Age-Specific Mortality During the 1918–19 Influenza Pandemic and Possible Relationship to the 1889–92 Influenza Pandemic
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JID 2014:210 (15 September)
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993
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
TO THE EDITOR—The uniquely increased mortality rate among adults aged 20–40 years during the 1918–1919 influenza pandemic has never been adequately explained. Viboud et al present extensive data from Kentucky death registrations indicating that peak mortality occurred between 24 and 26 years of age and concluded that a combination of risk factors determined mortality [1]. Subsequent work by Gagnon et al showed distinct modal mortality at 28 years of age from 8 Canadian and 3 US civilian data sources [2]. The actual age of peak mortality may be important as some have suggested that infection while a young child during the previous influenza pandemic of 1889– 1892 (thought to have been due to influenza A[H3Nx]) may have predisposed these individuals to a more severe outcome approximately 28 years later during the subsequent 1918–1919 influenza A (H1N1) pandemic [2, 3]. We sought similar mortality information from civilian and military populations in New Zealand and Australia to determine whether the pattern seen was the same as that observed in the United States and Canada. Death registration information for 4813 people who died during the 1918– 1919 pandemic was available in New Zealand from an earlier historical study [4]. Data from Auckland City have subsequently been lost, but data from all other parts of New Zealand were included. It is also likely that deaths among the
indigenous Māori had been underreported. Denominator data were calculated from the 1916 National Census with Statistics New Zealand estimates for the total population in 1918 [5]. We also considered influenza mortality data for 1239 soldiers in the Australian Army (with deaths mainly in Europe and the Middle East), aspects of which have previously been reported [6]. Age-specific rates of mortality due to pneumonia/influenza during the 1918– 1919 pandemic are shown in Figure 1 both for civilians in New Zealand, stratified by sex, and for Australian soldiers, which should be compared to Supplementary Figure 2 from Viboud et al [1]. The peak mortality rate for New Zealand civilian males occurred among those aged 28 years (118 deaths; 143 deaths per 10 000), and the peak mortality rate among civilian females occurred among those aged 32 years (63 deaths; 62 deaths per 10 000). The peak mortality rate among Australian soldiers occurred at 18 years of age (17 deaths; 202 deaths per 10 000), with a secondary peak at 27 years of age (101 deaths; 61 deaths per 10 000). The sex-specific mortality difference seen in New Zealand is consistent with a previously described lower female mortality rate in the United States [7]. The single greatest mortality risk factor during the 1918–1919 pandemic in the Australian Army was having joined the military in 1918, which very likely explains the large mortality rate among 18–19-year-old soldiers, many of whom were recent recruits [6]. One of the difficulties in using death registration information is estimating the population at risk to derive rates. Although death registration is precise, variation in estimating denominators likely accounts for some of the differences in mortality rates between studies [1, 2]. Multiple risk factors contributed to mortality in 1918, including age, sex, indigenous group, urban/rural status, time since recruitment into the military, and exposure to bacterial pathogens, as most deaths were caused by secondary bacterial pneumonia
(due to pathogens such as Streptococcus pneumoniae and Staphylococcus aureus) [6, 8–10]. Since there is no intrinsic reason to think that adults separated by few years in the range from 20 to 40 years of age would react differently to a severe viral respiratory infection, it seems possible that the otherwise inexplicable peak age of mortality near 28 years of age might be evidence of dysfunctional immunity to a previous influenza virus infection. Potential mechanisms to explain enhanced mortality caused by previous influenza virus infection include nonneutralizing antibodies 994
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JID 2014:210 (15 September)
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and/or dysfunctional CD8+ lymphocyte responses triggering excessive cytokine production [2, 3]. Persons aged 28 years in 1918 would have been members of the 1890 birth cohort, whose first influenza virus infection would have almost certainly been by the 1889–1892 pandemic virus. Since not all children are infected with influenza virus in their first year of age, some broadening of the peak mortality rate would not invalidate the hypothesis that infection during one pandemic predisposed to severe outcomes during a subsequent influenza pandemic.
CORRESPONDENCE
Besides the unique age-associated mortality pattern, the 1918–1919 pandemic caused very heterogeneous effects in what otherwise would have been expected to be identical populations. Although some populations experienced catastrophic mortality, others had a 10–50 times lower case-fatality proportion while experiencing similar infection rates. There is no simple explanation for the observed epidemiology as the reconstructed 1918 virus has no unique genomic features and is similar to the pandemic virus of 2009 [11]. Mortality
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
Figure 1. Age-specific mortality per 10 000 population by single year due to pneumonia and influenza during the 1918–1919 pandemic among civilians in New Zealand, stratified by sex (A), and among Australian soldiers (>99% male) predominately while in Europe and the Middle East (B).
risk is a composite of pathogen virulence, host susceptibility, and environmental factors. The peak age-specific mortality rate near 28 years of age in both the United States and Canada, as well as in 2 additional populations (from New Zealand and Australia), seems to provide some evidence for the dominance of host factors and possibly reflects a common exposure, such as early childhood infection during the 1889–1892 influenza pandemic. Notes
Nick Wilson,1 Jane Oliver,1 Geoff Rice,2 Jennifer A. Summers,3 Michael G. Baker,1 Michael Waller,4 and G. Dennis Shanks4,5 1
Department of Public Health, University of Otago, Wellington; 2Department of History, University of Canterbury, Christchurch, New Zealand; 3Division of Health and Social Care Research, King’s College London, United Kingdom; 4University of Queensland, Centre for Australian Military and Veteran’s Health, School of Population Health, Brisbane, and 5Australian Army Malaria Institute, Enoggera, Australia
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
Disclaimer. The opinions expressed are those of the authors and do not necessarily reflect those of the Australian Defence Force. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
6. Shanks GD, Mackenzie A, McLaughlin R, et al. Mortality risk factors during the 1918– 1919 influenza pandemic in the Australian army. J Infect Dis 2010; 201:1880–9. 7. Frost W. Statistics of Influenza morbidity with special reference to certain factors in case incidence and case-fatality. Public Health Rep 1920; 35:584–97. 8. Paynter S, Ware RS, Shanks GD. Host and environmental factors reducing mortality during the 1918–1919 influenza pandemic. Epidemiol Infect 2011; 139:1425–30. 9. Summers JA, Wilson N, Baker MG, Shanks GD. Mortality risk factors for pandemic influenza on New Zealand troop ship, 1918. Emerg Infect Dis 2010; 16:1931–7. 10. Shanks GD, Brundage JF. Pacific islands which escaped the 1918–1919 influenza pandemic and their subsequent morality experiences. Epidemiol Infect 2013: 141; 353–6. 11. Morens DM, Taubenberger JK, Fauci AS. The persistent legacy of the 1918 influenza virus. N Engl J Med 2009; 361:225–29. Received 26 January 2014; accepted 7 March 2014; electronically published 27 March 2014. Correspondence: G. Dennis Shanks, Australian Army Malaria Institute, Weary Dunlop Drive, Enoggera, QLD 4051, Australia ([email protected]). The Journal of Infectious Diseases 2014;210:993–5 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiu191
References 1. Viboud C, Eisenstein J, Reid AH, Janczewski TA, Morens DM, Taubenberger JK. Age- and sex-specific mortality associated with the 1918–1919 influenza pandemic in Kentucky. J Infect Dis 2013; 207:721–9. 2. Gagnon A, Miller MS, Hallman SA, et al. Agespecific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality. PLoS One 2013; 8: e69586. 3. Shanks GD, Brundage JF. Pathogenic responses among young adults during the 1918 influenza pandemic. Emerg Infect Dis 2012; 18:201–7. 4. Rice G. Black November: The 1918 influenza pandemic in New Zealand. Christchurch: Canterbury University Press, 2005. 5. Department of Statistics. Report on the Results of a Census of the Population of the Dominion of New Zealand Taken for the Night of the 15th October, 1916. Wellington: Department of Statistics, 1916. http://www. stats.govt.nz. Accessed 10 January 2014.
CORRESPONDENCE
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JID 2014:210 (15 September)
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995
CORRESPONDENCE
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JID 2014:210 (15 September)
•
993
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
TO THE EDITOR—The uniquely increased mortality rate among adults aged 20–40 years during the 1918–1919 influenza pandemic has never been adequately explained. Viboud et al present extensive data from Kentucky death registrations indicating that peak mortality occurred between 24 and 26 years of age and concluded that a combination of risk factors determined mortality [1]. Subsequent work by Gagnon et al showed distinct modal mortality at 28 years of age from 8 Canadian and 3 US civilian data sources [2]. The actual age of peak mortality may be important as some have suggested that infection while a young child during the previous influenza pandemic of 1889– 1892 (thought to have been due to influenza A[H3Nx]) may have predisposed these individuals to a more severe outcome approximately 28 years later during the subsequent 1918–1919 influenza A (H1N1) pandemic [2, 3]. We sought similar mortality information from civilian and military populations in New Zealand and Australia to determine whether the pattern seen was the same as that observed in the United States and Canada. Death registration information for 4813 people who died during the 1918– 1919 pandemic was available in New Zealand from an earlier historical study [4]. Data from Auckland City have subsequently been lost, but data from all other parts of New Zealand were included. It is also likely that deaths among the
indigenous Māori had been underreported. Denominator data were calculated from the 1916 National Census with Statistics New Zealand estimates for the total population in 1918 [5]. We also considered influenza mortality data for 1239 soldiers in the Australian Army (with deaths mainly in Europe and the Middle East), aspects of which have previously been reported [6]. Age-specific rates of mortality due to pneumonia/influenza during the 1918– 1919 pandemic are shown in Figure 1 both for civilians in New Zealand, stratified by sex, and for Australian soldiers, which should be compared to Supplementary Figure 2 from Viboud et al [1]. The peak mortality rate for New Zealand civilian males occurred among those aged 28 years (118 deaths; 143 deaths per 10 000), and the peak mortality rate among civilian females occurred among those aged 32 years (63 deaths; 62 deaths per 10 000). The peak mortality rate among Australian soldiers occurred at 18 years of age (17 deaths; 202 deaths per 10 000), with a secondary peak at 27 years of age (101 deaths; 61 deaths per 10 000). The sex-specific mortality difference seen in New Zealand is consistent with a previously described lower female mortality rate in the United States [7]. The single greatest mortality risk factor during the 1918–1919 pandemic in the Australian Army was having joined the military in 1918, which very likely explains the large mortality rate among 18–19-year-old soldiers, many of whom were recent recruits [6]. One of the difficulties in using death registration information is estimating the population at risk to derive rates. Although death registration is precise, variation in estimating denominators likely accounts for some of the differences in mortality rates between studies [1, 2]. Multiple risk factors contributed to mortality in 1918, including age, sex, indigenous group, urban/rural status, time since recruitment into the military, and exposure to bacterial pathogens, as most deaths were caused by secondary bacterial pneumonia
(due to pathogens such as Streptococcus pneumoniae and Staphylococcus aureus) [6, 8–10]. Since there is no intrinsic reason to think that adults separated by few years in the range from 20 to 40 years of age would react differently to a severe viral respiratory infection, it seems possible that the otherwise inexplicable peak age of mortality near 28 years of age might be evidence of dysfunctional immunity to a previous influenza virus infection. Potential mechanisms to explain enhanced mortality caused by previous influenza virus infection include nonneutralizing antibodies 994
•
JID 2014:210 (15 September)
•
and/or dysfunctional CD8+ lymphocyte responses triggering excessive cytokine production [2, 3]. Persons aged 28 years in 1918 would have been members of the 1890 birth cohort, whose first influenza virus infection would have almost certainly been by the 1889–1892 pandemic virus. Since not all children are infected with influenza virus in their first year of age, some broadening of the peak mortality rate would not invalidate the hypothesis that infection during one pandemic predisposed to severe outcomes during a subsequent influenza pandemic.
CORRESPONDENCE
Besides the unique age-associated mortality pattern, the 1918–1919 pandemic caused very heterogeneous effects in what otherwise would have been expected to be identical populations. Although some populations experienced catastrophic mortality, others had a 10–50 times lower case-fatality proportion while experiencing similar infection rates. There is no simple explanation for the observed epidemiology as the reconstructed 1918 virus has no unique genomic features and is similar to the pandemic virus of 2009 [11]. Mortality
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
Figure 1. Age-specific mortality per 10 000 population by single year due to pneumonia and influenza during the 1918–1919 pandemic among civilians in New Zealand, stratified by sex (A), and among Australian soldiers (>99% male) predominately while in Europe and the Middle East (B).
risk is a composite of pathogen virulence, host susceptibility, and environmental factors. The peak age-specific mortality rate near 28 years of age in both the United States and Canada, as well as in 2 additional populations (from New Zealand and Australia), seems to provide some evidence for the dominance of host factors and possibly reflects a common exposure, such as early childhood infection during the 1889–1892 influenza pandemic. Notes
Nick Wilson,1 Jane Oliver,1 Geoff Rice,2 Jennifer A. Summers,3 Michael G. Baker,1 Michael Waller,4 and G. Dennis Shanks4,5 1
Department of Public Health, University of Otago, Wellington; 2Department of History, University of Canterbury, Christchurch, New Zealand; 3Division of Health and Social Care Research, King’s College London, United Kingdom; 4University of Queensland, Centre for Australian Military and Veteran’s Health, School of Population Health, Brisbane, and 5Australian Army Malaria Institute, Enoggera, Australia
Downloaded from http://jid.oxfordjournals.org/ at New York Medical College on August 13, 2015
Disclaimer. The opinions expressed are those of the authors and do not necessarily reflect those of the Australian Defence Force. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
6. Shanks GD, Mackenzie A, McLaughlin R, et al. Mortality risk factors during the 1918– 1919 influenza pandemic in the Australian army. J Infect Dis 2010; 201:1880–9. 7. Frost W. Statistics of Influenza morbidity with special reference to certain factors in case incidence and case-fatality. Public Health Rep 1920; 35:584–97. 8. Paynter S, Ware RS, Shanks GD. Host and environmental factors reducing mortality during the 1918–1919 influenza pandemic. Epidemiol Infect 2011; 139:1425–30. 9. Summers JA, Wilson N, Baker MG, Shanks GD. Mortality risk factors for pandemic influenza on New Zealand troop ship, 1918. Emerg Infect Dis 2010; 16:1931–7. 10. Shanks GD, Brundage JF. Pacific islands which escaped the 1918–1919 influenza pandemic and their subsequent morality experiences. Epidemiol Infect 2013: 141; 353–6. 11. Morens DM, Taubenberger JK, Fauci AS. The persistent legacy of the 1918 influenza virus. N Engl J Med 2009; 361:225–29. Received 26 January 2014; accepted 7 March 2014; electronically published 27 March 2014. Correspondence: G. Dennis Shanks, Australian Army Malaria Institute, Weary Dunlop Drive, Enoggera, QLD 4051, Australia ([email protected]). The Journal of Infectious Diseases 2014;210:993–5 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/infdis/jiu191
References 1. Viboud C, Eisenstein J, Reid AH, Janczewski TA, Morens DM, Taubenberger JK. Age- and sex-specific mortality associated with the 1918–1919 influenza pandemic in Kentucky. J Infect Dis 2013; 207:721–9. 2. Gagnon A, Miller MS, Hallman SA, et al. Agespecific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality. PLoS One 2013; 8: e69586. 3. Shanks GD, Brundage JF. Pathogenic responses among young adults during the 1918 influenza pandemic. Emerg Infect Dis 2012; 18:201–7. 4. Rice G. Black November: The 1918 influenza pandemic in New Zealand. Christchurch: Canterbury University Press, 2005. 5. Department of Statistics. Report on the Results of a Census of the Population of the Dominion of New Zealand Taken for the Night of the 15th October, 1916. Wellington: Department of Statistics, 1916. http://www. stats.govt.nz. Accessed 10 January 2014.
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JID 2014:210 (15 September)
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995
