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Paragraph: In its disease course and pathologic features, the 1918
pandemic was different in degree, but not in kind, from
previous and subsequent pandemics. Despite the extraordi-
nary number of global deaths, most inﬂuenza cases in
1918 (>95% in most locales in industrialized nations) were
mild and essentially indistinguishable from inﬂuenza cases
today.  Furthermore, laboratory experiments with recombi-
nant inﬂuenza Viruses containing genes from the 1918
Virus suggest that the 1918 and 1918-like Viruses would be
as sensitive as other typical Virus strains to the Food and
Drug Administrationiapproved antiinﬂuenza drugs riman-
tadine and oseltamivir. However, some characteristics of the 1918 pandemic
appear unique: most notably, death rates were 5 7 20 times
higher than expected. Clinically and pathologically, these
high death rates appear to be the result of several factors,
including a higher proportion of severe and complicated
infections of the respiratory tract, rather than involvement
of organ systems outside the normal range of the inﬂuenza
Virus. Also, the deaths were concentrated in an unusually
young age group. Finally, in 1918, 3 separate recurrences
of inﬂuenza followed each other with unusual rapidity,
resulting in 3 explosive pandemic waves within a year’s
time (Figure 1). Each of these unique characteristics may
reﬂect genetic features of the 1918 Virus, but understand-
ing them will also require examination of host and envi-
ronmental factors. Until we can ascertain which of these factors gave rise
to the mortality patterns observed and learn more about the
formation of the pandemic, predictions are only educated
guesses. We can only conclude that since it happened once,
analogous conditions could lead to an equally devastating
pandemic. Like the 1918 Virus, H5N1 is an avian Virus (39),
though a distantly related one. The evolutionary path that
led to pandemic emergence in 1918 is entirely unknown,
but it appears to be different in many respects from the cur-
rent situation with H5N1. There are no historical data,
either in 1918 or in any other pandemic, for establishing
that a pandemic “precursor” Virus caused a highly patho-
genic outbreak in domestic poultry, and no highly patho-
genic avian inﬂuenza (HPAI) Virus, including H5N1 and a
number of others, has ever been known to cause a major
human epidemic, let alone a pandemic. While data bearing
on inﬂuenza Virus human cell adaptation (e.g., receptor
binding) are beginning to be understood at the molecular
level, the basis for Viral adaptation to efﬁcient human-to-
human spread, the chief prerequisite for pandemic emer-
gence, is unknown for any inﬂuenza Virus. The 1918 Virus
acquired this trait, but we do not know how, and we cur-
rently have no way of knowing whether H5N1 Viruses are
now in a parallel process of acquiring human-to-human
transmissibility. Despite an explosion of data on the 1918
Virus during the past decade, we are not much closer to
understanding pandemic emergence in 2006 than we were
in understanding the risk of H1N1 “swine ﬂu” emergence
in 1976. Even with modern antiviral and antibacterial drugs,
vaccines, and prevention knowledge, the return of a pan-
demic Virus equivalent in pathogenicity to the Virus of
1918 would likely kill >100 million people worldwide. A
pandemic Virus with the (alleged) pathogenic potential of
some recent H5N1 outbreaks could cause substantially
more deaths. Whether because of Viral, host or environmental fac-
tors, the 1918 Virus causing the ﬁrst or ‘spring’ wave was
not associated with the exceptional pathogenicity of the
second (fall) and third (winter) waves. Identiﬁcation of an
inﬂuenza RNA-positive case from the ﬁrst wave could
point to a genetic basis for Virulence by allowing differ-
ences in Viral sequences to be highlighted. Identiﬁcation of
pre-1918 human inﬂuenza RNA samples would help us
understand the timing of emergence of the 1918 Virus. Surveillance and genomic sequencing of large numbers of
animal inﬂuenza Viruses will help us understand the genet-
ic basis of host adaptation and the extent of the natural
reservoir of inﬂuenza Viruses. Understanding inﬂuenza
pandemics in general requires understanding the 1918 pan-
demic in all its historical, epidemiologic, and biologic
aspects. Dr Taubenberger is chair of the Department of Molecular
Pathology at the Armed Forces Institute of Pathology, Rockville,
Maryland. His research interests include the molecular patho-
physiology and evolution of inﬂuenza Viruses. Dr Morens is an epidemiologist with a long-standing inter-
est in emerging infectious diseases, Virology, tropical medicine,
and medical history. Since 1999, he has worked at the National
Institute of Allergy and Infectious Diseases. References

1. Frost WH. Statistics of inﬂuenza morbidity. Public Health Rep.
19203558497. 2. Bumet F, Clark E. Inﬂuenza: a survey ofthe last 50 years in the light
of modern work on the Virus of epidemic inﬂuenza. Melbourne:
MacMillan; 1942. 3. Marks G, Beatty WK. Epidemics. New York: Scribners, 1976. 4. Rosenau MJ, Last JM. Maxcy-Rosenau preventative medicine and
public health. New York: Appleton-Century-Crofts; 1980. 5. Crosby A. America’s forgotten pandemic. Cambridge (UK):
Cambridge University Press;1989. 6. Patterson KD, Pyle GF. The geography and mortality of the 1918
influenza pandemic. Bull Hist Med. 1991;65:4–21. 7. Johnson NPAS, Mueller J. Updating the accounts: global mortality of
the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med
2002;76:105–15. 8. Shope RE. The incidence of neutralizing antibodies for swine
influenza virus in the sera of human beings of different ages. J Exp
Med. 1936;63:669–84. 9. Kendal AP, Noble GR, Skehel JJ, Dowdle WR. Antigenic similarity
of influenza A (H1N1) viruses from epidemics in 1977–1978 to
“Scandinavian” strains isolated in epidemics of 1950–1951. Virology. 1978;89:632–6. 10. Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG. Initial genetic characterization of the 1918 “Spanish” influenza virus. Science. 1997;275:1793–6. 11. Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng
H, et al. Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses
bearing the 1918 NS genes. Proc Natl Acad Sci U S A
2001;98:2746–51. 12. Reid AH, Fanning TG, Hultin JV, Taubenberger JK. Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. Proc Natl Acad Sci U S A 1999;96:1651–6. 13. Reid AH, Fanning TG, Janczewski TA, Lourens RM, and
Taubenberger JK. Novel origin of the 1918 pandemic influenza virus
nucleoprotein gene segment. J Virol. 2004;78:12462–70. 14. Reid AH, Fanning TG, Janczewski TA, McCall S, Taubenberger JK. Characterization of the 1918 “Spanish” influenza virus matrix gene
segment. J Virol. 2002;76:10717–23. 15. Reid AH, Fanning TG, Janczewski TA, Taubenberger JK. Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. Proc Natl Acad Sci U S A 2000;97:6785–90. 16. Reid AH, Janczewski TA, Lourens RM, Elliot AJ, Daniels RS, Berry
CL, et al. 1918 influenza pandemic caused by highly conserved viruses with two receptor-binding variants. Emerg Infect Dis. 2003;9:1249–53. 17. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning
TG. Characterization of the 1918 influenza virus polymerase genes. Nature. 2005;437:889–93. 18. Reid AH, Taubenberger JK. The 1918 flu and other influenza pandemics: “over there” and back again. Lab Invest. 1999;79:95–101. 19. Reid AH, Taubenberger JK, Fanning TG. Evidence of an absence: the
genetic origins of the 1918 pandemic influenza virus. Nat Rev
Microbiol. 2004;2:909–14. 20. Taubenberger JK, Reid AH, Fanning TG. The 1918 influenza virus: a
killer comes into view. Virology. 2000;274:241–5. 21. Jordan E. Epidemic influenza: a survey. Chicago: American Medical
Association, 1927. 22. Capps J, Moody A. The recent epidemic of grip. JAMA. 1916;67:1349–50. 33. Oxford JS, Sefton A, Jackson R, Innes W, Daniels RS, Johnson NP. World War I may have allowed the emergence of “Spanish” influenza. Lancet Infect Dis. 2002;2:111–4. 24. Fanning TG, Slemons RD, Reid AH, Janczewski TA, Dean J,
Taubenberger JK. 1917 avian influenza virus sequences suggest that
the 1918 pandemic virus did not acquire its hemagglutinin directly
from birds. J Virol. 2002;76:7860–2. 25. Reid AH, Fanning TG, Slemons RD, Janczewski TA, Dean J,
Taubenberger JK. Relationship of pre-1918 avian influenza HA and
NP sequences to subsequent avian influenza strains. Avian Dis. 2003;47:921–5. 26. Bean W, Schell M, Katz J, Kawaoka Y, Naeve C, Gorman O, et al. Evolution of the H3 influenza virus hemagglutinin from human and
nonhuman hosts. J Virol. 1992;66:1129–38. 27. Weis W, Brown JH, Cusack S, Paulson JC, Skehel JJ, Wiley DC. Structure of the influenza virus haemagglutinin complexed with its
receptor, sialic acid. Nature. 1988;333:426–31. 28. Gambaryan AS, Tuzikov AB, Piskarev VE, Yamnikova SS, Lvov DK,
Robertson JS, et al. Specification of receptor-binding phenotypes of
influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and
influenza B viruses share a common high binding affinity for 6′-sialyl(N-acetyllactosamine). Virology. 1997;232: 345–50. 29. Matrosovich M, Gambaryan A, Teneberg S, Piskarev VE, Yamnikova
SS, Lvov DK, et al. Avian influenza A viruses differ from human
viruses by recognition of sialyloigosaccharides and gangliosides and
by a higher conservation of the HA receptor-binding site. Virology. 1997;233:224–34. 30. Glaser L, Stevens J, Zamarin D, Wilson IA, Garcia-Sastre A, Tumpey
TM, et al. A single amino acid substitution in the 1918 influenza virus
hemagglutinin changes the receptor binding specificity. J Virol. 2005;79:11533–6. 31. Kobasa D, Takada A, Shinya K, Hatta M, Halfmann P, Theriault S, et
al. Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature. 2004;431:703–7. 32. Kash JC, Basler CF, Garcia-Sastre A, Carter V, Billharz R, Swayne
DE, et al. Global host immune response: pathogenesis and transcriptional profiling of type A influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virus. J Virol. 2004;78:9499–511. 33. Grove RD, Hetzel AM. Vital statistics rates in the United States:
1940–1960. Washington: US Government Printing Office, 1968. 34. Linder FE, Grove RD. Vital statistics rates in the United States:
1900–1940. Washington: US Government Printing Office, 1943. 35. Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ,
Fukuda K. Pandemic versus epidemic influenza mortality: a pattern
of changing age distribution.

Question: Is there a difference in the pathologic feature and course of disease between modern influenza pandemics and the 1918 swine flu pandemic?
the 1918
pandemic was different in degree, but not in kind, from
previous and subsequent pandemics. Despite the extraordi-
nary number of global deaths, most inﬂuenza cases in
1918 (>95% in most locales in industrialized nations) were
mild and essentially indistinguishable from inﬂuenza cases
today.