Frailty and survival in the 1918 influenza pandemic.

One of the most well-known yet least understood aspects of the 1918 influenza pandemic is the disproportionately high mortality among young adults. Contemporary accounts further describe the victims as healthy young adults, which is contrary to the understanding of selective mortality, which posits that individuals with the highest frailty within a group are at the greatest risk of death. We use a bioarchaeological approach, combining individual-level information on health and stress gleaned from the skeletal remains of individuals who died in 1918 to determine whether healthy individuals were dying during the 1918 pandemic or whether underlying frailty contributed to an increased risk of mortality. Skeletal data on tibial periosteal new bone formation were obtained from 369 individuals from the Hamann-Todd documented osteological collection in Cleveland, Ohio. Skeletal data were analyzed alongside known age at death using Kaplan-Meier survival and Cox proportional hazards analysis. The results suggest that frail or unhealthy individuals were more likely to die during the pandemic than those who were not frail. During the flu, the estimated hazards for individuals with periosteal lesions that were active at the time of death were over two times higher compared to the control group. The results contradict prior assumptions about selective mortality during the 1918 influenza pandemic. Even among young adults, not everyone was equally likely to die-those with evidence of systemic stress suffered greater mortality. These findings provide time depth to our understanding of how variation in life experiences can impact morbidity and mortality even during a pandemic caused by a novel pathogen.

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

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

Did the 1918 influenza pandemic cause a 1920 baby boom? Demographic evidence from neutral Europe.

In 1919-20, the European countries that were neutral in the First World War saw a small baby bust followed by a small baby boom. The sparse literature on this topic attributes the 1919 bust to individuals postponing conceptions during the peak of the 1918-20 influenza pandemic and the 1920 boom to recuperation of those conceptions. Using data from six large neutral countries of Europe, we present novel evidence contradicting that narrative. In fact, the subnational populations and maternal birth cohorts whose fertility was initially hit hardest by the pandemic were still experiencing below-average fertility in 1920. Demographic evidence, economic evidence, and a review of post-pandemic fertility trends outside Europe suggest that the 1920 baby boom in neutral Europe was caused by the end of the First World War, not by the end of the pandemic.

Racial Disparities in Mortality During the 1918 Influenza Pandemic in United States Cities.

Against a backdrop of extreme racial health inequality, the 1918 influenza pandemic resulted in a striking reduction of non-White to White influenza and pneumonia mortality disparities in United States cities. We provide the most complete account to date of these reduced racial disparities, showing that they were unexpectedly uniform across cities. Linking data from multiple sources, we then examine potential explanations for this finding, including city-level sociodemographic factors such as segregation, implementation of nonpharmaceutical interventions, racial differences in exposure to the milder spring 1918 "herald wave," and racial differences in early-life influenza exposures, resulting in differential immunological vulnerability to the 1918 flu. While we find little evidence for the first three explanations, we offer suggestive evidence that racial variation in childhood exposure to the 1889-1892 influenza pandemic may have shrunk racial disparities in 1918. We also highlight the possibility that differential behavioral responses to the herald wave may have protected non-White urban populations. By providing a comprehensive description and examination of racial inequality in mortality during the 1918 pandemic, we offer a framework for understanding disparities in infectious disease mortality that considers interactions between the natural histories of particular microbial agents and the social histories of those they infect.

Mystery of love, goiter and death in flu pandemic.

Ivan Mestrovic (1883-1962), a Croatian sculptor and architect, portrayed his close friend Marija Banac (born Racic) with a goiter. She died from flu in 1918 in Rome, just few days apart from her brother Edi Racic and his fiancée. In the tragic memory of the Racic family that disappeared in the burst of a terrible pandemic, Mestrovic built a church and mausoleum in Cavtat near Dubrovnik.

Bird flu outbreak amidst COVID-19 pandemic in South Africa: Efforts and challenges at hand.

Over the months of April and May 2021, South Africa has witnessed several outbreaks of highly infective avian influenza (H5N1) in different poultry farms. This came as a shock to a country that was already battling with the deadly COVID-19 pandemic. The emergence of the virus has spurred import bans and massive culls in the poultry business. Local experts have also called for a restriction on the movement of people and cars in and out of their chicken farms. Employees have also been encouraged to shower in the mornings when they arrive at the farms and wear fresh clothes, as the flu spreads very quickly. In a country that is already facing the economic implications of the COVID-19, this has the potential to cause a significant dent in the economy, as well as severely impact people's day-to-day life. Bird flu-also called avian influenza-is a viral infection that can infect not only birds but also humans and other animals. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. This paper describes the South African burden, current efforts, and preparedness against the avian influenza virus.

Deciphering transmission dynamics and spillover of avian influenza viruses from avian species to swine populations globally.

Genome sequences of eleven avian influenza virus (AIV) subtypes have been reported in swine populations from seven countries until August 2020. To unravel the transmission dynamics and spillover events of AIVs from avian reservoirs to swine, full-length hemagglutinin (HA) sequences of AIV subtypes (n = 11) reported from various avian species and swine were retrieved from the 'Influenza Research Database'. Phylogenetic analysis identified closely related avian and swine AIV sequences suggesting potential spillover events from multiple domestic and wild avian species, including chicken, duck, pigeon, goose, quail, and aquatic birds to swine. Furthermore, N-linked glycosylation analysis of these closely related AIV sequences supported the possibility of multiple spillover events of highly pathogenic H5N1 and low pathogenic H9N2 viruses from various avian species to swine. The principal coordinate analysis further validated these findings for H5N1 and H9N2 viruses; however, spillover events of the other nine AIV subtypes were limited. Interestingly, the presence of potential mammalian adaptation markers, particularly in some of the swine H5N1, H7N9, and H9N2 viruses, suggested that these viruses may have already adapted in swine. The occurrence and circulation of these AIVs in swine, especially the H5N1 and H9N2 viruses with numerous spillover events from the avian reservoirs to swine, pose a significant threat in terms of their reassortment with endemic swine viruses or circulating human influenza viruses within the swine which may facilitate the emergence of a novel influenza virus strain with pandemic potential.

The 1918 influenza pandemic did not accelerate tuberculosis mortality decline in early-20th century Newfoundland: Investigating historical and social explanations.

OBJECTIVES: The selective mortality hypothesis of tuberculosis after the 1918 influenza pandemic, laid out by Noymer and colleagues, suggests that acute exposure or pre-existing infection with tuberculosis (TB) increased the probability of pneumonia and influenza (P&I) mortality during the 1918 influenza pandemic, leading to a hastened decline of TB mortality in post-pandemic years. This study describes cultural determinants of the post-pandemic TB mortality patterns in Newfoundland and evaluates whether there is support for this observation. MATERIALS AND METHODS: Death records and historical documents from the Provincial Archives of Newfoundland and Labrador were used to calculate age-standardized island-wide and sex-based TB mortality, as well as region-level TB mortality, for 1900-1939. The Joinpoint Regression Program (version 4.8.0.1) was used to estimate statistically significant changes in mortality rates. RESULTS: Island-wide, females had consistently higher TB mortality for the duration of the study period and a significant shift to lower TB mortality beginning in 1928. There was no similar predicted significant decline for males. On the regional level, no models predicted a significant decline after the 1918 influenza pandemic, except for the West, where significant decline was predicted in the late-1930s. DISCUSSION: Although there was no significant decline in TB mortality observed immediately post-pandemic, as has been shown for other Western nations, the female post-pandemic pattern suggests a decline much later. The general lack of significant decrease in TB mortality rate is likely due to Newfoundland's poor nutrition and lack of centralized healthcare rather than a biological interaction between P&I and TB.

Review of epidemic, containment strategies, clinical management, and economic evaluation of COVID-19 pandemic.

The spread of the emerging pathogen, named as SARS-CoV-2, has led to an unprecedented COVID-19 pandemic since 1918 influenza pandemic. This review first sheds light on the similarity on global transmission, surges of pandemics, and the disparity of prevention between two pandemics. Such a brief comparison also provides an insight into the potential sequelae of COVID-19 based on the inference drawn from the fact that a cascade of successive influenza pandemic occurred after 1918 and also the previous experience on the epidemic of SARS and MERS occurring in 2003 and 2015, respectively. We then propose a systematic framework for elucidating emerging infectious disease (EID) such as COVID-19 with a panorama viewpoint from natural infection and disease process, public health interventions (non-pharmaceutical interventions (NPIs) and vaccine), clinical treatments and therapies (antivirals), until global aspects of health and economic loss, and economic evaluation of interventions with emphasis on mass vaccination. This review not only concisely delves for evidence-based scientific literatures from the origin of outbreak, the spread of SARS-CoV-2 to three surges of pandemic, and NPIs and vaccine uptakes but also provides a new insight into how to apply big data analytics to identify unprecedented discoveries through COVID-19 pandemic scenario embracing from biomedical to economic viewpoints.

Not the great equalizers: Covid-19, 1918-20 influenza, and the need for a paradigm shift in pandemic preparedness.

Despite common perceptions to the contrary, pandemic diseases do not affect populations indiscriminately. In this paper, we review literature produced by demographers, historians, epidemiologists, and other researchers on disparities during the 1918-20 influenza pandemic and the Covid-19 pandemic. Evidence from these studies demonstrates that lower socio-economic status and minority/stigmatized race or ethnicity are associated with higher morbidity and mortality. However, such research often lacks theoretical frameworks or appropriate data to explain the mechanisms underlying these disparities fully. We suggest using a framework that considers proximal and distal factors contributing to differential exposure, susceptibility, and consequences as one way to move this research forward. Further, current pandemic preparedness plans emphasize medically defined risk groups and epidemiological approaches. Therefore, we conclude by arguing in favour of a transdisciplinary paradigm that recognizes socially defined risk groups, includes input from the social sciences and humanities and other diverse perspectives, and contributes to the reduction of health disparities before a pandemic hits.

[Monitoring of COVID-19 by extending existing surveillance for acute respiratory infections]. / Überwachung von COVID-19 durch Erweiterung der etablierten Surveillance für Atemwegsinfektionen.

As part of the national influenza pandemic preparedness, surveillance systems have been established in Germany in addition to the mandatory notifications according to the Protection Against Infection Act. The aim of these systems is the description, analysis, and evaluation of the epidemiology of acute respiratory infections (ARIs), the identification of the circulating viruses, and the trend. Since the beginning of the COVID-19 pandemic, the systems have been expanded to enable monitoring of infections with SARS-CoV­2.Three systems are presented: GrippeWeb, the primary care sentinel Arbeitsgemeinschaft Influenza with its electronic reporting module SEEDARE, and the ICD-10-based hospital sentinel ICOSARI. With these systems, ARIs can be monitored at the population, outpatient, and inpatient levels. In combination with the monitoring of mortality, these systems provide important information on the frequency of different stages of disease severity in the population. In order to expand the systems to SARS-CoV­2, only a few adjustments were needed.As the case definitions for ARIs were preserved, historical baselines of the systems can still be used for comparison. All systems are structured in such a way that stable and established reference values are available for calculating weekly proportions and rates.This is an important addition to the mandatory reporting system of infectious diseases in Germany, which depends on the particular testing strategy, the number of tests performed, and on specific case definitions, which are adapted as required.The surveillance systems have proven to be feasible and efficient in the COVID-19 pandemic, even when compared internationally.

Lessons From Influenza Pandemics of the Last 100 Years.

Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza.

Introduction: microbes, networks, knowledge-disease ecology and emerging infectious diseases in time of COVID-19.

This is an introduction to the topical collection Microbes, Networks, Knowledge: Disease Ecology in the twentieth Century, based on a workshop held at Queen Mary, University London on July 6-7 2016. More than twenty years ago, historian of science and medicine Andrew Mendelsohn asked, "Where did the modern, ecological understanding of epidemic disease come from?" Moving beyond Mendelsohn's answer, this collection of new essays considers the global history of disease ecology in the past century and shows how epidemics and pandemics have made "microbes complex".

Social and institutional Reactions to the Influenza Pandemic of 1918-20.

This essay challenges generalizations since the late enlightenment about the effects of epidemics and pandemics on collective mentalities: that from antiquity to the present, epidemics, regardless of the disease, have sparked distrust, social violence, and the blaming of others. By contrast, the pandemic that killed the greatest numbers in world history-the Influenza of 1918-20 - was a pandemic of compassion. No one has yet to uncover this pandemic sparking collective violence or blaming any minorities for spreading the disease anywhere in the globe. The essay then explores the variety of charitable reactions and abnegation that cut across social divisions in communities from theatres of war in Europe to nations thousands of miles from the direct military encounters. Most remarkable, however, was the overflowing volunteerism of women, especially in the US, Canada, and Australia. To explain this widespread charitable reaction, the essay investigates the milieu of the First World War, showing how that context in domestic war settings was not conducive to risking life to aid total strangers, especially when those strangers came from different foreign countries classes, races, or religious faiths. I end with a reflection on the unfolding socio-psychological reactions to Covid-19 from the perspective of 1918-20.

The 1918 "Spanish Flu" Pandemic in the Ottoman Capital, Istanbul.

Although the general course, possible transmission routes, and actual sociodemographic destruction of the 1918 influenza pandemic in the Western world are well documented, the literature lacks similar data about the Middle East. On the calamity's centenary, this article aims to contribute to filling this gap, investigating the presence and effects of the pandemic in Istanbul, the city bridging the West and East, then as the capital of the Ottoman Empire. After the retrieval of the most relevant articles in Vakit, a daily Istanbul newspaper active throughout the pandemic, a variety of items, including articles with firsthand pronouncements from contemporaneous medical authorities and a clinical account of supportive autopsy findings, are scrutinized and interpreted. The reviewed data are concluded to indicate no epidemiological or factual exception, showing significant parallelism with the Western experience of the pandemic in terms of increased influenza mortality and morbidity, severe clinical presentation, common misinformation and misdiagnosis, and failure to provide effective prevention and medical treatment.

Public Health-Driven Research and Innovation for Next-Generation Influenza Vaccines, European Union.

Influenza virus infections are a major public health threat. Vaccination is available, but unpredictable antigenic changes in circulating strains require annual modification of seasonal influenza vaccines. Vaccine effectiveness has proven limited, particularly in certain groups, such as the elderly. Moreover, preparedness for upcoming pandemics is challenging because we can predict neither the strain that will cause the next pandemic nor the severity of the pandemic. The European Union fosters research and innovation to develop novel vaccines that evoke broadly protective and long-lasting immune responses against both seasonal and pandemic influenza, underpinned by a political commitment to global public health.

The Long-Lasting Influenza: The Impact of Fetal Stress During the 1918 Influenza Pandemic on Socioeconomic Attainment and Health in Sweden, 1968-2012.

The 1918 influenza pandemic had not only a massive instant death toll but also lasting effects on its survivors. Several studies have shown that children born in 1919, and thus exposed to the H1N1 virus in utero, experienced worse health and socioeconomic outcomes in older ages than surrounding birth cohorts. This study combines several sources of contemporary statistics with full-population individual-level data for Sweden during 1968-2012 to examine the influence of fetal exposure to the Spanish flu on health, adulthood income, and occupational attainment. For both men and women, fetal exposure resulted in higher morbidity in ages 54-87, as measured by hospitalization. For males, exposure during the second trimester also affected mortality in cancer and heart disease. Overall, the effects on all-cause mortality were modest, with about three months shorter remaining life expectancy for the cohorts exposed during the second trimester. For socioeconomic outcomes, results fail to provide consistent evidence supporting any long-term consequences of fetal exposure. We conclude that although the immediate health effects of exposure to the 1918 pandemic were huge, the long-term effects were modest in size.

Selection and structural analysis of the NY25 peptide - A vaccine candidate from hemagglutinin of swine-origin Influenza H1N1.

The aim of this study was to construct a vaccine peptide candidate against pandemic Influenza H1N1 hemagglutinin and to test its structure. With the help of bioinformatic algorithms we showed that the sequence encoding the second polypeptide of pandemic Influenza H1N1 hemagglutinin (HA2) is protected from nonsynonymous mutations better than the sequence encoding its first polypeptide (HA1). With the help of secondary and ternary structure predicting algorithms we found the fragment of HA2 with the most reproducible secondary structure and synthesized the NY25 peptide corresponding to the residues Asn117 - Tyr141 of HA2. According to the circular dichroism spectra analysis, the peptide has short helix and beta hairpin. According to the analysis of differential fluorescence quenching results, two tyrosine residues are situated on a long distance from each other. These facts taken together with the positive results of affine chromatography with the serum of a person immunized by full-length hemagglutinin confirm that the structure of the fragment of viral full-length protein has been reproduced in the synthetic NY25 peptide. Amino acid sequence of the NY25 peptide (NLYEKVRSQLKNNAKEIGNGCFEFY) is relatively conserved in 18 subtypes of Influenza A virus hemagglutinin.

[One hundred years after the "Spanish" flu]. / A cien años de la gripe "española".

The "Spanish" flu pandemic, which occurred a century ago, is considered the most devastating in human history. An estimated one third of world population fell ill with flu and more than 2.5% of them died. The course of the epidemic had two main waves (1918 and 1919) and showed an unusual W-shaped morbidity/mortality distribution. Death was not a direct outcome of flu itself but rather a consequence of secondary bacterial bronchopneumonia, for which antibiotics had not yet been discovered. Pre-existing pulmonary tuberculosis was also accountable for increased flu death rates during the pandemic. As it happened in Europe, in Argentina the epidemic had two main waves, with ample variation in mortality by region. Available treatment at the time included diet, throat antiseptic rinses, low doses of quinine valerianate, salicylates, codeine as a cough suppressant, and camphor oil. Primitive anti-pneumococcal vaccines and immune sera were also applied. Upon the disclosure of the whole RNA sequence of the 1918 influenza virus genome, by means of reverse genetics it was possible to assemble viral particles resembling those of the deadly pandemic. The reconstituted virus proved to be extraordinarily virulent for mice. Current seasonal flu vaccines help to reduce, but not to abolish, the risk of another pandemic. The ongoing development of "universal" vaccines against influenza conferring reliable and long-lasting immunity may prevent its global spread in the future.

Markers of Disease Severity in Patients with Spanish Influenza in the Japanese Armed Forces, 1919-1920.

We examined preserved medical charts of 470 Spanish influenza patients (8 with fatal cases) hospitalized at former army hospitals in Japan during 1919-1920. The following factors were associated with longer periods of hospitalization: adventitious discontinuous lung sounds, maximum respiration rate, continuation of high fever after hospital admission, and diphasic fever.