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Introduction to pandemic influenza through history
European Journal of Epidemiology 10:451-453, 1994.
? 1994 Kluwer Academic Publishers. Printed in the Netherlands.
Introduction to pandemic influenza through history
Youri Ghendon
World Health Organization, Geneva, Switzerland
Abstract. For the past 400 years, epidemics resem-
bling influenza have been recorded in many coun-
tries. Epidemics from as early as the 16th Century
Key words: Control, Influenza, Pandemic
The influenza pandemic of 1918 was the largest in
recent history, causing 20 million deaths worldwide.
In more modern times since 1957 and 1968 influenza
pandemic also killed a million people.
While the relationship between antigenic change
and epidemic is complex, presumably involving
multiple factors attributable to the host as well as to
the viruses, antigenic drift or shift is the most readily
identifiable marker of epidemic potential.
Although influenza pandemics cannot be predicted
with certainty the plans for pandemic situations can
be developed and can play an important role in the
prompt and appropriate response when they occur.
In the year 412 BC Hippocrates described an
epidemic that modern doctors believe was influenza,
and history has recorded many influenza epidemics
and pandemics since that time.
In the Middle Ages several widespread outbreaks
that were probably influenza occurred in Europe. But
the first epidemics that can be regarded with confi-
dence as influenza were in 1173. However, the
position of some medical historians that only
epidemics which occurred in 1510 can be considered
as unquestionable influenza epidemics [1]. In 1580
a severe pandemic occurred that was possibly the first
global dissemination of influenza. It started in Asia
and spared to Africa, Europe and America. Almost
all of Europe was afflicted in six weeks and it was
said that only one twentieth of the people escaped the
illness. The case description of influenza was done
during this epidemic and is similar to influenza
illness seen currently.
In the eighteenth century there were 13 severe
epidemics and in the nineteenth century there were
12, and probably 8 or 9 of these 25 were influenza
pandemics in the modern sense. In the twentieth
century there have been several pandemics: 1918,
1946, 1957, 1968 and 1977 due to emergence of new
subtypes of influenza A virus.
The influenza viruses are unique in that they are
in England and the 18th Century in the USA are
recognizable as influenza, even in the absences of
precise knowledge of their causative agents.
able to circumvent immunity by gradually under-
going alteration of their two surface antigen -
haemagglutinin and neuraminidase -by accommo-
dation of a series of mutation (drift) and can also
undergo a complete change in one or more of their
surface antigens by genetic reassortment (shift). The
shift variants of influenza virus are responsible for
recent pandemics. It should be noted that the
influenza viruses demonstrates only antigenic drift
may also cause pandemics in the strictest epidemio-
logical sense of the word. For example, worldwide
epidemics occurred with the influenza A viruses of
1972, 1974 and 1975.
According to the dictionary definition, a pandemic
is simply a widespread epidemic, but when referring
to influenza a pandemic now signifies a worldwide
epidemic caused by a new subtype of influenza A
virus. Therefore only during the virological era can
we recognize a pandemic with certainty. However, in
the absence of virus identification, we can make an
informed guess that if the epidemic originated in one
place and from there spread worldwide with high
morbidity, it was probably a pandemic. Also epi-
demics occurring during the warmer months of the
year are a practically sure sign that they were pan-
demics; theses occurred in 1580, 1781, 1831 and
1918.
The greatest pandemic of the twentieth century
was the pandemic of 1918, popularly known as
Spanish flue owing to its high incidence in Spain,
which is believed to have been caused by the 'swine'
variant HlswN1 subtype of influenza virus.
The first wave of the pandemic of 19t8 swept
across North America in March and April 1918. The
infection moved on to Europe, when it first reached
epidemic levels in France in April 1918. Over the
next several months, influenza spread throughout the
whole of Europe. In the United States of America the
I918 influenza pandemic killed 550,000 people -
0.5% of the population, about ten times more the
number of Americans who died in the war [1, 2]. In
Europe the influenza in England and Wales alone
killed 200,000 people. In a few places such as Samoa
and Alaska some 25% or more died. Throughout the
world influenza pandemic 1918 killed 20 to 40
million people, and made one-quarter to one-half of
the population sick. The 1918 influenza pandemic
killed more people in less time than any other disease
before or since.
In a vain effort to halt the spread of influenza
during 1918 pandemic in the USA, in some cities
officials closed dance halls, theatres, schools and
even churches. There were placards on street cars and
railroad stations asking people not to spit and all
police wore masks. Police in Chicago were asked to
arrest people who sneezed in the streets [2].
Since the 1918 pandemic, there have been two
major global outbreaks of influenza A in the twen-
tieth century: In 1957, influenza was induced by
namely 'Asian' influenza virus A/H2N2, and in 1967,
influenza was induced by namely 'Hong Kong'
influenza virus - A/H3N2 - and two mild pandemics
in 1946 and in 1977, induced by H1N1.
In 1946 there was a worldwide epidemic that was
regarded as pandemic due to a new influenza virus
subtype -H1N1. It was a mild pandemic and the
excess of mortality was low. Influenza pandemic
1957 was not so bloodthirsty as in 1918, neverthe-
less in the USA alone 40,000 deaths were attributed
to the 'Asian' influenza and the mortality was much
the same in most countries. During the Hong Kong
pandemic 1967 the mortality in the USA alone was
estimated at around 30,000 deaths, 51 million
Americans were ill and the total economic burden
was 3.9 billion [3]. In Europe the mortality was
estimated at 30,000 deaths in Britain alone [4].
The next notable event in the history of influenza
was the reemergence in 1977 of the H1N1 influenza
virus that had been prevalent from 1947 to 1957. It
arose in China and spread world-wide but affected
mostly people born after 1957. From 1977 to the
present day it has continued to circulate along with
H3N2 and B influenza viruses.
The minimal requirement for the generation of a
pandemic seems to be the major change in external
antigens. The severity of the 1957 pandemic when
two external antigens changed, compared to the less
dramatic pandemic in 1946 and 1967 when only
haemagglutinin changed my reflect this fact.
What can we really do to control influenza pan-
demic? The main problem is that the real causative
virus of pandemic influenza cannot be completely
determined until at least the first phase of the
pandemic is underway. If influenza surveillance is
improved, especially in the areas in which most of
the pandemic influenza viruses arise, the potential
pandemic shift variants of influenza virus can be
detected early. Nevertheless the period of time
available for vaccine production from the potential
pandemic strain of influenza virus will always be
limited.
There is one example of an attempt to control
pandemic influenza: In the USA in 1976 the cases
of so-called swine influenza took place and a decision
was made to control the potential influenza pandemic
by mass vaccination. The sequence of events that
constituted the response on this outbreak began with
the initial recognition of the new virus and culmi-
nated in the production and use of a vaccine. But the
time from the isolation of the influenza virus and the
beginning of the Nationa Influenza Immunization
Programme took approximately one year [5]. If it is
influenza virus which really can induce pandemic
influenza, at the beginning of a vaccination period,
which is one year after the isolation of the virus,
all people susceptible to this virus can develop
influenza.
In the book Patterson [6], the author concluded:
'Pandemics have secured with a frequency of three
per 100 years since 1700. There is no periodicity to
the occurrence of pandemics and no basis for pre-
dicting where a new outbreak may arise'. Since 1889
pandemics of influenza have occurred at intervals of
28/29 and 10-11 years and in fact several supposi-
tions on the possibility to predict the influenza
pandemic on the basis of cyclical recurrence of the
pandemic strains or solar activity, or other factors,
are in fact only speculative. It is to be noted that the
accounts of a Florentine family in the fourteen/fifteen
centuries used the world 'influence' to suggest an
unusual conjunction of planets at times of epidemics
of coughs, colds and fevers. The word 'influenza'
was thus derived as a description name for the
epidemics due to 'influences'. In the twentieth
century Hope-Simpson published an article [7] in
which he suggests that antigenic shifts of influenza
A virus and accordingly pandemic coincided with
sunspot, and showed some examples of this from
1930 to 1970. But in 1979 sunspots activity took
place but there was no pandemic. So we should be
prepared for unforeseen influenza pandemic in any
given year.
In the Middle Ages the Germans thought influenza
was caused by eating too many sour applies and salt
fish. Now we know much more about the agent
induced influenza, but our knowledge on how to take
control of pandemic influenza is practically at the
same level as in the Middle Ages.
During the International Conference for the control
of influenza in 1992, at Courcheval, attempts were
made to work out several recommendations on pan-
demic planning [8]: Examples of these are as follows:
1. The enhanced surveillance of influence, espe-
cially in Southern China where most of the
pandemic strains of influenza virus originated, in
order to detect the emergence of the pandemic
strain and isolate the pandemic strain of influenza
virus as soon as possible.
2. The vaccine improvements are essential for
optimal pandemic control, especially for the
production of influenza vaccine in a short period
of time. The possibility to use new substrate for
vaccine production of new types of influenza
vaccine for vaccination needs investigation.
3. The antivirals can play a major role in the early
phases of a pandemic. Alternative agents to
amantadine/rimantadine which have different
mechanisms of antirival activity needs to be
developed.
4. The national, regional and global plans on the
control of pandemic influenza should be worked
out.
5. Public and mass-media need to be involved in the
control of pandemic at all stages.
References
1. Beveridge W. The chronicle of influenza pandemics.
Hist Phil Life Sci 1991; 13: 223-235.
2. Crosley A. The influenza pandemic of 1918. In:
Osborn J, ed. Influenza in America 1918-1976. New
York, 1977.
3. Kavet J. Influenza and Public Health. Harvard School
of Public Health, 1972.
4. Cockburn W. Influenza in man and animal. WHO
Publ, 1973.
5. Plan for pandemic influenza. Interagency Work Group
on Influenza. HEW, PHS, CDC. 8 May 1978.
6. Patterson K. Pandemic influenza 1700-1990: A study
in historical epidemiology. New Jersey: Rowman &
Littlefield, 1986.
7. Hope-Simpson R. Sunspots and flu: A correlation.
Nature 1978; 275: 86.
8. Tamblyn S, Hinman A. Pandemic planning: Conclu-
ion and recommendations. In: Hannoun C, et al., eds.
Options for the control of influenza II. Amsterdam:
Elsevier, 1993: 457-459.
Address for correspondence: Dr Y. Chendon, World
Health Organization, 20 Avenue Appia, CH-1211 Geneva
27, Switzerland
Phone: +41 22 791 2656; Fax: +41 22 788 2937
? 1994 Kluwer Academic Publishers. Printed in the Netherlands.
Introduction to pandemic influenza through history
Youri Ghendon
World Health Organization, Geneva, Switzerland
Abstract. For the past 400 years, epidemics resem-
bling influenza have been recorded in many coun-
tries. Epidemics from as early as the 16th Century
Key words: Control, Influenza, Pandemic
The influenza pandemic of 1918 was the largest in
recent history, causing 20 million deaths worldwide.
In more modern times since 1957 and 1968 influenza
pandemic also killed a million people.
While the relationship between antigenic change
and epidemic is complex, presumably involving
multiple factors attributable to the host as well as to
the viruses, antigenic drift or shift is the most readily
identifiable marker of epidemic potential.
Although influenza pandemics cannot be predicted
with certainty the plans for pandemic situations can
be developed and can play an important role in the
prompt and appropriate response when they occur.
In the year 412 BC Hippocrates described an
epidemic that modern doctors believe was influenza,
and history has recorded many influenza epidemics
and pandemics since that time.
In the Middle Ages several widespread outbreaks
that were probably influenza occurred in Europe. But
the first epidemics that can be regarded with confi-
dence as influenza were in 1173. However, the
position of some medical historians that only
epidemics which occurred in 1510 can be considered
as unquestionable influenza epidemics [1]. In 1580
a severe pandemic occurred that was possibly the first
global dissemination of influenza. It started in Asia
and spared to Africa, Europe and America. Almost
all of Europe was afflicted in six weeks and it was
said that only one twentieth of the people escaped the
illness. The case description of influenza was done
during this epidemic and is similar to influenza
illness seen currently.
In the eighteenth century there were 13 severe
epidemics and in the nineteenth century there were
12, and probably 8 or 9 of these 25 were influenza
pandemics in the modern sense. In the twentieth
century there have been several pandemics: 1918,
1946, 1957, 1968 and 1977 due to emergence of new
subtypes of influenza A virus.
The influenza viruses are unique in that they are
in England and the 18th Century in the USA are
recognizable as influenza, even in the absences of
precise knowledge of their causative agents.
able to circumvent immunity by gradually under-
going alteration of their two surface antigen -
haemagglutinin and neuraminidase -by accommo-
dation of a series of mutation (drift) and can also
undergo a complete change in one or more of their
surface antigens by genetic reassortment (shift). The
shift variants of influenza virus are responsible for
recent pandemics. It should be noted that the
influenza viruses demonstrates only antigenic drift
may also cause pandemics in the strictest epidemio-
logical sense of the word. For example, worldwide
epidemics occurred with the influenza A viruses of
1972, 1974 and 1975.
According to the dictionary definition, a pandemic
is simply a widespread epidemic, but when referring
to influenza a pandemic now signifies a worldwide
epidemic caused by a new subtype of influenza A
virus. Therefore only during the virological era can
we recognize a pandemic with certainty. However, in
the absence of virus identification, we can make an
informed guess that if the epidemic originated in one
place and from there spread worldwide with high
morbidity, it was probably a pandemic. Also epi-
demics occurring during the warmer months of the
year are a practically sure sign that they were pan-
demics; theses occurred in 1580, 1781, 1831 and
1918.
The greatest pandemic of the twentieth century
was the pandemic of 1918, popularly known as
Spanish flue owing to its high incidence in Spain,
which is believed to have been caused by the 'swine'
variant HlswN1 subtype of influenza virus.
The first wave of the pandemic of 19t8 swept
across North America in March and April 1918. The
infection moved on to Europe, when it first reached
epidemic levels in France in April 1918. Over the
next several months, influenza spread throughout the
whole of Europe. In the United States of America the
I918 influenza pandemic killed 550,000 people -
0.5% of the population, about ten times more the
number of Americans who died in the war [1, 2]. In
Europe the influenza in England and Wales alone
killed 200,000 people. In a few places such as Samoa
and Alaska some 25% or more died. Throughout the
world influenza pandemic 1918 killed 20 to 40
million people, and made one-quarter to one-half of
the population sick. The 1918 influenza pandemic
killed more people in less time than any other disease
before or since.
In a vain effort to halt the spread of influenza
during 1918 pandemic in the USA, in some cities
officials closed dance halls, theatres, schools and
even churches. There were placards on street cars and
railroad stations asking people not to spit and all
police wore masks. Police in Chicago were asked to
arrest people who sneezed in the streets [2].
Since the 1918 pandemic, there have been two
major global outbreaks of influenza A in the twen-
tieth century: In 1957, influenza was induced by
namely 'Asian' influenza virus A/H2N2, and in 1967,
influenza was induced by namely 'Hong Kong'
influenza virus - A/H3N2 - and two mild pandemics
in 1946 and in 1977, induced by H1N1.
In 1946 there was a worldwide epidemic that was
regarded as pandemic due to a new influenza virus
subtype -H1N1. It was a mild pandemic and the
excess of mortality was low. Influenza pandemic
1957 was not so bloodthirsty as in 1918, neverthe-
less in the USA alone 40,000 deaths were attributed
to the 'Asian' influenza and the mortality was much
the same in most countries. During the Hong Kong
pandemic 1967 the mortality in the USA alone was
estimated at around 30,000 deaths, 51 million
Americans were ill and the total economic burden
was 3.9 billion [3]. In Europe the mortality was
estimated at 30,000 deaths in Britain alone [4].
The next notable event in the history of influenza
was the reemergence in 1977 of the H1N1 influenza
virus that had been prevalent from 1947 to 1957. It
arose in China and spread world-wide but affected
mostly people born after 1957. From 1977 to the
present day it has continued to circulate along with
H3N2 and B influenza viruses.
The minimal requirement for the generation of a
pandemic seems to be the major change in external
antigens. The severity of the 1957 pandemic when
two external antigens changed, compared to the less
dramatic pandemic in 1946 and 1967 when only
haemagglutinin changed my reflect this fact.
What can we really do to control influenza pan-
demic? The main problem is that the real causative
virus of pandemic influenza cannot be completely
determined until at least the first phase of the
pandemic is underway. If influenza surveillance is
improved, especially in the areas in which most of
the pandemic influenza viruses arise, the potential
pandemic shift variants of influenza virus can be
detected early. Nevertheless the period of time
available for vaccine production from the potential
pandemic strain of influenza virus will always be
limited.
There is one example of an attempt to control
pandemic influenza: In the USA in 1976 the cases
of so-called swine influenza took place and a decision
was made to control the potential influenza pandemic
by mass vaccination. The sequence of events that
constituted the response on this outbreak began with
the initial recognition of the new virus and culmi-
nated in the production and use of a vaccine. But the
time from the isolation of the influenza virus and the
beginning of the Nationa Influenza Immunization
Programme took approximately one year [5]. If it is
influenza virus which really can induce pandemic
influenza, at the beginning of a vaccination period,
which is one year after the isolation of the virus,
all people susceptible to this virus can develop
influenza.
In the book Patterson [6], the author concluded:
'Pandemics have secured with a frequency of three
per 100 years since 1700. There is no periodicity to
the occurrence of pandemics and no basis for pre-
dicting where a new outbreak may arise'. Since 1889
pandemics of influenza have occurred at intervals of
28/29 and 10-11 years and in fact several supposi-
tions on the possibility to predict the influenza
pandemic on the basis of cyclical recurrence of the
pandemic strains or solar activity, or other factors,
are in fact only speculative. It is to be noted that the
accounts of a Florentine family in the fourteen/fifteen
centuries used the world 'influence' to suggest an
unusual conjunction of planets at times of epidemics
of coughs, colds and fevers. The word 'influenza'
was thus derived as a description name for the
epidemics due to 'influences'. In the twentieth
century Hope-Simpson published an article [7] in
which he suggests that antigenic shifts of influenza
A virus and accordingly pandemic coincided with
sunspot, and showed some examples of this from
1930 to 1970. But in 1979 sunspots activity took
place but there was no pandemic. So we should be
prepared for unforeseen influenza pandemic in any
given year.
In the Middle Ages the Germans thought influenza
was caused by eating too many sour applies and salt
fish. Now we know much more about the agent
induced influenza, but our knowledge on how to take
control of pandemic influenza is practically at the
same level as in the Middle Ages.
During the International Conference for the control
of influenza in 1992, at Courcheval, attempts were
made to work out several recommendations on pan-
demic planning [8]: Examples of these are as follows:
1. The enhanced surveillance of influence, espe-
cially in Southern China where most of the
pandemic strains of influenza virus originated, in
order to detect the emergence of the pandemic
strain and isolate the pandemic strain of influenza
virus as soon as possible.
2. The vaccine improvements are essential for
optimal pandemic control, especially for the
production of influenza vaccine in a short period
of time. The possibility to use new substrate for
vaccine production of new types of influenza
vaccine for vaccination needs investigation.
3. The antivirals can play a major role in the early
phases of a pandemic. Alternative agents to
amantadine/rimantadine which have different
mechanisms of antirival activity needs to be
developed.
4. The national, regional and global plans on the
control of pandemic influenza should be worked
out.
5. Public and mass-media need to be involved in the
control of pandemic at all stages.
References
1. Beveridge W. The chronicle of influenza pandemics.
Hist Phil Life Sci 1991; 13: 223-235.
2. Crosley A. The influenza pandemic of 1918. In:
Osborn J, ed. Influenza in America 1918-1976. New
York, 1977.
3. Kavet J. Influenza and Public Health. Harvard School
of Public Health, 1972.
4. Cockburn W. Influenza in man and animal. WHO
Publ, 1973.
5. Plan for pandemic influenza. Interagency Work Group
on Influenza. HEW, PHS, CDC. 8 May 1978.
6. Patterson K. Pandemic influenza 1700-1990: A study
in historical epidemiology. New Jersey: Rowman &
Littlefield, 1986.
7. Hope-Simpson R. Sunspots and flu: A correlation.
Nature 1978; 275: 86.
8. Tamblyn S, Hinman A. Pandemic planning: Conclu-
ion and recommendations. In: Hannoun C, et al., eds.
Options for the control of influenza II. Amsterdam:
Elsevier, 1993: 457-459.
Address for correspondence: Dr Y. Chendon, World
Health Organization, 20 Avenue Appia, CH-1211 Geneva
27, Switzerland
Phone: +41 22 791 2656; Fax: +41 22 788 2937
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