Probabilistic Records Linkage using Historical Canadian Censuses and Vital Statistics

Poster Presentation This poster presents the results of a records linkage project to analyze potential mortality risks for young adults in Ontario during the 1918 influenza epidemic. With a team of research assistants at Western University, McMaster University, and the Université de Montréal, death records were linked to birth records in order to determine exact date of birth for the calculation of exact age at death. This date of birth is then compared to age as listed on other historical documents, such as the 1901 and 1911 Canadian censuses. The family environment (or living situation) was transcribed for each individual at each census to examine the impact of socioeconomic conditions throughout the lifecourse on mortality in 1918. Of the 23,183 deaths registered in Ontario between September and December 1918 and transcribed by the International Infectious Disease Data Archive at McMaster University, 3,316 individuals met the inclusion criteria. Both birth and death must have occurred in Ontario to establish exact date of birth and the individual must have died between the ages of 23 and 35 (born between 1883 and 1895). Of the 3,316 included death records, 2,965 were linked to at least one other record, giving a linkage success rate of 89.4%. This poster analyzes the linkage rates of the death records to birth records from 1883-1895 and the 1901 and 1911 Canadian censuses and uses logistic regression to investigate the important factors that precluded linkage. It evaluates declared age at all three time periods to discuss the suitability of these records for historical demographic analyses of past epidemic disease

The Demographic Links Between the 1890 and 1918 Influenza Pandemics in Ontario

Previous research has shown larger than expected numbers of deaths at the age of 28 during the 1918 Spanish influenza pandemic in Canada. To analyze whether this was related to the Russian influenza pandemic that occurred 28 years previously in 1890, the Western, McMaster, Montreal Influenza Pandemic (WMMIP) database was created. It utilizes the death records of 3,316 individuals who died in Ontario between the ages of 23 and 35 from September to December, 1918, and who were also born in Ontario. These were linked to birth records, the 1901 and 1911 Canadian censuses, marriage records, and attestation papers. A reconstructed date of birth was created for each individual to analyze date of potential exposure in 1890. Those who were in utero in 1890 died in greater numbers than would be expected and those in the first trimester of gestation had an unusual sex-ratio at death. Of the various hypotheses proposed to account for the high young adult mortality, these data most closely support that of antigenic imprinting. There is cautious support for the fetal growth restrictions hypothesis, but these data do not support the scarring mechanism. Further, these data do not support the hypothesized relationship between tuberculosis infection and influenza mortality. More individuals left agricultural homes of origin among the decedents than among the Ontario population in general. There were proportionally more French Canadians, more catholic individuals, and more people from Eastern Ontario. The decedents also came from larger families than were found in the general population, although this may be an artifact of the records linkage process. This research shows that the mortality pattern in Ontario during the pandemic was similar to what it was prior to the epidemic: mortality continued along the fault lines in society and did not equalize risk in a “democratic” manner. The extant records are appropriate for historical demographic analyses and the strength and weaknesses for each are detailed. As expected, individuals from the north, who were aboriginal, from smaller families, or in transient occupations were harder to link

Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics

Determinants of Influenza Mortality Trends: Age-Period-Cohort Analysis of Influenza Mortality in the United States, 1959-2016.

This study examines the roles of age, period, and cohort in influenza mortality trends over the years 1959-2016 in the United States. First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2). Second, we use age-period-cohort (APC) methods to explore APC linear trends and identify changes in the slope of these trends (contrasts). Our analyses reveal a series of breakpoints where the magnitude and direction of birth cohort trends significantly change, mostly corresponding to years in which important antigenic drifts or shifts took place (i.e., 1947, 1957, 1968, and 1978). Whereas child, youth, and adult influenza mortality appear to be influenced by a combination of cohort- and period-specific factors, reflecting the interaction between the antigenic experience of the population and the evolution of the influenza virus itself, mortality patterns of the elderly appear to be molded by broader cohort factors. The latter would reflect the processes of physiological capital improvement in successive birth cohorts through secular changes in early-life conditions. Antigenic imprinting, cohort morbidity phenotype, and other mechanisms that can generate the observed cohort effects, including the baby boom, are discussed

Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic.

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect

Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics

Determinants of Influenza Mortality Trends: Age-Period-Cohort Analysis of Influenza Mortality in the United States, 1959-2016.

This study examines the roles of age, period, and cohort in influenza mortality trends over the years 1959-2016 in the United States. First, we use Lexis surfaces based on Serfling models to highlight influenza mortality patterns as well as to identify lingering effects of early-life exposure to specific influenza virus subtypes (e.g., H1N1, H3N2). Second, we use age-period-cohort (APC) methods to explore APC linear trends and identify changes in the slope of these trends (contrasts). Our analyses reveal a series of breakpoints where the magnitude and direction of birth cohort trends significantly change, mostly corresponding to years in which important antigenic drifts or shifts took place (i.e., 1947, 1957, 1968, and 1978). Whereas child, youth, and adult influenza mortality appear to be influenced by a combination of cohort- and period-specific factors, reflecting the interaction between the antigenic experience of the population and the evolution of the influenza virus itself, mortality patterns of the elderly appear to be molded by broader cohort factors. The latter would reflect the processes of physiological capital improvement in successive birth cohorts through secular changes in early-life conditions. Antigenic imprinting, cohort morbidity phenotype, and other mechanisms that can generate the observed cohort effects, including the baby boom, are discussed

Percentages of deaths by age from pandemic-related causes and from all other causes in Ontario and US locations, September to December 1918.

<p><b>^&&Key for </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069586#pone-0069586-g004" target="_blank"><b>Figure 4:</b></a> Yearly age-specific deaths counts were available from age 0 to 4 and from 18 to 31 for the US locations in the special tables that were tabulated for these locations in 1920 (27); outside these ranges, death counts were only available for collapsed age-groups (i.e., 5–9, 10–14, 15–17, 32–34, 35–39, 40–44, ..., and 60–64). We divided the number of deaths in the interval by its length and plotted the obtained number at the midpoint value of the interval. Deaths above age 65 were not available by age or age-groups for the U.S. locations. Ontario locations: Toronto, Hamilton, Ottawa, London, and Welland & Lincoln; US locations: Philadelphia, Indiana, and Kansas.</p

Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 “swine flu” pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 “Spanish flu.” Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 “swine flu” pandemic and during the resurgent 2013–2014 H1N1 outbreak for those born at the time of the 1957 H2N2 “Asian flu” pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics