Warren T. Vaughan,1921, Influenza an epidemiological study
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001 GENERAL EPIDEMIOLOGIC CONSIDERATIONS
047 INFLUENZA EPIDEMICS SINCE 1893
127 AN INVESTIGATION OF INFLUENZA IN BOSTON (WINTER OF 1920.)
175 AN INTENSIVE STUDY OF THE SPREAD OF INFLUENZA IN SMALL GROUPS OF
CLOSELY ASSOCIATED INDIVIDUALS
199 IMMUNITY
212 INFLUENZA AND OTHER DISEASES
224 COMPARISON or INFLUENZA WITH OTHER EPIDEMIC DISEASES
234 THE PREVENTION AND CONTROL OF INFLUENZA
245 BIBLIOGRAPHY
257-260 APPENDIX
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-001 GENERAL EPIDEMIOLOGIC CONSIDERATIONS
002 Historical
013 Clinical and epidemiologic identification
014 General characteristics of early epidemic outbreaks
019 Symptoms in former epidemics
020 Manner of spread
023 Human intercourse
026 Crowd gatherings
027 Mass attack
030 Healthy carriers and convalescents
031 General manner of spread in individual localities
031 Primary type of epidemic
033 Secondary type of epidemic
036 Mortality curves
037 Duration of explosive outbreak
041 Morbidity curves in 1920 recurrences
042 Spread in countries and continents
042 Spread in primary waves
044 Spread in recurrences
-047 INFLUENZA EPIDEMICS SINCE 1893
047 Occurrence since 1893
047 Period from 1893-1918
049 Increase in 1900-1901
051 Period from 1901-1915
055 Influenza in 1915-1916
058 Influenza between 1916 and 1918
059 The pandemic of 1918
065 Date of first increased prevalence in various localities
080 Influenza in China
081 Autumn spread in the United States
087 Recrudescences
089 Recurrences in the winter of 1919-1920
090 The winter of 1920
095 Incubationperiod
096 Predisposing causes
097 Periodicity
108 Virulence enhancement
113 Meteorologic conditions
114 Secondary invaders
116 Origin of the 1918 pandemic
-127 AN INVESTIGATION OF INFLUENZA IN BOSTON (WINTER OF 1920.)
134 Diagnostic standards for the 1918 epidemic
134 Standards for 1920
137 Morbidity
143 Relation of sex to morbidity
145 Relation of sex to severity
145 Morbidity by age
150 Relationship of occupation to morbidity
155 Effect of race stock
156 Mortality
165 Mortality by sex
167 Relationship to age
170 Relationship of occupation
170 Density of population
173 Race stock and mortality
-175 AN INTENSIVE STUDY OF THE SPREAD OF INFLUENZA IN SMALL GROUPS
OF CLOSELY ASSOCIATED INDIVIDUALS
179 Effect of overcrowding
187 Domestic cleanliness
189 Economic status
191 Distribution of the disease through the household
194 The first case in the family
197 Intimacy of family contact
198 Recurrent cases
-199 IMMUNITY
-212 INFLUENZA AND OTHER DISEASES
212 Influenza and tuberculosis
220 Other infectious diseases
222 Encephalitis lethargica
-224 COMPARISON or INFLUENZA WITH OTHER EPIDEMIC DISEASES
224 Epizootics
228 Asiatic cholera
228 Epidemic meningitis
229 Plague
231 Measles
-234 THE PREVENTION AND CONTROL OF INFLUENZA
236 Anticipatory or preventive measures
237 Organizationof health services
239 Palliative measures in the presence of an epidemic
241 Problems for the future.Constructive research
245 Bibliography
Vaughan,1920
page 137, MORBIDITY.
There has been great actual variation in the morbidity from influenza
in the various epidemics and even in different localities during single
epidemics. Previous to 1889 there were no reliable statistics for the
disease incidence, and subsequent to that date the records, for the
reasons previously mentioned, have still been not entirely adequate.
In the history of influenza morbidity,as in that of its mortality, we must
content ourselves for information prior to the nineteenth century with
the very general estimates made by contemporary historians.During
the last century the statistics have been more numerous and more
nearly correct.-----------------------------------------------------------------------------------------------------------------------
As far back as the first recognized pandemic, 1510,
the extremely high morbidity has been a recognized characteristic.
Thomas Short in speaking of this pandemic says, "The disease
attacked at once and raged all over Europe, not missing a family
and scarce a person." ---------------------------------------------------------------------------1510-------------------------
Pasquierin 1557 spoke of the disease as
common to all individuals, and Valleriola describes the widespread
distribution of the epidemic throughout the whole of France during
that year.It spared neither sex, age, nor rank, neither children nor
aged,rich nor poor.The mortality, however,was low,"children only,
dying." Again,Thomas Short remarks, "This disease seized most
countries very suddenly when it entered, catching thousands the
same moment." ------------------------------------------------------------------------------------1557? or still 1510--------------
Of the second pandemic, 1580,Short says,
"Though all had it,few died in these countries except such as were
let blood of,or had unsound viscera." ----------------------------------------------------------------------1580-----------------
Thomas Sydenham remarks that in the epidemic of 1675 no one
escaped, whatever might be his age or temperament,and the disease
ran throughout whole families at once.--------------------------------------------------------------------1675----------------
Molineux recorded concerning 1693,"All conditions of persons were
attacked,those residing in the country as well as those in the city;
those who lived in the fresh air and those who kept to their rooms;
those who were very strong and hardy were taken in the same manner
as the weak and spoiled; men, women and children, persons of all
ranks and stations in life,the youngest as well as the oldest."---------------------------------1693------------
Schrook tells us that in Augsburg in 1712 not a house was spared
by the disease.
According to Waldschmidt in Kiel, ten and more persons were
frequently taken ill in one house,and Slevogt says that the disease
was fearful because so many persons contracted it at the same time.
The disease was, however, not dangerous, for Slevogt continues:
"Fear soon vanished when it was seen that although it had spread
all over the city,it left the sick with equal rapidity."-----------------------------------------------1712-----------------------
It is estimated that in the epidemic of 1729-1730, 60000 people
developed the disease in Rome, 50000 in Mayence, and 14000 in
Turin. In London "barely one per cent,escaped." In Lausanne
one-half of the population,then estimated at 4000,was stricken.
In Vienna over 60000 persons were affected. In the monasteries
of Paris so many of the inmates were suffering from the disease
that no services could be held. -----------------------------------------------------------------1729f---------------------
Huxham is quoted in Thomson's
"Annals" as declaring concerning the epidemic of 1732-33:
"Not a house was free from it,the beggar's hut and the nobleman's
palace were alike subject to its attack,scarce a person escaping
either in town or country;old and young, strong and infirm,shared
the same fate."------------------------------------------------------------------------------------1732f------------------------
Finkler writes as follows concerning the epidemic of 1758: "On
Oct. 24th, Whytt continues,the pestilence began to abate.
He is not sure whether this was due to a change in the weather,
or because the disease had already attacked most people,
although the latter seems more plausible to him, particularly as
he says that 'in Edinburgh and its vicinity not one out of six or
seven escaped, 'and in other localities it is said to have been even
worse. In the north of Scotland also, the epidemic was greatly
disseminated from the middle of October to the end of November.
A young physician wrote to Robert Whytt: 'It was the most
universal epidemic I ever saw,and I am persuaded that more
people were seized with it than escaped.'
This same physician reported that 'it was not at all mortal here.'"--------------------1758---------------
In the epidemic of 1762,we learn from Razoux,de Brest, Saillant,
Ehrmann, that the morbidity was great while the mortality was low.----------------1762---------------
According to Grimm,nine-tenths of the inhabitants of Eisenach
contracted the disease in 1767.------------------------------------------------------------------1767---------------------
Daniel Rainy,of Dublin,in describing the invasion of an institution
in 1775-76,tells us that from among 367 persons varying in age
from 12 to 90 years, 200 were taken sick.
Thomas Glass says:
"There sickened in Exeter Hospital all the 173 inmates, 162 had
coughs. Two or three days after the hospital was invaded the
cityworkhouse as attacked;of the 200 paupers housed there only
very few escaped the disease." -------------------------------------------------------------1775f---------------------
Gilibert described an extraordinary morbidity in Russia in 1780-81.------------1780f-------------------
Metzger says that in 1782 the Russian catarrh was so universal
during the month of March that in many houses all the inhabitants
were attacked.During this period, "in St.Petersburg, 30000, and
in Konigsberg, 1000 persons fell ill each day;"in Rome two-thirds
of the inhabitants were attacked; in Munich, three-fourths; and in
Vienna the severity of the epidemic compelled the authorities to
close the theaters for eight days.----------------------------------------------------------1782--------------------------
The epidemics of 1788-89, 1799-1800 and of 1802-1803 were----------------------1788f , 1799f, 1802f-------------
characterized by a relatively lower morbidity than that of 1830-32,
in which the morbidity was again enormous.--------------------------------------------1830-2---------------------------
Likewise in 1833, the morbidity was very great. In Prague "scarcely
a house was spared by the plague." In Petrograd, 10000 persons
were attacked; in Berlin at least 50000.These are the figures of
Hufeland.The Gazette M&iicale records the morbidity as being
four-fifths of the total number of inhabitants of Paris. --------------------------------1833----------------------------
In 1836, according
to Gluge, 40000 persons suffered from the disease in Berlin alone. ------------------1836-----------------------
In London, in the 1847 epidemic, it has been calculated
that at least 250000 individuals took sick, and in Paris, according to
Marc d'Espine,between one-fourth and one-half of the population
developed the disease,and in Geneva not less than one-third.. --------------------1847-----------------------------
Leichtenstern informs us that in 1890 the early reports were made
by clinical men and were mere presumptions. They were almost
universally higher than the later statistical findings.
The early estimates for the morbidity in several German cities were
from 40-50 percent. On the other hand,one of the highest statistical
reports recorded by Leichtenstern was for Strasbourg in which 36.5
per cent, of the individuals became sick.
The average morbidity reported by him ran between 20 and 30 percent.
The difference is accounted for in part by the fact that some of the
very mild cases were not recorded in the statistics,and in part by
the tendency in giving estimates,to exaggerate.Auerbach has collected
the statistics of 200 families distributed throughout the city of Cologne.
He found that 149 of these families (75 per cent.) were attacked.
In these, 235 were ill 59 men, 95 women,and 81 children.The larger
number of women was explained as due to the illness of the female
servants.He estimates each family as consisting on an average of
six individuals,and concludes that 20 percent, were taken with the
disease.
Following the 1889 epidemic,Abbott concluded,on a basis of
questionnaries sent out to various individuals and institutions in the
State of Massachusetts,that 39 percent, of the entire population had
been attacked,in all about 850000 persons. -----------------------------------------------------1889f---------------------------
Moody and Capps,in
December, 1915, and January, 1916, made a survey of the personnel
and inmates of four institutions in Chicago, the Michael Reese Hospital,
the Illinois Training School for Nurses, the Old Men's Home,and
St. Luke's Hospital Nurses Training School, making a total of 677
persons surveyed, of whom 144 developed influenza, making a
percentage morbidity of 21. They remarked that there were many
others with colds who remained on duty and were not included in the
table and were not diagnosed as influenza. ---------------------------------------------------1915f---------------------------
We have already described the relatively low morbidity and mortality
in the early spring epidemic in the United States.
According to Soper, the total number affected in March, 1918, at Camp
Forrest and the Reserve Officers Training Camp in the Oglethorpe
Camps was estimated at 2900. The total strength at that time was
28586. The percentage morbidity then was probably a little over
10 percent.
Dunlop, in describing the May, 1918, epidemic in Glasgow, says that
it was more limited in extent,as well as milder,than the later epidemic. ------------------1918 1st wave-------------
It has been estimated that in the autumn epidemic in the United
States Army Camps one out of every four men had influenza,and one
out of every twenty-four men encamped in this country had pneumonia.
During the four autumn months of 1918, 338343 cases of influenza
were reported to the Surgeon General's Office;there were 61691 cases
of pneumonia.
Woolley reports that among the soldiers at Camp Devens,Mass.
30 percent, of the population was affected.
At Camp Humphreys,16 percent, of the entire personnel developed
the disease. The camp had an average strength of 26600 individuals.
52 percent, of the entire number of cases occurred during the peak
week,which ended October 4th.The outbreak began September 13th
and ended October 18th. Hirsch and McKinney report that an
epidemic of unusual virulence swept with great rapidity through
several organizations in Camp Grant between September 21, 1918,
and October 18, 1918. During this time 9037 patients were admitted
to the Base Hospital, representing about one-fourth of the strength
of the camp,and of these, 26 percent,developed pneumonia.
About 11 percent, of the total admissions or 43 percent, of the total
cases of pneumonia died.
...
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page 156
MORTALITY.
According to Marchese, in 1387 at Forli in Italy, not a person
escaped the disease,but only a few died.
Gassar says that during the same epidemic in Germany the patients
suffered four,or at most five, days with the most disagreeable
catarrhal symptoms and delirium,but recovered,and only very few
were removed by death.-------------------------------------------------------------------------------1387---------------------
Pasquier remarks concerning an epidemic in 1411 that an infinitude
of individuals were attacked but that none died.-----------------------------------------------1411-------------------
Concerning the epidemic of 1414 in France,Lobineau relates that
the disease was fatal only for the aged.
Mezeray also speaks of the high mortality of the old in this epidemic.----------1414-----------------
Regarding the pandemic of 1510,Thomas Short remarks that none
died except some children.
Mezeray,on the other hand, says that the disease had claimed
many victims. ----------------------------------------------------------------------------------------------1510----------------
Pasquier and Valleriola both write of the epidemic of 1557,
in France, as being distinctly mild in character.
Children only who could not freely cough out the phlegm died.
Coyttar speaks of the absence of death except in tuberculous
patients. --------------------------------------------------------------------------------------------------------------1557-------------------
In the pandemic of 1580 individual observers report enormous
death rates.Thus, according to Schenkius,the disease killed 9000
persons in Rome,while Madrid, Barcelona and other Spanish cities
were said to have been nearly depopulated by the disease.
This high mortality was, however,even at that time attributed
by some physicians to the injudicious employment
of venesection.
Throughout the more recent history of pandemic influenza opinion
seems to have been nearly unanimous that bloodletting has had
very bad results in the outcome of influenza cases.
Remarks to this effect have been made by the contempories
of nearly every epidemic since 1580.-----------------------------------------------------------------------------1580--------------
According to Rayger and others during the epidemic of 1675,
nobody died of the disease itself with the exception of debilitated
persons, although it spared neither the weak nor the strong. ----------------------------------1675-------------------
Concerning the epidemic of 1688,Thomas Short writes for England
that though not one of fifteen escaped it, yet not one of a thousand
that had it died.------------------------------------------------------------------------------------------------1688---------------
In 1712, Slevogt writes that in Germany "Fear soon vanished when
it was seen that although it had spread all over the city,
it left the sick with equal rapidity."---------------------------------------------------------------------------1712--------------------
Finkler remarks, concerning 1729-30, that, "The great mortality
which attended the epidemic in England and Italy seems
somewhat remarkable.
Thus Hahn states that in London in the month of September
1000 persons died each week,and in Mayence 40 persons
daily. Most likely, however,other diseases which were present at the
same time added their quota to the mortality, especially as the
disease in other places,for example in Germany,ran a benign course." ----------------------1729f-------------------
Perkins, Huxham,Pelargus,Carl and others, concerning the
epidemic of 1732-33, all testify that the disease was of very low fatality.--------------1732f--------------
In 1742 the epidemic was evidenced by an enormous morbidity but
the disease was not dangerous as a general rule although Huxham
occasionally speaks of the virulent character of the disease in England,
and Cohansen says that in January, 1743, over 8000 persons
died from influenza in Rome and 5000 in Mayence.-----------------------------------------------1742f------------------
We have the testimony of Robert Whytt,for 1758,and that of ----------------------------1758----------------------
Razoux and Saillant and Ehrman for 1762,as to the low mortality of------------------1762-----------------------
the epidemic for those years.
According to Heberden the same was true for 1775,------------------------------------1775--------------------
while Webster tells us for 1780 that the disease was not dangerous
but its effects were seen the following year in the increased number
of cases of phthisis. --------------------------------------------------------------------------------1780------------
Finkler remarks concerning the epidemic of 1802,
"The mortality in this epidemic was small, only the abuse
of venesection brought many to the grave.
Thus,so many farmers are said to have died in Russia
from it that venesection was forbidden by an imperial
ukase.
Jonas says that many patients were bled either on the advice
of a simple village barber or by their own wish, and most of them died.
In Prussia also bleeding was declared detrimental by the Government." ------------------1802---------------
He continues regarding 1836-37, that, "In London there died,
during the week ending January 24, 1837,a total of 871 persons,and
among these deaths there were 295 from disease of the respiratory
organs; during the week ending January 31st, out of a total of 860
deaths there were 309 from diseases of the respiratory organs." ----------------------------1836f-------------------
Watson, in describing the epidemic of 1847,discusses the mortality
"The absolute mortality has been enormous; yet the relative
mortality has been small.
You will hear people comparing the ravages of
the influenza with those of the cholera,and inferring that the latter is
the less dangerous complaint of the two;but this is plainly a great
misapprehension.
Less dangerous to the community at large (in this
country at least) it certainly has been; but infinitely more dangerous to
the individuals attacked by it.
More persons have died of the influenza in the present year than died
of the cholera when it raged in 1832;
but then a vastly greater number have been affected with the one
disease than with the other.
I suppose that nearly one-half of those who were seized with the
cholera perished;while but a very small fraction, indeed, not
more probably than two percent, of those who suffered influenza
have sunk under it." ---------------------------------------------------------------------------------------1847-------------------------
Leichtenstern remarks on the very low mortality of 1889-90.
In Munich 0.6% died;in Rostock 0.8%; in Leipzig 0.5%
in 15 Swiss cities 0.1%; in Karlsruhe 0.075%;
in Mecklenburg-Schwerin 1.2%.
This does not, however, include the numerous deaths from
complications,as from pneumonia, and does not
express the true mortality.
Newsholme gives the following table for mortality from influenza,
bronchitis and pneumonia,in England and Wales during the epidemic
years and the years immediately preceding them.
The figures express annual death rate per million of population.
The highest rate was reached in 1891.
The table does not include deaths registered as from
other diseases,but due directly or indirectly to influenza.
Respiratory diseases in general show a greatly increased
death rate in years in which influenza is epidemic.
Such is also true to some extent with
diseases of the nervous and the circulatory systems.
---------------------------------------------------------------------------------------------------------1889ff------------------------------
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Vaughan, 202
We have previously shown that the relatively low morbidity among
the older age groups in 1918 is not satisfactorily explained by an
immunity lasting over from the epidemic of 1889-93.
If such were the case the change in mortality rate in large groups of individuals
would occur at the age of 30.
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Vaughan page 199ff IMMUNITY.
Opinions of all observers who have studied in detail the question
of immunity in influenza are remarkedly in accord.
The conclusions reached by Parkes in 1876 are valid today,
and form as excellent an abstract of our present knowledge as any
produced since his time.
"There is some discrepancy of evidence, but,on the whole,
it seems clear that, while persons seldom have a second attack in the same
epidemic (though even this may occur),an attack in one does not
protect against a subsequent epidemic.
Indeed,it has been supposed rather to render the body more liable."
In 1890, Abbott wrote: "There is but little if any evidence in
support of the protective power of one attack to confer immunity against
a second;and hence adults are not exempt,as they usually are in
epidemics of scarlet fever or other exanthemata;so that the proportion
of adults to children attacked in an epidemic is necessarily greater
than that which is observed in epidemics of other infectious diseases."
Parsons made somewhat similar observations: "One attack of
influenza does not seem to be protective against another;the disease in
this respect resembling diphtheria, erysipelas,and cholera rather than
smallpox, measles,or whooping cough.
The duration of the epidemic in a locality is so short that it is difficult
to distinguish between second attacks properly so-called,
and relapses,which are frequent enough.
A case is recorded in the 'British Medical Journal' of February 15, 1890,
in which a patient who had suffered from influenza in France in
December,1889, had another attack in England in January, 1890.
It was noticed in 1837 that many persons suffered from influenza
who had had the disease during the previous epidemic in 1834.
The shortness of the interval between these two epidemics,as compared
with that between 1848 and 1889, seems to show that the periodical
return of the disease in an epidemic form does not depend upon the
accumulation in the interval of susceptible individuals unprotected
against the disease by aprevious attack.
If one attack afforded protection against another a large proportion
of the population in 1837 must have been protected, yet an epidemic
occurred,and on the other hand for many years before 1889 a large
majority of the population must have been unprotected by a previous
attack, yet the epidemic did not recur.
"The persons now living who passed through the disease in 1847
are of course comparatively few, but such persons have not been
exempt from the present epidemic.
"I should be inclined to attribute the short duration of the influenza
epidemic in a locality to the establishment of a tolerance for the
specific poison among the persons exposed to it,similar to the tolerance
for dust possessed by workmen in rag factories,as mentioned,but
which is soon lost on their ceasing to be exposed to it,rather than
to a true immunity being established.
"Relapses in influenza are of frequent occurrence; they occurred
in 9.2%, of the cases at the Morningside Asylum, Edinburgh,
and in some cases indeed a second relapse has been recorded.
The time at which the relapse occurs is usually from a week to a
fortnight after the primary attack,and it can often be distinctly traced
to an exposure to cold,or return to work before complete recovery.
The symptoms of the relapse are similar to those of the primary attack,
except that they are commonly more severe."
In his report of 1893, Parsons goes into the subject of recurrent
attacks in individuals in greater detail. He quotes several communications
received from various physicians and health officers.
These opinions differ,some believing that the disease predisposes to
another attack; others, that there is no effect on the incidence in
recurring epidemics;and still others believing that there is a small
amount of acquired immunity.
The communications are not based upon statistical evidence.
He does find, however, an opportunity
for statistical study in the industrial schools at Swinton near
Manchester: "These schools were severely affected in March, 1890,
171 out of 589 children having suffered,or 29% In the first epidemic
of 1891 they were again affected,but to a less extent, only 35
cases occurring. At that time there were in the schools 449 children
who had been there at the time of the former epidemic. Of these
150 had had influenza in 1890 and 4 of them had it again,or 2.6%
299 had escaped influenza in 1890 and 17 of these had it now,or 5.7%
Thus,so far as these figures go,an attack of influenza confers a
degree of protection which after the lapse of a year diminishes
by one half the liability to contract the disease."
Leichtenstern, like Parsons, recognizes the importance of
distinguishing between relapses and recurrent cases.
Relapses in influenza are not common. They usually occur after the patient
is up, and about when he is ready to leave the house.
These are not recurrent cases, but in the epidemics in the years
following 1889 there were plenty of well substantiated cases
of recurrent typical influenza in the
same individual and some times even in entire families.
During the 1889 epidemic, as during the 1918 epidemic
it has been suggested by various observers that the apparent
immunity among the very old was due to immunity developed
as the result of previous epidemics, such as that of 1837,1847 and 1857.
Leichtenstern has collected the statistics from five different
hospitals in which 8%,32%,35%,24%,and 24% of individuals attacked
in 1891-92 had already had the disease in 1889.
Allbutt in 1905 remarked that whereas he had previously believed
that immunity to influenza usually persists as long as six months,
many cases had recently been brought to his notice where such an
interval seemed improbable, where the succeeding attack was probably
not a relapse but a new infection.He has seen two attacks apparently
separate occurring in the same individual within two months.
In the same year Moore wrote that influenza shows a decided tendency
to relapse,a feature to which the indirect fatality of the disease is in
great measure due. "So far from establishing immunity,an attack
of this malady seems to render an individual more liable to contract
the disease upon any future exposure to its contagion."
Again West,in the same year wrote,"From our present experience
we must conclude that influenza is infectious in a very high degree
indeed, and that the protection afforded by an attack is imperfect,
or of very short duration.Indeed, one attack -seems actually to
predispose,after a time to another, or, to put it differently,that the
positive phase of protection is followed by a negative phase, in which
the individual seems rather more than less liable to succumb to infection
if exposed to it. It seems more likely that an individual may
never have influenza at all than that, having had it once, he should
never have it again. Some, indeed,seem to offer so little resistance
that they develop it regularly once or twice a year."
We have previously shown that the relatively low morbidity among
the older age groups in 1918 is not satisfactorily explained by an
immunity lasting over from the e pidemicof 1889-93. If such were the
case the change in mortalityrate in large groups of individuals would
occur at the age of 30.
During the autumn of 1918 many observations were made, particularly
in the armies, of light incidence in those groups or communities
that had had the disease in mild form in the spring of the same year.
Parsons quotes many similar observations for the period 1890-1893.
V. C.Vaughan relates that at Camp Shelby, Mississippi,"there
was in April a division of troops numbering about 26000.
An epidemic of mild influenza struck this camp in April, 1918,and within
ten days there were about 2000 cases.This included not only those
who were sent to the hospitals,but also those who were cared for in
barracks."This was the only division that remained in this country without
change of station from April until the fall of 1918.
"During the summer this camp received 20000 recruits.In
October, 1918, the virulent form of influenza struck this camp.
It confined itself almost exclusively to the recruits of the summer and
scarcely touched the men who had lived through the epidemic of April.
Not only the 2000 who had the disease in April,but the 24000
who apparently were not affected escaped the fall epidemic.
It appears from this that the mild form of influenza of April gave a
marked degree of immunity against the virulent form in October.
There is another observation which points the same way.Looking
over the statistics of the fall epidemic in cities in the United States we
find that certain cities had a low death rate,while others had a
relatively highrate. Among those cities which had a low death rate we will
mention Atlanta,Ga.;Kansas City,Mo.; Detroit, Mich.,and Columbus, Ohio.
Going to the spring records of these cities we find that in
all of them in March and April of 1918 there was an unusually high
death rate from pneumonia and undoubtedly in these cities at that
time there was a relatively mild epidemic of influenza.
In this way I am inclined to account for the relatively low death rate in these cities
in the fall of 1918. I make no claim that this and other instances of a
similar kind prove that the mild and virulent forms of influenza are
manifestations of the same disease, but I do hold that the evidence
points that way."
Lemierre and Raymond report the following observation in favor
of the development of a certain degree of immunity in the French
troops in April, 1918. After an intervening period of quiescence
there was a manifest recrudescence at the end of August.
Many military formations were attacked during both periods.This was
true especially in three groups of an artillery regiment under their
observation.In the first of these groups there were three cases in
April, while 114 men were attacked in August.In the third group
there were 100 cases in April and only 3 in August.In the second
group there were 20 cases in April and 59 in August.Their report
does not state the total number of individuals in each of the three
groups. Jolt rain and Baufle discuss the flaring up of the epidemic in
October, and relate that a troop of soldiers from Indo-Chinan early all had
the disease lightly in the spring, but when the disease appeared again
it spared this troop completely,while troops and civilians around
developed it in a severe form.Gibbon writes:
"During the last three waves of the epidemic I had
to deal with the sick of 2000 troops,and during this time we treated
in hospital over 400 cases.No cases admitted in June, July or August
were re-admitted in October, November,or December,and no cases
admitted in either of these two periods were re-admitted in February
this year.
Unfortunately I am unable to trace the cases into March
as the troops were changed."
Dopter reports recurrent epidemics of influenza in a French Army
Division in 1918.The division,of which he was surgeon,was one of
the first to contract la grippe at the time of its first appearance in the
zone of the armies at the end of April,1918.
At this time nearly the entire body of infantry troops was attacked.
The disease was mild, and without complications.
The regiment of artillery escaped nearly entirely.
This epidemic subsided very rapidly,and by the end of May
it had entirely disappeared.Early in August a group of heavy artillery
was attached to the division, bringing influenza with it.Then a
few cases appeared in the regiment of light artillery which had hitherto
escaped. By the end of August all three groups of this regiment had
been attacked.
In this second epidemic the men who had come
through the first unattacked were very severely
ill in the second.With rare exceptions those sick in the
first did not contract it again.
Dopter notes that in the battery the most severely affected
in August,of which the effectives were reduced almost to none, only
those men were considered well enough for duty who had had
influenza in the first period.They escaped the second in spite of the close
contact with their comrades.
The infantry regiments,which were in
close association with the artillery,remained unaffected.
Finally,toward the middle of September new troops were attached
to the division,in view of an imminent attack by the enemy.These
troops, coming from neighboring and distant formations were suffering
at the time from grip,and continued to have the disease in the new
sector.Again,those attacked in May passed without damage through
this new epidemic.Among them there were only rare isolated mild
cases.The recurrences made only 1.6%, of the total incidence.
Opie and his associates found that at Camp Funston after the first
wave of influenza in March and April, 1918, the succeeding waves
usually affected only new recruits,who had not been in camp during
previous waves.
In Calcutta influenza appeared as an epidemic in July, 1918,and
in November, 1918. During the first quarter of 1919,at Calcutta as
elsewhere, many cases were still recurring.Malone investigated the
incidence of the disease in three institutions of Calcutta : He found that
in 'the Gourepore Jute Mills where the population was practically
stationary,those individuals who were attacked in July, 1918, passed
through two later epidemics, in December, 1918, and February, 1919,
without contracting the disease a second time,in spite of intimate
contact with infected persons. The same was true according to
Malone in the Alipore Central Jail and the Presidency Jail in Calcutta.
He believes that his evidence strongly suggests an immunity lasting
for at least nine months.
Dunlop found that Glasgow had a mild epidemic in the month of
May, 1918,in which the death rate rose from 14.1 to 20.1.There is
no record of any similar outbreak in Edinburgh. In the July epidemic
the Glasgow death rate rose from 11.7 to 15.9, while the Edinburgh
death rate went from 11.3 to 18.0,a higher increase. In the October-
November epidemic the Glasgow rate rose from 11.0 to 38.4, while the
Edinburgh rate went from 10.8 to 46.2. In the February-March
epidemic theGlasgow rate rose from 14.9 to 48.3,and the Edinburgh
rate from 18.9 to 52. 1 In the July and October epidemics Edinburgh
showed a greater increase in death rate, while in February,1919,
the increase in the two cities was the same.
However,in this case probably other factors play a part.
Also, we must remember that
here we are dealing with death rates,not with incidence rates.
The Inspector General of Health,in Spain, reported in January,
1918, that those cities which had the disease in May, 1918,suffered
lightly in the autumn of that year, while others of the large cities
which had been spared in the first invasion suffered most in the second.
Maillard and Brune report an epidemic of influenza in an epileptic
colony.There were 32 deaths among the 63 cases. None of the
inmates of the hospital who had influenza during the June epidemic
contracted it anew during the October wave.
Ovazza records that although a number of persons contracted
the influenza anew on its return in the fall after having had it in the
spring, yet the return cases were strikingly mild,and always free from
complications.
Barthe'lemy describes the successive waves of epidemic influenza
at Bizerte.He found that the "doctors and nurses who had been
through the first epidemic did not develop influenza in the second one
a few months later,even though they came in the closest contact with
the patients.
Hamilton and Leonard have studied two successive outbreaks due
to lapses in a rigid quarantine in an institution of 180 girls between
12 and 18 years of age. The girls were distributed through six cottages.
In the first epidemic November, 1918, 76 girls contracted the disease,
at which time it was entirely limited to the occupants of cottages 2, 3,
and 4. The second outbreak occurred in January, 1919,when 82 took
ill. Only five of these were located in cottages 2 and 4, the remainder
being in 1,5 and 6. No cases occurred in cottage 3 during the second spread.
Both epidemics lasted a little under two weeks.
Those who had suffered in the first spread appeared to be immune to
the second. There were no recurrences.The second epidemic was
much milder in character.Twelve percent, of the total remained
well throughout both epidemics.
Dr.Niven,in his study of 1021 households previously described,
found that 105 families suffered in both the summer and autumn 1918
epidemics."They comprised a population of 565 persons,of whom
205 suffered in summer and 360 escaped. In the autumn epidemic
82(=40%) of the presumably 'protected' persons
succumbed again,whereas only 120 (=33%) of the 'unprotected' suffered.
Of the former, however, only one died,while five of the latter terminated fatally.
These are interesting figures.If
they are borne out by subsequent inquiry, they are somewhat difficult
of explanation.
The persistent susceptibility to the primary disease
and yet comparative immunity from the fatal sequel, would seem to
suggest a dual infection, against one element of which the body is able
to produce protection,while it is unable to do so against the other."
Frost made a canvass of 33776 individuals in Baltimore between
November 20th and December llth,1918. The same population was
again covered in January, 1919, to determine the extent of the recru-
descence reported in December. Among 32600 people,724 cases of
influenza had occurred in the interval since the first survey.Of this
number only 26 or 3.6%, were definitely cases of second attack
in the same individual.
Even in these cases the diagnosis is necessarily uncertain.
Frost says that considering that 23%, of the population had had
influenza prior to December llth, the proportion of
second attacks should have been much greater
if no immunity had been acquired.
A second canvas in San Francisco gave generally
corresponding results.
Our own experience was quite similar.We have divided the whole
period from March, 1918 to March, 1920,into two portions separated
at August 1,1919.In the first portion we have knowledge of but four
individuals suffering from what the records would indicate to be two
genuine attacks of influenza.Similarly,five individuals appeared to
have had two attacks within the second interval.These are to be
contrasted with a total incidence in the fall and winter of 1918-1919
of 1971 cases,and in the winter of 1919-20,of 965 cases.Among the
total nine individuals the intervals between attacks varied from 26
days to five months.All except one had an interval of one month or over.
In two cases there was an interval of one month,in one an
interval of two months,in two an interval of three months,in one of
four months,and in one of five months. None of the four individuals
who had two attacks in the first group of months had a subsequent
attack in the second. On the contrary, two of the five suffering two
attacks in the second group of months had one previous attack in the
first.The second attack, following the first by a relatively short
interval tended to be milder than the first.In five out of the entire
nine the second attack was milder,in two it was of the same degree
of severity,and in only two was it more severe than the first.
The order of severity in the two individuals having three attacks each
was, in the first, severe, mild, severe;in the second, severe, average,
average. Zinsser makes the following remark: "The writer himself believes
that he had three attacks during the last epidemic.The first and
second were mild ones and the third complicated and therefore severe;
and innumerable others with whom he has spoken have had similar
experiences." From a consideration of these reports by divers authorities it
is reasonable to conclude that for a period of a few months at least,one
attack of influenza protects against a second. As is to be expected,
this relative immunity is not of constant duration in all individuals.
If there were no lessened susceptibility following an attack we would be
faced with the phenomenon of individuals succumbing time and again
to rapidly successsive attacks of the disease.
Such a circumstance is very rare.
It is difficult to determine how long even on an average this relative
protection or insusceptibility lasts. Evidence is fairly uniform in
indicating a protection of at least three months. Usually it is longer.
There seems to be some basis for the supposition that a group of
individuals exposed to an attack of influenza displays within the
succeeding three months, or slightly longer,a relative general group immunity.
If the group be considered as a whole those even who did not develop
the disease previously appear to have become less susceptible.
Whether we can ascribe this to the individual as a unit,or whether we
must explain it by some assumption with the community as a unit,
is uncertain. Is it because the exposed individuals in the group who
did not contract the disease have individually received some of the
virus into their systems and developed a certain immunity, or is it a
much more complex phenomenon depending on greater relative dis-
persion of susceptibles and other communal factors ?
We may place the minumum period of "immunity"at from three to
five months, rarely less.
There is additional evidence by which we may
delimit fairly closely the other extreme,that time at which individuals
considered as a group no longer manifest increased resistance to the
disease. The author found that 19.17%, of his population contracted
influenza in 1918,and 9.55%, contracted the disease in 1920.
240 individuals, or 2.4%, of the entire population developed the disease in both epidemics.
Out of 1971 individuals having the disease in the 1918 spread, 240, or 12.1%
recurred in 1920. This is to be compared with the total 1920 incidence of 9.55%.
More correctly we should separate the
1920 cases into 2 groups, those who had and who had not had
influenza previously. The former group, 240 individuals, constitute
as just stated, 12.1%, of all who had had the disease previously.
The second group, 715 individuals, constitute 8.9%, of the
8034 who had not had the disease in 1918-19.
From these results we must conclude that a previous attack con-
tracted on an average of from 10 to 17 months before, conferred no pro-
tection whatever against a second attack.On the contrary, the attack
rate was slightly higher in this group than in those who had not previously
had the disease.
Yet another evidence of the insignificant part played by any immu-
nityin the occurrence of influenza in individuals in 1920 is indicated by
our series of 319 infants living in 1920 but who had not been born dur-
ing the 1918 spread and who were presumably not immune to the
disease.We have not investigated whether the mothers had had the
disease in 1918.From among these 319 infants, 30=10%.,
developed the disease in 1920. This is practically the same percentage
as for the population at large.
These findings also correspond with our previously recorded con-
clusion made after studying the disease incidence with three increasing
degrees of exposure, sleep,room and family (page 198).
TABLE IX.
Comparison of the severity of the first and second attacks in individuals contracting
influenzain 1918-19 and again in 1920.
Severity.
1918,and that 22.6%, were attacked in 1920.
Of those who had the disease in 1918-19, 21.2%, had a repeated attack in 1920,
while of those who had not had a previous attack, 23.1%, were attacked in 1920.
A similar study among 2472 men at Camp Grant showed that 15.8%
had had influenza in 1918-19, and 11.7% in 1920.
Of those with previous influenza history 15.6%, had a repeated
attack, while of the remainder without previous history of influenza
10.9%, were attacked in 1920. They conclude that no marked
immunity to influenza exists 12 to 15 months after a previous attack,
but that the results do not show that some degree of immunity may
not obtain at an earlier period.
It is interesting while considering the subject of immunity to pay
particular attention to those who did not develop the disease as well as
to those who did.
In our series 70%, of all individuals escaped the disease in both epidemics.
With some variation this figure will hold for all communities.
Or, again, among those who had the disease
in 1920, 75%, had not had it in the preceding waves.
Hall states that in Copenhagen at the Bispebjaerg Hospital, among
the 500 patients with influenza in the four weeks early in 1920,
91.8%, had not had the influenza during the 1918-19 epidemic.
H. F.Vaughan found in a review of 2500 cases occurring in Detroit
in January, 1920, that 84%, had never had the influenza before.
The true significance of these figures cannot be recognized,because
we are not informed as to the percent, of these populations attacked
in 1918-19.
We observed such a universal distribution of influenza during the
epidemic period that it is frequently assumed that all individuals are
exposed to the disease, that the virus must enter the body of all or
nearly all,and that it is due chiefly to a relative natural immunity that
some do not fall victims. Is this the actual state,or is it true that the
distribution of the virus is limited to about one-third of the population
and that practically all of those who are actually exposed develop the
disease ? These are the two extremes; more probably the actual
state is somewhere between.
This question cannot be definitely answered, and yet it is one of
extreme importance, particularly with regard to prevention and
combat of the disease. How universally is the influenza virus distributed
during pandemics ? What proportion of the population is actually
exposed by invasion with the virus ? What proportion of actually
exposed individuals develops the disease? We will refer to this again
when comparing influenza with other infectious diseases, but it is of
particular interest now to review our individuals who were exposed by
sleeping with cases of influenza. 55% of all individuals
sleeping in the same bed with cases of influenza in 1918 did not
contract clinical influenza. 70% of all individuals sleeping
with influenza cases in 1920 did not contract the disease in
recognizable form.69% of all individuals in 1920 who had
not had the disease previously and who slept with cases did not
develop evidence of the disease.
It is a bit difficult to conceive of a degree of exposure much closer than
that of sleeping in the same bed with a sick individual. And yet it is
equally conceivable that many individuals sleeping sleeping in the same bed
with a patient were not penetrated by the virus of influenza. This
does not aid us in answering our question. We do not know whether
the more important factor is that of a natural immunity or that of
absence of actual invasion by the virus.
... experiments with volunteers....
================================================== =========
several problems:
1.) how to explain the unusual age-distribution of cases in 1918, if not with immunity ?
it could come from 1889, but age-dependent, short-lived in children before puberty
2.) immunity was reported in 2009 , by showing antibodies, aged 60 or more,
having had exposure to a strain from the 40s or 50s
3.) mice immunized with the 1918 virus showed longlived immunity
4.) CFR in 1920 was way down, although the age-distribution could still be seen,
that vanished almost completely in subsequent years
How to explain this, if not by exposure to the virus in 1918,1919 ?
From the sequences we have no signs, that the virus changed
substantially from 1918 to 1920.
And those regions who were spared in 1918 had it worse in 1920
5.) in Mexico City, Bojoca,Lima we had only incomplete protection of the elderly in 1918
6.) isolated populations had no protection of the elderly (Mamelund)
7.) isolated populations were shown to have more severe attacks
even in 1968, Tristan da Cunha. American Indians, Aleutes,Maori,Aborigenes
8.) we now know that there are several forms of immunity and several different
influenza viruses
================================================== =======
http://www.ncbi.nlm.nih.gov/pubmed/23863506 , 14 months, mice
http://www.ncbi.nlm.nih.gov/pubmed/23637797 , 15 months, mallards
http://www.ncbi.nlm.nih.gov/pubmed/22884662 , 24 months, boosted, humans
http://www.ncbi.nlm.nih.gov/pubmed/22130546 , 16 months, mice
http://www.ncbi.nlm.nih.gov/pubmed/19596414 , chickens, 32 months
http://www.ncbi.nlm.nih.gov/pubmed/23812238, humans, 45 years (?)
http://www.ncbi.nlm.nih.gov/pubmed/23785769 , humans, 45y , B-cell
http://www.ncbi.nlm.nih.gov/pubmed/23785204 , NA
------------------------------------------
Preclinical studies have shown that these candidate vaccines stimulate broadly
cross-reacting antibody responses when administered either alone or in combination
with adjuvants or carrier proteins, and several of these vaccines are now undergoing
clinical testing. 61-64
61. Steel J, Lowen AC, Wang T, et al. An influenza virus vaccine based on the con-
served hemagglutinin stalk domain. MBio 2010;1(1):e00018.
62. Schotsaert M, De Filette M, Fiers W, Saelens X. Universal M2 ectodomain-based influenza
A vaccines: preclinical and clini-cal developments. Expert Rev Vaccines 2009;8:499-508.
63. ClinicalTrials.gov. Comparative safety and immunogenicity of 1.0 ?g intramuscular (i.m.) and 2.0 ?g
subcutaneous (s.c.) dosing with VAX102 (M2e-flagellin) universal influenza vaccine in healthy adults. 2009
64. Idem. Safety study of recombinant M2e influenza-A vaccine in healthy adults (FLU-A). 2008.
--------------------------------------------------------------------------------------------
The development of influenza A virus (IAV) vaccines capable of inducing
cytotoxic CD8 T cell responses could potentially provide superior, long-term
protection against multiple, heterologous strains of IAV
Granzyme B-high, lung-resident T-cell populations persist for at least 4 months
and can control a lethal influenza challenge without harmful cytokine responses,
weight loss, or lung injury.
================================================== =======
Comby found that in Paris only the new-born were noticeably insusceptible
to influenza,that children up to 15 years were attacked at 40%,and adults at 60%
Danchez believed that in families in which all the adults became ill,the
little children usually escaped.
Finkler states that in the schools at Bordeaux the older children
were first and most frequently attacked.
Of the 248 male and female teachers in 41 schools, 153 (61.7%) developed the disease.
Children up to five or six years of age at any rate seem to have been
very little affected,while older children were no less susceptible than adults.
Among 47,000 cases of influenza treated by physicians in Bavaria in 1889,
the various ages were as follows:
1,1.5%,2-5,5.4%,6-10,6.6%,11-15,7.2%,16-20,11.4%,21-30,22.2%,
31-40,19.3%,41-50,12.6%,51-60,7.7%,61-70,3.6%,71-80,2.0%,>80,0.5%
Leubuscher recorded that in Jena the proportion of cases in the
individual age classes did not correspond with the figures reported
from other localities.
Children, and especially very young children,
suffered relatively less than adults.
The following statistics of the 1889-90 incidence of influenza
among school children in Cologne were collected by Lent:
age,%affected in Cologne,% in suburbs
13-14,33.8,42.9%
11-12,31.9,37.9
10,30.5,37.1
9,25.9,31.4
8,28.0,28.2
7,22.3,26.3
Theages showing highest mortalityin the autumn of 1918appear
to have beenessentiallythe same as those whichpredominated thirty
years ago.
Thereappearsto benothingin theagedistribution that
could beexplained byanimmunity persistingover from theepidemic
of 1889-93.
================================================== ==============
--------------------------------------------------------------------------------------------
001 GENERAL EPIDEMIOLOGIC CONSIDERATIONS
047 INFLUENZA EPIDEMICS SINCE 1893
127 AN INVESTIGATION OF INFLUENZA IN BOSTON (WINTER OF 1920.)
175 AN INTENSIVE STUDY OF THE SPREAD OF INFLUENZA IN SMALL GROUPS OF
CLOSELY ASSOCIATED INDIVIDUALS
199 IMMUNITY
212 INFLUENZA AND OTHER DISEASES
224 COMPARISON or INFLUENZA WITH OTHER EPIDEMIC DISEASES
234 THE PREVENTION AND CONTROL OF INFLUENZA
245 BIBLIOGRAPHY
257-260 APPENDIX
------------------------------------------------------------------------------------------------------------------------------------
-001 GENERAL EPIDEMIOLOGIC CONSIDERATIONS
002 Historical
013 Clinical and epidemiologic identification
014 General characteristics of early epidemic outbreaks
019 Symptoms in former epidemics
020 Manner of spread
023 Human intercourse
026 Crowd gatherings
027 Mass attack
030 Healthy carriers and convalescents
031 General manner of spread in individual localities
031 Primary type of epidemic
033 Secondary type of epidemic
036 Mortality curves
037 Duration of explosive outbreak
041 Morbidity curves in 1920 recurrences
042 Spread in countries and continents
042 Spread in primary waves
044 Spread in recurrences
-047 INFLUENZA EPIDEMICS SINCE 1893
047 Occurrence since 1893
047 Period from 1893-1918
049 Increase in 1900-1901
051 Period from 1901-1915
055 Influenza in 1915-1916
058 Influenza between 1916 and 1918
059 The pandemic of 1918
065 Date of first increased prevalence in various localities
080 Influenza in China
081 Autumn spread in the United States
087 Recrudescences
089 Recurrences in the winter of 1919-1920
090 The winter of 1920
095 Incubationperiod
096 Predisposing causes
097 Periodicity
108 Virulence enhancement
113 Meteorologic conditions
114 Secondary invaders
116 Origin of the 1918 pandemic
-127 AN INVESTIGATION OF INFLUENZA IN BOSTON (WINTER OF 1920.)
134 Diagnostic standards for the 1918 epidemic
134 Standards for 1920
137 Morbidity
143 Relation of sex to morbidity
145 Relation of sex to severity
145 Morbidity by age
150 Relationship of occupation to morbidity
155 Effect of race stock
156 Mortality
165 Mortality by sex
167 Relationship to age
170 Relationship of occupation
170 Density of population
173 Race stock and mortality
-175 AN INTENSIVE STUDY OF THE SPREAD OF INFLUENZA IN SMALL GROUPS
OF CLOSELY ASSOCIATED INDIVIDUALS
179 Effect of overcrowding
187 Domestic cleanliness
189 Economic status
191 Distribution of the disease through the household
194 The first case in the family
197 Intimacy of family contact
198 Recurrent cases
-199 IMMUNITY
-212 INFLUENZA AND OTHER DISEASES
212 Influenza and tuberculosis
220 Other infectious diseases
222 Encephalitis lethargica
-224 COMPARISON or INFLUENZA WITH OTHER EPIDEMIC DISEASES
224 Epizootics
228 Asiatic cholera
228 Epidemic meningitis
229 Plague
231 Measles
-234 THE PREVENTION AND CONTROL OF INFLUENZA
236 Anticipatory or preventive measures
237 Organizationof health services
239 Palliative measures in the presence of an epidemic
241 Problems for the future.Constructive research
245 Bibliography
Vaughan,1920
page 137, MORBIDITY.
There has been great actual variation in the morbidity from influenza
in the various epidemics and even in different localities during single
epidemics. Previous to 1889 there were no reliable statistics for the
disease incidence, and subsequent to that date the records, for the
reasons previously mentioned, have still been not entirely adequate.
In the history of influenza morbidity,as in that of its mortality, we must
content ourselves for information prior to the nineteenth century with
the very general estimates made by contemporary historians.During
the last century the statistics have been more numerous and more
nearly correct.-----------------------------------------------------------------------------------------------------------------------
As far back as the first recognized pandemic, 1510,
the extremely high morbidity has been a recognized characteristic.
Thomas Short in speaking of this pandemic says, "The disease
attacked at once and raged all over Europe, not missing a family
and scarce a person." ---------------------------------------------------------------------------1510-------------------------
Pasquierin 1557 spoke of the disease as
common to all individuals, and Valleriola describes the widespread
distribution of the epidemic throughout the whole of France during
that year.It spared neither sex, age, nor rank, neither children nor
aged,rich nor poor.The mortality, however,was low,"children only,
dying." Again,Thomas Short remarks, "This disease seized most
countries very suddenly when it entered, catching thousands the
same moment." ------------------------------------------------------------------------------------1557? or still 1510--------------
Of the second pandemic, 1580,Short says,
"Though all had it,few died in these countries except such as were
let blood of,or had unsound viscera." ----------------------------------------------------------------------1580-----------------
Thomas Sydenham remarks that in the epidemic of 1675 no one
escaped, whatever might be his age or temperament,and the disease
ran throughout whole families at once.--------------------------------------------------------------------1675----------------
Molineux recorded concerning 1693,"All conditions of persons were
attacked,those residing in the country as well as those in the city;
those who lived in the fresh air and those who kept to their rooms;
those who were very strong and hardy were taken in the same manner
as the weak and spoiled; men, women and children, persons of all
ranks and stations in life,the youngest as well as the oldest."---------------------------------1693------------
Schrook tells us that in Augsburg in 1712 not a house was spared
by the disease.
According to Waldschmidt in Kiel, ten and more persons were
frequently taken ill in one house,and Slevogt says that the disease
was fearful because so many persons contracted it at the same time.
The disease was, however, not dangerous, for Slevogt continues:
"Fear soon vanished when it was seen that although it had spread
all over the city,it left the sick with equal rapidity."-----------------------------------------------1712-----------------------
It is estimated that in the epidemic of 1729-1730, 60000 people
developed the disease in Rome, 50000 in Mayence, and 14000 in
Turin. In London "barely one per cent,escaped." In Lausanne
one-half of the population,then estimated at 4000,was stricken.
In Vienna over 60000 persons were affected. In the monasteries
of Paris so many of the inmates were suffering from the disease
that no services could be held. -----------------------------------------------------------------1729f---------------------
Huxham is quoted in Thomson's
"Annals" as declaring concerning the epidemic of 1732-33:
"Not a house was free from it,the beggar's hut and the nobleman's
palace were alike subject to its attack,scarce a person escaping
either in town or country;old and young, strong and infirm,shared
the same fate."------------------------------------------------------------------------------------1732f------------------------
Finkler writes as follows concerning the epidemic of 1758: "On
Oct. 24th, Whytt continues,the pestilence began to abate.
He is not sure whether this was due to a change in the weather,
or because the disease had already attacked most people,
although the latter seems more plausible to him, particularly as
he says that 'in Edinburgh and its vicinity not one out of six or
seven escaped, 'and in other localities it is said to have been even
worse. In the north of Scotland also, the epidemic was greatly
disseminated from the middle of October to the end of November.
A young physician wrote to Robert Whytt: 'It was the most
universal epidemic I ever saw,and I am persuaded that more
people were seized with it than escaped.'
This same physician reported that 'it was not at all mortal here.'"--------------------1758---------------
In the epidemic of 1762,we learn from Razoux,de Brest, Saillant,
Ehrmann, that the morbidity was great while the mortality was low.----------------1762---------------
According to Grimm,nine-tenths of the inhabitants of Eisenach
contracted the disease in 1767.------------------------------------------------------------------1767---------------------
Daniel Rainy,of Dublin,in describing the invasion of an institution
in 1775-76,tells us that from among 367 persons varying in age
from 12 to 90 years, 200 were taken sick.
Thomas Glass says:
"There sickened in Exeter Hospital all the 173 inmates, 162 had
coughs. Two or three days after the hospital was invaded the
cityworkhouse as attacked;of the 200 paupers housed there only
very few escaped the disease." -------------------------------------------------------------1775f---------------------
Gilibert described an extraordinary morbidity in Russia in 1780-81.------------1780f-------------------
Metzger says that in 1782 the Russian catarrh was so universal
during the month of March that in many houses all the inhabitants
were attacked.During this period, "in St.Petersburg, 30000, and
in Konigsberg, 1000 persons fell ill each day;"in Rome two-thirds
of the inhabitants were attacked; in Munich, three-fourths; and in
Vienna the severity of the epidemic compelled the authorities to
close the theaters for eight days.----------------------------------------------------------1782--------------------------
The epidemics of 1788-89, 1799-1800 and of 1802-1803 were----------------------1788f , 1799f, 1802f-------------
characterized by a relatively lower morbidity than that of 1830-32,
in which the morbidity was again enormous.--------------------------------------------1830-2---------------------------
Likewise in 1833, the morbidity was very great. In Prague "scarcely
a house was spared by the plague." In Petrograd, 10000 persons
were attacked; in Berlin at least 50000.These are the figures of
Hufeland.The Gazette M&iicale records the morbidity as being
four-fifths of the total number of inhabitants of Paris. --------------------------------1833----------------------------
In 1836, according
to Gluge, 40000 persons suffered from the disease in Berlin alone. ------------------1836-----------------------
In London, in the 1847 epidemic, it has been calculated
that at least 250000 individuals took sick, and in Paris, according to
Marc d'Espine,between one-fourth and one-half of the population
developed the disease,and in Geneva not less than one-third.. --------------------1847-----------------------------
Leichtenstern informs us that in 1890 the early reports were made
by clinical men and were mere presumptions. They were almost
universally higher than the later statistical findings.
The early estimates for the morbidity in several German cities were
from 40-50 percent. On the other hand,one of the highest statistical
reports recorded by Leichtenstern was for Strasbourg in which 36.5
per cent, of the individuals became sick.
The average morbidity reported by him ran between 20 and 30 percent.
The difference is accounted for in part by the fact that some of the
very mild cases were not recorded in the statistics,and in part by
the tendency in giving estimates,to exaggerate.Auerbach has collected
the statistics of 200 families distributed throughout the city of Cologne.
He found that 149 of these families (75 per cent.) were attacked.
In these, 235 were ill 59 men, 95 women,and 81 children.The larger
number of women was explained as due to the illness of the female
servants.He estimates each family as consisting on an average of
six individuals,and concludes that 20 percent, were taken with the
disease.
Following the 1889 epidemic,Abbott concluded,on a basis of
questionnaries sent out to various individuals and institutions in the
State of Massachusetts,that 39 percent, of the entire population had
been attacked,in all about 850000 persons. -----------------------------------------------------1889f---------------------------
Moody and Capps,in
December, 1915, and January, 1916, made a survey of the personnel
and inmates of four institutions in Chicago, the Michael Reese Hospital,
the Illinois Training School for Nurses, the Old Men's Home,and
St. Luke's Hospital Nurses Training School, making a total of 677
persons surveyed, of whom 144 developed influenza, making a
percentage morbidity of 21. They remarked that there were many
others with colds who remained on duty and were not included in the
table and were not diagnosed as influenza. ---------------------------------------------------1915f---------------------------
We have already described the relatively low morbidity and mortality
in the early spring epidemic in the United States.
According to Soper, the total number affected in March, 1918, at Camp
Forrest and the Reserve Officers Training Camp in the Oglethorpe
Camps was estimated at 2900. The total strength at that time was
28586. The percentage morbidity then was probably a little over
10 percent.
Dunlop, in describing the May, 1918, epidemic in Glasgow, says that
it was more limited in extent,as well as milder,than the later epidemic. ------------------1918 1st wave-------------
It has been estimated that in the autumn epidemic in the United
States Army Camps one out of every four men had influenza,and one
out of every twenty-four men encamped in this country had pneumonia.
During the four autumn months of 1918, 338343 cases of influenza
were reported to the Surgeon General's Office;there were 61691 cases
of pneumonia.
Woolley reports that among the soldiers at Camp Devens,Mass.
30 percent, of the population was affected.
At Camp Humphreys,16 percent, of the entire personnel developed
the disease. The camp had an average strength of 26600 individuals.
52 percent, of the entire number of cases occurred during the peak
week,which ended October 4th.The outbreak began September 13th
and ended October 18th. Hirsch and McKinney report that an
epidemic of unusual virulence swept with great rapidity through
several organizations in Camp Grant between September 21, 1918,
and October 18, 1918. During this time 9037 patients were admitted
to the Base Hospital, representing about one-fourth of the strength
of the camp,and of these, 26 percent,developed pneumonia.
About 11 percent, of the total admissions or 43 percent, of the total
cases of pneumonia died.
...
================================================== ====
page 156
MORTALITY.
According to Marchese, in 1387 at Forli in Italy, not a person
escaped the disease,but only a few died.
Gassar says that during the same epidemic in Germany the patients
suffered four,or at most five, days with the most disagreeable
catarrhal symptoms and delirium,but recovered,and only very few
were removed by death.-------------------------------------------------------------------------------1387---------------------
Pasquier remarks concerning an epidemic in 1411 that an infinitude
of individuals were attacked but that none died.-----------------------------------------------1411-------------------
Concerning the epidemic of 1414 in France,Lobineau relates that
the disease was fatal only for the aged.
Mezeray also speaks of the high mortality of the old in this epidemic.----------1414-----------------
Regarding the pandemic of 1510,Thomas Short remarks that none
died except some children.
Mezeray,on the other hand, says that the disease had claimed
many victims. ----------------------------------------------------------------------------------------------1510----------------
Pasquier and Valleriola both write of the epidemic of 1557,
in France, as being distinctly mild in character.
Children only who could not freely cough out the phlegm died.
Coyttar speaks of the absence of death except in tuberculous
patients. --------------------------------------------------------------------------------------------------------------1557-------------------
In the pandemic of 1580 individual observers report enormous
death rates.Thus, according to Schenkius,the disease killed 9000
persons in Rome,while Madrid, Barcelona and other Spanish cities
were said to have been nearly depopulated by the disease.
This high mortality was, however,even at that time attributed
by some physicians to the injudicious employment
of venesection.
Throughout the more recent history of pandemic influenza opinion
seems to have been nearly unanimous that bloodletting has had
very bad results in the outcome of influenza cases.
Remarks to this effect have been made by the contempories
of nearly every epidemic since 1580.-----------------------------------------------------------------------------1580--------------
According to Rayger and others during the epidemic of 1675,
nobody died of the disease itself with the exception of debilitated
persons, although it spared neither the weak nor the strong. ----------------------------------1675-------------------
Concerning the epidemic of 1688,Thomas Short writes for England
that though not one of fifteen escaped it, yet not one of a thousand
that had it died.------------------------------------------------------------------------------------------------1688---------------
In 1712, Slevogt writes that in Germany "Fear soon vanished when
it was seen that although it had spread all over the city,
it left the sick with equal rapidity."---------------------------------------------------------------------------1712--------------------
Finkler remarks, concerning 1729-30, that, "The great mortality
which attended the epidemic in England and Italy seems
somewhat remarkable.
Thus Hahn states that in London in the month of September
1000 persons died each week,and in Mayence 40 persons
daily. Most likely, however,other diseases which were present at the
same time added their quota to the mortality, especially as the
disease in other places,for example in Germany,ran a benign course." ----------------------1729f-------------------
Perkins, Huxham,Pelargus,Carl and others, concerning the
epidemic of 1732-33, all testify that the disease was of very low fatality.--------------1732f--------------
In 1742 the epidemic was evidenced by an enormous morbidity but
the disease was not dangerous as a general rule although Huxham
occasionally speaks of the virulent character of the disease in England,
and Cohansen says that in January, 1743, over 8000 persons
died from influenza in Rome and 5000 in Mayence.-----------------------------------------------1742f------------------
We have the testimony of Robert Whytt,for 1758,and that of ----------------------------1758----------------------
Razoux and Saillant and Ehrman for 1762,as to the low mortality of------------------1762-----------------------
the epidemic for those years.
According to Heberden the same was true for 1775,------------------------------------1775--------------------
while Webster tells us for 1780 that the disease was not dangerous
but its effects were seen the following year in the increased number
of cases of phthisis. --------------------------------------------------------------------------------1780------------
Finkler remarks concerning the epidemic of 1802,
"The mortality in this epidemic was small, only the abuse
of venesection brought many to the grave.
Thus,so many farmers are said to have died in Russia
from it that venesection was forbidden by an imperial
ukase.
Jonas says that many patients were bled either on the advice
of a simple village barber or by their own wish, and most of them died.
In Prussia also bleeding was declared detrimental by the Government." ------------------1802---------------
He continues regarding 1836-37, that, "In London there died,
during the week ending January 24, 1837,a total of 871 persons,and
among these deaths there were 295 from disease of the respiratory
organs; during the week ending January 31st, out of a total of 860
deaths there were 309 from diseases of the respiratory organs." ----------------------------1836f-------------------
Watson, in describing the epidemic of 1847,discusses the mortality
"The absolute mortality has been enormous; yet the relative
mortality has been small.
You will hear people comparing the ravages of
the influenza with those of the cholera,and inferring that the latter is
the less dangerous complaint of the two;but this is plainly a great
misapprehension.
Less dangerous to the community at large (in this
country at least) it certainly has been; but infinitely more dangerous to
the individuals attacked by it.
More persons have died of the influenza in the present year than died
of the cholera when it raged in 1832;
but then a vastly greater number have been affected with the one
disease than with the other.
I suppose that nearly one-half of those who were seized with the
cholera perished;while but a very small fraction, indeed, not
more probably than two percent, of those who suffered influenza
have sunk under it." ---------------------------------------------------------------------------------------1847-------------------------
Leichtenstern remarks on the very low mortality of 1889-90.
In Munich 0.6% died;in Rostock 0.8%; in Leipzig 0.5%
in 15 Swiss cities 0.1%; in Karlsruhe 0.075%;
in Mecklenburg-Schwerin 1.2%.
This does not, however, include the numerous deaths from
complications,as from pneumonia, and does not
express the true mortality.
Newsholme gives the following table for mortality from influenza,
bronchitis and pneumonia,in England and Wales during the epidemic
years and the years immediately preceding them.
The figures express annual death rate per million of population.
The highest rate was reached in 1891.
The table does not include deaths registered as from
other diseases,but due directly or indirectly to influenza.
Respiratory diseases in general show a greatly increased
death rate in years in which influenza is epidemic.
Such is also true to some extent with
diseases of the nervous and the circulatory systems.
---------------------------------------------------------------------------------------------------------1889ff------------------------------
================================================== ================
Vaughan, 202
We have previously shown that the relatively low morbidity among
the older age groups in 1918 is not satisfactorily explained by an
immunity lasting over from the epidemic of 1889-93.
If such were the case the change in mortality rate in large groups of individuals
would occur at the age of 30.
================================================== =======
Vaughan page 199ff IMMUNITY.
Opinions of all observers who have studied in detail the question
of immunity in influenza are remarkedly in accord.
The conclusions reached by Parkes in 1876 are valid today,
and form as excellent an abstract of our present knowledge as any
produced since his time.
"There is some discrepancy of evidence, but,on the whole,
it seems clear that, while persons seldom have a second attack in the same
epidemic (though even this may occur),an attack in one does not
protect against a subsequent epidemic.
Indeed,it has been supposed rather to render the body more liable."
In 1890, Abbott wrote: "There is but little if any evidence in
support of the protective power of one attack to confer immunity against
a second;and hence adults are not exempt,as they usually are in
epidemics of scarlet fever or other exanthemata;so that the proportion
of adults to children attacked in an epidemic is necessarily greater
than that which is observed in epidemics of other infectious diseases."
Parsons made somewhat similar observations: "One attack of
influenza does not seem to be protective against another;the disease in
this respect resembling diphtheria, erysipelas,and cholera rather than
smallpox, measles,or whooping cough.
The duration of the epidemic in a locality is so short that it is difficult
to distinguish between second attacks properly so-called,
and relapses,which are frequent enough.
A case is recorded in the 'British Medical Journal' of February 15, 1890,
in which a patient who had suffered from influenza in France in
December,1889, had another attack in England in January, 1890.
It was noticed in 1837 that many persons suffered from influenza
who had had the disease during the previous epidemic in 1834.
The shortness of the interval between these two epidemics,as compared
with that between 1848 and 1889, seems to show that the periodical
return of the disease in an epidemic form does not depend upon the
accumulation in the interval of susceptible individuals unprotected
against the disease by aprevious attack.
If one attack afforded protection against another a large proportion
of the population in 1837 must have been protected, yet an epidemic
occurred,and on the other hand for many years before 1889 a large
majority of the population must have been unprotected by a previous
attack, yet the epidemic did not recur.
"The persons now living who passed through the disease in 1847
are of course comparatively few, but such persons have not been
exempt from the present epidemic.
"I should be inclined to attribute the short duration of the influenza
epidemic in a locality to the establishment of a tolerance for the
specific poison among the persons exposed to it,similar to the tolerance
for dust possessed by workmen in rag factories,as mentioned,but
which is soon lost on their ceasing to be exposed to it,rather than
to a true immunity being established.
"Relapses in influenza are of frequent occurrence; they occurred
in 9.2%, of the cases at the Morningside Asylum, Edinburgh,
and in some cases indeed a second relapse has been recorded.
The time at which the relapse occurs is usually from a week to a
fortnight after the primary attack,and it can often be distinctly traced
to an exposure to cold,or return to work before complete recovery.
The symptoms of the relapse are similar to those of the primary attack,
except that they are commonly more severe."
In his report of 1893, Parsons goes into the subject of recurrent
attacks in individuals in greater detail. He quotes several communications
received from various physicians and health officers.
These opinions differ,some believing that the disease predisposes to
another attack; others, that there is no effect on the incidence in
recurring epidemics;and still others believing that there is a small
amount of acquired immunity.
The communications are not based upon statistical evidence.
He does find, however, an opportunity
for statistical study in the industrial schools at Swinton near
Manchester: "These schools were severely affected in March, 1890,
171 out of 589 children having suffered,or 29% In the first epidemic
of 1891 they were again affected,but to a less extent, only 35
cases occurring. At that time there were in the schools 449 children
who had been there at the time of the former epidemic. Of these
150 had had influenza in 1890 and 4 of them had it again,or 2.6%
299 had escaped influenza in 1890 and 17 of these had it now,or 5.7%
Thus,so far as these figures go,an attack of influenza confers a
degree of protection which after the lapse of a year diminishes
by one half the liability to contract the disease."
Leichtenstern, like Parsons, recognizes the importance of
distinguishing between relapses and recurrent cases.
Relapses in influenza are not common. They usually occur after the patient
is up, and about when he is ready to leave the house.
These are not recurrent cases, but in the epidemics in the years
following 1889 there were plenty of well substantiated cases
of recurrent typical influenza in the
same individual and some times even in entire families.
During the 1889 epidemic, as during the 1918 epidemic
it has been suggested by various observers that the apparent
immunity among the very old was due to immunity developed
as the result of previous epidemics, such as that of 1837,1847 and 1857.
Leichtenstern has collected the statistics from five different
hospitals in which 8%,32%,35%,24%,and 24% of individuals attacked
in 1891-92 had already had the disease in 1889.
Allbutt in 1905 remarked that whereas he had previously believed
that immunity to influenza usually persists as long as six months,
many cases had recently been brought to his notice where such an
interval seemed improbable, where the succeeding attack was probably
not a relapse but a new infection.He has seen two attacks apparently
separate occurring in the same individual within two months.
In the same year Moore wrote that influenza shows a decided tendency
to relapse,a feature to which the indirect fatality of the disease is in
great measure due. "So far from establishing immunity,an attack
of this malady seems to render an individual more liable to contract
the disease upon any future exposure to its contagion."
Again West,in the same year wrote,"From our present experience
we must conclude that influenza is infectious in a very high degree
indeed, and that the protection afforded by an attack is imperfect,
or of very short duration.Indeed, one attack -seems actually to
predispose,after a time to another, or, to put it differently,that the
positive phase of protection is followed by a negative phase, in which
the individual seems rather more than less liable to succumb to infection
if exposed to it. It seems more likely that an individual may
never have influenza at all than that, having had it once, he should
never have it again. Some, indeed,seem to offer so little resistance
that they develop it regularly once or twice a year."
We have previously shown that the relatively low morbidity among
the older age groups in 1918 is not satisfactorily explained by an
immunity lasting over from the e pidemicof 1889-93. If such were the
case the change in mortalityrate in large groups of individuals would
occur at the age of 30.
During the autumn of 1918 many observations were made, particularly
in the armies, of light incidence in those groups or communities
that had had the disease in mild form in the spring of the same year.
Parsons quotes many similar observations for the period 1890-1893.
V. C.Vaughan relates that at Camp Shelby, Mississippi,"there
was in April a division of troops numbering about 26000.
An epidemic of mild influenza struck this camp in April, 1918,and within
ten days there were about 2000 cases.This included not only those
who were sent to the hospitals,but also those who were cared for in
barracks."This was the only division that remained in this country without
change of station from April until the fall of 1918.
"During the summer this camp received 20000 recruits.In
October, 1918, the virulent form of influenza struck this camp.
It confined itself almost exclusively to the recruits of the summer and
scarcely touched the men who had lived through the epidemic of April.
Not only the 2000 who had the disease in April,but the 24000
who apparently were not affected escaped the fall epidemic.
It appears from this that the mild form of influenza of April gave a
marked degree of immunity against the virulent form in October.
There is another observation which points the same way.Looking
over the statistics of the fall epidemic in cities in the United States we
find that certain cities had a low death rate,while others had a
relatively highrate. Among those cities which had a low death rate we will
mention Atlanta,Ga.;Kansas City,Mo.; Detroit, Mich.,and Columbus, Ohio.
Going to the spring records of these cities we find that in
all of them in March and April of 1918 there was an unusually high
death rate from pneumonia and undoubtedly in these cities at that
time there was a relatively mild epidemic of influenza.
In this way I am inclined to account for the relatively low death rate in these cities
in the fall of 1918. I make no claim that this and other instances of a
similar kind prove that the mild and virulent forms of influenza are
manifestations of the same disease, but I do hold that the evidence
points that way."
Lemierre and Raymond report the following observation in favor
of the development of a certain degree of immunity in the French
troops in April, 1918. After an intervening period of quiescence
there was a manifest recrudescence at the end of August.
Many military formations were attacked during both periods.This was
true especially in three groups of an artillery regiment under their
observation.In the first of these groups there were three cases in
April, while 114 men were attacked in August.In the third group
there were 100 cases in April and only 3 in August.In the second
group there were 20 cases in April and 59 in August.Their report
does not state the total number of individuals in each of the three
groups. Jolt rain and Baufle discuss the flaring up of the epidemic in
October, and relate that a troop of soldiers from Indo-Chinan early all had
the disease lightly in the spring, but when the disease appeared again
it spared this troop completely,while troops and civilians around
developed it in a severe form.Gibbon writes:
"During the last three waves of the epidemic I had
to deal with the sick of 2000 troops,and during this time we treated
in hospital over 400 cases.No cases admitted in June, July or August
were re-admitted in October, November,or December,and no cases
admitted in either of these two periods were re-admitted in February
this year.
Unfortunately I am unable to trace the cases into March
as the troops were changed."
Dopter reports recurrent epidemics of influenza in a French Army
Division in 1918.The division,of which he was surgeon,was one of
the first to contract la grippe at the time of its first appearance in the
zone of the armies at the end of April,1918.
At this time nearly the entire body of infantry troops was attacked.
The disease was mild, and without complications.
The regiment of artillery escaped nearly entirely.
This epidemic subsided very rapidly,and by the end of May
it had entirely disappeared.Early in August a group of heavy artillery
was attached to the division, bringing influenza with it.Then a
few cases appeared in the regiment of light artillery which had hitherto
escaped. By the end of August all three groups of this regiment had
been attacked.
In this second epidemic the men who had come
through the first unattacked were very severely
ill in the second.With rare exceptions those sick in the
first did not contract it again.
Dopter notes that in the battery the most severely affected
in August,of which the effectives were reduced almost to none, only
those men were considered well enough for duty who had had
influenza in the first period.They escaped the second in spite of the close
contact with their comrades.
The infantry regiments,which were in
close association with the artillery,remained unaffected.
Finally,toward the middle of September new troops were attached
to the division,in view of an imminent attack by the enemy.These
troops, coming from neighboring and distant formations were suffering
at the time from grip,and continued to have the disease in the new
sector.Again,those attacked in May passed without damage through
this new epidemic.Among them there were only rare isolated mild
cases.The recurrences made only 1.6%, of the total incidence.
Opie and his associates found that at Camp Funston after the first
wave of influenza in March and April, 1918, the succeeding waves
usually affected only new recruits,who had not been in camp during
previous waves.
In Calcutta influenza appeared as an epidemic in July, 1918,and
in November, 1918. During the first quarter of 1919,at Calcutta as
elsewhere, many cases were still recurring.Malone investigated the
incidence of the disease in three institutions of Calcutta : He found that
in 'the Gourepore Jute Mills where the population was practically
stationary,those individuals who were attacked in July, 1918, passed
through two later epidemics, in December, 1918, and February, 1919,
without contracting the disease a second time,in spite of intimate
contact with infected persons. The same was true according to
Malone in the Alipore Central Jail and the Presidency Jail in Calcutta.
He believes that his evidence strongly suggests an immunity lasting
for at least nine months.
Dunlop found that Glasgow had a mild epidemic in the month of
May, 1918,in which the death rate rose from 14.1 to 20.1.There is
no record of any similar outbreak in Edinburgh. In the July epidemic
the Glasgow death rate rose from 11.7 to 15.9, while the Edinburgh
death rate went from 11.3 to 18.0,a higher increase. In the October-
November epidemic the Glasgow rate rose from 11.0 to 38.4, while the
Edinburgh rate went from 10.8 to 46.2. In the February-March
epidemic theGlasgow rate rose from 14.9 to 48.3,and the Edinburgh
rate from 18.9 to 52. 1 In the July and October epidemics Edinburgh
showed a greater increase in death rate, while in February,1919,
the increase in the two cities was the same.
However,in this case probably other factors play a part.
Also, we must remember that
here we are dealing with death rates,not with incidence rates.
The Inspector General of Health,in Spain, reported in January,
1918, that those cities which had the disease in May, 1918,suffered
lightly in the autumn of that year, while others of the large cities
which had been spared in the first invasion suffered most in the second.
Maillard and Brune report an epidemic of influenza in an epileptic
colony.There were 32 deaths among the 63 cases. None of the
inmates of the hospital who had influenza during the June epidemic
contracted it anew during the October wave.
Ovazza records that although a number of persons contracted
the influenza anew on its return in the fall after having had it in the
spring, yet the return cases were strikingly mild,and always free from
complications.
Barthe'lemy describes the successive waves of epidemic influenza
at Bizerte.He found that the "doctors and nurses who had been
through the first epidemic did not develop influenza in the second one
a few months later,even though they came in the closest contact with
the patients.
Hamilton and Leonard have studied two successive outbreaks due
to lapses in a rigid quarantine in an institution of 180 girls between
12 and 18 years of age. The girls were distributed through six cottages.
In the first epidemic November, 1918, 76 girls contracted the disease,
at which time it was entirely limited to the occupants of cottages 2, 3,
and 4. The second outbreak occurred in January, 1919,when 82 took
ill. Only five of these were located in cottages 2 and 4, the remainder
being in 1,5 and 6. No cases occurred in cottage 3 during the second spread.
Both epidemics lasted a little under two weeks.
Those who had suffered in the first spread appeared to be immune to
the second. There were no recurrences.The second epidemic was
much milder in character.Twelve percent, of the total remained
well throughout both epidemics.
Dr.Niven,in his study of 1021 households previously described,
found that 105 families suffered in both the summer and autumn 1918
epidemics."They comprised a population of 565 persons,of whom
205 suffered in summer and 360 escaped. In the autumn epidemic
82(=40%) of the presumably 'protected' persons
succumbed again,whereas only 120 (=33%) of the 'unprotected' suffered.
Of the former, however, only one died,while five of the latter terminated fatally.
These are interesting figures.If
they are borne out by subsequent inquiry, they are somewhat difficult
of explanation.
The persistent susceptibility to the primary disease
and yet comparative immunity from the fatal sequel, would seem to
suggest a dual infection, against one element of which the body is able
to produce protection,while it is unable to do so against the other."
Frost made a canvass of 33776 individuals in Baltimore between
November 20th and December llth,1918. The same population was
again covered in January, 1919, to determine the extent of the recru-
descence reported in December. Among 32600 people,724 cases of
influenza had occurred in the interval since the first survey.Of this
number only 26 or 3.6%, were definitely cases of second attack
in the same individual.
Even in these cases the diagnosis is necessarily uncertain.
Frost says that considering that 23%, of the population had had
influenza prior to December llth, the proportion of
second attacks should have been much greater
if no immunity had been acquired.
A second canvas in San Francisco gave generally
corresponding results.
Our own experience was quite similar.We have divided the whole
period from March, 1918 to March, 1920,into two portions separated
at August 1,1919.In the first portion we have knowledge of but four
individuals suffering from what the records would indicate to be two
genuine attacks of influenza.Similarly,five individuals appeared to
have had two attacks within the second interval.These are to be
contrasted with a total incidence in the fall and winter of 1918-1919
of 1971 cases,and in the winter of 1919-20,of 965 cases.Among the
total nine individuals the intervals between attacks varied from 26
days to five months.All except one had an interval of one month or over.
In two cases there was an interval of one month,in one an
interval of two months,in two an interval of three months,in one of
four months,and in one of five months. None of the four individuals
who had two attacks in the first group of months had a subsequent
attack in the second. On the contrary, two of the five suffering two
attacks in the second group of months had one previous attack in the
first.The second attack, following the first by a relatively short
interval tended to be milder than the first.In five out of the entire
nine the second attack was milder,in two it was of the same degree
of severity,and in only two was it more severe than the first.
The order of severity in the two individuals having three attacks each
was, in the first, severe, mild, severe;in the second, severe, average,
average. Zinsser makes the following remark: "The writer himself believes
that he had three attacks during the last epidemic.The first and
second were mild ones and the third complicated and therefore severe;
and innumerable others with whom he has spoken have had similar
experiences." From a consideration of these reports by divers authorities it
is reasonable to conclude that for a period of a few months at least,one
attack of influenza protects against a second. As is to be expected,
this relative immunity is not of constant duration in all individuals.
If there were no lessened susceptibility following an attack we would be
faced with the phenomenon of individuals succumbing time and again
to rapidly successsive attacks of the disease.
Such a circumstance is very rare.
It is difficult to determine how long even on an average this relative
protection or insusceptibility lasts. Evidence is fairly uniform in
indicating a protection of at least three months. Usually it is longer.
There seems to be some basis for the supposition that a group of
individuals exposed to an attack of influenza displays within the
succeeding three months, or slightly longer,a relative general group immunity.
If the group be considered as a whole those even who did not develop
the disease previously appear to have become less susceptible.
Whether we can ascribe this to the individual as a unit,or whether we
must explain it by some assumption with the community as a unit,
is uncertain. Is it because the exposed individuals in the group who
did not contract the disease have individually received some of the
virus into their systems and developed a certain immunity, or is it a
much more complex phenomenon depending on greater relative dis-
persion of susceptibles and other communal factors ?
We may place the minumum period of "immunity"at from three to
five months, rarely less.
There is additional evidence by which we may
delimit fairly closely the other extreme,that time at which individuals
considered as a group no longer manifest increased resistance to the
disease. The author found that 19.17%, of his population contracted
influenza in 1918,and 9.55%, contracted the disease in 1920.
240 individuals, or 2.4%, of the entire population developed the disease in both epidemics.
Out of 1971 individuals having the disease in the 1918 spread, 240, or 12.1%
recurred in 1920. This is to be compared with the total 1920 incidence of 9.55%.
More correctly we should separate the
1920 cases into 2 groups, those who had and who had not had
influenza previously. The former group, 240 individuals, constitute
as just stated, 12.1%, of all who had had the disease previously.
The second group, 715 individuals, constitute 8.9%, of the
8034 who had not had the disease in 1918-19.
From these results we must conclude that a previous attack con-
tracted on an average of from 10 to 17 months before, conferred no pro-
tection whatever against a second attack.On the contrary, the attack
rate was slightly higher in this group than in those who had not previously
had the disease.
Yet another evidence of the insignificant part played by any immu-
nityin the occurrence of influenza in individuals in 1920 is indicated by
our series of 319 infants living in 1920 but who had not been born dur-
ing the 1918 spread and who were presumably not immune to the
disease.We have not investigated whether the mothers had had the
disease in 1918.From among these 319 infants, 30=10%.,
developed the disease in 1920. This is practically the same percentage
as for the population at large.
These findings also correspond with our previously recorded con-
clusion made after studying the disease incidence with three increasing
degrees of exposure, sleep,room and family (page 198).
TABLE IX.
Comparison of the severity of the first and second attacks in individuals contracting
influenzain 1918-19 and again in 1920.
Severity.
1918,and that 22.6%, were attacked in 1920.
Of those who had the disease in 1918-19, 21.2%, had a repeated attack in 1920,
while of those who had not had a previous attack, 23.1%, were attacked in 1920.
A similar study among 2472 men at Camp Grant showed that 15.8%
had had influenza in 1918-19, and 11.7% in 1920.
Of those with previous influenza history 15.6%, had a repeated
attack, while of the remainder without previous history of influenza
10.9%, were attacked in 1920. They conclude that no marked
immunity to influenza exists 12 to 15 months after a previous attack,
but that the results do not show that some degree of immunity may
not obtain at an earlier period.
It is interesting while considering the subject of immunity to pay
particular attention to those who did not develop the disease as well as
to those who did.
In our series 70%, of all individuals escaped the disease in both epidemics.
With some variation this figure will hold for all communities.
Or, again, among those who had the disease
in 1920, 75%, had not had it in the preceding waves.
Hall states that in Copenhagen at the Bispebjaerg Hospital, among
the 500 patients with influenza in the four weeks early in 1920,
91.8%, had not had the influenza during the 1918-19 epidemic.
H. F.Vaughan found in a review of 2500 cases occurring in Detroit
in January, 1920, that 84%, had never had the influenza before.
The true significance of these figures cannot be recognized,because
we are not informed as to the percent, of these populations attacked
in 1918-19.
We observed such a universal distribution of influenza during the
epidemic period that it is frequently assumed that all individuals are
exposed to the disease, that the virus must enter the body of all or
nearly all,and that it is due chiefly to a relative natural immunity that
some do not fall victims. Is this the actual state,or is it true that the
distribution of the virus is limited to about one-third of the population
and that practically all of those who are actually exposed develop the
disease ? These are the two extremes; more probably the actual
state is somewhere between.
This question cannot be definitely answered, and yet it is one of
extreme importance, particularly with regard to prevention and
combat of the disease. How universally is the influenza virus distributed
during pandemics ? What proportion of the population is actually
exposed by invasion with the virus ? What proportion of actually
exposed individuals develops the disease? We will refer to this again
when comparing influenza with other infectious diseases, but it is of
particular interest now to review our individuals who were exposed by
sleeping with cases of influenza. 55% of all individuals
sleeping in the same bed with cases of influenza in 1918 did not
contract clinical influenza. 70% of all individuals sleeping
with influenza cases in 1920 did not contract the disease in
recognizable form.69% of all individuals in 1920 who had
not had the disease previously and who slept with cases did not
develop evidence of the disease.
It is a bit difficult to conceive of a degree of exposure much closer than
that of sleeping in the same bed with a sick individual. And yet it is
equally conceivable that many individuals sleeping sleeping in the same bed
with a patient were not penetrated by the virus of influenza. This
does not aid us in answering our question. We do not know whether
the more important factor is that of a natural immunity or that of
absence of actual invasion by the virus.
... experiments with volunteers....
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several problems:
1.) how to explain the unusual age-distribution of cases in 1918, if not with immunity ?
it could come from 1889, but age-dependent, short-lived in children before puberty
2.) immunity was reported in 2009 , by showing antibodies, aged 60 or more,
having had exposure to a strain from the 40s or 50s
3.) mice immunized with the 1918 virus showed longlived immunity
4.) CFR in 1920 was way down, although the age-distribution could still be seen,
that vanished almost completely in subsequent years
How to explain this, if not by exposure to the virus in 1918,1919 ?
From the sequences we have no signs, that the virus changed
substantially from 1918 to 1920.
And those regions who were spared in 1918 had it worse in 1920
5.) in Mexico City, Bojoca,Lima we had only incomplete protection of the elderly in 1918
6.) isolated populations had no protection of the elderly (Mamelund)
7.) isolated populations were shown to have more severe attacks
even in 1968, Tristan da Cunha. American Indians, Aleutes,Maori,Aborigenes
8.) we now know that there are several forms of immunity and several different
influenza viruses
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http://www.ncbi.nlm.nih.gov/pubmed/23863506 , 14 months, mice
http://www.ncbi.nlm.nih.gov/pubmed/23637797 , 15 months, mallards
http://www.ncbi.nlm.nih.gov/pubmed/22884662 , 24 months, boosted, humans
http://www.ncbi.nlm.nih.gov/pubmed/22130546 , 16 months, mice
http://www.ncbi.nlm.nih.gov/pubmed/19596414 , chickens, 32 months
http://www.ncbi.nlm.nih.gov/pubmed/23812238, humans, 45 years (?)
http://www.ncbi.nlm.nih.gov/pubmed/23785769 , humans, 45y , B-cell
http://www.ncbi.nlm.nih.gov/pubmed/23785204 , NA
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Preclinical studies have shown that these candidate vaccines stimulate broadly
cross-reacting antibody responses when administered either alone or in combination
with adjuvants or carrier proteins, and several of these vaccines are now undergoing
clinical testing. 61-64
61. Steel J, Lowen AC, Wang T, et al. An influenza virus vaccine based on the con-
served hemagglutinin stalk domain. MBio 2010;1(1):e00018.
62. Schotsaert M, De Filette M, Fiers W, Saelens X. Universal M2 ectodomain-based influenza
A vaccines: preclinical and clini-cal developments. Expert Rev Vaccines 2009;8:499-508.
63. ClinicalTrials.gov. Comparative safety and immunogenicity of 1.0 ?g intramuscular (i.m.) and 2.0 ?g
subcutaneous (s.c.) dosing with VAX102 (M2e-flagellin) universal influenza vaccine in healthy adults. 2009
64. Idem. Safety study of recombinant M2e influenza-A vaccine in healthy adults (FLU-A). 2008.
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The development of influenza A virus (IAV) vaccines capable of inducing
cytotoxic CD8 T cell responses could potentially provide superior, long-term
protection against multiple, heterologous strains of IAV
Granzyme B-high, lung-resident T-cell populations persist for at least 4 months
and can control a lethal influenza challenge without harmful cytokine responses,
weight loss, or lung injury.
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Comby found that in Paris only the new-born were noticeably insusceptible
to influenza,that children up to 15 years were attacked at 40%,and adults at 60%
Danchez believed that in families in which all the adults became ill,the
little children usually escaped.
Finkler states that in the schools at Bordeaux the older children
were first and most frequently attacked.
Of the 248 male and female teachers in 41 schools, 153 (61.7%) developed the disease.
Children up to five or six years of age at any rate seem to have been
very little affected,while older children were no less susceptible than adults.
Among 47,000 cases of influenza treated by physicians in Bavaria in 1889,
the various ages were as follows:
1,1.5%,2-5,5.4%,6-10,6.6%,11-15,7.2%,16-20,11.4%,21-30,22.2%,
31-40,19.3%,41-50,12.6%,51-60,7.7%,61-70,3.6%,71-80,2.0%,>80,0.5%
Leubuscher recorded that in Jena the proportion of cases in the
individual age classes did not correspond with the figures reported
from other localities.
Children, and especially very young children,
suffered relatively less than adults.
The following statistics of the 1889-90 incidence of influenza
among school children in Cologne were collected by Lent:
age,%affected in Cologne,% in suburbs
13-14,33.8,42.9%
11-12,31.9,37.9
10,30.5,37.1
9,25.9,31.4
8,28.0,28.2
7,22.3,26.3
Theages showing highest mortalityin the autumn of 1918appear
to have beenessentiallythe same as those whichpredominated thirty
years ago.
Thereappearsto benothingin theagedistribution that
could beexplained byanimmunity persistingover from theepidemic
of 1889-93.
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