Is avian influenza virus A(H5N1) a real threat to human health?

The A(H5N1) influenza remains a disease of birds with a significant species barrier: in the presence of some tens million cases of infection in poultry - with a wide geographical spread -, only a few hundreds cases have occurred in humans. To date, human cases have been reported in 15 countries - mainly in Asia - and all were related to the onset of outbreaks in poultry. A peak of H5N1 human cases was recorded in 2006, then decreasing in subsequent years. Despite this trend, the H5N1 virus still represents a possible threat to human health, considering that more than half of human cases of H5N1 have been fatal. Moreover, despite the drop in the number of cases, the risk of a novel pandemic cannot be excluded, since H5N1 continues to circulate in poultry in countries with elevated human population density and where monitoring systems are not fully appropriate. In addition, there is a major global concern about the potential occurrence of a reassortment between the 2009 pandemic H1N1 and the highly pathogenic H5N1 influenza viruses following a co-infection in a susceptible host. Therefore, the implementation of appropriate surveillance and containment measures is crucial in order to minimize such risk. In conclusion, H5N1 avian influenza is still a rare disease in humans but its clinical severe outcome requires a careful monitoring of the virus?s ability to evolve and to trigger a new pandemic

Molecular characterization and phylogenetic analysis of human influenza A viruses in three consecutive seasons with different epidemiological profiles

Introduction. Influenza activity and influenza virus circulation were observed in Lombardy (northern Italy) during three con- secutive seasons and the molecular characteristics of circulating viruses analysed to control for introduction of new variants. Methods. The molecular characterization of 38 isolates, namely 20 A/H3N2 and 18 A/H1N1 influenza strains from the 2005/06, 2006/07 and 2007/08 seasons, was performed by sequence analy- sis of the globular head region of the HA protein (HA1 subunit), specific for influenza virus A/H3 and A/H1. Results and discussion. The last three influenza seasons in the study region were characterized by medium-low activity. A typical co-circulation of several variants was shown for A/H3 viruses for approximately two years and were subsequently almost entirely substituted by new emerging variants. Vice versa, A/H1 viruses had a more homogeneous circulation with a single lineage clearly dominating each season. The HA sequences of the A/H3 and the A/H1 viruses isolated in the last three seasons fell into 4 and 3 principal phylogenetic groups, respectively. No evidence of positive or negative selection in the sequence align- ments was observed. Conclusions. Molecular characterization of the influenza viruses in three consecutive seasons highlighted considerable heteroge- neity in their HA sequences. A careful surveillance of genetic changes in the HA1 domain during seasonal influenza epidemics may reveal immune escape and provide early information on newly emerging strains with epidemiologic inference

Early co-circulation of different clades of influenza A/H1N1v pandemic virus in Northern Italy

Introduction. The spatial diffusion over time of pandemic influenza A/H1N1 virus (A/H1N1v) was surveyed in Northern Italy (nearly 10 million inhabitants) from April to December 2009, and the molecular characteristics of circulating viruses were analyzed to identify the appearance of drift variants. About 45% of analyzed samples were laboratory-confirmed cases of A/H1N1v. Sporadic cases occurred until the middle of June 2009, then, case numbers began to increase delineating distinct epidemiological phases of viral circulation. Methods. RNA was extracted using RNeasy Mini kit (QIAGEN GmbH, Germany). Virological diagnosis of A/H1N1v infection was carried out by real-time RT-PCR assay. Sequence analysis of hemagglutinin (HA) gene was performed through a RT-PCR assay specific for a 995 bp fragment (nt. 64-1,058) in the HA1 domain. The nucleotide sequences were obtained by automated DNA sequencing. The HA1 sequences were aligned with other sequences collected from GenBank database by ClustalX software. The multiple sequence alignment was used to perform a basic phylogenetic analysis and a phylogenetic tree from HA sequences was constructed. Results. The HA gene sequences of A/H1N1v analyzed segregated into three genetically distinct clades and were characterized by the appearance of amino acid variations that were progressively fixed in the field viral population under scrutiny. Conclusions. These data suggest an early co-circulation of genetically distinct A/H1N1v variants and emphasize the importance of a close molecular surveillance to detect rapidly the spread of new viral variants and to define their epidemiological impact

Estimation of Reduction in Influenza Vaccine Effectiveness Due to Egg-Adaptation Changes—Systematic Literature Review and Expert Consensus

Background: Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines. Methods: Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts’ responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated. Results: The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7–21% and reduce IVE by 4–16%. According to the experts, antigenic drift results in a similar impact on VM (8–24%) and IVE (5–20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons. Conclusions: Expert estimates suggest there is a potential for 9% on average (weighted average of “All strains” over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the <65 age group) if egg adaptations that arise when employing the traditional egg-based manufacturing process are avoided

Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir-an orally available inhibitor of the 3-chymotrypsin-like cysteine protease-has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals

Prevalence of Influenza B/Yamagata Viruses From Season 2012/2013 to 2021/2022 in Italy as an Indication of a Potential Lineage Extinction

Background: Influenza B/Yamagata viruses exhibited weak antigenic selection in recent years, reducing their prevalence over time and requiring no update of the vaccine component since 2015. To date, no B/Yamagata viruses have been isolated or sequenced since March 2020. Methods: The antibody prevalence against the current B/Yamagata vaccine strain in Italy was investigated: For each influenza season from 2012/2013 to 2021/2022, 100 human serum samples were tested by haemagglutination inhibition (HAI) assay against the vaccine strain B/Phuket/3073/2013. In addition, the sequences of 156 B/Yamagata strains isolated during the influenza surveillance activities were selected for analysis of the haemagglutinin genome segment. Results: About 61.9% of the human samples showed HAI antibodies, and 21.7% had protective antibody levels. The prevalence of antibodies at protective levels in the seasons between the isolation of the strain and its inclusion in the vaccine was between 11% and 25%, with no significant changes observed in subsequent years. A significant increase was observed in the 2020/2021 season, in line with the increase in influenza vaccine uptake during the pandemic. Sequence analysis showed that from 2014/2015 season onward, all B/Yamagata strains circulating in Italy were closely related to the B/Phuket/2013 vaccine strain, showing only limited amino acid variation. Conclusions: A consistent prevalence of antibodies to the current B/Yamagata vaccine strain in the general population was observed. The prolonged use of a well‐matched influenza vaccine and a low antigenic diversity of B/Yamagata viruses may have facilitated a strong reduction in B/Yamagata circulation, potentially contributing to the disappearance of this lineage

On the lookout for influenza viruses in Italy during the 2021-2022 season: along came A(H3N2) viruses with a new phylogenetic makeup of their hemagglutinin

Aims: To assess influenza viruses (IVs) circulation and to evaluate A(H3N2) molecular evolution during the 2021-2022 season in Italy. Materials and methods: 12,393 respiratory specimens (nasopharyngeal swabs or broncho-alveolar lavages) collected from in/outpatients with influenza illness in the period spanning from January 1, 2022 (week 2022-01) to May 31, 2022 (week 2022-22) were analysed to identify IV genome and molecularly characterized by 12 laboratories throughout Italy. A(H3N2) evolution was studied by conducting an in-depth phylogenetic analysis of the hemagglutinin (HA) gene sequences. The predicted vaccine efficacy (pVE) of vaccine strain against circulating A(H3N2) viruses was estimated using the sequence-based Pepitope model. Results: The overall IV-positive rate was 7.2% (894/12,393), all were IV type A. Almost all IV-A (846/894; 94.6%) were H3N2 that circulated in Italy with a clear epidemic trend, with 10% positivity rate threshold crossed for six consecutive weeks from week 2022-11 to week 2022-16. According to the phylogenetic analysis of a subset of A(H3N2) strains (n=161), the study HA sequences were distributed into five different genetic clusters, all of them belonging to the clade 3C.2a, sub-clade 3C.2a1 and the genetic subgroup 3C.2a1b.2a.2. The selective pressure analysis of A(H3N2) sequences showed evidence of diversifying selection particularly in the amino acid position 156. The comparison between the predicted amino acid sequence of the 2021-2022 vaccine strain (A/Cambodia/e0826360/2020) and the study strains revealed 65 mutations in 59 HA amino acid positions, including the substitution H156S and Y159N in antigenic site B, within major antigenic sites adjacent to the receptor-binding site, suggesting the presence of drifted strains. According to the sequence-based Pepitope model, antigenic site B was the dominant antigenic site and the p(VE) against circulating A(H3N2) viruses was estimated to be -28.9%. Discussion and conclusion: After a long period of very low IV activity since public health control measures have been introduced to face COVID-19 pandemic, along came A(H3N2) with a new phylogenetic makeup. Although the delayed 2021-2022 influenza season in Italy was characterized by a significant reduction of the width of the epidemic curve and in the intensity of the influenza activity compared to historical data, a marked genetic diversity of circulating A(H3N2) strains was observed. The identification of the H156S and Y159N substitutions within the main antigenic sites of the most of sequences also suggested the circulation of drifted variants with respect to the 2021-2022 vaccine strain. Molecular surveillance plays a critical role in the influenza surveillance architecture and it has to be strengthened also at local level to timely assess vaccine effectiveness and detect novel strains with potential impact on public health

Population-level benefits of increasing influenza vaccination uptake among Italian older adults: results from a granular panel model

BackgroundThe impact of seasonal influenza vaccination (SIV) on mortality is still controversial; some studies have claimed that increasing vaccination coverage rates is beneficial, while others have found no significant association. This study aimed to construct a granular longitudinal dataset of local VCRs and assess their effect on pneumonia- and influenza-related (P&amp;I) mortality among Italian adults aged ≥ 65 years.MethodsNUTS-3 (nomenclature of territorial units for statistics) level data on SIV coverage were collected via a survey of local data holders. Fixed- and random-effects panel regression modeling, when adjusted for potential confounders, was performed to assess the association between local SIV coverage rates and P&amp;I mortality in older adults.ResultsA total of 1,144 local VCRs from 2003 to 2019 were ascertained. In the fully adjusted fixed-effects model, each 1% increase in vaccination coverage was associated (P &lt; 0.001) with a 0.6% (95% CI: 0.3–0.9%) average over-time decrease in P&amp;I mortality. With an annual average of 9,293 P&amp;I deaths in Italy, this model suggested that 56 deaths could have been avoided each year by increasing SIV coverage by 1%. The random-effects model produced similar results. The base-case results were robust in a sensitivity analysis.ConclusionOver the last two decades, Italian jurisdictions with higher SIV uptake had, on average, fewer P&amp;I deaths among older adults. Local policy-makers should implement effective strategies to increase SIV coverage in the Italian senior population

Concentración de flúor y arsénico en el agua de red de General Pico (Argentina) durante el periodo 2007-2013/ Fluor and Arsenic concentration in tap water of General Pico from the period of 2007 to 2013

The province of La Pampa (Argen­tina) is characterized by high concentrations of arsenic and fluorine in groundwater. In this work, the concentration of fluorine and arse­nic in public potable water from General Pico and its evolution were determined. The aver­age concentration of both arsenic (0.059 mg/l) and fluorine (2,339 mg/l) in the public tap water during the period 2007-2013 exceeded those figures allowed for human consumption by the Argentine Food Code and the World Health Organization, whose maximum acceptable fig­ures are 0.01 mg/l for arsenic and 1.2 mg /l for fluoride. The arsenic concentration in the public potable water tended to decrease when rainfall increased, while the fluoride concentration was independent of the level of precipitations. Peo­ple exposed to high concentrations of arsenic tend to be also exposed to high concentrations of fluorideLa provincia de La Pampa (Argentina) se caracteriza por presentar en sus aguas subterráneas alta concentración de arsénico y flúor. En este trabajo, se determinó la concentración de flúor y arsénico en el agua de red que llega a los habitantes de la ciudad de General Pico y su evolución. La concentración promedio tanto de arsénico (0,059 mg/l) como de flúor (2,339 mg/l) en el agua de red superó en el periodo 2007-2013 los valores permitidos por el Código Alimentario Argentino y la Organización Mundial de la Salud, cuyos valores máximos aceptables son de 0,01 mg/l para el arsénico y de 1,2 mg/l para el flúor. La concentración de arsénico disminuyó en el agua de red cuando aumentó la cantidad de precipitaciones, mientras que la concentración de flúor fue in dependiente del nivel de precipitiaciones. La población expuesta a altas concentraciones de arsénico tiende a encontrarse también expuesta a altas concentraciones de flúor DOI:http://dx.doi.org/10.19137/cienvet2014161