Pandemic Influenza Research Articles

Contribution of immunoglobulin products in influencing seasonal influenza infection and severity in antibody immune deficiency patients receiving immunoglobulin replacement therapy

Seasonal and pandemic influenza infection present a potential threat to patients with antibody deficiency. The acceptance and effect of the current recommendation for annual vaccination against influenza for patients with antibody deficiency is not well investigated and due to antigenic drift or shift the protective capacity of regular IgG replacement therapy (IgRT) is considered low. This narrative review considers the effect of influenza vaccination in immunodeficient patients and discusses available information on the effect of immunoglobulin products on seasonal influenza infectivity and severity in antibody deficiency patients receiving IgRT. The humoral immune response to seasonal influenza vaccination is reduced in patients with antibody immune deficiency. However, there is no evidence that the proportion of patients with primary antibody deficiency who develop influenza illness, and the severity of such illness, is increased when compared with the general population. The IgRT that patients receive has been shown to contain neutralizing antibodies as a consequence of past flu infections against both the hemagglutinin and neuraminidase surface proteins and other viral internal proteins of different influenza A virus strains. Studies have demonstrated not only significant levels of specific but also cross-reactive antibodies against seasonal influenza virus strains. Thus, despite the yearly changes in influenza viral antigenicity that occur, IgRT could potentially contribute to the protection of patients against seasonal influenza. Currently, only limited clinical data are available confirming a preventative effect of IgRT with respect to seasonal influenza infection. In conclusion, there is some evidence that IgRT could contribute to protection against seasonal influenza in patients with antibody-related immunodeficiency. However, additional clinical data are needed to confirm the extent and relevance of this protection and identify the main responsible virus targets of that protection.

Andrew Walls, the Pandemic, and the Reinterpretation of Christian Faith

The recent Covid pandemic may well be introducing historic changes to Christian faith that we cannot yet see. Looking back, we can see religious shifts that occurred in response to the influenza pandemic of 1918, including the rise of new forms of Christian community in Africa. Christian faith, Andrew Walls (1928–2021) saw, is not just something you receive; faith remakes you, and you remake it. Walls urged the Western theological academy to embrace the changes taking place as a result of the shift in the centre of Christian gravity. Going forward, we may be seeing the seeds of change from the pandemic in a more holistic Christian faith, one that emphasizes the evangel for all of creation.

Potent Anti-Influenza Synergistic Activity of Theobromine and Arainosine.

Influenza represents one of the biggest health threats facing humanity. Seasonal epidemics can transition to global pandemics, with cross-species infection presenting a continuous challenge. Although vaccines and several anti-viral options are available, constant genetic drifts and shifts vitiate any of the aforementioned prevention and treatment options. Therefore, we describe an approach targeted at the virus's channel to derive new anti-viral options. Specifically, Influenza A's M2 protein is a well-characterized channel targeted for a long time by aminoadamantane blockers. However, widespread mutations in the protein render the drugs ineffective. Consequently, we started by screening a repurposed drug library against aminoadamantane-sensitive and resistant M2 channels using bacteria-based genetic assays. Subsequent in cellulo testing and structure-activity relationship studies yielded a combination of Theobromine and Arainosine, which exhibits stark anti-viral activity by inhibiting the virus's channel. The drug duo was potent against H1N1 pandemic swine flu, H5N1 pandemic avian flu, aminoadamantane-resistant and sensitive strains alike, exhibiting activity that surpassed Oseltamivir, the leading anti-flu drug on the market. When this drug duo was tested in an animal model, it once more outperformed Oseltamivir, considerably reducing disease symptoms and viral RNA progeny. In conclusion, the outcome of this study represents a new potential treatment option for influenza alongside an approach that is sufficiently general and readily applicable to other viral targets.

Risk Management in Deadly Times: The U.S. Life Insurance Industry in the 1918–9 Influenza Pandemic

AbstractUsing a novel, hand‐collected dataset of U.S. life insurance companies during the influenza pandemic of 1918–9, we show that high‐exposure life insurers charged higher prices on new policies vis‐à‐vis less exposed firms. Although the disease surprisingly increased the mortality rates among younger adults, it also increased awareness of the importance of life insurance. We argue that price increases were a crucial risk management tool. Coupled with a surge in demand and coverage, it prevented further financial distress. Although devastating for public health, the influenza pandemic was not too severe for the life insurance industry.

Investigation of the Effect of the COVID-19 Pandemic Period on Respiratory Tract Viruses at Istanbul Medical Faculty Hospital, Turkey.

Aim: Respiratory viruses significantly impact public health, contributing to high morbidity and mortality rates in both children and adults. This study evaluates the distribution and incidence of respiratory tract viruses in our hospital from 2019 to 2022, focusing on changes post-COVID-19 pandemic. Material and Methods: Utilizing molecular methods, we analyzed nasopharyngeal swabs with the FTD Respiratory Pathogens 21 kit and the QIAStat Dx Respiratory Panel kit at Istanbul Faculty of Medicine. A total of 1186 viruses were detected in 2488 samples (47.6% of the total) examined with the FTD Respiratory Pathogens 21 kit between 2019 and 2022. Results: It was determined that the detection rates were 52.8% in 2019, 44.3% in 2020, 50.0% in 2021, and 40.0% in 2022. Notable changes in prevalence were observed for pandemic influenza A (IAV-H1N1pdm2009), parainfluenza virus (PIV)-3, rhinovirus (RV), and respiratory syncytial virus (RSV)-A/B (p < 0.05). RV consistently showed the highest detection rates across all years (17.6% to 7.9%). Additionally, 1276 viruses were detected in 1496 samples using the QIAStat DX kit, with 91.3% positivity in 2021 and 78.6% in 2022, highlighting the kit's effectiveness in rapid diagnosis. Conclusions: This study enhances understanding of respiratory virus epidemiology during and after the pandemic, emphasizing the need for ongoing surveillance and strategic public health measures to address the evolving landscape of respiratory infections.

Community and Care: Black Civil Society and the Influenza Pandemic of 1918 in the United States

Abstract During the deadliest pandemic of the twentieth century, the Great Influenza pandemic of 1918–1920, African Americans in the United States appeared to be an especially vulnerable population. The health effects of racialized segregation, produced by congested housing conditions, environmental racism, and exclusion from or discrimination in healthcare services, threatened a devastating situation during the second wave of the pandemic in late 1918. This paper argues that a network of Black civil society organizations and activists sprang into action to ameliorate the worst effects of this public health emergency, and that it was able to provide care and relief that would have largely been denied by white-led public and private institutions. This network had been built up in the preceding decades and can therefore serve as an important model and informational resource in utilizing community-centered planning to prepare marginalized peoples for the spread of pandemic disease.

Occupational Participation Among Older Adults During the COVID-19 Pandemic.

Background. The COVID-19 pandemic led to abrupt occupational disruption for all people. However, some populations, like older adults, were disproportionately impacted particularly in the earlier waves. Purpose. The purpose of this study was to explore and understand how the occupational participation of community-dwelling older adults was experienced during the COVID-19 pandemic, using the Canadian Model of Occupational Participation (CanMOP) to contextualize findings. Method. Sixty-seven older adults participated in semi-structured interviews from September 2020 to May 2021, 37 of which also participated in a follow-up interview one-year later. Findings. Using reflexive thematic analysis, four themes were generated: (1) experiences of loss are complex and layered for older adults, (2) technology as a medium for occupational participation, (3) risk perception influences return to occupation, and (4) age-related challenges for older adults resuming volunteer work. Conclusion. Increasing frequency and severity of influenza pandemics and other disasters are a global concern, and OTs can use their skillsets to foster participation and expand occupational possibilities for older adults. The CanMOP was a helpful tool to understand the nuances underlying the participation of older adults in this context.

A protocol for a living mapping review of global research funding for infectious diseases with a pandemic potential - Pandemic PACT.

The COVID CIRCLE initiative Research Project Tracker by UKCDR and GloPID-R and associated living mapping review (LMR) showed the importance of sharing and analysing data on research at the point of funding to improve coordination during a pandemic. This approach can also help with research preparedness for outbreaks and hence our new programme the Pandemic Preparedness: Analytical Capacity and Funding Tracking Programme (Pandemic PACT) has been established. The LMR described in this protocol builds on the previous UKCDR and GloPID-R COVID-19 Research Project database with addition of the priority diseases from the WHO Blueprint list plus initial additions of pandemic influenza, mpox and plague. We capture data on new funding commitments directly from funders and map these against a core ontology (aligned to existing research roadmaps). We will analyse regularly collated new research funding commitments to provide an open, accessible, near-real-time overview of the funding landscape for a wide range of infectious disease and pandemic preparedness research and assess gaps. The periodicity of updates will be increased in the event of a major outbreak. We anticipate that this LMR and the associated online tool will be a useful resource for funders, policy makers and researchers. In the future, our work will inform a more coordinated approach to research funding by providing evidence and data, including identification of gaps in funding allocation with a particular focus on low- and middle-income countries.

A Rapid Virus-Free Method for Producing Influenza HA Immunogen Needed for Preparation of Influenza Vaccine Potency Antisera Reagents.

The potency of inactivated and recombinant influenza vaccines is measured using the single-radial immunodiffusion (SRID) assay. The strain-specific antigen and antibody potency reagents required for the assay are prepared and distributed by regulatory agencies to ensure vaccine standardization, but timely reagent production is always challenging. This poses unique concerns for rapid pandemic responses. Alternative methods have been described for generating strain-specific potency antibody reagents without the need for live influenza virus, but such methods are infrequently used, suggesting the need for additional antigen expression approaches. We describe a rapid process using a mammalian expression system to produce recombinant influenza hemagglutinin (rHA). This platform was used to generate rHA from two H5 clade 2.3.4.4 influenza viruses, in both soluble ectodomain or full-length HA forms, and a soluble ectodomain rHA from an influenza H2 virus. The purified rHAs were used as immunogens to produce HA antibody reagents that were tested for suitability in the SRID assay to accurately measure the potency of inactivated pandemic influenza vaccines. Antibody reagents generated to either ectodomain or full-length rHA worked well in the SRID assay and resulted in vaccine potency values equivalent to those generated with standard reference antibodies. The results demonstrate that rHA produced from a simple mammalian cell transfection method can be used to generate HA antibody suitable for use in the influenza vaccine SRID potency assay and suggest a practical means by which an extensive library of pandemic reagents can easily be prepared in advance of and during an influenza emergency.

Synthesis and anti-influenza virus activity of substituted dibenzoxepine-based baloxavir derivatives

Seasonal influenza poses a significant threat to global public health, driving the need for effective anti-influenza agents. The PA protein, which captures the pre-mRNA cap structure, is crucial for the replication of the influenza virus and serves as an important target for developing such agents. Baloxavir, a PA inhibitor, has shown excellent activity against influenza A and B viruses. In this study, its structure was optimized using bioisosteric replacement to develop novel dibenzoxepine-based derivatives for combating influenza. As the lead compounds, ATV03 (EC50 = 0.78 ± 0.10 nM, SI > 64103) and ATV07 (EC50 = 0.78 ± 0.01 nM, SI = 31603) demonstrated excellent anti-influenza A (H3N2) activity and SI, and possessed favorable anti-influenza B activity, with 2.02 ± 0.40 nM and 2.32 ± 0.29 nM of EC50 respectively. They showed improved bioavailability and metabolic stability. Mechanism studies revealed that ATV03 and ATV07 both possessed significant activity in inhibiting PA and RdRp as well as disturbing NP. Consequently, ATV03 was selected for further investigation in the fight against seasonal and pandemic influenza due to its superior bioavailability, metabolic stability, and efficacy against multiple influenza A viruses.

Optical biosensor based on the dual-functional gold nanoparticles for rapid and accurate multiplex detection of influenza A and B viruses

Due to the global pandemic of influenza and related respiratory diseases, rapid and accurate detection is in high demand to control virus spread and facilitate early treatment. However, most current molecular detection methods either require long turnaround times, suffer from low sensitivity and/or can only detect single pathogens. To overcome these challenges, we constructed a novel colorimetric gold nanoparticle (AuNPs) biosensor containing functionalized probes to detect multiple targets simultaneously. Utilizing the salt aging method, AuNPs were functionalized by the designed oligonucleotides to fabricate biosensors. This biosensor can show visible color change within 20 min, and could minimally detect the target influenza viruses at 10 nM. This detection technique presents high sensitivity in a short time, meanwhile identifying two different influenza viruses simultaneously. It opens a window to a multiplex-in-one strategy for a clinical viral diagnostic.

Tahiti Population (Re)Estimates and Ideologies

The question of Tahiti population at contact was first addressed by assessing the reliability of early and later estimates, and then by a retrodiction based on the first reliable censuses and data on trends. Cook’s famous estimate of 204,000 Tahitians, affected by a wrong number of districts, has been reworked based on his own and the Forsters’ observations, using coast length and the age and sex structure of Tahiti population at contact in relation to infanticide, resulting in a range of 156,000-188,000 persons in 1774, before Boenechea’s flu in 1772 and the 1774 flu epidemics. The discrepancies between Wilson’s 16,050 and other missionaries’ estimate of 50,000 as of 1797 are puzzling, but the 1829-1830 missionary estimates were strongly affected by Tahitians’ resistance to Christianization. The twentieth century estimates are affected by a political context related to colonization - decolonisation, leading to the fact that researchers favour low estimates. McArthur uses missionary data, assuming that baptisms are births, although before the conversion was completed, baptisms included adults and children of all ages. She bases her estimate of 30,000 Tahitians at contact in 1767 on Wilson’s number of 16,050, who applied the size of nuclear households, 6 persons, to clans. Oliver followed her, however not excluding numbers twice as high or more. Our retrodiction on the 1848 and 1881 censuses, based on qualitative missionary reports on sanitary situation and data of Rarotonga that experienced similar events as Tahiti, yield, with conservative assumptions, 180,000 persons at contact, showing consistent results with early navigators’ estimates. My own PhD experience in the late 1980s shows that scholars’ re-estimates were constrained, directly or indirectly, by political considerations related to the guilt syndrome and colonialist ideology. This appears in the frequent contradictions found in their works to support low estimates in order to reduce the decline, despite evidence of dramatic epidemics and a steady decline extending almost throughout the 19th century. The same attitude of denial is found in some missionary, administrative and medical reports, particularly on the Marquesas in the late 19th century. Colonisation was associated with various ideologies, related to anthropology’s early attempts based on theories of evolutionism, functionalism and structuralism, occasionally resulting in fictions such as “primitive thinking”, “ahistorical societies” and “collective unconscious”, that were part of the justification of colonisation and its mistakes.

Impact of the Swine flu pandemic on General Practitioner (GP) visits in Finland: sex and age differences

BackgroundSwine flu might serve as a model for challenges that primary care faces during pandemics. This study examined changes in the numbers and diagnoses of general practitioner (GP) visits during and after the Swine flu pandemic in Vantaa, a Finnish city, and how GP activities recovered after the pandemic. Putative sex and age group differences were also evaluated.MethodsThe study was an observational retrospective study. The monthly number of patient visits to primary care GPs by women and men in age groups 0–19, 20–64 and 65 + years was recorded before, during and two years after the Swine flu pandemic. The recorded diagnoses were also examined. The investigation period was from 2008 to 2012.ResultsThe numbers of monthly visits to primary care decreased from 12 324 (mean) to 10 817 in women and from 8563 to 7612 in men during the first six months of the Swine flu, returning to the original level afterwards. This decrease was thus slightly more prominent in women. However, as the size of the population increased during the follow-up period, the actual number of GP visits adjusted for the size of population remained at a decreased level for two years after the Swine flu. This decrease was observed especially in office-hours visits of men (from 3692 to 3260) and women (from 6301 to 5428) of 20–64 years. Swine flu did not alter the number of visits to the primary care Emergency Department. The proportion of visits with diagnostic recordings of common infectious diseases mostly decreased during the Swine flu. Only a minor impact on the distribution of recordings of chronic diagnoses was found.ConclusionA pandemic, such as Swine flu, may decrease office-hours visits to primary care GPs. This in turn may lead to activities of primary care being adjusted downward for a long time following the pandemic. Especially the age group 20–64 years may be affected. This risk should be considered when recovery from the COVID-19 pandemic begins. Swine flu did not affect the proportion of consultations of chronic diseases, but the number of diagnoses of common infectious diseases had diminished.

The Influential Influenza: The "Russian Catarrh" Pandemic of 1781-1782.

The influenza pandemic of 1781-1782 was remarkably well-documented, with investigations and treatment records produced in Britain, France, Germany, Italy, and Russia. Everyone agreed that outbreak began in St. Petersburg in December 1781 and then spread across northern Europe, but the medical communities' consensus did not solve all issues. Two questions would inspire years of debate. The first concerned the transmission vector of the pandemic: was it the result of neo-Hippocratic, miasmatic, or contagionist exposure? This was perhaps the greatest concern of the late-eighteenth century, and multiple physicians hoped the latest influenza pandemic could provide an answer. The second was no less difficult - where did the disease originate? This was not only because geography affected both prophylactic measures and treatment options but also produced diplomatic and commercial consequences. Was a quarantine necessary, preventing commercial exchanges? Did the risk of infection result in peace negotiations being delayed, potentially extending the American Revolution and the ongoing naval conflict in the Atlantic? Even if a consensus could be reached that this was a "Russian" catarrh, this would not resolve the method of disease transmission. The pandemic of 1781-1782 was not a turning point in the arguments among neo-Hippocratic, miasmatic, and contagionist physicians, but rather reveals all three positions could be held simultaneously.

Occupation exposure to coal dust and vulnerability to Influenza: Scottish miners and the 1918 Influenza Pandemic.

ObjectiveThere has been little work on the high level of mortality, noted that the time, in coal mining areas during the 1918 Influenza pandemic. Increased risk during viral infection from exposure to particulates (eg cigarette smoke, air pollution) has been studied. ApproachWe use the historic administrative data for Scotland, 1900 to 1930, with standardised codes for occupation and cause of death, and a pseudo household design and Quasi Poisson models, where the spouses of miners are their controls, to test whether miners (aged 20 to 50) were more at risk of death during the main waves of the 1918 pandemic than a matched population. Secondly, we repeat the analysis for Labourers to test if [1] Sex or [2] hard labour and for clerks, if [3] Pulmonary Tuberculosis might explain the effect. ResultsWe find that miners compared to their spouses were significantly more likely to die during all waves of the pandemic but considerably more so during the Autumn wave (RR 4.7). This difference was even greater for younger miners (20 to 35) (RR 7.6). In contrast labourers and clerks had a much lower and often non-significant comparative risk of death during all waves than their spouses. This was true even for those aged 20-35. ConclusionsMale coal miners appear to have been at much higher risk of death compared to matched populations. ImplicationsWorkers with exposure to airborne particulates should be a priority for public health planning during periods of high virus infections.

‘It’s really embarrassing […] to ask for help:’ navigating invisible and intersecting inequities in barriers to getting vaccinated

The arrival of COVID-19 vaccines in Canada marked the first time since the H1N1 influenza pandemic that adult vaccination became central in public health discourse, thus evoking feelings and discourse about individuals’ responsibility to get vaccinated. Public health institutions made efforts to ensure vaccines were accessible, and various local organizations worked to fill gaps in accessibility (e.g. vaccine clinics for equity-denied communities). However, despite knowledge of barriers to accessing healthcare, and specifically vaccines, public and health discourses emphasized individual objection as the main barrier to optimal vaccine uptake. This study explored how individuals who identified as a racialized minority or Indigenous person, perceived their personal responsibility to get vaccinated. We gathered perspectives in qualitative interviews (N = 27) when vaccines were first becoming available to adults living in Canada (May-June 2021). Theory about moral regulation, risk governance, and emotion informed our analysis. Findings suggest that individuals engaged in the governance of oneself and others towards getting vaccinated. However, participants also critiqued discourses that hold individuals responsible for accessing vaccines. They identified substantial barriers to accessing vaccines for individuals with fewer resources (e.g. travel time, missing work, childcare). When referencing individuals who do not know how to access information about vaccination, one participant stated, ‘it’s really embarrassing […] to ask for help.’ Feelings of individual responsibility may prevent some people uncertain about vaccines from asking for more information and support. We argue that the focus on vaccine hesitancy without attention to systemic barriers deflects responsibility for making vaccines accessible from centralized institutions to individuals.

A Recombinant Mosaic HAs Influenza Vaccine Elicits Broad-Spectrum Immune Response and Protection of Influenza a Viruses.

The annual co-circulation of two influenza A subtypes, H1N1 and H3N2, viruses in humans poses significant public health threats worldwide. However, the continuous antigenic drift and shift of influenza viruses limited the effectiveness of current seasonal influenza vaccines, necessitating the development of new vaccines against both seasonal and pandemic viruses. One potential solution to this challenge is to improve inactivated vaccines by including multiple T-cell epitopes. In this study, we designed stabilized trimeric recombinant mosaic HA proteins named HAm, which contain the most potential HA T-cell epitopes of seasonal influenza A virus. We further evaluated the antigenicity, hemagglutinin activity, and structural integrity of HAm and compared its immunogenicity and efficacy to a commercial quadrivalent inactivated influenza vaccine (QIV) in mice. Our results demonstrated that the HAm vaccine was able to induce broadly cross-reactive antibodies and T-cell responses against homologous, heterologous, and heterosubtypic influenza-naive mice. Additionally, the HAm antigens outperformed QIV vaccine antigens by eliciting protective antibodies against panels of antigenically drifted influenza vaccine strains from 2009 to 2024 and protecting against ancestral viruses' lethal challenge. These results suggest that the HAm vaccine is a promising potential candidate for future universal seasonal and pandemic influenza vaccine development.

Multi-Step Forecasting Method For Influenza Pandemic Using Long Short-Term Memory Model To Improve Public Health Conditions

The flu spread is a major global public health problem that gets attention around the world because it can cause serious illness, cost a lot of money, and kill a lot of people every year. To avoid influenza-like disease (ILD) and run healthcare systems well, predicting when an influenza outbreak will happen is essential. Researchers have used Machine Learning (ML) techniques but have yet to find the best ways to see complicated, non-linear trends in sequential data about flu outbreaks. A Long Short-Term Memory (LSTM) and a Genetic Algorithm (GA) are used together in this study to show a new way to predict multi-step influenza breakouts. Every week, the study gathers information on ILD, which covers flu and other illnesses with signs similar to the flu. When measuring performance during busy times, the suggested model does much better than other advanced Machine Learning (ML) methods and Fully Connected Neural Networks (F-CNN).

An examination of the influenza pandemic in early 20th century in Crete through the lens of the 1918 editions of Nea Ephimeris, a Cretan newspaper.

Crete, strategically situated at the crossroads of three continents, was historically embroiled in incessant conflicts between colonisers and Greek revolutionaries, as well as recurrent battles against disease. In 1918, the island faced a novel adversary: influenza. In response, the state, local authorities, and medical professionals on the island mounted a formidable defence. Hospitals, health centres, and the military all contributed to the effort. Essential provisions of medicine and food were distributed to support the populations in areas most inflicted. The Heraklion-based newspaper Nea Ephimeris played a crucial role in documenting these events. Through its articles, reports, interviews, and reviews of the influenza situation, it disseminated vital information that helped the public understand both preventive measures and the necessary actions to combat the spread of the virus. This study examines the coverage by Nea Ephimeris from January 1918 to January 1919, assessing how the newspaper informed, supported, and uplifted the urban and rural populations of Crete. The data collected reconstruct the events of that period and demonstrate how historical pandemics offer lessons that can prepare health professionals for future challenges.

Asian Flu Pandemic in Indonesia, 1957: Government and Public Response

Asian Flu Pandemic in Indonesia, 1957: Government and Public Response