Pandemic Influenza Outbreak Research Articles

Preliminary results on novel adjuvant combinations suggest enhanced immunogenicity of whole inactivated pandemic influenza vaccines

Due to the inherent risk of a further pandemic influenza outbreak, there is a need and growing interest in investigating combinations of prophylactic vaccines and novel adjuvants, particularly to achieve antigen dose sparing and improved immunogenicity. Influenza is a highly variable virus, where the specific vaccine target is constantly changing, representing a major challenge to influenza vaccine development. Currently, commercial inactivated influenza vaccines have a poor CD8+ T response, which impacts cross-reactivity and the duration of response. Adjuvanted influenza vaccines can increase immune responses, thereby achieving better protection and cross-reactivity to help contain the spread of the disease. An early exploration of a hybrid cholesterol-PLGA nanoparticle delivery system containing the saponin tomatine and a NOD2 (nucleotide-binding oligomerization domain 2) agonist called SG101 was conducted. This combination was preliminarily evaluated for its ability to induce cellular immunity when combined with whole inactivated virus (WIV) influenza vaccine. After the adjuvants were manufactured using a single emulsion process, two formulations with different drug loadings were selected and physico-chemically characterized, showing sizes between 224 ± 32 and 309 ± 45 nm and different morphologies. After ensuring the lack of in vitro toxicity and hemolytic activity, a pilot in vivo assay evaluated the hybrid nanoparticle formulation for its ability to induce humoral and cellular immunity when combined with whole inactivated virus (WIV) H5N1 influenza vaccine by intramuscular administration in mice. Hemagglutinin inhibition (HAI) titers for adjuvanted groups showed no significant difference compared to the group vaccinated with the antigen alone. It was similar for CD4+ and CD8+ T cell responses, although the high drug loading formulation induced higher titers of IFNγ-positive CD8+ T cells. These proof-of-concept results encourage further investigations to develop the hybrid formulation with increased or different loading ratios, to investigate manufacturing optimization, and to evaluate the role of the individual immunostimulatory compounds in immune responses.

Performance evaluation of a SARS-CoV-2 and influenza A/B combo rapid antigen test

Introduction: The global COVID-19 pandemic and seasonal influenza outbreaks have drawn attention to the critical need for accurate and efficient diagnostic tools.Methods: The performance of the InstaView COVID-19/Flu Ag Combo Test, which was designed to simultaneously detect the SARS-CoV-2, influenza A, and influenza B viruses, was analytically and clinically evaluated.Results: The InstaView COVID-19/Flu Ag Combo Test exhibited robust detection capabilities, accurately identifying SARS-CoV-2, influenza A, and influenza B viruses over a wide concentration range (1.41 × 103 to 7.05 × 104 TCID50/mL). Extensive testing against potential cross-reactants and interferences yielded no false-positive results, indicating the high specificity of the test. Clinical evaluation further confirmed the kit’s reliability, with sensitivity ranging from 95.1% to 98.2% for SARS-CoV-2, 88.9%–95.2% for influenza A, and 91.7%–100% for influenza B depending on the sample type. The specificity was consistently 100% for all of the targeted viruses.Discussion: The InstaView COVID-19/Flu Ag Combo Test thus demonstrated high performance, ease of use, rapid results, and the ability to precisely detect SARS-CoV-2 and influenza A/B infections, making it an effective tool in streamlining diagnostic workflows, optimizing resource allocation, and improving patient outcomes.

Comparison of geological clusters between influenza and COVID-19 in Thailand with unsupervised clustering analysis.

The coronavirus disease (COVID-19) pandemic has considerably impacted public health, including the transmission patterns of other respiratory pathogens, such as the 2009 pandemic influenza (H1N1). COVID-19 and influenza are both respiratory infections that started with a lack of vaccination-based immunity in the population. However, vaccinations have been administered over time, resulting in a transition of the status of both diseases from a pandemic to an endemic. In this study, unsupervised clustering techniques were used to identify clusters of disease trends in Thailand. The analysis incorporated three distinct surveillance datasets: the pandemic influenza outbreak, influenza in the endemic stage, and the early stages of COVID-19. The analysis demonstrated a significant difference in the distribution of provinces between Cluster -1, representing those with unique transmission patterns, and the other clusters, indicating provinces with similar transmission patterns among their members. Specifically, for Pandemic Influenza, the ratio was 61:16, while for Pandemic COVID-19, it was 65:12. In contrast, Endemic Influenza exhibited a ratio of 46:31, with a notable emergence of more clustered provinces in the southern, western, and central regions. Furthermore, a pair of provinces with highly similar spreading patterns were identified during the pandemic stages of both influenza and COVID-19. Although the similarity decreased slightly for endemic influenza, they still belonged to the same cluster. Our objective was to identify the transmission patterns of influenza and COVID-19, with the aim of providing quantitative and spatial information to aid public health management in preparing for future pandemics or transitioning into an endemic phase.

Cost effectiveness of preemptive school closures to mitigate pandemic influenza outbreaks of differing severity in the United States

BackgroundNonpharmaceutical interventions (NPIs) may be considered as part of national pandemic preparedness as a first line defense against influenza pandemics. Preemptive school closures (PSCs) are an NPI reserved for severe pandemics and are highly effective in slowing influenza spread but have unintended consequences.MethodsWe used results of simulated PSC impacts for a 1957-like pandemic (i.e., an influenza pandemic with a high case fatality rate) to estimate population health impacts and quantify PSC costs at the national level using three geographical scales, four closure durations, and three dismissal decision criteria (i.e., the number of cases detected to trigger closures). At the Chicago regional level, we also used results from simulated 1957-like, 1968-like, and 2009-like pandemics. Our net estimated economic impacts resulted from educational productivity costs plus loss of income associated with providing childcare during closures after netting out productivity gains from averted influenza illness based on the number of cases and deaths for each mitigation strategy.ResultsFor the 1957-like, national-level model, estimated net PSC costs and averted cases ranged from $7.5 billion (2016 USD) averting 14.5 million cases for two-week, community-level closures to $97 billion averting 47 million cases for 12-week, county-level closures. We found that 2-week school-by-school PSCs had the lowest cost per discounted life-year gained compared to county-wide or school district–wide closures for both the national and Chicago regional-level analyses of all pandemics. The feasibility of spatiotemporally precise triggering is questionable for most locales. Theoretically, this would be an attractive early option to allow more time to assess transmissibility and severity of a novel influenza virus. However, we also found that county-wide PSCs of longer durations (8 to 12 weeks) could avert the most cases (31–47 million) and deaths (105,000–156,000); however, the net cost would be considerably greater ($88-$103 billion net of averted illness costs) for the national-level, 1957-like analysis.ConclusionsWe found that the net costs per death averted ($180,000-$4.2 million) for the national-level, 1957-like scenarios were generally less than the range of values recommended for regulatory impact analyses ($4.6 to 15.0 million). This suggests that the economic benefits of national-level PSC strategies could exceed the costs of these interventions during future pandemics with highly transmissible strains with high case fatality rates. In contrast, the PSC outcomes for regional models of the 1968-like and 2009-like pandemics were less likely to be cost effective; more targeted and shorter duration closures would be recommended for these pandemics.

Effect of planned school breaks on student absenteeism due to influenza-like illness in school aged children-Oregon School District, Wisconsin September 2014-June 2019.

School-aged children and school reopening dates have important roles in community influenza transmission. Although many studies evaluated the impact of reactive closures during seasonal and pandemic influenza outbreaks on medically attended influenza in surrounding communities, few assess the impact of planned breaks (i.e., school holidays) that coincide with influenza seasons, while accounting for differences in seasonal peak timing. Here, we analyze the effects of winter and spring breaks on influenza risk in school-aged children, measured by student absenteeism due to influenza-like illness (a-ILI). We compared a-ILI counts in the 2-week periods before and after each winter and spring break over five consecutive years in a single school district. We introduced a "pseudo-break" of 9days' duration between winter and spring break each year when school was still in session to serve as a control. The same analysis was applied to each pseudo-break to support any findings of true impact. We found strong associations between winter and spring breaks and a reduction in influenza risk, with a nearly 50% reduction in a-ILI counts post-break compared with the period before break, and the greatest impact when break coincided with increased local influenza activity while accounting for possible temporal and community risk confounders. These findings suggest that brief breaks of in-person schooling, such as planned breaks lasting 9-16 calendar days, can effectively reduce influenza in schools and community spread. Additional analyses investigating the impact of well-timed shorter breaks on a-ILI may determine an optimal duration for brief school closures to effectively suppress community transmission of influenza.

Identification of Anti-Influenza A Compounds Inhibiting the Viral Non-Structural Protein 1 (NS1) Using a Type I Interferon-Driven Screening Strategy.

There is an urgent need to identify efficient antiviral compounds to combat existing and emerging RNA virus infections, particularly those related to seasonal and pandemic influenza outbreaks. While inhibitors of the influenza viral integral membrane proton channel protein (M2), neuraminidase (NA), and cap-dependent endonuclease are available, circulating influenza viruses acquire resistance over time. Thus, the need for the development of additional anti-influenza drugs with novel mechanisms of action exists. In the present study, a cell-based screening assay and a small molecule library were used to screen for activities that antagonized influenza A non-structural protein 1 (NS1), a highly conserved, multifunctional accessory protein that inhibits the type I interferon response against influenza. Two potential anti-influenza agents, compounds 157 and 164, were identified with anti-NS1 activity, resulting in the reduction of A/PR/8/34(H1N1) influenza A virus replication and the restoration of IFN-β expression in human lung epithelial A549 cells. A 3D pharmacophore modeling study of the active compounds provided a glimpse of the structural motifs that may contribute to anti-influenza virus activity. This screening approach is amenable to a broader analysis of small molecule compounds to inhibit other viral targets.

Quasispecies Nature of RNA Viruses: Lessons from the Past.

Viral quasispecies are distinct but closely related mutants formed by the disparity in viral genomes due to recombination, mutations, competition, and selection pressure. Theoretical derivation for the origin of a quasispecies is owed to the error-prone replication by polymerase and mutants of RNA replicators. Here, we briefly addressed the theoretical and mathematical origin of quasispecies and their dynamics. The impact of quasispecies for major salient human pathogens is reviewed. In the current global scenario, rapid changes in geographical landscapes favor the origin and selection of mutants. It comes as no surprise that a cauldron of mutants poses a significant risk to public health, capable of causing pandemics. Mutation rates in RNA viruses are magnitudes higher than in DNA organisms, explaining their enhanced virulence and evolvability. RNA viruses cause the most devastating pandemics; for example, members of the Orthomyxoviridae family caused the great influenza pandemic (1918 flu or Spanish flu), the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) outbreak, and the human immunodeficiency viruses (HIV), lentiviruses of the Retroviridae family, caused worldwide devastation. Rapidly evolving RNA virus populations are a daunting challenge for the designing of effective control measures like vaccines. Developing awareness of the evolutionary dispositions of RNA viral mutant spectra and what influences their adaptation and virulence will help curtail outbreaks of past and future pathogens.

Timing and temporal trends of influenza and pertussis vaccinations during pregnancy in three Australian jurisdictions: The Links2HealthierBubs population-based linked cohort study, 2012-2017.

Antenatal inactivated influenza (IIV) and pertussis-containing vaccines (dTpa) offer protection against severe respiratory infections for pregnant women and infants <6months of age. Both vaccines are recommended in pregnancy; however, little is known about temporal or jurisdictional trends and predictors of uptake. To identify gaps and predictors of IIV and/or dTpa vaccinations in Australian pregnancies from 2012 to 2017. We conducted a probabilistically linked, multi-jurisdictional population-based cohort study, drawing from perinatal data collections and immunisation databases. We used a generalised linear mixed model with a random effect term to account for clustering of multiple pregnancies within mothers, to calculate vaccination uptake, and identify predictors of uptake by maternal demographic, pregnancy, and health characteristics. Of 591 868 unique pregnancies, IIV uptake was 15%, dTpa 27% and 12% received both vaccines. Pertussis vaccinations in First Nations pregnancies were 20% lower than non-Indigenous pregnancies; dTpa was strongly associated with IIV uptake (risk ratio (RR): 8.60, 95% CI 8.48-8.73). This trend was temporally and jurisdictionally consistent. First Nations women were more likely to have had IIV in pregnancy before the introduction of dTpa in the pregnancy program: (RR: 1.48, 95% CI 1.40-1.57), but less likely after dTpa implementation (RR: 0.78, 95% CI 0.76-0.80). Inequity in vaccine uptake between First Nations and non-Indigenous pregnancies, and dismal rates of vaccination in pregnancy overall need urgent review, particularly before the next influenza pandemic or pertussis outbreak. If antenatal dTpa is driving IIV uptake, changes in antenatal healthcare practices are needed to ensure vaccines are offered equitably and optimally to protect against infection.

Resilience as a measure of preparedness for pandemic influenza outbreaks

ABSTRACT The global crisis generated by COVID-19 has heightened awareness of pandemic outbreaks. From a public health preparedness standpoint, it is essential to assess the impact of a pandemic and also the resilience of the affected communities, which is the ability to withstand and recover quickly after a pandemic outbreak. The infection attack rate has been the common metric to assess community response to a pandemic outbreak, while it focuses on the number of infected it does not capture other dimensions such as the recovery time. The aim of this research is to develop community resilience measures and demonstrate their estimation using a simulated pandemic outbreak in a region in the USA. Three scenarios are analysed with different combinations of virus transmissibility rates and non-pharmaceutical interventions. I The inclusion of the resilience framework in the pandemics outbreak analysis will enable decision makers to capture the multi dimensional nature of community response.

Clinical impact of nosocomial infection with pandemic influenza A (H1N1) 2009 in a respiratory ward in Guangzhou.

BackgroundNosocomial outbreaks of pandemic influenza A (H1N1) 2009 virus [A(H1N1)pdm09] easily develop due to its high transmissibility. This study aimed to investigate the clinical impacts of a nosocomial outbreak of A(H1N1)pdm09 between 21 January and 17 February 2016.MethodsPatients who developed influenza-like illness (ILI) more than 48 hours after hospitalization in the index ward were enrolled as suspected patients, defined as group A and quarantined. Patients in other wards were defined as group B. A phylogenetic tree was constructed to determine the origins of the hemagglutinin and neuraminidase genes.ResultsAfter the implementation of an infection control measure bundle, the outbreak was limited to eight patients with ILIs in group A. Nasal swabs from seven patients were positive for A(H1N1)pdm09. All the patients recovered after treatment. Prolonged viral shedding was observed in a patient with bronchiectasis and Penicillium marneffei infection. Compared to the expected duration of hospitalization in patients without fever, those with fever had a median 7-day delay in discharge and a mean excess cost of 3,358 RMB. The four influenza strains identified were genetically identical to the A/California/115/2015 strain. Six of the 54 patients in group B who underwent bronchoscopy developed transient fever. These patients were hospitalized in various wards of the hospital and recovered after a short-term course of empirical antibiotics.ConclusionsAfter the implementation of infection control measures, the nosocomial A(H1N1)pdm09 outbreak was rapidly contained; infected patients had a delay in discharge and excess costs, but no deaths occurred.

A location-allocation model for influenza pandemic outbreaks: A case study in India

Previous pandemics in 1918, 1957, 1968, and the ongoing COVID-19 pandemic have provided sufficient evidence of health concerns caused by influenza pandemics. The existing health care system is overwhelmed by the surging demand of susceptible and infected individuals due to the COVID-19 outbreak. It is crucial to identify and isolate infected individuals to prevent pandemic spread. Thus, a mixed-integer linear programming model is proposed in this study for the location-allocation of health care facility networks (i.e., temporary testing laboratories). The objective of this study is to ensure that test samples from various geographical locations reach testing laboratories as soon as possible and at minimum cost to ensure timely testing. Hence, the proposed model has two objectives: (i) minimization of the total cost and (ii) minimization of the maximum travel time from a patient node to a testing facility. Furthermore, to prevent capacity underutilization, the capacity of temporary testing laboratories is tailored in the model. A case study in Maharashtra, India, is used to demonstrate the real-life applicability of the proposed model. The study results has interesting implications for decision- and policy-makers.

Downstream processing for influenza vaccines and candidates: An update.

Seasonal and pandemic influenza outbreaks present severe health and economic burdens. To overcome limitations on influenza vaccines' availability and effectiveness, researchers chase universal vaccines providing broad, long-lasting protection against multiple influenza subtypes, and including pandemic ones. Novel influenza vaccine designs are under development, in clinical trials, or reaching the market, namely inactivated, or live-attenuated virus, virus-like particles, or recombinant antigens, searching for improved effectiveness; all these bring downstream processing (DSP) new challenges. Having to deal with new influenza strains, including pandemics, requires shorter development time, driving the development of faster bioprocesses. To cope with better upstream processes, new regulatory demands for quality and safety, and cost reduction requirements, new unit operations and integrated processes are increasing DSP efficiency for novel vaccine formats. This review covers recent advances in DSP strategies of different influenza vaccine formats. Focus is given to the improvements on relevant state-of-the-art unit operations, from harvest and clarification to purification steps, ending with sterile filtration and formulation. The development of more efficient unit operations to cope with biophysical properties of the new candidates is discussed: emphasis is given to the design of new stationary phases, 3D printing approaches, and continuous processing tools, such as continuous chromatography. The impact of the production platforms and vaccine designs on the downstream operations for the different influenza vaccine formats approved for this season are highlighted.

Effectiveness of isolation policies in schools: evidence from a mathematical model of influenza and COVID-19.

BackgroundNon-pharmaceutical interventions such as social distancing, school closures and travel restrictions are often implemented to control outbreaks of infectious diseases. For influenza in schools, the Center of Disease Control (CDC) recommends that febrile students remain isolated at home until they have been fever-free for at least one day and a related policy is recommended for SARS-CoV-2 (COVID-19). Other authors proposed using a school week of four or fewer days of in-person instruction for all students to reduce transmission. However, there is limited evidence supporting the effectiveness of these interventions.MethodsWe introduced a mathematical model of school outbreaks that considers both intervention methods. Our model accounts for the school structure and schedule, as well as the time-progression of fever symptoms and viral shedding. The model was validated on outbreaks of seasonal and pandemic influenza and COVID-19 in schools. It was then used to estimate the outbreak curves and the proportion of the population infected (attack rate) under the proposed interventions.ResultsFor influenza, the CDC-recommended one day of post-fever isolation can reduce the attack rate by a median (interquartile range) of 29 (13–59)%. With 2 days of post-fever isolation the attack rate could be reduced by 70 (55–85)%. Alternatively, shortening the school week to 4 and 3 days reduces the attack rate by 73 (64–88)% and 93 (91–97)%, respectively. For COVID-19, application of post-fever isolation policy was found to be less effective and reduced the attack rate by 10 (5–17)% for a 2-day isolation policy and by 14 (5–26)% for 14 days. A 4-day school week would reduce the median attack rate in a COVID-19 outbreak by 57 (52–64)%, while a 3-day school week would reduce it by 81 (79–83)%. In both infections, shortening the school week significantly reduced the duration of outbreaks.ConclusionsShortening the school week could be an important tool for controlling influenza and COVID-19 in schools and similar settings. Additionally, the CDC-recommended post-fever isolation policy for influenza could be enhanced by requiring two days of isolation instead of one.

Transcriptional and Immunologic Correlates of Response to Pandemic Influenza Vaccine in Aviremic, HIV-Infected Children

People living with HIV (PWH) often exhibit poor responses to influenza vaccination despite effective combination anti-retroviral (ART) mediated viral suppression. There exists a paucity of data in identifying immune correlates of influenza vaccine response in context of HIV infection that would be useful in improving its efficacy in PWH, especially in younger individuals. Transcriptomic data were obtained by microarray from whole blood isolated from aviremic pediatric and adolescent HIV-infected individuals (4-25 yrs) given two doses of Novartis/H1N1 09 vaccine during the pandemic H1N1 influenza outbreak. Supervised clustering and gene set enrichment identified contrasts between individuals exhibiting high and low antibody responses to vaccination. High responders exhibited hemagglutination inhibition antibody titers >1:40 post-first dose and 4-fold increase over baseline. Baseline molecular profiles indicated increased gene expression in metabolic stress pathways in low responders compared to high responders. Inflammation-related and interferon-inducible gene expression pathways were higher in low responders 3 wks post-vaccination. The broad age range and developmental stage of participants in this study prompted additional analysis by age group (e.g. <13yrs and ≥13yrs). This analysis revealed differential enrichment of gene pathways before and after vaccination in the two age groups. Notably, CXCR5, a homing marker expressed on T follicular helper (Tfh) cells, was enriched in high responders (>13yrs) following vaccination which was accompanied by peripheral Tfh expansion. Our results comprise a valuable resource of immune correlates of vaccine response to pandemic influenza in HIV infected children that may be used to identify favorable targets for improved vaccine design in different age groups.

Neutralizing antibody PR8-23 targets the footprint of the sialoglycan receptor binding site of H1N1 hemagglutinin.

Influenza virus cause seasonal influenza epidemic and seriously sporadic influenza pandemic outbreaks. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Variation in the sialic acid receptor binding site leads to strain-specific binding and results in different binding modes to the host receptors. Here, we evaluated the neutralizing activity and hemagglutination inhibition activity of a prepared murine anti-H1N1 monoclonal antibody PR8-23. Then we identified the epitope peptide of antibody PR8-23 by phage display technique from phage display peptide libraries. The identified epitope, 63-IAPLQLGKCNIA-74, containing two α-helix and two β-fold located at the footprint of the sialoglycan receptor on the RBS in the globular head domain of HA. It broads the growing arsenal of motifs for the amino acids on the globular head domain of HA in sialic acid receptor binding site and neutralizing antibody production.

Nucleic Acid-Based Sensing Techniques for Diagnostics and Surveillance of Influenza

Influenza virus poses a threat to global health by causing seasonal outbreaks as well as three pandemics in the 20th century. In humans, disease is primarily caused by influenza A and B viruses, while influenza C virus causes mild disease mostly in children. Influenza D is an emerging virus found in cattle and pigs. To mitigate the morbidity and mortality associated with influenza, rapid and accurate diagnostic tests need to be deployed. However, the high genetic diversity displayed by influenza viruses presents a challenge to the development of a robust diagnostic test. Nucleic acid-based tests are more accurate than rapid antigen tests for influenza and are therefore better candidates to be used in both diagnostic and surveillance applications. Here, we review various nucleic acid-based techniques that have been applied towards the detection of influenza viruses in order to evaluate their utility as both diagnostic and surveillance tools. We discuss both traditional as well as novel methods to detect influenza viruses by covering techniques that require nucleic acid amplification or direct detection of viral RNA as well as comparing advantages and limitations for each method. There has been substantial progress in the development of nucleic acid-based sensing techniques for the detection of influenza virus. However, there is still an urgent need for a rapid and reliable influenza diagnostic test that can be used at point-of-care in order to enhance responsiveness to both seasonal and pandemic influenza outbreaks.

Public Health Interventions, Epidemic Growth, and Regional Variation of the 1918 Influenza Pandemic Outbreak in a Swiss Canton and Its Greater Regions.

Public health interventions implemented during the coronavirus disease 2019 (COVID-19) pandemic are based on experience gained from past pandemics. The 1918 influenza pandemic is the most extensively researched historical influenza outbreak. All 9335 reports available in the State Archives on 121 152 cases of influenza-like illness from the canton of Bern from 473 of 497 municipalities (95.2%) were collected; the cases were registered between 30 June 1918 and 30 June 1919. The overall incidence rates of newly registered cases per week for the 9 greater regions of Bern for both the first and second waves of the pandemic were calculated. Relative incidence rate ratios (RIRRs) were calculated to estimate the change in the slope of incidence curves associated with public health interventions. During the first wave, school closures (RIRR, 0.16 [95% CI, 0.15 to 0.17]) and restrictions of mass gatherings (RIRR, 0.57 [CI, 0.54 to 0.61]) were associated with a deceleration of epidemic growth. During the second wave, in autumn 1918, cantonal authorities initially reacted hesitantly and delegated the responsibility to enact interventions to municipal authorities, which was associated with a lack of containment of the second wave. A premature relaxation of restrictions on mass gatherings was associated with a resurgence of the epidemic (RIRR, 1.18 [CI, 1.12 to 1.25]). Strikingly similar patterns were found in the management of the COVID-19 outbreak in Switzerland, with a considerably higher amplitude and prolonged duration of the second wave and much higher associated rates of hospitalization and mortality.

The study of neuraminidase immunity in protection against secondary bacterial pneumonia induced by &lt;i&gt;S. aureus&lt;/i&gt; after influenza infection in mice

Introduction. Pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. We previously have shown that vaccination with Virus-like particles (VLPs) containing hemagglutinin (HA) of influenza virus reduces mortality caused by bacterial infections after an influenza infections in mice.The aim of this work is to study whether this protective effect may be potentiated by supplementing the HA preparation with the influenza neuraminidase (NA).Materials and methods. We studied the effect of Gag-VLPs with the influenza HA or NA from А/PR/8/34 alone or in combination, in a lethal BALB/c mouse model of S. aureus infection after vaccine-matched or mismatched influenza virus challenge.Results. A cocktail of HA-Gag and NA-Gag-VLPs fully protected from weight loss, mortality and viral replication and significantly reduced the bacterial burden in the lungs of А/PR/8/34 infected animals. Immunization with this cocktail HA-Gag-VLPs 100 ng + NA-Gag-VLPs 20 ng also protected 60% of animals from mortality associated with secondary bacterial S. aureus infection following a heterologous H1N1 influenza virus challenge, and led to the significant protection from weight loss and pulmonary pathogen replication even in the absence of HA-inhibition and NA-inhibition antibodies.Conclusion. Our results indicate that influenza vaccination may improve the outcome of a secondary bacterial pneumonia induced by S. aureus after influenza even when the virus is antigenically different from the vaccine strain. At the same time, in our model, the significance of the immunity to influenza virus HA was prevalent.

Application of Telemedicine in Diabetes Care: The Time is Now.

The utilization of telemedicine solutions to reduce outpatient clinic visits and visits to physicians' offices, thus saving financial and personal resources as well as time, has gained substantial importance in recent years. The COVID19 pandemic has made it necessary to abruptly adjust outpatient care methods in various medical settings that needlessly require consultations in person to monitor and change the disease management of patients in specific risk groups. People with diabetes represent a vulnerable population who need to be protected from avoidable outpatient clinic visits, particularly in times of influenza or other pandemic outbreaks. However, the treatment and care of patients with diabetes and its comorbidities require careful and regular monitoring and therapy adjustments by medical staff. Advanced age or cognitive impairment and insufficient access to the health care system due to low socioeconomic status can complicate the use of possible alternatives to in-person consultations in outpatient clinics or physicians' offices. Telemedicine solutions may offer suitable alternatives to standard face-to-face consultations in outpatient settings and provide sufficient access to appropriate diabetes care. Nevertheless, telemedicine methods for monitoring diabetes issues are yet to find widespread use due to numerous barriers, such as a lack of acceptance and doubt about its time- and cost-effectiveness, availability, and potential technical and regulatory issues. This article offers an overview of existing applications that provide telemedicine diabetes care. Furthermore, it discusses potential ways to restructure and revolutionize diabetes outpatient care.

Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice

During the influenza pandemic or seasonal influenza outbreak, influenza infection can cause acute influenza-associated encephalopathy/encephalitis (IAE), even death. Patients with severe IAE will also have severe neurological sequelae. Neurologic disorders have been demonstrated in the mice treated with peripheral influenza viruses infection, whether neurotropic or non-neurotropic viruses. However, previous studies focused on the acute phase of infection, and rarely paid attention to a longer range of observations. Therefore, the long-term effect of non-neurotropic virus infection on the host is not very clear. In this study, adult mice were infected with influenza virus H1N1/PR8. Then, spontaneous behavior, body weight, expression of cytokines in brain, spatial learning ability and spatial memory ability were observed, until the complete recovery period. The results showed that cytokines in the brain were highly expressed in the convalescent phase (14 day post inoculation, dpi), especially BDNF, IBA1, CX3CL1 and CD200 were still highly expressed in the recovery phase (28 dpi). Otherwise the emotional and spatial memory ability of mice were impacted in the convalescent phase (14 dpi) and the recovery phase (28 dpi). In brief, BALB/c mice infected with non-neurotropic influenza virus H1N1, the weight and motor ability decreased in acute stage. During the recovery period, the body weight and activity ability were completely restored, whereas the emotion disordered, and the ability of spatial learning and memory were impacted in the infected mice. This long-term behavior impact may be the lag injury caused by non-neurotropic influenza infection.