Excess Deaths and Immunoprotection during 1918�C1920 Influenza Pandemic, Taiwan

To determine the difference in age-specific immunoprotection during waves of influenza epidemics, we analyzed excess monthly death data for the 1918–1920 influenza pandemic in Taiwan. For persons 10–19 years of age, percentage of excess deaths was lowest in 1918 and significantly higher in 1920, perhaps indicating lack of immunoprotection from the first wave.     

A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern France during the Great War provided the conditions for the emergence of the "Spanish" influenza pandemic of 1918-1919

The Great Influenza Pandemic of 1918-1919 was a cataclysmic outbreak of infection wherein over 50 million people died worldwide within 18 months. The question of the origin is important because most influenza surveillance at present is focussed on S.E. Asia. Two later pandemic viruses in 1957 and 1968 arose in this region. However we present evidence that early outbreaks of a new disease with rapid onset and spreadability, high mortality in young soldiers in the British base camp at Etaples in Northern France in the winter of 1917 is, at least to date, the most likely focus of origin of the pandemic. Pathologists working at Etaples and Aldershot barracks later agreed that these early outbreaks in army camps were the same disease as the infection wave of influenza in 1918. The Etaples camp had the necessary mixture of factors for emergence of pandemic influenza including overcrowding (with 100,000 soldiers daily changing), live pigs, and nearby live geese, duck and chicken markets, horses and an additional factor 24 gases (some of them mutagenic) used in large 100 ton quantities to contaminate soldiers and the landscape. The final trigger for the ensuing pandemic was the return of millions of soldiers to their homelands around the entire world in the autumn of 1918.     

A review of the 1918 herald pandemic wave: importance for contemporary pandemic response strategies

Mounting epidemiological evidence supports the occurrence of a mild herald pandemic wave in the spring and summer of 1918 in North America and Europe, several months before the devastating autumn outbreak that killed an estimated 2% of the global population. These epidemiological findings corroborate the anecdotal observations of contemporary clinicians who reported widespread influenza outbreaks in spring and summer 1918, with sporadic occurrence of unusually severe clinical manifestations in young adults. Initially seen as controversial, these findings were eventually confirmed by retrospective identification of influenza specimens collected from U.S. soldiers who died from acute respiratory infections in May–August 1918. Other studies found that having an episode of influenza illness during the spring herald wave was highly protective in the severe autumn wave. Here, we conduct a systematic review of the clinical, epidemiological, and virological evidence supporting the global occurrence of mild herald waves of the 1918 pandemic and place these historic observations in the context of pandemic preparedness. Taken together, historic experience with the 1918 and subsequent pandemics shows that increased severity in second and later pandemic waves may be the rule rather than the exception. Thus, a sustained pandemic response in the first years following a future pandemic is critical; conversely, multiwave pandemic patterns allow for more time to rollout vaccines and antivirals.     

中国流感大流行的百年历史

流感大流行在过去100年间出现过5次（1918年"西班牙流感"、1957年"亚洲流感"、1968年"香港流感"、1977年"俄罗斯流感"和2009年甲型H1N1流感）,累计数亿人感染和数千万人死亡。历史文献表明5次大流行均波及我国多个地区,产生了较大规模的影响,其中1957、1968和1977年流感大流行被认为是从我国开始暴发。流感大流行直接促使我国设立公共卫生机构和流感专业部门,并在科学研究与疫情防控上加大投入。我国应当进一步加强流感大流行的准备与应对,承担流感领域领导者的责任,为全球健康作出贡献。     

Epidemiology and transmission dynamics of the 1918-19 pandemic influenza in Florence, Italy

To investigate the 1918/19 influenza pandemic daily number of new hospitalizations in the only hospital in Florence (Central Italy) were analyzed. In order to describe the transmission dynamics of the 1918/1919 pandemic influenza a compartmental epidemic model was used. Model simulations show a high level of agreement with the observed epidemic data. By assuming both latent and infectious period equal to 1.5 days, the estimated basic reproduction number was R(0)(1) = 1.03 (95% CI: 1.00-1.08) during the summer wave and R(0)(2) = 1.38 (95% CI: 1.32-1.48) during the fall wave. Varying the length of the generation time or the estimation method, R(0)(2) ranges from 1.32 to 1.71. The hospitalization rate was found significantly different between summer and fall waves. Notably, the estimated basic reproductive numbers are lower compared to those observed in other countries, while the age distribution of deaths resulted to be consistent with the patterns generally observed during of the 1918-1919 pandemic. Our knowledge on past pandemics, as for the 1918-19 Spanish influenza, would help improving mathematical modeling accuracy and understanding the mechanisms underlying the dynamics of future pandemics.     

Adaptation to health states: Sick yet better off?

Healthcare funding decisions in the UK rely on health state valuations of the general public. However, it has been shown that there is disparity between the valuation of the impact of hypothetical conditions on health and the reported health by those experiencing them. Patients' adaptation to health states is among the most common explanations for this discrepancy. Being diagnosed with a disease appears to affect individual perception of health over time so that better subjective health may be reported over a disease trajectory. This paper examines adaptation to health states using a longitudinal dataset. We use four waves of the British Cohort Study (BCS70), which tracks a sample of British individuals since birth in 1970 and contains information on self‐assessed health (SAH), morbidity, and socioeconomic characteristics. We implement a dynamic ordered probit model controlling for health state dependence. Results are supportive of the existence of adaptation: Time since diagnosis has a positive impact on SAH. Moreover, adaptation happens over relatively long durations. We do not find significant results proving different adaptation paths for patients reporting prior better SAH. The analysis by specific conditions generally supports the existence of adaptation, but results are statistically significant only for a subset of conditions.     

Estimates of the reproduction numbers of Spanish influenza using morbidity data

BACKGROUND: There have been several studies of the transmissibility of the 1918 (Spanish) influenza virus, which has attributed to >20 million deaths. Many of the analyses to date have involved fitting predictions from a transmission model to the observed epidemic curves from different settings. METHODS: Using morbidity data from cities in Europe and America and from confined settings during the 1918 influenza pandemic, we contrast the use of several different methods based on the growth rate and final size of the epidemic, which do not rely on transmission models, to estimate the effective and basic reproduction numbers. RESULTS: The effective reproduction number (the average number of secondary infectious cases produced by a typical infectious case in a given population) for the 1918 influenza virus was in the range 1.2-3.0 and 2.1-7.5 for community-based and confined settings, respectively. CONCLUSIONS: Assuming further that 30 and 50% of individuals were immune to Spanish influenza after the wave in April 1918 and the first subsequent wave, respectively, these findings imply that, in a totally susceptible population, an infectious case could have led to 2.4-4.3 and 2.6-10.6 cases in community-based and confined settings, respectively. These findings for community-based populations confirm the relatively low transmissibility of the 1918 (Spanish) influenza virus, which has been found by other studies using alternative data sources and methods.     

Pathogenic responses among young adults during the 1918 influenza pandemic

Of the unexplained characteristics of the 1918-19 influenza pandemic, the extreme mortality rate among young adults (W-shaped mortality curve) is the foremost. Lack of a coherent explanation of this and other epidemiologic and clinical manifestations of the pandemic contributes to uncertainty in preparing for future pandemics. Contemporaneous records suggest that immunopathologic responses were a critical determinant of the high mortality rate among young adults and other high-risk subgroups. Historical records and findings from laboratory animal studies suggest that persons who were exposed to influenza once before 1918 (e.g., A/H3Nx 1890 pandemic strain) were likely to have dysregulated, pathologic cellular immune responses to infections with the A/H1N1 1918 pandemic strain. The immunopathologic effects transiently increased susceptibility to ultimately lethal secondary bacterial pneumonia. The extreme mortality rate associated with the 1918-19 pandemic is unlikely to recur naturally. However, T-cell-mediated immunopathologic effects should be carefully monitored in developing and using universal influenza vaccines.     

Early Life Exposure to the 1918 Influenza Pandemic and Old-Age Mortality by Cause of Death

Objectives. We sought to analyze how early exposure to the 1918 influenza pandemic is associated with old-age mortality by cause of death.Methods. We analyzed the National Health Interview Survey (n = 81 571; follow-up 1989–2006; 43 808 deaths) and used year and quarter of birth to assess timing of pandemic exposure. We used Cox proportional and Fine-Gray competing hazard models for all-cause and cause-specific mortality, respectively.Results. Cohorts born during pandemic peaks had excess all-cause mortality attributed to increased noncancer mortality. We found evidence for a trade-off between noncancer and cancer causes: cohorts with high noncancer mortality had low cancer mortality, and vice versa.Conclusions. Early disease exposure increases old-age mortality through noncancer causes, which include respiratory and cardiovascular diseases, and may trigger a trade-off in the risk of cancer and noncancer causes. Potential mechanisms include inflammation or apoptosis. The findings contribute to our understanding of the causes of death behind the early disease exposure–later mortality association. The cancer–noncancer trade-off is potentially important for understanding the mechanisms behind these associations.Adverse early life conditions may have lasting effects on old-age health and mortality.1–8 Some even consider reductions in early life disease exposure to be a primary driver of historical mortality declines.9 Although the precise mechanisms linking early disease exposure to poor adult health remain unclear, numerous pathways have been postulated including those relating to fetal undernutrition and dysregulation of immune function.3,10,11In animal models, experimental evidence suggests a negative causal effect of early disease exposure on later health.12–14 For humans, historical epidemics have been used to study the effects of early disease exposure on later health.1,2,4,15 These studies often find that those born around the time of an epidemic exhibit worse adult health and mortality than do neighboring cohorts.1,2,4 However, the causes of death contributing to the excess mortality are not known. Moreover, research on early exposure to the deadliest epidemic of the 20th century—the 1918 influenza pandemic—is mixed, showing increased cardiovascular disease prevalence and lower socioeconomic attainment,1,4 but no long-term mortality effects.15We investigated whether US cohorts with early exposure to the 1918 pandemic experience differential mortality at old ages compared with neighboring cohorts. The 1918 pandemic, caused by the influenza A virus (subtype H1N1), arrived in the United States in 3 waves.16 During the first wave, which began in March 1918 and was completed by July 1918, incidence rates were high, but mortality was only slightly elevated. The second and the deadliest wave began in September 1918 and lasted until the end of the year. The third wave, with a mortality impact between those of the first 2 waves, occurred from January 1919 to March 1919. Approximately 30% of the US population was infected and about 0.5% of the population died because of the pandemic, mostly from pneumonia.16 Excess mortality had an unusual pattern as those aged 20 to 40 years were affected particularly strongly.16The advantages of focusing on the 1918 pandemic are threefold. First, the pandemic arrived unexpectedly and lasted for only a short period, allowing treatment of the pandemic as a “natural experiment” wherein cohorts born months apart experienced different exposures but were otherwise compositionally similar in terms of other childhood characteristics and environmental conditions. Moreover, the exposed and nonexposed cohorts were born in a narrow enough time interval that timing of birth is not systematically linked to subsequent differences in the adult environment. Second, in contrast to older epidemics, existing data permit cause-of-death analyses. Third, although food shortages and disease tended to co-occur in historical populations, the 1918 pandemic allows focusing on disease because there were no generalized food shortages in the United States during the pandemic. Nutritional deprivation caused by disease, however, may function as a mediator.We extended previous research in 3 important dimensions. First, although earlier studies have analyzed the relationship between early disease exposure and later-life mortality,2,15,17 it is not known what causes of death drive the association. We analyzed mortality by cause, which can enhance our understanding of potential mechanisms. Second, previous research on early disease exposure and later mortality has analyzed annual birth cohorts.2,5,15 We distinguished cohorts by year and quarter of birth, which provides a far more nuanced analysis of exposure timing. Third, previous work on the long-lasting effects of the pandemic has not accounted for the fact that the pandemic arrived in waves.1,4,15 Because of variation in the immediate mortality effects of each wave, there may be differences with respect to long-lasting effects. Our analysis accounted for exposure to each wave.     

Influenza transmission in households during the 1918 pandemic

Analysis of historical data has strongly shaped our understanding of the epidemiology of pandemic influenza and informs analysis of current and future epidemics. Here, the authors analyzed previously unpublished documents from a large household survey of the "Spanish" H1N1 influenza pandemic, conducted in 1918, for the first time quantifying influenza transmissibility at the person-to-person level during that most lethal of pandemics. The authors estimated a low probability of person-to-person transmission relative to comparable estimates from seasonal influenza and other directly transmitted infections but similar to recent estimates from the 2009 H1N1 pandemic. The authors estimated a very low probability of asymptomatic infection, a previously unknown parameter for this pandemic, consistent with an unusually virulent virus. The authors estimated a high frequency of prior immunity that they attributed to a largely unreported influenza epidemic in the spring of 1918 (or perhaps to cross-reactive immunity). Extrapolating from this finding, the authors hypothesize that prior immunity partially protected some populations from the worst of the fall pandemic and helps explain differences in attack rates between populations. Together, these analyses demonstrate that the 1918 influenza virus, though highly virulent, was only moderately transmissible and thus in a modern context would be considered controllable.     

Excess mortality patterns during 1918–1921 influenza pandemic in the state of Arizona,USA

Purpose

Our understanding of the temporal dynamics and age-specific mortality patterns of the 1918–1921 influenza pandemic remains scarce due to lack of detailed respiratory mortality datasets in the United States and abroad.

Estimation of the reproductive number of the Spanish flu epidemic in Geneva, Switzerland

The 1918 influenza pandemic known as the "Spanish Flu" has been the worst in recent history with estimated worldwide mortality ranging from 20 to 100 million deaths. Using epidemic modeling and hospital notification data during the 1918 influenza pandemic in the Canton of Geneva, Switzerland, we estimated the reproductive numbers of the first and second waves of influenza infection to be R(1)=1.49 (95% CI: 1.45-1.53) and R(2)=3.75 (95% CI: 3.57-3.93), respectively. Our estimates indicate that containment of the next influenza pandemic could require strict interventions that include effective isolation strategies in hospitals and reductions in the susceptibility of the general population.     

Does in utero exposure to Illness matter? The 1918 influenza epidemic in Taiwan as a natural experiment

This paper tests whether in utero conditions affect long-run developmental outcomes using the 1918 influenza pandemic in Taiwan as a natural experiment. Combining several historical and current datasets, we find that cohorts in utero during the pandemic are shorter as children/adolescents and less educated compared to other birth cohorts. We also find that they are more likely to have serious health problems including kidney disease, circulatory and respiratory problems, and diabetes in old age. Despite possible positive selection on health outcomes due to high infant mortality rates during this period (18%), our paper finds a strong negative impact of in utero exposure to influenza.     

Deaths from bacterial pneumonia during 1918-19 influenza pandemic

Deaths during the 1918-19 influenza pandemic have been attributed to a hypervirulent influenza strain. Hence, preparations for the next pandemic focus almost exclusively on vaccine prevention and antiviral treatment for infections with a novel influenza strain. However, we hypothesize that infections with the pandemic strain generally caused self-limited (rarely fatal) illnesses that enabled colonizing strains of bacteria to produce highly lethal pneumonias. This sequential-infection hypothesis is consistent with characteristics of the 1918-19 pandemic, contemporaneous expert opinion, and current knowledge regarding the pathophysiologic effects of influenza viruses and their interactions with respiratory bacteria. This hypothesis suggests opportunities for prevention and treatment during the next pandemic (e.g., with bacterial vaccines and antimicrobial drugs), particularly if a pandemic strain-specific vaccine is unavailable or inaccessible to isolated, crowded, or medically underserved populations.     

Railways, disease and health in South Africa

The role of South African Railways and Harbours in spreading disease and health care is examined. Attention is focused on the Railways' campaigns against malaria, plague and infectious diseases. A case study of the 1918 'Spanish Influenza' epidemic illustrates how the Railways diffuse disease and health care, and also demonstrates the disruption of services caused by the influenza.     

Nonpharmaceutical influenza mitigation strategies, US communities, 1918-1920 pandemic

We studied nonpharmaceutical interventions used to mitigate the second, and most deadly, wave of the 1918-1920 influenza pandemic in the United States. We conclude that several small communities implemented potentially successful attempts at preventing the introduction of influenza.     

Spanish influenza in Japanese armed forces, 1918-1920

With the recent outbreaks of avian influenza A (H5N1), the risk for the next influenza pandemic has increased. For effective countermeasures against the next pandemic, investigation of past pandemics is necessary. We selected cases diagnosed as influenza from medical records and hospitalization registries of Japanese army hospitals during 1918-1920, the Spanish influenza era, and investigated clinical features and circumstances of outbreaks. Admission lists showed a sudden increase in the number of inpatients with influenza in November 1918 and showed the effect of the first wave of this pandemic in Tokyo. The death rate was high (6%-8%) even though patients were otherwise healthy male adults.     

From African health and influenza pandemics to disease in Russia: the medical history of K. David Patterson.

This paper is a personal commentary on the contributions of noted medical historian K. David Patterson. The eightieth anniversary of the onset of the Great Influenza Pandemic of 1918-19 serves as a reminder of his contributions. His works on slavery and disease in Africa, influenza diffusion and the history of cholera and other diseases periodically appeared in Social Science and Medicine. With a publishing career that lasted from 1971 to 1996, his enduring contributions include revised estimates of mortality in Africa during the influenza pandemic of 1918-1919.     

A socially neutral disease? Individual social class, household wealth and mortality from Spanish influenza in two socially contrasting parishes in Kristiania 1918-19

The Spanish influenza pandemic of 1918-19 was one of the most devastating diseases in history, killing perhaps as many as 50-100 million people worldwide. Much of the literature since 1918 has favored the view that mortality from Spanish influenza was class neutral. This view has prevailed, even though several contemporary surveys showed that there indeed were clear differences between the classes in disease incidence and that case fatality rates from influenza and pneumonia also varied according to socioeconomic status. Furthermore, studies of more recent influenza epidemics have also shown that there can be clear class differentials in mortality in this type of illness--is there any reason to believe that Spanish influenza was different? This paper is the first study in which individual- and household-level data which are unique for the period are utilized to test the conservative hypothesis that Spanish influenza was a socially neutral disease with respect to mortality. Through the use of Cox regressions in an analysis of two socially contrasting parishes in the Norwegian capital city of Kristiania, it is shown that apartment size as an indicator of wealth of a household, in addition to social status of place of residence, were the only socioeconomic variables that had an independent and significant effect on mortality after controlling for age, sex and marital status.