SPF chicken embryos, and then the HA genes were sequenced by MiSeq of Illumina Inc. The homology of HA gene was analyzed by MegAlign of the DNASTAR, and the phylogenetic tree was constructed using the Neighbor Joining (NJ) method in the Molecular Evolutionary Genetics Analysis version 11 (MEGA11). Results The homology of the HA gene of A(H1N1)pdm virus in Changsha from 2016 to 2023 was between 94.8%-99.9%, with the HA gene homology decreasing annually. The homology between the isolated strains of A(H1N1)pdm09 in Changsha City from 2016 to 2023 and the WHO recommended vaccine strain ranged from 96.8% to 99.0%, indicating a relatively good match between the flu isolates and the recommended vaccine strain. The phylogenetic tree of the HA gene of the A(H1N1)pdm09 influenza virus in Changsha City showed that the HA gene evolved into several different branches within the 6B branch, and it had currently evolved to 6B.1A.5a.2a branch. Constant mutations had occurred at the amino acid sites of the four antigenic determinant clusters of HA protein. Currently, amino acid mutations had occurred at 15 antigenic sites within the four antigenic determinant clusters, and the newly emerged A186T antigen mutant site in the isolates from 2023 was worth recent notice. The receptor-binding sites are relatively conserved in loop 130, minor amino acid mutations occurred in loop 220, whether the amino acid mutation site in loop 190 is becoming more stable needs to be further monitored. Taking A/California/07/2009 (CY121680) as the reference strain, most of the A(H1N1) pdm09 isolates in Changsha was increased 162 NQTY glycosylation site and was decreased 276 NTTC glycosylation site, and the glycosylation mutations at these two sites have become more stable recently. Conclusions The HA genes of influenza A(H1N1)pdm virus in Changsha are constantly evolving and mutating, suggesting influenza surveillance should be strengthened continuously.
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The aim of this study is to provide basic information that contributes to vaccine inoculation policy after COVID-19. We used the secondary data of the influenza vaccine inoculation behavior survey for community-dwelling adults conducted in 2011, before the COVID-19 pandemic, but after the 2009 novel influenza A (H1N1) pdm 09 pandemic. All factors such as socio-demographic characteristics, health-related behaviors, family environment, physical and social environment, and area of residence were adjusted, and factors related to vaccine inoculation behavior were analyzed. Those living with pregnant women had a significantly higher odds ratio of inoculation; this was self-evident in that those people considered infection to their family. Regarding the social environment, those aged 20-64 years with a significantly higher adjusted odds ratio of inoculation were those with "at least five people with which they interacted in the neighborhood". This result can be interpreted in two ways relating to altruism in Japan. Finally, we indicated the importance of learning from the past, including the case of 2009.
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In Russia, during the COVID-19 pandemic, a decrease in influenza circulation was initially observed. Influenza circulation re-emerged with the dominance of new clades of A(H3N2) viruses in 2021-2022 and A(H1N1)pdm09 viruses in 2022-2023. In this study, we aimed to characterize influenza viruses during the 2022-2023 season in Russia, as well as investigate A(H1N1)pdm09 HA-D222G/N polymorphism associated with increased disease severity. PCR testing of 780 clinical specimens showed 72.2% of them to be positive for A(H1N1)pdm09, 2.8% for A(H3N2), and 25% for influenza B viruses. The majority of A(H1N1)pdm09 viruses analyzed belonged to the newly emerged 6B.1A.5a.2a clade. The intra-sample predominance of HA-D222G/N virus variants was observed in 29% of the specimens from A(H1N1)pdm09 fatal cases. The D222N polymorphic variant was registered more frequently than D222G. All the B/Victoria viruses analyzed belonged to the V1A.3a.2 clade. Several identified A(H3N2) viruses belonged to one of the four subclades (2a.1b, 2a.3a.1, 2a.3b, 2b) within the 3C.2a1b.2a.2 group. The majority of antigenically characterized viruses bore similarities to the corresponding 2022-2023 NH vaccine strains. Only one influenza A(H1N1)pdm09 virus showed reduced inhibition by neuraminidase inhibitors. None of the influenza viruses analyzed had genetic markers of reduced susceptibility to baloxavir.
RESUMEN
Background: Co-infection has been a significant contributor to morbidity and mortality in previous influenza pandemics. However, the current influenza A (H1N1) pdm09 virus pandemic, as the first major outbreak following the SARS-CoV-2 pandemic, may differ epidemiologically. Further investigation is necessary to understand the specific features and impact of this influenza A pandemic. Study design: We conducted a retrospective cohort study at a Chinese hospital between January and April 2023, focusing on patients with lower respiratory tract infections. Pathogen detection employed targeted next-generation sequencing (tNGS) on bronchoalveolar lavage fluid (BALF) or sputum samples. Results: This study enrolled 167 patients with lower respiratory tract infections, and the overall positivity rate detected through tNGS was around 80%. Among them, 40 patients had influenza A (H1N1) pdm09 virus infection, peaking in March. In these patients, 27.5% had sole infections, and 72.5% had co-infections, commonly with bacteria. The frequently detected pathogens were Aspergillus fumigatus, SARS-CoV-2, and Streptococcus pneumoniae. For non-influenza A virus-infected patients, the co-infection rate was 36.1%, with 42.3% having SARS-CoV-2. Patients with influenza A virus infection were younger, had more females and diabetes cases. Among them, those with sole infections were older, with less fever and asthma but more smoking history. Regarding prognosis, compared to sole influenza A virus infection, co-infected patients demonstrated higher 21-day recovery rates and a higher incidence of heart failure. However, they exhibited lower proportions of respiratory failure, acute kidney failure, septic shock, and hospital stays lasting more than 10 days. Interestingly, patients with non-influenza A virus infection had a significantly lower 21-day recovery rate. Correlation analysis indicated that the 21-day recovery rate was only associated with influenza A (H1N1) pdm09 virus. Conclusion: During the current pandemic, the influenza A (H1N1) pdm09 virus may have been influenced by the SARS-CoV-2 pandemic and did not exhibit a strong pathogenicity. In fact, patients infected with influenza A virus showed better prognoses compared to those infected with other pathogens. Additionally, tNGS demonstrated excellent detection performance in this study and showed great potential, prompting clinical physicians to consider its use as an auxiliary diagnostic tool.