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Centennial Reflections on the 1918 Spanish Influenza Pandemic: Insights and Remaining Puzzles
Lone SimonsenProfessor, Dept of Science and Environment, Roskilde University, Denmark
Research Professor, Dept Global Health, George Washington University, DC, USA
New Zealand, February 7 & 8, 2018
Pandemic preparednessLearns from historicalPandemics
1918 is ”poster child”So important to get it right
GAPMINDERhttp://www.gapminder.org/world
https://www.youtube.com/watch?v=E6t7ZZ_FY4o
1918
1918
WW1+ 1918
WW2
1918 influenza pandemic1-2% of global population died
C. Byerly, PH Rep 2010
heliotropecyanosis
All kinds of dataUsed to compileEvidence of Pandemic activity(newspapers, Rapports, more)
Patterson & Pyle
See Lisa Sattenspiel papers
"The flu? Why yes, my son, I remember the flu. That’s why everybody here is related the way they are. When my grandmother died from it, my grandfather had to marry XX because her husband died of it. …”
By 2005: complete genome sequenced
H3N8? 1907 H1N8? 1918 H1N1
But Worobey et al disagree….
Influenza A Virus Pandemics and Circulation for a Century
A/H3N2
A/H2N2A/H1N1 A/H1N1
1918 1957 1968SpanishInfluenza
Avianinfluenza
Hong Konginfluenza
AvianH5N1H7N9others--threatSince1997
19772009H1N1p
A/H1N1-p
?
1889RussianInfluenza
?
Origin: Zoonotic viruses (1918?, 2009) or genetic re-assortment Involving zoonotic viruses and human viruses (1957, 1968)
How to Measure Influenza-Related Mortality Burden Modeling National Time Series Mortality Data
122 cities weekly P&I mortality data
Oct
-200
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2001
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Date
Observed P&I ratio
Predicted Baseline
2009 Pandemic
%P&I deathsSevereFujian 2003-04
2009 Pandemic2nd wave fall’09
Murray et al, Lancet 2006
Estimate based on 13 countries dataNotice ~40-fold difference ! Caveat: Low income areas represented by 5 Indiansub-national estimates
Chandra & Kassens-NoorBMC ID 2014
Calcutta completely escaped 1918 autumn wave – how?Across India, 5% population died
United States: Pandemic Mortality and Mean Age for all 5 pandemicsadjusted to 2000 population – great for between-pandemic comparison
Pandemic Season
Number deaths*
% of population died
Mean age at deaths (years)
1889 ? ?
1918 1,300,000 0.5% 27
1957 150,600 0.1% 65
1968 86,000 0.03% 62
2009 7,500-44,100 0.003-0.2% 37
Seasonal influenza (avg)
~30,000 0.01% 76
Viboud et al, Plos Currents 2009
2009 Pandemic-- A Perplexing Situation
-- Since 2011 WHO includes clinical severity in pandemic definition
(Case Fatality, CFR)
R0
Extreme, unusualmortality in youngadults aged 20-40
What is shown is ANNUAL deaths –Not influenza-related deaths
Olsen et al PNAS 2005, Andreasen et al, JID 2008
1918 Pandemic: Elderly were completely spared Monthly All Cause Deaths / 10,000 pop, for 1910-1919
1918 1920
Seniors ≥65 years
Young Adults15-44years
1910
All ages were affectedIn S America
Interpretation under the ”recycling”Hypothesis:
Remote locales had not encounteredH1-like influenza in their childhood
Chowell et al, multiple publicationsof data from Colombia, Peru, Mexico…
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Apr 2006-8 Apr-09
% o
f Apr
il pn
eum
onia
dea
ths
Elderly spared
Younger adults die
Age
Geographic heterogeneity~200,000 deaths globally~20-fold higher in S.America than Europe WHO GLaMOR projectSimonsen et al, PLoS Med 2013
2009 Pandemic age shiftPneumonia mortality in MexicoChowell et al, NEJM, August 2009
Pandemic deathsmay be delayedto 2nd or 3rd wave
Good news: There is time to vaccinate!
Pandemic A/H1N1 virus eventually identified in US soldiers who died in summer 1918 (Sheng et al, PNAS 2011)
Copenhagen Population: 540,000
1918 summer wave
1918 fall wave
Excess Illness 25,000 61,000
Excess DeathsCase Fatality
% occurred in young <65Transmissibility Ro
850.3%
95%>2
1,3002.1%
95%1.3
Pandemic A/H1 virus later identified in May-Aug 1918 in specimensFrom dead US soldiers (Sheng….Taubenberger, PNAS 2011)
-- YES! by 56%-94% according to Barry et al, JID 2008
Poster Child PandemicDisaster scenarioWhich pandemic Planning/imaginationconsiders
JID 2008
Shanks & Brundage, Epidemiol & Infect 2013
PNAS 2017
Is bacterial coinfectionthe explanation for variability in 1918 mortality risk ?
New Zealand Maori population was at 7 x 1918 pandemic mortality risk
Wilson et al, Emerg Inf Dis 2012
CONTENDERS• Genetic predisposition?• Previous influenza exposure less in remote populations?• Differences in background mortality levels?
TB a leadingCause of death in young adultsAround 1918
ManyYoung adultswerelatentlyinfectedOr had active TB
Tuberculosis
1918 pandemic
Noymer& GarennePopul Dev Rev 2002
19188
US Annual TB mortality rates
Science 2016Birth year as a risk factor?
A/H7N9 A/H5N1
Cases and Deaths, by birth year, for two avian influenza viruses, one of each type
Two Influenza HA types
-Type1: H1, H2, H5
- Type2: H3, H7
Novel influenza A H1N1 virus (sequenced)
High transmissibility (Ro>2; susceptible population) rapid global dissemination; disrespects typical seasonality
High mortality (1-2% of population) w unusual age pattern
Young adults at extreme risk
Seniors often spared
Geographical heterogeneity in mortality burden
30-fold differences between countries
Multiple waves 1918-1921 Mild 1st wave that appears to have been protective
What Comes Next?
Support: • RAPIDD fellowship: Fogarty-NIH and Dept Homeland Security• Danish Medical Research Council, • Lundbeck Foundation• World Health Organization• EU/Horizon2020 Marie Curie Action
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