With army camps and cantonments situated in nearly every section of the

country it is difficult to follow the general direction of spread from

camp to camp. During the period of the epidemic, troop movements were in

general from West to East toward points of embarkation rather than in

the reverse direction. This was in the opposite direction to that taken

by the pandemic. Away from the coast there were, however, many movements

of troops from camp to camp, in the redistribution of forces. That these

troop movements were not discontinued during the epidemic is indicated

by the report of Howard and Love: “The virulent type of influenza had

spread rapidly from camp to camp, from the Atlantic seaboard to the

South and West, due to the continual interchange of personnel from

infected to non-infected camps. Such movements of troops at this time

were recognized as dangerous and inadvisable, and prompt recommendations

were made by the Medical Department that such movements be discontinued

or greatly restricted, if compatible with military interests, which, of

course, were at the time paramount. The War Department was unable to

approve any marked restriction of movement of men from camp to camp at

this time. One result of the free inter-communication of military

personnel was that practically all military stations in the United

States were in the throes of the epidemic at the same time.”

In addition to this means of inter-communication we had the possibility

of spread to the various camps by the ordinary course of civilian and

commercial travel as in spread to different communities, and also the

possibility of importing large amounts of virus at one time on the

incoming trains with new draft troops.

Soper gives the following order for camps attacked:

═════════════════╤═════════════════╤═════════════════╤═════════════════

Order. │ Camp. │ Location. │ Date.

─────────────────┼─────────────────┼─────────────────┼─────────────────

1│Devens │Massachusetts │Sept. 12

2│Upton │New York │Sept. 13

3│Lee │Virginia │Sept. 17

4│Dix │New Jersey │Sept. 18

4│Jackson │South Carolina │Sept. 18

│ │ │

5│Hoboken │New Jersey │Sept. 19

5│Syracuse │New York │Sept. 19

5│Gordon │Georgia │Sept. 19

5│Humphreys │Virginia │Sept. 19

6│Logan │Texas │Sept. 20

│ │ │

6│Funston │Kansas │Sept. 20

6│Meade │Maryland │Sept. 20

7│Grant │Illinois │Sept. 22

7│Taylor │Kentucky │Sept. 22

8│Sevier │South Carolina │Sept. 23

│ │ │

8│Lewis │Washington │Sept. 23

8│Newport News │Virginia │Sept. 23

9│Pike │Arkansas │Sept. 24

10│Beauregard │Louisiana │Sept. 25

10│Eustis │Virginia │Sept. 25

│ │ │

11│Greene │North Carolina │Sept. 26

11│McClellan │Alabama │Sept. 26

12│Kearney │California │Sept. 27

12│Bowie │Texas │Sept. 27

13│Johnston │Florida │Sept. 28

│ │ │

13│Sheridan │Alabama │Sept. 28

14│Sherman │Ohio │Sept. 29

14│Dodge │Iowa │Sept. 29

14│Shelby │Mississippi │Sept. 29

15│Custer │Michigan │Sept. 30

│ │ │

16│Travis │Texas │Oct. 1

17│Cody │New Mexico │Oct. 3

18│Forrest │Georgia │Oct. 6

19│MacArthur │Texas │Oct. 7

20│Wadsworth │South Carolina │Oct. 11

│ │ │

20│Wheeler │Georgia │Oct. 11

20│Greenleaf │Georgia │Oct. 11

─────────────────┴─────────────────┴─────────────────┴─────────────────

Howard and Love have established definitely that the extension of the

virulent influenza from Camp Devens to other camps south and west in

September, 1918, can be traced in many instances directly to the

interchange of military personnel from infected to non-infected camps.

The height of the September outbreak in the United States Army extended

over a period of about nine weeks, from Sept. 13th to November 15th, and

during this period over 20,000 deaths occurred among troops in the

United States alone in excess of the number that would have occurred, if

the disease death rate for the corresponding period of the preceding

year had prevailed.

It is interesting to note with respect to Camp Humphreys, Virginia, that

there were possibly some sporadic cases previous to the autumn outbreak.

Brewer in reporting on the epidemic in September and October records the

first case as having occurred shortly after July 1st. He makes no

mention of there having been any outbreak whatever prior to that date.

Between July 1st and September 12th there were only sporadic cases

diagnosed as influenza. The autumn outbreak began at Camp Humphreys

September 13th and ended October 18th.

RECRUDESCENCES.

We have already seen from the work of Pearl that recrudescences

following the original spread in any one locality were the rule rather

than the exception in this country. He found that in sixty-five per

cent. of the forty cities studied there were two distinct peaks in the

mortality curve and in twenty per cent. there were three, while only

fifteen per cent. had but one peak. The first peak was as a rule the

highest. Although there was no absolute regularity in the time of

occurrence of the recrudescences, Pearl established that the high peak

cities had the second peaks on an average 7.1 weeks after the first, and

the third peak on an average 13.1 weeks after the second. The two-peak

cities are divided into two classes, the first comprising about a third

of the total number, had the second mortality peak around eight weeks

after the first, while the remaining two-thirds had the second peak

about thirteen weeks after the first. The cycle in the epidemic wave

appears to be nearly a multiple of seven weeks. He suggests that the

smaller group of two-peak cities with early second peak may have been

cities which at the time were presumably destined to show a third

distinct wave and peak of mortality, but in which for some reason not

now apparent the third wave did not eventuate. In contradistinction the

larger group of two-peak cities with the second peak occurring around

thirteen weeks after the first are presumably cities in which the

complex of factors determining the form of the mortality curve was such

as to lead definitely to a two and only two-peak curve. In three-peak

cities the first interval was around seven weeks, the second around

thirteen weeks. The two-peak cities with an interval around thirteen

were probably not destined, according to Pearl, to have another

repetition, but those with an interval of seven were presumably destined

to have a second interval, the thirteen-week interval, which for some

reason did not occur.

This raises the question of periodicity, a subject which we will discuss

at a more appropriate place.

This experience of recrudescences was similar in the American

Expeditionary Forces. The first outbreak lasted through April and May

and into June. The second came in September and October. The spring

epidemic had been characterized by mildness and was known as three-day

fever, but in the autumn, complications of the respiratory tract

predominated in the symptom complex. By August 18th a severe epidemic

had occurred in an artillery camp at La Valdahon in the Jura Mountains,

near Bezançon. Early in September a larger epidemic occurred in an

artillery camp near Bordeaux. The epidemic in our troops in France, as

well as in the French civil and military population, reached its height

during October. The Service of Supply was more heavily affected than

were the troops situated on the battle front. The morbidity rate

appeared to have been almost the same as that in the United States. That

it was not quite as high has been shown by Howard and Love. Longcope

states that it prevailed particularly among the troops at the base ports

where during a part of the epidemic transports laden with infected

troops were being landed; in those organizations which contained the

largest number of replacement troops; and in organizations being moved

on troop trains, where the men were necessarily closely crowded.

The second outbreak subsided during the early part of November. A third

occurred in January and February, very much as it had done in the United

States. In the interval between the second and third recurrences there

was no time at which the entire Expeditionary Forces were free from the

disease. The author had occasion to study an outbreak occurring early in

December in the 26th Division stationed in rest area at Montigny-le-Roi.

In this outbreak the respiratory complications predominated, as in

October, and the mortality was comparatively high. We had had occasion

to study the same disease at Camp Sevier, South Carolina in September

and early October, 1918, and in two different localities in France in

December, 1918, and February, 1919, and found that the clinical

characteristics were identical on both continents.

The more severe recurrence in England, in October, has been carefully

studied. In fact this recurrence was almost universal in all countries.

The autumn epidemic has been reported as being at its height in October,

1918, in such widely separated localities as the United States, England,

France, Greece, Brazil, India, Japan and Korea.

In Europe at any rate the third wave occurring in the winter of 1919 was

quite generally distributed. At about the same time the disease broke

out in England, making a third wave in less than a year. Once again the

third attack began less suddenly and less violently and resulted in a

lower number of fatalities. During February there was reported to have

been a great increase in the number of cases in Paris. It had terminated

by March 27, 1919. In March the disease broke out anew, this time

assuming grave proportions, not only in that city but in several of the

Departments.

The second recrudescence has also been reported as being present in

Spain.

On May 5, 1919, report was received from Buenos Ayres that in one of the

concentration zones for naval troops located in the harbor there had

been an epidemic of short duration, but with high morbidity, with two

hundred cases being frequently reported each day.

Just as Pearl has observed a certain periodic recrudescence in the

United States, there has been described a similar periodicity in

England. The interval, however, is described as twelve weeks. The first

wave began in July and died down about the end of August, running a two

months course. Twelve weeks after the commencement of the first wave, at

the beginning of October, the second appeared. It had disappeared around

the middle of December. Again, twelve weeks from the beginning of the

second wave, that is, in January, the third appeared.

RECURRENCES IN WINTER OF 1919–1920.

We distinguish between the flareups following the autumn spread of 1918,

and which lasted until the spring of 1919, and yet another widely

distributed recurrence in the winter of 1920. We have called the former

recrudescences to distinguish them in point of time from the latter, but

do not imply thereby any difference in the character or origin of the

secondary waves. Between them all there occurred almost continuously

isolated or solitary cases of influenza which served to keep the fires

smouldering. In our own work in the city of Boston we found record of

scattered infrequent cases of clinical influenza of apparently low

infectivity in every month from March, 1919, until the recurrence in

January, 1920.

Moreover, in some localities there were during this interval small

epidemic outbreaks. Thus a report from Lisbon, Portugal, on June 1,

1919, states that the deaths from influenza in that city during the

preceding two weeks had been more than the total deaths from all causes

during the preceding four months. A report from London, October 30,

1919, states that during the preceding few weeks there had been in the

ninety-six great towns of England and Wales a slight but gradual

increase in the number of deaths attributed to the disease, and a

coincident rise in the number of notifications of acute primary and

acute influenzal pneumonia. The feeling at that time was that the

increase was associated with prevailing meteorological conditions, and

did not apparently signify more than the usual variation in respiratory

diseases which was to be expected at that season of the year. On

November 3, 1919, the disease was reported prevailing at Chile and it

was spreading throughout Bolivia. At the same time influenza had spread

over the entire country surrounding Buenos Ayres and had even reached

the neighboring city of Montevideo. In the latter part of November more

than 2,000 cases had been reported at Lemaies, about fifteen miles

northeast of Granada, Spain.

_The winter of 1920._—In the United States the death rates from

influenza and pneumonia in the large cities over the entire country were

below the usual average from May, 1919, until January 1, 1920. In the

week ending January 17th there was a sharp increase in the

influenza-pneumonia rate, which occurred simultaneously in Kansas City

and Chicago. In the latter city an excess over the average was not

reached until some days later, but the maximum mortality occurred in the

week ending January 31st, while in Kansas City the mortality did not

reach its height until one week later. New York, Washington, San

Francisco, Milwaukee and St. Paul soon followed with an increase in the

week ending January 24th, and in the subsequent two weeks many other

cities were added to the list. By February 14th thirty-two out of the

thirty-six large cities reporting had an increase in the death rate from

influenza and pneumonia as compared with the same period in 1917. The

maximum was reached at this time, and according to the Bureau of the

Census reports there were 7,059 deaths from influenza and pneumonia

during the week ending February 14th. In the next week the number of

deaths from these causes in the cities reporting had dropped to 5,088.

The February weekly average for 1917 was 1,489. In the week ending

February 14th, 267,643 cases of influenza were reported from forty-one

states; the excess annual death rate as compared with the average for

the period from 1910 to 1916 was 1,319.

In general the 1920 recurrence was decidedly milder than the autumn

outbreak of 1918. Certain cities, however, suffered severely,

particularly Detroit, Milwaukee, Kansas City, Minneapolis and St. Louis.

In these the death rate, while the epidemic lasted, was higher than that

of 1918. The duration of the epidemic was generally, however, shorter in

these cities. Columbus, Ohio, and Indianapolis suffered severely, but to

a less extent than the cities just mentioned. In Chicago the death rate

was not as high as in the fall of 1918, but it did rise far above the

point reached during the 1889–90 outbreak, and the influenza in the last

two weeks of January brought the total mortality for that month up to

5,149, the highest mortality in the history of the city with the

exception of October, 1918.

We have already discussed the recurrent epidemic as it was studied in

Detroit. The salient characteristics were a rapid and fairly symmetrical

evolution, a shorter duration than in 1918, a lower morbidity with a

higher mortality rate, and finally, a smaller total number of deaths

than in 1918.

The 1920 recurrence was widespread. It was not confined entirely to the

large cities. Semi-official reports from small towns and villages show

very much the same conditions as were observed in the larger cities. On

the whole, however, most communities, both large and small, suffered

less severely than in the first spread. The few exceptions to this were

distributed over the continent without uniformity.

The first among the large cities to show an increase in death rate from

the epidemic was Kansas City, in which the mortality first climbed in

the week ending January 17th. The following week there was an increased

rate in Chicago, New York and Milwaukee, and one week later, Boston,

Detroit, San Francisco and Philadelphia were affected. New Orleans was

one of the last large cities affected, not showing a definite increase

until the week ending February 14th. In contrast to the 1918 pandemic,

the influenza of 1920 showed no clearcut direction of spread, and was as

in the years following 1889 due, without doubt, to firing up of the

pandemic virus as it had been left scattered in many endemic foci

throughout the earth. There probably were instances of spread from the

larger centers to outlying districts, but there was no continuous spread

over large areas. The accompanying table shows clearly that the disease

this year commenced in the center of the continent, a fact which would

seem to disconnect it entirely from the late epidemics of 1919,

occurring in Europe:

_Annual death rates from all causes by week in certain large cities of

the United States from week ending January 3d to week ending February

21st._

═══════════════╤═══════════════════════════════════════════════════════

City. │ Week Ending

───────────────┼───────────────────────────┬───────────────────────────

„ │ January. │ February.

───────────────┼──────┬──────┬──────┬──────┼──────┬──────┬──────┬──────

„ │ 3│ 10│ 17│ 24│ 31│ 7│ 14│ 21

───────────────┼──────┼──────┼──────┼──────┼──────┼──────┼──────┼──────

Kansas City │ 16.3│ 15.8│ 19.3│ 32.7│ 39.5│ 61.5│ 44.0│ 29.1

Chicago │ 14.4│ 13.8│ 15.1│ 23.5│ 41.3│ 39.1│ 24.6│ 17.7

New York │ 14.0│ 15.3│ 14.6│ 19.5│ 28.0│ 35.0│ 35.1│ 24.8

Milwaukee │ 11.6│ 12.5│ 9.0│ 15.6│ 29.4│ 34.5│ 27.1│ 16.9

Detroit │ 13.7│ 13.0│ 14.2│ 15.5│ 33.9│ 60.9│ 42.9│ 21.6

Boston │ 16.8│ 16.9│ 14.1│ 16.8│ 20.3│ 27.1│ 33.7│ 32.1

San Francisco │ 16.5│ 15.4│ 19.6│ 19.2│ 22.9│ 25.2│ 31.8│ 28.8

Philadelphia │ 15.6│ 16.7│ 16.2│ 16.8│ 18.3│ 22.1│ 34.3│ 37.2

New Orleans │ 18.8│ 19.6│ 22.6│ 18.8│ 20.9│ 20.1│ 25.0│ 32.3

───────────────┴──────┴──────┴──────┴──────┴──────┴──────┴──────┴──────

The relative severity of the two epidemics in certain of the large

cities has been compared by H. F. Vaughan, and he has found as is seen

by the table that Kansas City and Detroit, two of the early cities

affected, had the highest mortality in 1920. Philadelphia in 1918 lost

nearly three times as many people as Detroit did in 1920. Detroit was

higher than Chicago in 1920, but lower in 1918.

_Per cent. of population killed by influenza._

═════════════════╤═════════════════╤═══════════════════════════════════

│ 1920. │ 1918–1919.

─────────────────┼─────────────────┼─────────────────┬─────────────────

│ First seven │ First seven │Twenty-one weeks.

│ weeks. │ weeks. │

─────────────────┼─────────────────┼─────────────────┼─────────────────

Detroit │ 0.20│ 0.17│ 0.28

Chicago │ 0.12│ 0.34│ 0.41

Kansas City │ 0.24│ 0.30│ 0.63

Philadelphia │ 0.10│ 0.76│ 0.82

New Orleans │ 0.05│ 0.55│ 0.77

─────────────────┴─────────────────┴─────────────────┴─────────────────

The following table taken from the “Final Influenza Bulletin,” by E. R.

Kelley, Commissioner of Health in Massachusetts, shows distinctly the

difference that must be always borne in mind between curves of influenza

incidence and death curves. In his table the mortality climbed first on

the week ending January 13th, as in the table above, but the increase in

influenza cases began at least one week earlier. It is characteristic of

influenza epidemics that the rise of mortality curves follows that of

morbidity by about a week:

_Influenza and pneumonia cases in Massachusetts in the first three

months of 1920._

═══════════════════════════╤═════════════════════╤═════════════════════

│ Influenza. │ Lobar pneumonia.

───────────────────────────┼──────────┬──────────┼──────────┬──────────

│ Cases. │ Deaths. │ Cases. │ Deaths.

───────────────────────────┼──────────┼──────────┼──────────┼──────────

Week ending January 3d │ 41│ 0│ 109│ 9

Week ending January 10th │ 46│ 2│ 142│ 50

Week ending January 17th │ 58│ 0│ 145│ 52

Week ending January 24th │ 489│ 4│ 201│ 56

Week ending January 31st │ 4,495│ 48│ 313│ 96

Week ending February 7th │ 9,627│ 272│ 382│ 212

Week ending February 14th │ 10,747│ 133│ 583│ 140

Week ending February 21st │ 5,601│ 181│ 510│ 147

Week ending February 28th │ 2,375│ 147│ 313│ 114

Week ending March 6th │ 1,144│ 54│ 206│ 34

Week ending March 13th │ 490│ 31│ 130│ 54

Week ending March 20th │ 254│ 20│ 105│ 44

Week ending March 27th │ 147│ 14│ 102│ 94

Week ending April 3d │ 218│ 6│ 97│ 12

───────────────────────────┴──────────┴──────────┴──────────┴──────────

In Massachusetts in the first three months of 1920 there were reported

35,633 cases of influenza and 3,158 of lobar pneumonia, with 906 deaths

from the former disease and 1102 from the latter. The case rate per

100,000 from influenza was 883.4; from lobar pneumonia, 78.3; the death

rate from influenza, 22.4; from lobar pneumonia, 27.4; and the fatality

per cent. from the former disease was 2.5, and from the latter, 34.9.

The epidemics in Detroit and Boston both showed a symmetrical evolution

and a single wave. This appears to have been the more frequent type of

recurrence in this country. There are examples of the secondary curve.

At the Great Lakes Naval Training Station the epidemic began during the

week ending January 17th. On January 12th there were fifty-one cases.

The peak was reached on the third day with the admission of 182 new

cases during twenty-four hours. Although the peak came early the decline

was less rapid and there were four secondary peaks, but the outbreak

terminated on the twenty-fourth day. On the whole the epidemic was less

severe than in 1918. Pneumonia was a complication in about ten per cent.

of the reported cases of influenza at the training station.

On the European continent there were similar recurrences in the first

three months of 1920. In the large towns of England the recorded deaths

from influenza made an increase in a steady curve from sixty-six in the

last week of January until the week ending March 27th. After that date

there was a gradual falling off. That the situation was in no way as

serious as it was at the same time in the American cities and in certain

other parts of Europe is indicated by an annotation in the Lancet of

March 6th. According to this annotation, the weekly totals of deaths

attributed to influenza in London and the 96 great towns had on the

whole tended to increase in the early part of 1920, but the absolute

increment was so small and the necessary uncertainty of classification

so great that no unfavorable inferences could be drawn from these

fluctuations alone. On the other hand, the notifications of cases of

pneumonia increased appreciably, too much to be set down as a mere

chance fluctuation. But notification for this disease had not been in

force long enough to enable accurate comparison. There were no

indications of epidemic influenza in any of the large factories situated

throughout the country. But on the other hand there was proof of the

existence of epidemic influenza of an infectious, but relatively

non-fatal type in certain large schools situated in the South and

Southwest of England.

The annotation concludes that influenza was epidemic in a few localized

English and Welsh communities, and that the type was similar to, but

less severe than that of 1918–19.

In the city of Paris between the 11th and 31st of January there was a

very definite increase in the death rate from inflammation of the

respiratory tract above the average for other years.

Renon and Mignot studied 141 cases of influenza (71 men and 70 women)

during January and February, 1920, at L’Hopital Necker. Fifteen of the

141 died. According to these observers the grip of 1920 attacked all

ages in contradistinction to the 1918 epidemic which affected especially

the young and vigorous. One-third of their group were over forty years

of age, while some were seventy and eighty years old. In spite of this

the disease remained relatively mild. Sixty-four were cases of simple

grip. Forty-three had associated bronchitis and pulmonary congestion and

edema. Twenty-seven had pneumonia. One had acute pulmonary edema. There

were cases of influenza in tuberculosis individuals. One developed an

acute serofibrinous pleurisy. One had purulent pleurisy, and one

meningitis.

In Copenhagen there occurred between the 18th and 24th of January, 1920,

1,204 cases of influenza with four deaths; in the following week, from

the 25th to the 31st of January, 7,445 cases with forty-two deaths; from

the 1st to the 7th of February, 11,038 cases with 207 deaths; from the

8th to the 14th of February, 8,308 cases and 327 deaths. This is to be

contrasted with the month of December, 1919, in which there were 1,845

cases of influenza in Denmark, of which only 272 were at Copenhagen. In

Christiania, Norway, during the week of January 25th to 31st, there

occurred eleven deaths from influenza, whereas during the preceding two

weeks there had not been a single death from this disease.

In December, 1919, there were reported in Switzerland only 511 cases of

influenza. During the month of January, 1920, this increased to 13,162,

and in February to 83,008, the estimated population being 4,000,000.

From February the disease decreased in prevalence. In Zurich, with a

population of 210,000, the epidemic resulted in 14,534 cases. The first

increase began around January 4th. The total number of cases for January

was 1,071. In February the records of the four weeks showed 2,721,

4,140, 3,341 and 1,899 cases, respectively; in March the decrease was

rapid, 886, 442 and 45 cases being reported in the first three weeks.

The total number of deaths, mostly due to pneumonia, was 229, a

mortality of 1.5 per cent.

During 1920 epidemics were also observed in Valencia, Santander and

other towns in Spain, and in Mexico City. In the latter city the number

of deaths was reported as 1,649, as contrasted with 3,000 in 1918.

INCUBATION PERIOD.

An accurate determination of the period of incubation in influenza

presents great difficulties. The large number of cases with the

consequent multiple opportunities for infection in the case of every

individual add to the difficulty. Under any circumstances the period is

very short. Parkes, many years before the 1889 epidemic, believed that

an incubative period sometimes exists; that it was sometimes very short

and sometimes of many days duration.

“In the Transactions of the College of Physicians it is stated that in

the epidemic of 1782, seventeen persons came to London to an hotel, and

on the following day three were attacked with influenza. Haygarth says

that a gentleman came to Chester from London, on the 24th of May, 1782,

ill of influenza; a lady, into whose family he came, was seized on the

26th, and was the first case in the town. Haygarth states, evidently

with the view to point out the possibility of a direct contagion, that

the gentleman was engaged to be, and was afterwards, married to this

lady. In this case the longest possible incubative period was two days.

In 1782 a family landed at Harwich, from Portugal, and came to London

directly; the day after their arrival the lady, two servants and two

children were all seized. Two men-of-war arrived at Gravesend from the

West Indies; three Custom-house officers went on board; a few hours

afterwards the crews of both vessels were attacked. Some other cases are

on record where the incubative period, if it existed, could not have

been more than a single day. On the other hand, some cases are on record

in which the incubative period must have been two or three weeks.”

Leichtenstern believed that the usual incubation period is from one to

three days although some cases have been reported in which it is without

doubt no longer than twelve hours. Parsons in reporting for England also

gives the incubation period as from one to three days as a rule.

It is reported in France in 1918 that in one institution thirty-one

cases out of thirty-three individuals occurred within three days, all of

them infected by one nurse.

MacDonald and Lyth report in the British Medical Journal for November,

1918, an interesting observation concerning the incubation period in

influenza. These two individuals were traveling from London to York in

the same compartment with an individual who was just convalescing from

influenza. Exactly forty-one hours after being on the train with this

individual, they both came down with the disease. One suffered lightly

while the other was severely ill. The wife and two children of the

latter contracted the disease in turn, and with them also the first

symptoms appeared suddenly after a delay of about forty-eight hours.

Stanley, in studying the epidemics of influenza in San Quentin Prison,

found that as a rule there was an increase in incidence following the

Sunday picture shows. This usually occurred on Tuesdays and Wednesdays,

giving an apparent incubation period of from thirty-six to sixty hours.

He tabulated the records of twenty-nine individuals who had presumably

become exposed at the show and found that the incubation period averaged

about forty-eight hours.

The majority of observers give the incubation period as from twenty-four

hours to four or five days, most often two or three days.

PREDISPOSING CAUSES.

Not every individual acquires influenza. There are those who assume that

the disease is so wide spread that every individual in each community

attacked has been actually exposed to the disease. In that case there

must be a certain amount of natural immunity which protects around sixty

to eighty per cent. of most populations from the disease. The other

extreme would be that every exposed individual falls victim to the

disease and that only twenty to thirty or forty per cent. are actually

exposed. The true state probably lies between these two extremes.

Nevertheless it is a fact that some individuals naturally insusceptible

to the disease fall victim as a result of the action of some extraneous

force, something which lowers their resistance. Raw recruits in the army

camps in the fall of 1918 contracted the disease in much greater

proportion than did the hardened soldiers. Fatigue, intercurrent

illness, environmental changes and exposure to inclement weather may all

predispose to infection in the individual. Greenwood found that the

compulsory rationing of food in England during the war was probably not

a predisposing cause of infection. The incidence of the disease in the

South Africa Union where food was abundant was even higher than that for

the British Isles. Hamer calls attention to the fact that the ages of

highest incidence during the pandemic were those ages in which the diet

was perhaps more restricted than in other ages. This, however, is but

one factor and cannot be accepted as conclusive.

It had been suggested that in the army camps in the United States

typhoid vaccination during the epidemic predisposed to the disease. The

similarity of the symptoms in vaccine reaction and in influenza may have

suggested this. V. C. Vaughan has investigated this possibility and

finds that those organizations in which anti-typhoid vaccine was

discontinued for a time after the appearance of the influenza suffered

quite as severely as those which submitted to vaccination.

Other predisposing causes, such as the incidence of crowding in a

household and the sanitary surroundings of the individual will be

discussed later.

PERIODICITY.

The phenomenon of occurrence of epidemic influenza in many countries,

even on different continents almost simultaneously and often without any

clearcut progressive spread from one of these countries to another

raises the question of periodicity in influenza. Is this simultaneous

occurrence due to some mechanism in the life cycle of the influenza

virus whereby it regularly acquires increased invasiveness, no matter

what its geographical distribution, or is it merely a feature of the

meteorologic conditions that makes the epidemic appear to be

simultaneous in widely scattered communities?

Influenza characteristically returns. An influenza period usually

comprises from three to five years, with one or two very mild epidemics

at the beginning which may frequently be overlooked, then of wide

pandemic spread, to be followed by endemic recurrences for as long as

two or three years. During these influenza periods the intervals between

waves are frequently so nearly equal or multiples of each other as to

force the question of a periodic law. Not only thus, but even on a

larger scale does the disease appear with a certain uniform regularity.

The great epidemics are separated frequently by intervals approximating

decades. Stallybrass calls attention to the epidemic years in England,

which are 1789–90, 1802–03, 1830–32, 1840–41, 1848–49 and 1851, 1854,

1869–70, 1879, 1890–91, 1898, and 1918–19. With the exception of 1854

all of these dates are around the end of a decennium.

Yet, again, in the successive waves of an individual epidemic, as has

been pointed out by Pearl, there is very roughly some periodicity.

Are these admittedly obvious phenomena fundamental features of the life

cycle of the influenza virus, or are they incidental, due to extrinsic

causes, changes in the pabulum, in the host as an individual, or in the

host as a community, or changes in climatic conditions? Is it a basic

feature upon which we must build our conception of the epidemiology of

epidemic influenza, or is it more a feature of chance? The evidence to

date is conflicting and incomplete. The answer lies in the future.

Periodicity in the acute infections is not a new subject. It has been

discussed in various other diseases, particularly in measles. For many

years epidemiologists in many parts of the world have reported the

observation of a periodicity in epidemics of measles. It is generally

regarded as an established fact that each locality suffers from epidemic

waves of this disease and that the period is somewhere about two years.

In certain relatively small localities in England where registration

statistics have been kept for many years the Health Officers count on an

epidemic every two years. In some places the epidemic is expected to

fall during the even years, while in others it occurs in the odd years.

Brownlee has been one of the foremost investigators in the periodicity

of influenza, but since his communication on that subject was very

brief, we take occasion to quote first from his article on the

periodicity of measles, thereby gaining a more comprehensive knowledge

of his theory, and at the same time becoming able to compare the

periodicity in the two diseases.

“The common explanation of the periodicity of epidemics of children’s

diseases is that the susceptible children take the disease in sufficient

numbers to limit the further spread. The epidemic thus dies out to recur

when a further sufficient number of susceptible children have

accumulated. This is quite a feasible theory and certainly explains the

periodicity of epidemics. The forms of epidemic curve which arise on

this hypothesis are not unlike those actually found, the differences

being no more than might be expected between a mathematical form based

on a hypothesis and the natural conditions to which the hypothesis is

only an approximation. This explanation, however, must fail if epidemics

of different periods can be shown to exist in the same town at the same

time, and I think this has been shown. In London, which on account of

its size might be assumed deserving of special treatment, the existence

of periods of different length have been demonstrated. In Edinburgh,

Glasgow, and Birmingham also it has been shown that epidemics with

periods in the neighborhood of ninety-eight weeks and one hundred and

ten weeks intermix. The same epidemicity even applies to districts in

London. In the West end of London we have almost a replica of what

occurs in Glasgow, Birmingham and Edinburgh. The main period there is 97

weeks, the secondary period 109.5 weeks. In the South of London one

period is that of 97 weeks, but almost equally prominent is that of 87

weeks. The whole evidence, therefore, seems to point to some condition

in the organism which produces the disease as the potent cause of the

difference rather than to the number of susceptible children. Compare

the _Paramoecium_ which under natural conditions divides asexually for

several hundred times and then dies out unless conjugation takes place.

The resting stage following conjugation persists for some time.

“There is, however, one point of great importance which must be

considered. If an epidemic begin in a definite locality and spread from

that locality, and if there is no loss of infectivity on the part of the

organism, it is demonstrable that a similar proportion of the population

should be attacked in each zone as the epidemic spreads outward. On the

other hand, if the organism lose the power of infecting with the lapse

of time, in each additional zone invaded the proportion of susceptible

persons infected should become smaller and smaller. Of course this might

not be true for any one epidemic, as in many parts of the area invaded

the population might be more or less susceptible because of recent

attack of the disease, but when an average of twenty outbreaks has been

taken this effect should be eliminated, the number of times the invading

organism comes into contact with an insusceptible population being

balanced by the number of times which it meets one more susceptible than

the average. The method of spread of epidemics on the average should

thus give some indication regarding the laws which determine the course

of the phenomenon. Now with regard to London, the clearest facts refer

to the 87-weeks, the 97-weeks and the 109.5-weeks period. The 97-weeks

period starts at the same time all over the city and there is no

evidence of any special center. The infection seems generalized. With

regard to the 87-weeks epidemic, however, the case is different. This

seems to start in St. Saviour’s Parish and to spread thence to

Camberwell, Lambeth, etc. In this epidemic the rate of spread can be

definitely measured. The maximum occurs later and later as the distance

from the center is increased and the percentage of children infected is

also easily observed to fall as the time increases. With regard to the

109.5 weeks’ period epidemic the facts are similar though not quite so

definite. This seems to show that for at least two strains of organisms

the epidemic ceases because the organism has lost its power of

infecting. It may be inferred that an epidemic ceases because the

organism varies in its potency to cause infection. A cycle of epidemics

now coinciding and now differing in their maxima can thus be explained.

Some kind of life cycle exists in the infecting organism. In this life

cycle high powers of infecting are attained probably after a resting

state: a period of activity follows and gives place to a period of rest;

the average length of the cycle is determined by the strain of the

organism.”

There are certain drawbacks to Brownlee’s work and conclusions. We quote

from V. C. Vaughan, who has discussed Brownlee’s work, not only because

of his good summary of the difficulties and disadvantages of the method,

but particularly because the same disadvantages and possibility of

inaccurate conclusions hold in the case of influenza.

“There is no reason for supposing that the virus of measles is

controlled in any way by our calendar. In order to get anywhere in

determining any law of periodicity in epidemics we must know the

morbidity and mortality of the disease by days, or at least by weeks. In

different parts of a large city there may be, and undoubtedly are,

epidemic waves of measles on the flow or on the ebb at the same time.

The best work that has been done along this line is that of Brownlee,

who has figured out epidemic waves of measles, based on the weekly

numbers of deaths in London between 1840 and 1912.

“The figures presented by Brownlee are of great value, and his theory is

fascinating and has much in its favor, not only in a study of epidemics

of measles, but of the other infectious diseases of infancy and

childhood, especially scarlet fever, whooping cough, and chicken-pox. In

order to solve the problem of periodicity in measles we must have more

exact information than we now possess. Brownlee’s figures pertain to

deaths only. There are, so far as we know, nowhere in the world

satisfactory statistics concerning morbidity in this disease. Deaths

from measles are so largely determined by the care bestowed upon the

sick and upon the extent to which secondary infection is prevented that

we are inclined to hesitate about the acceptance of a death rate or

number of deaths from this disease as an index to the virulence of the

organism causing the disease; in other words, we are not convinced that

the death rate in a given outbreak of this disease is a measure of the

virulence of the organism causing it. This involves the question whether

measles _per se_ is a disease of wide variation in malignancy or are the

widely different death rates observed in different epidemics due to

secondary infections. The streptococcus, a common invader of the body

during the progress of a measles infection, is known to possess a most

variable degree of malignancy. We are inclined to the opinion that if

all cases of measles could be recognized before secondary infection

occurs and could be cared for ideally the death rate from this disease

in different epidemics would be much more uniform than is now shown and

would be low. The greatest danger to life in an attack of measles lies

in the fact that the virus lowers the resistance of the body cells and

opens gateways to more deadly organisms, such as the streptococcus. We

believe that there are demonstrated facts which support these ideas.

Quite uniformly in measles there is a well marked leukopenia. As we now

interpret it, this means a decrease in the number of the forces that

naturally protect the body against the invasion of foreign cells. Again

as we interpret it, the failure of the body cells to respond to the

tuberculin test during a course of measles or soon thereafter is

evidence that the resistance of the body is lowered. If our

interpretation on these points be correct we fail to see how deaths from

measles can be properly employed as a standard in the measurement of the

virulence of the organism of the disease.”

Recognizing then the obvious disadvantages of the method, we will turn

to the work done on periodicity in influenza. We should call attention

at this point to the fact that the establishment of periodicity would

carry with it the assumption that the third of our three hypotheses

concerning the origin of influenza is the correct one. For example, the

July and autumn epidemic in England, as well as all occurring subsequent

to them, would be due to a virus or several viruses which have been

endemic in England since 1889, in fact since man has been in England,

and the epidemics and their recurrences would be due to increase in the

virulence of this local virus. The virus is distributed over the earth

and may become virulent periodically in many countries at the same time,

or if the periodicity is different on two continents the epidemics would

occur at different times.

Periodicity is not a new hypothesis. Hirsch denied any periodicity

distinct enough to be revealed by the comparatively crude statistical

methods of his time. Periodicity if present can only be revealed by

detailed and complicated mathematical procedures. Brownlee has

investigated the weekly number of deaths from influenza in London

between 1889 and 1896, and also up to the present time. He has compared

these with the weekly number of deaths from bronchitis and pneumonia in

London, the records of which have been available since 1870. By the

method of the periodogram he showed that there was a regular periodicity

of 33 weeks in deaths from influenza between the years 1889 and 1896,

but that in later years there was some considerable aberration. He

concluded that for some reason influenza periods tend to recur at

33-week intervals after the primary epidemic, and that the favorable

season for its recurrence is from January to the end of May. Should the

33d week fall in other than these winter months the epidemic may be mild

or even missed, appearing after another 33-week interval. Epidemic

influenza does not assume a form which causes any large number of deaths

until a bronchitic or pneumonic constitution has been established. The

fatal form is usually a disease of the winter or spring. He also found

that in the absence of influenza, bronchitis and pneumonia did not show

a 33-week periodicity, but when associated with influenza these

conditions also became periodic (33 weeks), and he assumes that this

change is definitely associated with the appearance of influenza.

Between 1876 and 1890 there was no tendency to the 33-week periodicity

with regard to bronchitis and pneumonia, but it was very marked between

1889 and 1896. During this epidemic period the deaths from pneumonia

precede those from influenza by one week and those of bronchitis precede

those of influenza by two weeks. The number of deaths from bronchitis

and pneumonia ascertained by this method of grouping is fully twice the

number obtained from influenza alone.

He believes that in these years, influenza appeared, on its epidemic

onset, first with bronchitic symptoms, later with pneumonic symptoms,

and lastly with those symptoms more definitely associated with influenza

proper. When the several sets of deaths are added together in 33-week

periods a very typical epidemic makes its appearance.

Brownlee finds that in the monthly statistics of Glasgow, Aberdeen,

Massachusetts, etc., there has been nothing differing essentially from

this phenomenon found in London.

Between 1876 and 1889 the annual curve for bronchitis and pneumonia

shows two maxima, one at the end of January and the second in the middle

of March. From March the decline in deaths from bronchitis is very

rapid. The disease re-appears around the beginning of October. During

the period 1889–96 the maximum number of deaths from bronchitis occurred

in the second week of January and the last week of February. Both of

these maxima are a fortnight before the maxima of the epidemics of

influenza. This suggests that the advent of influenza has brought a

change in the seasonal prevalence of bronchitis and supports the view

that the earlier portion of the influenza epidemic is associated with

bronchitic symptoms. The same phenomenon holds for pneumonia.

Brownlee was able to predict correctly the date of the recent 1920

epidemic. He did not attempt, however, to explain the short interval

between the summer and autumn, 1918, epidemics in England. He speaks of

the second as “aberrant.” In other words, it does not fall within his

classification. October is not a high respiratory disease month. The

epidemic should have been mild.

Stallybrass has confirmed Brownlee’s 33-week periodicity and suggests an

explanation for the “aberrant” October epidemic. Using periodograms with

a 33-week basis, and plotting deaths from influenza and respiratory

diseases from January, 1890, through January, 1920, he finds that the

most definite 33-week periodicity is shown during the years 1890–99.

During this period there is one maximum, when all 33-week periods are

superimposed, which occurs at the seventh week of the cycle. Beginning

about 1899 a new maximum appears in the nineteenth week of the cycle,

which continues to recur until the culminating point is reached in the

week ending October 26, 1918. An additional 66 weeks carries the date

forward to the first week in February, 1920. The maximum at the seventh

week of the periodogram during the years 1899–1913 is greatly diminished

from that in 1890–98. The periodogram for 1914–1919 shows clearly both

maxima, that in the seventh and that in the nineteenth weeks.

We quote Stallybrass in some detail (see Chart XII):

“Dr. John Brownlee pointed out that from July 13th to March 1st (the

maxima of the summer wave of 1918 and of the spring wave of 1919) is 33

weeks, but that the wave having its crest in this country on November 2,

1918, does not fall into the sequence, leaving one to infer that there

were two strains of the influenzal virus in operation.

“I supplement his investigation by the weekly deaths occurring in

Liverpool during the period 1890–1919 that were ascribed to influenza

and to all respiratory diseases. Prior to 1890 there were no deaths

attributed to influenza for a number of years.

“Closely corresponding with Brownlee’s observations on London by far the

most definite periodicity is shown during the years 1890–1899, during

which period there is one well marked maximumly at the seventh week of

the cycle. During the period 1899–1913 a new maximum in the nineteenth

week of the cycle comes into play and continues to recur until the

culminating point is reached in the week ending October 26, 1918, a week

earlier than in most English towns (Wave III); a further 66 weeks

carries one forward to the first week in February of this year, as

Brownlee pointed out, and the outbreaks that are being reported in

Japan, Paris, Chicago, New York, etc., would show that this strain has

punctually reappeared.

“There is also evidence in the table of a small maximum at the

twenty-seventh week of the cycle in the earlier sub-period, and at the

twenty-ninth week in the later sub-period; slight movements of the

maxima forwards or backwards in the cycle over a number of years may,

perhaps, indicate a periodicity slightly greater or less than 33 weeks.

The twenty-ninth week of the cycle fell on the weeks ending May 18,

1918, and January 10, 1919. An examination of the figures in Dr. Hope’s

annual report for Liverpool for 1918 shows that there was a definite

wave of influenza reaching its crest on May 18th (Wave I), and there is

also a definite rise in the deaths from influenza, respiratory diseases,

and from all causes, making a small peak in the week ending January 3,

1919, but it is hidden by the enormous waves of October and March, so

that it only appears as an irregularity in the curve; but it was noted

at the time that influenza had not declined in Liverpool in January in

the way that it had in practically all other English towns. These two

waves do not appear to have played a large part in this country, but the

outbreaks in the Grand Fleet in May, 1918, and also in Spain, Glasgow,

etc., may, perhaps, be attributed to it. In the United States in

January, 1919, it would appear to have played a much larger part. In a

large number of American cities two waves are experienced, the first

being the October wave; the crest of the second wave sometimes fell in

March, as did one of the crests in this country, but in a number of

instances, _e.g._, Cambridge, Washington, San Francisco, New Orleans,

etc., it fell in January, or to be exact, in the thirty-first and

thirty-second weeks of the cycle. The close relationship of Liverpool

and Glasgow with the United States through the incoming stream of

American troops may perhaps account for the presence of this May wave in

these two towns, and not the rest of England.

CHART XII.

[Illustration:

Periodogram based on the weekly influenza deaths in Liverpool between

1890 and 1919. The curves are based on a thirty-three week

periodicity. (_Stallybrass._)

]

“The third maximum in the fourth week of the cycle is represented during

the late outbreak by the waves culminating in Liverpool, and also the

greater number of English towns on the weeks ending July 13 (Wave II)

and March 1 (Wave IV). This is a 33-week interval. This wave recurred at

an interval of 32–34 weeks in a large number of English towns.

“Of 65 towns which experienced all three waves 47 (72 per cent.) had

their maxima in the summer and spring epidemics within an interval of

32–34 weeks; but comparing the week in which any given town had its

epidemic peak in the summer and autumn, and autumn and spring epidemics

only 27 (41 per cent.) and 31 (47 per cent.) respectively fell within

the limit of a week on either side. The time relationships of the maxima

in summer and spring were much closer to each other than they were to

the autumn maxima.

“If it should prove correct that there were three strains of the

influenzal virus, each with a periodicity of about 33 weeks, and that

simultaneously all three strains became enhanced in both virulence and

infectivity, then we are faced with a phenomenon without an exact

parallel, although the behavior of the meningococcal viruses during the

war presents some points of similarity. So far the weight of evidence

leans to such an exaltation of a widespread endemic strain or strains

rather than to dissemination from any particular focus in the world. In

any case doubtless a good deal of spread of infection took place.”

Spear takes exception to the work of Brownlee and Stallybrass, and

points out that the periodogram is not applicable to the study of

recurrent epidemics unless the recurring waves are of approximately

uniform “amplitude.” In that case nothing could be less appropriate for

this study than the influenza waves which vary from very small to

extremely high, as in 1918.

Spear describes two simple tests which he applied to demonstrate the

existence or non-existence of periodicity.

First he divided each of the last thirty years into 13 four-weekly

periods, and tabulated the frequency with which the observed week of

maximum mortality falls into one or other of the 13 groups. He

discovered that the climax of an influenza prevalence falls more

frequently in the second and third four-weekly period than in

others—_i.e._, the months of February and March. Had there been a

33-week periodicity there would have been an equal number of these

climaxes in each of the 13 divisions of the year.

Brownlee, according to Spear, was correct in his prediction that

influenza would occur in February, 1920, for the reason that January or

February is the most likely time for an influenza prevalence in any

year.

Spear’s second test of periodicity consisted in plotting the

interepidemic periods according to the number of weeks intervening. Were

there a 33-week periodicity, he says, that nearly all interepidemic

periods should fall in this group. As a matter of fact, more than twice

as many periods fall in the 42–58 weeks interval than in any other

interval. Fifteen fall within this period, six in the period 59–75

weeks, five in the period 8–24 weeks, and only four in the period 25–41

weeks. There was one in the period 76–92 and one 110 plus. Finally in

the thirty years 1890–1919 there were thirty-two climaxes or peaks in

the “influenza” mortality.

Spear concludes that if there is any periodicity it is around fifty

weeks, or a year.

The fallacy in the work of Stallybrass and of Brownlee, according to

him, is that the mortality in the third week of 1892, the twentieth week

of 1891, and the tenth week of 1895, and in the big epidemic of 1918 so

overshadowed all the other peaks that the smaller ones became lost in

these larger waves.

Brownlee does not claim a 33-week periodicity during interepidemic

periods. This part of Spear’s criticism is not valid.

Vaughan’s objections to the conclusions on measles hold equally well

with regard to influenza. Finally, we must remember that in parts, at

least, of the work of Brownlee and Stallybrass, they are not studying

chiefly influenza deaths, but deaths reported as due to bronchitis and

pneumonia.

After a study of the pros and cons of the question of periodicity the

author submits by way of summary his conclusions:

1. Influenza does tend to recur at intervals. It has not been proven

that these intervals are always of equal length.

2. At the present the opinions concerning the periods are divergent. We

have the 33-week periodicity of Brownlee and Stallybrass, the one-year

period of Spear, the seven-week intervals suggested by Pearl, and the

apparent twelve-week recurrences in England in 1918 and 1919.

3. It is to be noted that particularly in the work of Stallybrass, in

order to prove his periodicity, he finds it necessary at times to quote

epidemics occurring, not in England, but in fairly remote parts of the

world, as in the United States and Japan. We have shown that in the

interval between 1918 and 1920 an epidemic could be discovered somewhere

on the earth in many months, perhaps even in every month during this

interval. It is to be regretted that following the criticism by Spear

there has been no further report, so far as we know, by either Brownlee

or Stallybrass.

4. It is quite possible, even probable, that influenza is endemic in

mild form throughout the interpandemic years in England, as well as in

many, or all other countries, but it is equally possible or probable

that the particular virus which gave rise to the pandemic was not one

which simultaneously increased in virulence in all countries, but was

one which had its origin in one comparatively well localized focus.

5. Our own theory does not explain the autumn recurrence in 1918 in

England, following that of May, June and July. We have traced the

original spread to England and have left it at that point. We have again

taken it up in the autumn when it became severe, and was returned to the

United States. The interval of quiescence in England and elsewhere may

need further explanation. Two alternative hypotheses suggest themselves:

First, that the autumn recrudescence is entirely comparable to later

ones, and is but a manifestation of the characteristic feature of

recurrence in influenza. Had the autumn epidemic been mild and had it

not so overshadowed all others, we would have classified it with those

of early 1919 as being merely recrudescences of the summer spread.

Evidence, particularly in favor of this, is the report of Greenwood

previously mentioned which shows that in England the autumn spread

partook of the nature of a secondary type of epidemic, as compared with

the primary type in the summer.

The second hypothesis is that the occurrence in the summer in England of

an epidemic due to a virus imported from America or France or China,

with its consequent increase in morbidity, so enhanced the virulence of

a local endemic British virus that the latter produced the autumn

epidemic. We see no necessity for complicating the question by the

assumption of this second hypothesis.

6. Whether or not there is a regular periodicity of a definite number of

weeks in the case of influenza, the fact remains beyond cavil that one

of the dominant characteristics of epidemic influenza is its recurrence

at intervals. The evidence is ample that the disease is distributed

throughout many countries in interepidemic times and that intermittent

outbreaks of large or small extent occur.

The most striking phenomenon is the fact that in March of 1918 influenza

is reported as having been present in China, in the United States and in

France. It is scarcely possible that the disease in its epidemic form

could have been carried from any one of these three points to the other

two in the remarkably short time between the onset of the three

outbreaks. We are faced with the phenomenon of a simultaneous exaltation

of the influenza virus in three remotely separated countries of the

world. This one fact more than any other indicates that the fluctuation

in virulence is dependent upon some factor intrinsic in the virus itself

and not upon environmental factors.

It is impossible at the present time to decide whether the world

epidemic spread simultaneously from these three foci or whether in only

one of these three the virus became so exalted as to produce pandemic

prevalence. All we can say is that we are able to trace consecutively

the spread of the influenza from the focus in the United States

throughout the world. The information upon which we base our findings is

not statistical, and as we have previously said this latter type of

demographic study should be brought into use to either corroborate or

disprove our findings.

VIRULENCE ENHANCEMENT.

Before attempting to study the mechanism of origin of the 1918 pandemic

it is highly essential that we devote some attention to a consideration

of the processes by which the germs of infection, particularly the virus

of influenza, may develop an increase in virulence. Followers of the

theory of periodicity would base virulence enhancement primarily on some

intrinsic property of the virus itself. We know from past experience and

particularly from animal experiments that this is not the only manner by

which virulence may be increased.

As far as we know there is no new infectious disease. Individuals who

delve into the history of the past inform us of more and more diseases

which were well known to the ancients. We are frequently amazed at the

variety of diseases now known to be infectious that were very correctly

described by the Hippocratic writers. The infectious diseases are with

us always and live nearly always in man, the host. There are few

exceptions. Very few of the contagious viruses can live for any long

period of time outside of the human body. A few, such as the plague

bacillus, may live on other hosts, but these are the exception. The

remarkable feature is that for long periods of time the virus exists in

the host in a quiescent state and only at intervals does it become

highly invasive and thereby produces epidemics of greater or less

extent. Under what conditions does the metamorphosis of the

microorganisms occur?

Topley, in the Goulstonian lectures, discusses this subject. He says:

“The first difficulty with which we were faced in forming any theory of

the spread of bacterial infection, which should conform to the known

facts of epidemiology, was to find some explanation of the perpetuation

of the virus during interepidemic periods. The bacteriologic data which

have accumulated, especially during the last twenty years, have shown

that the causative agents of specific diseases are to be found in

apparently normal persons who give no history of having been in contact

with the disease in question, as well as in contact with actual cases of

the disease. Moreover, the organisms in question have been shown, in

certain cases, to persist for long periods of time in or upon the

tissues of their hosts, and we must always remember that the difficulty

of bacteriologic technic is likely to lead to a serious under-estimate.

Clinical and epidemiologic investigations have yielded confirmatory

evidence, and we are thus left with a conception of the virus of a given

disease being distributed fairly widely throughout the world as an

apparently harmless parasite on the human host, but taking on during

epidemic periods a new and sinister role, only to relapse again into

comparative quiescence as the epidemic subsides.”

He explains the rise of the epidemic wave as follows: “There are at

least three possible explanations—an increase in the power of the

parasite to produce disease, a decrease in the resistance of the host,

and some attraction in the surrounding circumstances which favor the

transference of parasites from case to case without any alteration of

the pathogenicity of the one or in the resistance of the other. The

third of these hypotheses may, I think, be disregarded. That alterations

in environment may be the determining cause in initiating an outbreak of

bacterial disease is probable enough; but they will almost certainly act

through the variations which they bring about in the other two factors.

The whole of bacteriologic knowledge is clearly against the occurrence

of a considerable epidemic in which the pathogenicity of the parasite

and the resistance of the host remain constant. Again, while we may well

believe a lowered resistance of a certain number of the host-species to

be an important factor in the initiation of the process, yet we cannot

believe that it is the whole story. The widespread ravages of many

epidemics would seem altogether to preclude such an explanation. We seem

forced therefore to the conclusion that an increase in the pathogenicity

of the specific parasite is an essential factor in the rise of

epidemics, excluding from this category small sporadic outbreaks which

may be due to the introduction of a fully virulent parasite by a healthy

carrier in some other way.”

If a disease like measles is quiescent in a given community it must be

that in that locality the hosts and parasites are existing in a state of

biological equilibrium. They are living in a state somewhat akin to

symbiosis. Such a condition could be attained either by a diminution of

the invasive powers of the parasite, or by an increase in resistance of

the host. Probably both elements are active; as the relative immunity of

the host rises the infectivity or virulence of the parasite must rise to

an equal extent to maintain the equilibrium. If this were true we would

find that in those localities in which the disease is endemic and where

the population is relatively resistant there is a normally more virulent

virus in existence. A stranger coming into such a community would, in

view of his lower resistance to the virus, be more susceptible of

becoming actively infected. There would, however, be little danger of an

epidemic spread because the number of susceptibles would, roughly, be

limited to the number of strangers in the community. If, however, an

individual from the community carrying the more virulent virus were to

travel to another community where the greater proportion of the

population was relatively less immune the field would be fertile for the

beginning of an epidemic. Furthermore, there is the possibility of an

outbreak in the first community if there should occur gross changes in

its constitution; another infectious disease, a redistribution of the

population with greater crowding, anything to change the balance between

host and parasite.

Theobald Smith has described this possibility very clearly:

“During the elimination of the more virulent races of microorganisms,

there goes on as well a gradual weeding out of the most susceptible

hosts. In a state of nature in which medical science plays no part,

there must occur a slight rise in the resistance of individuals, due to

selection and perhaps acquired immunity, which meets the decline of

virulence on the part of microbes until a certain norm or equilibrium

between the two has been established. The equilibrium is different for

every different species of microorganism, and is disturbed by any

changes affecting the condition of the host or the means of transmission

of the parasite. One result of the operation of this law is the low

mortality of endemic as compared with epidemic diseases. Certain animal

diseases while confined to the enzootic territory, cause only

occasional, sporadic disease, but as soon as they are carried beyond

this territory epizootics of high mortality may result. Climate in some

cases enters as an important factor, but the most important, perhaps, is

the slight elevation in virulence brought about by a more highly

resistant host. The most susceptible animals are weeded out and the rest

strengthened by non-fatal attacks. The virulence of the microbe rises

slightly to maintain the equilibrium. In passing into a hitherto

unmolested territory, the disease rises to the level of an epizootic

until an equilibrium has been established.

“The same is true of human diseases, among which smallpox is a

conspicuous example. The great pandemics of influenza, which seem to

travel from east to west every one or two decades, soon give away to

sporadic cases, and the careful work of many bacteriologists would

indicate that the influenza bacilli found at present have fallen to the

level of secondary invaders, and are parasites of the respiratory tract

in many affections.”

Smith describes his hypothesis that the tendency of microbes in

perfecting the parasitic habit is to act solely on the defensive. The

aim of microorganisms, if we may speak of such, is to become able to

live unharmed on the host. If they kill the host they have lost their

home. The biologic tendency would be in this case for diseases which

were once acute to become more and more chronic and indolent.

The extremely virulent parasite, which kills its host, will die with the

host unless it has effected a means of exit before its death and escapes

into a new host. For this reason Pasteur failed to exterminate the

rabbits of Australia. He believed that with races of the bacillus of

rabbit septicemia, which were very virulent, and which destroyed life

very quickly, all that would be necessary was to start the disease among

the rabbits of Australia and that it would tend to spread and would kill

off all of the rabbits. But the parasite killed the animals before it

had perfected for itself a means of escape from the body and thereupon

died.

“From the biologic standpoint which I have endeavored to present, we may

conceive of all highly pathogenic bacteria as incompletely adapted

parasites, or parasites which have escaped from their customary

environment into another in which they are struggling to adapt

themselves, and to establish some equilibrium between themselves and

their host. The less complete the adaptation, the more virulent the

disease produced. The final outcome is a harmless parasitism or some

well-established disease of little or no fatality, unless other

parasites complicate the invasion. The logical inference to be drawn

from the theory of a slowly progressive parasitism would be that in the

long run mortality from infectious diseases would be greatly reduced

through the operation of natural causes. But morbidity would not be

diminished, possibly greatly increased by the wider and wider diffusion

of these parasites, or potential disease producers. The few still highly

mortal plagues would eventually settle down to sporadic infections or

else disappear wholly because of adverse conditions to which they cannot

adapt themselves.

“In this mutual adaptation of microorganism to host, there is, however,

nothing to hinder a rise in virulence in place of the gradual decline if

proper conditions exist. In fact, it is not very difficult to furnish

adequate explanations for the recrudescence and activities of many

diseases today, though the natural tendencies are toward a decline in

virulence. In the more or less rapid changes in our environment due to

industrial and social movements the natural equilibrium between host and

parasite established for a given climate, locality, and race or

nationality is often seriously disturbed and epidemics of hitherto

sporadic diseases result.

“These illustrations indicate that so-called natural law does not stand

in the way of our having highly virulent types of disease, if we are

ignorant enough to cultivate them. The microorganism is sufficiently

plastic to shape itself for an upward as well as a downward movement.

Among the most formidable of the obstacles toward a steady decline of

mortality is the continual movement of individuals and masses from one

part of the world to another, whereby the partly adapted parasites

become planted as it were into new soil and the original equilibrium

destroyed. These various races of disease germs become widely

disseminated by so-called germ carriers, and epidemics here and there

light up their unseen paths.”

An example of increasing virulence from changing environmental

conditions, is the experience in the United States Army camps in 1917

and 1918 with the streptococcus. This microorganism, which at first was

but a secondary invader, particularly to measles, became so exalted in

virulence that it soon became the cause of primary disease. This is

likewise true of the various secondary invaders of the influenza

epidemics. They become so highly virulent that they dominate the picture

in the later stages. The organisms included in this group are

particularly the streptococcus, the various pneumococci, and the

meningococcus. Probably the tubercle bacillus should be added to this

list.

It requires a certain amount of time for such organisms to attain

increased virulence. The earliest cases in any epidemic are

comparatively very mild. Thus Major Billings, epidemiologist at Camp

Custer, says that for the first five days of the autumn influenza

epidemic in that camp the cases admitted to the hospital were very mild

in character and were recorded as simple bronchitis and pharyngitis, of

no great severity, the majority soon recovering. Five days after the

first case was admitted, however, the entire symptom complex seemed to

change, and the cases admitted to the hospital from then on were a very

different and much more severe type. Major Billings, after going over

the records, feels that both types of cases were the same disease, the

second being a more severe form. Woolley reports essentially the same

condition from Camp Devens.

The same phenomena were found in 1889. During the 1889 epidemic Prudden

examined by current bacteriologic methods seven cases of influenza and

six cases of influenza-pneumonia. In them he found staphylococcus

pyogenes aureus, streptococcus pyogenes, diplococcus pneumoniae, and in

other cases he found a streptococcus. He concludes that the use of

culture methods and media commonly employed has brought to light no

living germ which there is reason to believe has anything to do with

causing the disease. He emphasizes the probable importance of

streptococcus pyogenes in particular in inducing the various

complications.

At this point we should include for the sake of completeness reference

to a recent theory propounded by Sahli explaining influenza epidemics, a

theory to which we do not subscribe. He believes that the pneumococcus,

the streptococcus, the influenza bacillus, and possibly other organisms,

form a complex group, an obligate complex, a symbiosis, a higher unit,

which infects the organism as a unit. It is all of these organisms

acting together which produce the influenza. After infection has

occurred one or the other member of the group may develop

preferentially. In favor of this he says that in one of his cases the

sputum was swarming with influenza bacilli on one day, and that the next

day the sputum was a thick pure culture of the pneumococcus. He says

that if an ultramicroscopic germ should yet be discovered this would not

invalidate the theory, but would merely add another member to the group

forming the obligate complex virus unit.

_Meteorologic conditions._—Formerly attempts were made to demonstrate

etiologic relationships between the occurrence of influenza and unusual

conditions of the atmosphere. In most cases no relationship has been

discovered. Nevertheless it is conceivable that the changes in the

atmosphere, particularly seasonal variations, might influence the

virulence of the organism. It has been found that nearly all of the many

epidemics apparently originating in Russia took their origin there

either in the late autumn or in the winter months. The spread of

influenza appears to be uninfluenced by atmospheric conditions, but the

severity of the disease is definitely increased in the winter months,

and Leichtenstern believes that the development of a primary spread from

its point of origin is also influenced by the season. Hirsch found that

out of 175 correlated pandemics or epidemics, 50 occurred in the winter

between December and February, 85 in the spring from March to May, 16 in

the summer from June to August and 24 in the autumn.

The soil plays no part in the spread of the disease. It prevails on

every soil or geologic formation; on the mountain top, in the low

malarial swamps, in the tropics and within the arctic circle. Volcanic

eruptions, fogs, electrical conditions, ozone, direction of the wind,

have all been considered in previous epidemics and successively

eliminated as etiologic factors.

It must be stated, however, that Teissier, who investigated the

influenza in Russia in 1890 and has compared his conclusions at that

time with the results of investigation of the recent visitation,

believes that some particular cosmic conditions suddenly enhanced the

virulence of an endemic etiologic microorganism—probably some ordinary

germ—and that this opened the portals to secondary infections.

_Secondary invaders._—We have considered a possible manner in which the

virulence of the organism causing influenza may become enhanced.

Whatever this organism may be, another and equally important virulence

enhancement occurs in the opportunist group of the germs, so-called

secondary invaders of influenza. As we have previously remarked, it is a

characteristic of influenza outbreaks in all communities that the

earliest cases are very mild. Secondary infection has not as yet

obtained a foothold. After about a week the character of the illness

changes, becoming distinctly more severe. Billings reported that at Camp

Custer in the autumn of 1918 cases admitted to the hospital during the

first five days were very mild in character and were reported as simply

bronchitis or pharyngitis of no great severity, the majority soon

recovering. After this time the entire symptom complex seemed to change

and the cases admitted to the hospital were of a very different and more

severe type.

Benjafield reports that in the Egyptian Expeditionary Force the epidemic

commenced in May, 1918, and that the cases occurring during the earlier

portion of the epidemic were mild in type and of short duration, only a

very small proportion being complicated by bronchopneumonia. Wooley

found at Camp Devens that the first cases were of a mild form and were

usually diagnosed “naso-pharyngitis, acute catarrhal.” After a few days

the disease became more severe and pneumonia cases developed.

Bezançon found that among the repatriated French soldiers from

Switzerland those cases occurring in May and June had a much lower

severity than in the later epidemic. Zinsser’s description of the mild,

earlier epidemic in Chaumont has already been quoted.

The secondary invaders of pathogenic importance are the various forms of

the streptococcus and pneumococcus, the meningococcus, the

staphylococcus, and probably the tubercle bacillus and the influenza

bacillus. In the last epidemic as in that of thirty years previously,

the chief complications were bronchitis and pneumonia. Capps and Moody

found these to be the chief complications in December, 1915. Also they

found a high incidence of sinusitis. This has been a feature of the last

epidemic. Wooley cites a good example of the damage done by these

opportunist organisms when they are present. Among the troops stationed

at Camp Devens in the fall of 1918 pneumonia following influenza was

particularly prevalent in a battalion of negroes from the South. This

battalion had, a short time previously, passed through an epidemic of

pneumonia and Wooley believes that many of the blacks were harboring the

pneumococci which were only awaiting a favorable opportunity to invade

their hosts. The influenza furnished the required opportunity.

That the meningococcus should be classed in this group is certain. The

author observed at Camp Sevier cases of epidemic meningitis occurring in

various influenza wards scattered throughout the hospital, with no

demonstrable relationship. Usually there was but one case in a ward and

almost invariably meningitis occurred when convalescence was beginning.

No epidemic occurred in any ward. Others have reported actual epidemics

of meningitis following influenza. Moss found that a large proportion of

his influenza cases had the meningococcus in the circulating blood, as

demonstrated by culture. Fletcher cultivated meningococci from the lungs

in all of eleven autopsies, and in all eleven cases the influenza

bacillus was also present.

In considering the effect of influenza on the death rate in general, and

in considering the relationship of influenza to other diseases in

general, it is important to distinguish those diseases which are

apparently unrelated and those diseases which occur as direct

complications or sequelae. Bronchopneumonia, bronchitis, empyema, otitis

media, frequently tonsillitis and sometimes erysipelas, occur as

sequelae. Meningitis should frequently be included in this group.

Not only is there an increase in certain other diseases following

influenza outbreaks, genetically related, as we have seen, but also some

observers, particularly Crookshank, believe that previous to epidemic

influenza prevalences there occurs an increase in the incidence of other

entirely unrelated infectious diseases, such as poliomyelitis. This

theory of simultaneous increase in invasiveness of many apparently

unrelated germs is comparatively new and will probably receive deep

consideration in the future. For the present the information on the

subject is so limited that attempted conclusions would have no value.

ORIGIN OF THE 1918 PANDEMIC.

In discussing the spread of the 1918 pandemic over the earth, the author

has traced it from an apparent origin in the United States. Localized

early epidemics are reported simultaneously in the United States,

France, and China. From the literature at his disposal he has been

unable to find convincing proof of an earlier origin in Asia, but he did

emphasize at the time the necessity of a much more thorough study of

influenza in all countries to be made by more competent statisticians.

Nevertheless it is highly interesting to formulate an hypothesis which

appears to meet all demands, on the assumption that the disease

originated in America. In order to hold a theory with this basis we must

assume that the third of our previously mentioned hypotheses of the

origin of the disease is the more nearly correct.

Let us assume that in the interpandemic periods the influenza virus is

widely distributed over the earth, existing in an avirulent form. The

basis for this assumption is the previously described occurrence of

localized epidemics in interpandemic periods. The occurrence of solitary

cases, although of interest, could scarcely be considered as evidence of

the widespread distribution of the virus, but in the case of the small

outbreaks as in 1900, 1907 and 1915, and as in the numerous small

outbreaks described by Hirsch, the character of the epidemic curve is

characteristic. Let us, then, assume that the disease has been endemic

in the United States, together with other localities. It requires no

keen observation to discover in the years 1917 and 1918, Theobald

Smith’s “movement of individuals and masses from one part of the world

to another, whereby the partly adapted parasites become planted, as it

were, into new soil, and the original equilibrium is disturbed.” Not

only was there a tremendous redistribution and concentration of

individuals in our camps in this country, but also there was a further

disturbance of the equilibrium in the outbreak of other infectious

diseases, particularly measles. The effect of the measles epidemic on

the virulence of the streptococcus and allied organisms has been

discussed; presumably the same occurred with respect to the influenza

virus. Howard and Love report that approximately 40,512 cases of

influenza were reported in the United States Army during 1917. They

write:

“In 1917, the death rate for the acute respiratory diseases (influenza,

pneumonias and the common types) increased to 1.71. During the fall of

1917, after the camps were filled with drafted men, acute epidemic

diseases swept through a number of them. Measles was one of the most

prevalent and one of the most fatal of the infectious diseases that

occurred. It was noted during the fall and early winter that there were

a number of cases of pneumonia which were unlike the pneumonia that

ordinarily occurred. This was apparent both to the physicians in civil

life and in the army camps. It was reported by all classes of

practitioners that numerous cases of pneumonia were occurring which

resembled the pneumonia following measles, but occurring among men who

had not had measles recently. In a number of the camps, both in the

north and in the south, rather extensive epidemics of pneumonia occurred

and a number of deaths resulted. The same variety of pneumonia occurred

in the late winter and spring of 1918. In many of the camps pneumonia

was practically epidemic during March and April. In many camps a number

of cases occurred later in the spring and summer. It was again reported

by a number of medical men that these cases of pneumonia that were

occurring were different from the types of pneumonia ordinarily

encountered and very similar to pneumonia following measles, but, again,

that the cases occurred among men who had not had measles recently.”

MacNeal has observed similar conditions in the American Expeditionary

Forces in France in 1917:

“The American troops in France in 1917 began to show, as early as

October, 1917, a very considerable rise in the influenza morbidity. The

data available in the office of the Chief Surgeon, A. E. F., show an

influenza morbidity per 100,000 of 321 in July, 438 in August, and 404

in September, rising to 1,050 in October, 1,980 in November, and 2,480

in December, 1917, in which month the total number of new cases of

influenza reported was 3,520. That a considerable proportion of these

cases were actual infections with the bacillus of Pfeiffer is proven by

the necropsy findings in fatal cases of bronchitis and bronchopneumonia,

especially those performed by Major H. E. Robertson at Army Laboratory

No. 1, Neufchateau, in November and December, 1917, and January, 1918.

In these cases the bacillus of Pfeiffer was found in the scattered

patches of lung involved in the bronchopneumonia and also with great

frequency in the cranial sinuses. These necropsy findings were, at the

time, recognized as essentially new for young adult Americans, and, in a

discussion at Army Laboratory No. 1, during December, 1917, they were

considered as being of possible important significance for the future

morbidity of American soldiers in France. In the British Army in France

there is definite evidence of epidemics showing the same pathologic

condition, during the winter of 1916–17, and at Aldershot in September,

1917. There can be little, if any doubt that this disease was

essentially the same which attacked the American soldiers late in 1917.”

Schittenhelm and Schlecht have reported that a disease was studied among

the German troops on the Eastern front which resembled greatly the

influenza. It occurred from the beginning of August to the middle of

October, 1917. It attacked simultaneously and in epidemic form units and

divisions very widely separated over a large territory. It was

characterized clinically by a very sudden onset, in the greater number

of cases with chill, headache, pain in the extremities, sometimes

thoracic pain and cough. The fever lasted seven to nine days. The spleen

was enlarged in 11 per cent. of the individuals. There was diarrhea in

12 per cent., frequently conjunctivitis, and quite often a

scarlatiniform rash. Bacteriologic examination of the blood was

negative. There was usually leucopenia. No treatment seemed especially

efficacious. Aspirin gave the best results. The authors call attention

to the close similarity to influenza and also suggest that it might have

been due to transmission by insects as in pappataci fever or in dengue.

Carnwath concluded that the finding of influenza bacilli in necropsies

in British soldiers in 1917 was without epidemiologic significance in

considering the origin of the 1918 pandemic. He had studied the disease

among the British in detail and appeared to be of the opinion that the

first influenza morbidity of significance among the British troops did

not appear previous to April, 1918.

MacNeal further says: “The influenza rates per 100,000 of 1,050 in

November and 2,480 in December, 1917, really indicate a greater relative

prevalence of influenza at that time in the A. E. F. than occurred in

the fall of 1918, when the respective morbidity rates were 826 in

September, 2,176 in October, and 1,356 in November. The total number of

American troops in France was relatively small during that

winter—141,995 effective mean strength in December—so that the

prevalence of influenza did not lead to the recognition of an actual

epidemic. Furthermore, the overcrowding in quarters, which seems to have

had a definite relation to many of the later explosive outbreaks, had

not become such a distinct feature at that time. In addition, the cold,

wet weather, exposure and unusual living conditions furnished

explanations for the morbidity which were no longer adequate during the

hot weather of May and June, 1918. Until May, 1918, therefore, the

prevalence was that of an endemic disease, with perhaps an occasional

outbreak suggesting epidemic character.”

We admit that MacNeal’s report furnishes excellent evidence of an

independent origin in France. Two points should be borne in mind. First,

that MacNeal’s figures are not for the French, but for the Americans who

were transported to that country, and that we may consequently consider

influenza among the American Expeditionary Forces as being possibly from

the same source as influenza among the troops in our own country,—that

the American Expeditionary Forces may be considered a subdivision of the

American Army in the United States, equally well as a subdivision of the

French population; second, that we have been unable to find detailed

evidence of similar conditions occurring among the French troops or

French population, where the conditions have been ripe in a way since

1914. MacNeal records that in March and April, 1918, there was a great

increase in the number of troops brought over from the United States to

France. Previous to that time there had been 287,000 in that country and

during the two months 150,000 were added, with a consequent increase of

more than fifty per cent.

We should insert a word of caution regarding the diagnosis of influenza

among troops in the absence of any sign of an epidemic. Internists who

served in base hospitals during the war will agree that a diagnosis of

influenza is very frequently made on the admission card when the disease

turns out to be some other malady. This was not equally true in all

camps, but regimental surgeons could often be found who would transfer a

patient to the hospital with the diagnosis of influenza used almost

interchangeably with the diagnosis “Fever of unknown origin.” It would

be interesting to see statistics from one or two of those base hospitals

which were manned with especially competent internists, as to the

frequency with which the admission diagnosis of influenza remained

unchallenged in the hospital, during the year 1917.

There would be such cases in greater or smaller numbers. The magnitude

of this number would not influence our hypothesis.

Aside from this discussion of the disease among our troops in France it

is most important that we establish, if possible, the identity of the

disease reported among British troops in Northern France during the

winter of 1916–1917 and designated by the name “Purulent Bronchitis.”

The disease first appeared in December, 1916. It reached its height

during February and early March of 1917, and appears to have disappeared

early in the spring. Hammond, Rolland and Shore report that during

February and early March 45 per cent. of the necropsies under

observation showed the presence of purulent bronchitis, and they

remarked that the disease assumed such proportions as to constitute

almost a small epidemic. They described the clinical aspects as follows:

“The cases which came under our notice can be divided broadly into two

types: The first and more acute presents a clinical picture which

closely simulates ordinary lobar pneumonia with a sustained temperature

of about 103°, and expectoration at first blood-streaked—rather than

rusty—which, however, rapidly becomes quite purulent. The pulse-rate in

these cases is out of all proportion to the temperature in its rapidity.

Dyspnoea and cyanosis are prominent features. The patient usually dies

from ‘lung block,’ resulting in embarrassment of the right side of the

heart on the fifth or sixth day. For the last day or two there is often

incontinence of the feces, due, no doubt, to the condition of partial

asphyxia. The mental state is one of torpor; delirium is the exception.

“The second and less acute type is marked by a more swinging temperature

with a range of two or three degrees. The expectoration at first may be

frothy and mucopurulent, but it very soon assumes the typically purulent

character. This form may run a long course of from three to six weeks,

during which time the patient wastes a great deal and has frequent and

profuse sweats; indeed, at a certain stage the illness is most

suggestive of acute tubercular infection, and it is only by repeated

examination of the expectoration that the clinician can satisfy himself

he is not really over-looking a case of acute pulmonary tuberculosis.

The majority of our cases conforming to this type have ultimately

recovered, but the convalescence is slow and tedious.

“Onset.—Whilst a history of a previous catarrhal condition lasting for a

few days is often obtained, the disease quickly assumes an acute

character; we have been able to observe this in patients admitted into

this hospital with purulent bronchitis; we find the temperature is

between 102° and 103°, the pulse 120 or over, and the respiration about

35. The patient frequently complains of shivering and looks pathetically

miserable, but we have not seen an actual rigor. Despite his obvious

shortness of breath, the sisters have noticed that, at any rate at

first, he prefers a lateral position low down in the bed, and resents

any attempt to prop him up.

“Cough.—This for the first day or two may be irritable and distressing,

with a little frothy expectoration, but as the latter becomes more

purulent the cough is less troublesome, and soon the patient is

expectorating easily and frequently, until the later stages are reached;

when owing to increasing asphyxia the patient becomes more and more

torpid, the cough subsides, and hardly any secretion is brought up. This

failure becomes an added factor in bringing about a rapidly fatal

termination.

“Expectoration.—The sputum, with its yellowish-green purulent masses, is

very characteristic, and may be one of the first indications of the

serious nature of the illness the patient is suffering from.

“Temperature.—The fever of this complaint does not follow any very

constant type. In nearly all our cases the pyrexia was of sudden onset,

and for the first few days was more or less sustained at about 103°.

Later it conformed more to the swinging type with a range of several

degrees. In a few cases a curious gradual ante mortem drop has been

observed.

“Pulse.—Tachycardia is a very constant feature throughout the illness.

The rate is frequently well over 120, though the volume may remain

surprisingly good until immediately before death.

“Some degree of dyspnoea is always present, and is usually progressive,

though towards the end in the fatal cases when the mental acuteness is

dulled by the increasing asphyxia the patient is not distressed by its

presence. In some cases there have been paroxysmal exacerbations of the

breathlessness, accompanied by a state of panic, in which the patient

struggles wildly and tries to get out of bed in order to gain relief.

Cyanosis is another prominent feature throughout the illness. At first

it may not be more than duskiness, but in the later stages it becomes

very evident. It is only slightly relieved by oxygen; this, no doubt, is

partly explained by the difficulty in giving the oxygen efficiently,

owing to the patient’s objection to any mouthpiece that fits at all

tightly, and partly by the blocked condition of the bronchioles

interfering with the absorption of the oxygen.

“The condition usually begins with the presence of a moderate number of

sharp crepitant râles, often first heard in the region of the root of

the lung; these quickly become generalized. In the majority of the cases

signs of bronchopneumonia patches can be made out; these are generally

situated near the root of the lungs. In a certain number of cases these

patches spread and become confluent, giving practically all of the

physical signs of a lobar pneumonia. As the disease progresses the air

entry is diminished; on listening one is often struck by the small

volume of sound heard. The resonance of the lungs may also be lessened.

A slight pleuritic rub was heard in a few of our cases, but this was

soon masked by the bronchitis signs.”

Detailed sputum examination in twenty cases showed the presence of the

influenza bacillus in eighteen, and in ten out of these eighteen the

organism was isolated by culture. The next most frequent organism found

was the pneumococcus, which was present in thirteen cases. The

streptococcus was found in five.

Abrahams, Hallows, Eyre and French report the same epidemic:

“A typical case is as follows. The onset is usually acute; the early

symptoms are those of a ‘cold in the head.’ The temperature may be 101

or 102°, but there are no features to distinguish the condition from

acute ‘coryza’ or febricula, so that in the majority of cases the

patient does not report sick for two or three days, by which time he is

sent to the hospital. At this state two features attract particular

attention. First, the character of the expectoration: this consists of

thick pale yellow, almost pure pus, not the frothy expectoration

familiar in ordinary bronchitis; it has no particular odor and it

becomes increasingly abundant until in a day or two it may amount to

several ounces in the twenty-four hours. Secondly, the rapidity of the

patient’s breathing: this may be so evident that pneumonia suggests

itself, yet on examining the chest the only physical signs consist of

few or many rhonchi scattered widely, but most marked at the bases of

the lungs behind, associated with a wheezy vesicular murmur; resonance

everywhere is unimpaired and bronchial breathing is absent. A little

later a third point attracts notice; a peculiar dusky heliotrope type of

cyanosis of the face, lips, and ears, so characteristic as to hall-mark

the nature of the patient’s malady even on superficial inspection. By

this time dyspnoea is very pronounced; respiration consists of short,

shallow movements, which in bad cases amount almost to gasps,

reminiscent of the effects of gas poisoning. Recovery at this stage may

occur, but by the time the cyanosis has become at all pronounced the

prognosis is extremely bad, though the number of days the patient may

still live, in spite of the severity of his distress, is often

surprising. The character of the sputum remains the same throughout,

though sometimes it is blood-tinged or actual blood may be expectorated

instead of, or in addition to, the more typical pale yellow pus. In the

later stages of the illness areas of impaired note or of actual dullness

may be found, particularly over the posterior aspects of the lungs,

associated with bronchial breathing and crepitant râles. These may be

due to the progression of the purulent bronchitis into hypostatic

pneumonia, or into actual bronchopneumonia at the bases; or, on the

other hand, they may be due to massive collapse of the lungs secondary

to the bronchitis and obstruction of the bronchioles by pus. In a few

cases, not necessarily the most serious, a frank lobar pneumonia has

developed later, and has been followed by an empyema from which 15–30

ounces of thin pneumococcal pus has been aspirated—in one case alone was

resection of a rib unavoidable. The condition, however, is not primarily

a lobar or a bronchopneumonia, but a bronchitis, and although a small

amount of basal bronchopneumonia has been present in one or two of our

post-mortem examinations, in other fatal cases there has been no

bronchopneumonia at all, not even the smallest portions of either lung

being found to sink in water.

“We have no doubt that the condition is primarily an affection of the

bronchi and bronchioles, and not of the alveoli, though the alveoli may

be affected later if the patient survives long enough. In a typical

post-mortem examination it would be difficult, or almost impossible, to

define the actual cause of death unless one knew the clinical history.”

Abrahams and his collaborators describe in detail eight consecutive

cases. A study of the type of onset may be of help in determining the

character of the disease. The first patient had been subject to

bronchitis for years. He had been ill with cough and some pyrexia for

five days previous to his admission. There is no further description of

his admission symptoms. Case two was admitted on March 17th, having

taken ill the previous day with shivering, cold and pain in the chest.

The temperature was 104°, the pulse-rate 118, and the respirations were

44. The patient was very restless and had much dyspnoea but was not

cyanosed. The third patient had taken ill three days previous to

admission with symptoms of cold in the head and a sore throat. He

complained of headache and dry cough without expectoration, shortness of

breath, and a pain behind the sternum.

Case four was admitted with a history of having been out of sorts with a

cold and bronchial cough for ten days previously. On admission his

temperature was 103°, pulse-rate 112 and respiration-rate 36. He had

abundant blood-stained purulent sputum.

Case five is the first case that shows a type of onset distinctly

resembling that of influenza. The patient had been ill three days with

headache, cough and generalized pain previous to his admission. The

temperature on admission to the hospital was 103°, pulse-rate 112,

respiration-rate 20. There were no abnormal physical signs in the chest

on admission. They did appear two days later. Case six related that he

had been sleeping under canvas for three nights before coming to the

hospital, and that during the first of these nights he was taken ill

with a cold which became associated with a cough and increasing

shortness of breath. On admission there was slight cyanosis, and

dyspnoea was very pronounced. Shortly afterwards he became orthopnoeic,

with heliotrope cyanosis. On the slightest exertion, such as turning

over in bed, the cyanosis increased markedly, and although the

respiration-rate remained under forty when he was at rest, on the least

exertion it increased to nearly sixty. The sputum was purulent and

abundant, pale yellow, not frothy and not blood-stained, and the day

after admission contained Bacillus influenzae, pneumococcus and

Micrococcus catarrhalis.

Case seven had been ill seven days before admission with cough and

fever. On admission his temperature was 105°, pulse 116, respiration 24.

Case eight gave a history of having had a cough for eight days previous

to admission. This cough had not incapacitated him much at first, but he

became progressively worse during the four days before admission, with

increasing shortness of breath and abundant yellow sputum which he found

it difficult to raise. On admission dyspnoea with cyanosis was very

evident.

Even from these detailed clinical descriptions it is impossible to say

definitely whether the disease was or was not influenza. There is no

doubt, however, but that clinically the disease resembled more the

so-called streptococcus pneumonias that were observed in the United

States camps in the winter of 1917–18. The descriptions of the mode of

onset are particularly at variance with the onset as we know it in

influenza.

Those who believe that the influenza bacillus is the cause of influenza

maintain that the finding of this organism in a large per cent. of cases

by both groups of observers is valuable evidence. For reasons previously

stated we cannot agree.

Description of the epidemic features is not detailed enough to be of

assistance. The first group of authors remark that the disease

constituted “almost a small epidemic.” The second group say that six out

of eight cases in their series of candidly reported patients came from

one command. The former report on twenty cases, the latter on eight. The

latter remark that although they have dealt with only eight cases in

detail, they had a much larger number altogether. Presumably there were

a decidedly larger number of patients in both hospitals, but the actual

number is not stated. In short, we do not know whether the disease

appeared to be more or less epidemic than the apparently similar disease

among our troops in the winter of 1917–18.

Both groups of observers have described in some detail the pathology of

the cases which were necropsied. The author in attempting to obtain

further comparative information has submitted the pathologic

descriptions given by the British authors to Dr. E. W. Goodpasture, who

has very kindly pointed out the points of similarity and difference

between the gross and microscopic findings in these cases of purulent

bronchitis, and the same findings in typical influenza. He says that the

lung picture, as described, is not the same as that which was typical of

the acute influenza observed in the autumn of 1918 and again in the

winter of 1920. The characteristic picture in the latter is primarily an

extensive involvement of the alveolar structure, while as Abrahams and

his associates remarked, the condition in their case is primarily “an

affection of the bronchi and bronchioles, and not of the alveoli, though

the alveoli may be affected later, if the patient survives long enough.”

Goodpasture states that the pathology as described by the British

authors is very similar to the lung picture in interstitial

bronchopneumonia described by MacCallum for the post-measles and primary

bronchopneumonia among our troops in the winter of 1917–18. The

streptococcus and the influenza bacillus were dominant organisms in

MacCallum’s series. It also resembles the pathologic picture described

by Pfeiffer in his original article on one of the late recurrences of

the 1889–93 epidemics of influenza.

In summing up, we must admit that it is impossible to reach a definite

conclusion, but that both clinically and pathologically the disease

described among the British troops in 1916 and 1917 was not typical of

influenza as we have known it more recently. The similar conclusion

reached by Carnwath, presumably chiefly from epidemiologic

considerations, has already been described. We do not deny that this

“purulent bronchitis” _may_ have been influenza. On the contrary, it is

a part of our hypothesis that influenza under the proper conditions may

become epidemic in practically any land. But we do believe that the

evidence has not shown that the disease among the British troops in 1916

and 1917 was an etiologic precursor of the great pandemic.

To return to a discussion of influenza in China, we quote from an

article by Cadbury in the China Medical Journal: “Unfortunately no

health reports are available for the greater part of the Chinese

Republic. We have consulted, however, the Health Reports of the Shanghai

Municipal Council from 1898 to 1917, and among the total foreign deaths

we find that only the following were attributed to influenza: 1899, one

death; 1900, one death; 1907, four deaths; 1910, one death. After this

no deaths are recorded from this cause up to and including the year

1917.

“In the Hongkong Medical and Sanitary Reports, which give the total

deaths registered in the Colony, we have examined the records from 1909

to 1917. During these nine years only two deaths were attributed to

influenza, and both occurred in 1909.

“From a personal letter from Dr. Arthur Stanley, Health Officer in

Shanghai, dated February 11, 1919, I quote the following:

“‘As to influenza we had an attack beginning at the end of May and

lasting through June and again in the latter part of October and lasting

through November. The latter was somewhat more severe. The noteworthy

features were general absence of catarrhal symptoms, congestive pharynx

frequent, as also was a slight erythematous blush on the neck and chest,

which made one think at first of scarlet fever. Fatal pneumonia common

among the Chinese and Japanese, but among Europeans very little

pneumonia.’

“In his report for May, 1918, Dr. Stanley says that the disease was

reported to have reached Peking before it came to Shanghai, but

subsequent reports showed that most of the river ports were almost

simultaneously infected, the rate of spread conforming to the rate of

conveyance by railways and boats of infected persons. The mortality was

very low.

“Newspaper reports indicate that a third appearance of the disease in

Shanghai occurred from the middle of February, 1919, which was still

prevalent in April. The symptoms were much more severe.

“For Hongkong I quote from a personal letter from Dr. Hickling, the

Principal Medical Officer of Health, dated January 29, 1919:

“‘The epidemic of influenza in the spring was a very mild one, so far as

we can judge. The disease did not last more than a few days in most

cases. The recent epidemic (October, November, December and January) has

been much more severe, often lasting two or three weeks.’

“Only one death, which occurred on May 14th, was reported from Hongkong

in the spring. In the later epidemic the deaths reported were as

follows: October, 70; November, 95; December, 67. The first of these

deaths occurred on October 5th. The figures for January had not been

compiled, but the disease was diminishing.

“Dr. C. W. McKenny of Hongkong has kindly furnished me with the

following facts: ‘During the first five months of 1918 there were

twenty-two admissions for influenza to the Civil and Tung Wa hospitals

(3 in May). In June there were 269 cases with three deaths. In July,

August and September, 43 cases; and during October-November, 130 cases

with four deaths....

“‘The June epidemic in Canton appeared first at the Pui Ying School,

then among the employees of the Post Office, the staff of the Canton

Hospital, the Canton Christian College, and the Kung Yee Hospital. The

other schools entirely escaped. Eleven days were taken by the disease to

spread from one part of the city to the various other parts.’”

Plague appeared in the north of China in 1917, originating apparently in

inner Mongolia. The spread extended over quite an area, and it is

reported that this epidemic of pneumonic plague has been more extensive

than any since that of 1910–11. The disease was first reported prevalent

in Patsebolong December 6, 1917. The diagnosis was confirmed

bacteriologically, and there can be little doubt but that the cases of

plague reported in various parts of China even up to March 18th were

true plague, and not unrecognized influenza.