Part 28

Thucydides describes a plague in Athens occurring before Christ. This is generally believed to have been “the plague.” The time of the earliest appearance of the disease in Italy is not known but it was well established there in the first century of our era. The plague was endemic in Italy at that time and it developed in epidemic form with each increase in susceptible material. At about 68 A.D. the disease spread over the whole of Asia, Northern Africa and Europe. Exacerbations of the disease are described in the years 80, 88 and 92 A.D. In Rome they occurred in 102, 107 and 117 A.D. The disease was present in Wales in 114 A.D. In 167 an unusually severe outbreak of the plague occurred in Rome. There were other outbreaks in the Roman army in 173, 175 and 178. Had we the space to record here the history of the plague we would find that the disease was widely distributed throughout Europe for several hundreds of years, that it was particularly prevalent in certain areas and that at intervals it spread from one or a few foci, throughout the continent.

We can compare the epidemic features of influenza with these other contagious diseases, but we will always find some points of difference from one or another. Let us consider again for a moment epidemic meningitis. There is no combination of predisposing causes, environmental, meteorologic or bacteriologic which will produce epidemics of cerebrospinal meningitis in the absence of the meningococcus itself. The organism causing the disease must be present before the disease will occur. The specificity of the invading organism in the different diseases will always produce some variation among the epidemiologic features. Other things being equal, that locality in which this germ is most extensively distributed will be the locality in which epidemics, when they do break out, will be most extensive.

In the case of our army camps, those individuals carrying the disease virus from the endemic foci to the camps were not the ones who fell ill. Generally it was those, coming from other areas in which meningitis was not extensively distributed and who had, therefore, not acquired an increased resistance to the disease, who fell ill. But after the disease had acquired increased virulence at Camp Jackson, not only did it occur in the troops at that camp, but it also became quite extensive throughout the civilian population, presumably among those who had previously been exposed to it in its endemic form.

In our comparison of influenza with other infectious diseases we wish to show particularly that the disease is not in a class by itself, but that its epidemiologic features are not unlike those of other respiratory infections, that the manner of spread and the mode of infection are similar to those of the other diseases. Nothing unusual or unknown need be called into use in explaining any differences. Those differences that very palpably exist can be explained by facts which we already know. Leichtenstern, thirty years ago, believed that the disease was similar in its manner of spread to other infectious diseases. He observed this particularly in the earliest and the latest phases of epidemic spreads where cases were scattered. He saw that in households the disease attacked some and spared others even of those intimately connected with the sick, just as was the case in diphtheria or meningitis. He writes: “Comparing these later periods the disease evidences the same contagious characteristics as the other endemic contagious diseases, such as scarlet fever, measles, diphtheria, epidemic cerebrospinal meningitis, etc.”

Parkes made very similar observations even before the 1889 epidemic.

_Measles._—A comparison of influenza and measles will offer some explanation of the differences between the epidemic constitution of the former and that of the other respiratory diseases.

We are accustomed to think of measles as a disease which, like meningitis, is disseminated throughout the civilized world, and which although constantly with us causes only sporadic cases. True epidemics of measles do occur, even when there is no gross change in the constitution of the population. We have discussed examples of this particularly in London. Flare-ups of measles prevalence are in fact so much the rule that in certain localities health officers anticipate a measles epidemic about once in two years. Furthermore measles has been known more than once to occur in extensive epidemic form, attacking large proportions of the population invaded. We know that there is an immunity to measles which is nearly absolute in those who have once acquired the disease. The epidemics have, therefore, occurred exclusively in those localities where the proportion of immune individuals was relatively small. According to Noah Webster in 1772 measles appeared in all parts of America and was accompanied by an unusually high mortality. In Charleston 800 or 900 children died of the disease. The following year measles “finished its course and was followed by a disorder of the throat.”

In 1781 measles disappeared from the Faroe Islands, and for the following sixty-five years there was not a case of this disease anywhere on any of the seventeen islands constituting the inhabited parts of this group. When the disease was finally re-introduced into these islands, it spread throughout the population, attacking practically every individual in a relatively short interval of time, showing a much higher attack rate than did influenza in 1918. There was this difference, that the only individuals who did not acquire measles on its re-introduction into the islands were those who had had it sixty-five years before. Panum did not find an authentic case of recurrence in the same individual. There was not a single instance of second attack of measles, although the shortest possible interval between the previous attack and the subsequent exposure was sixty-five years.

In 1875 measles first reached the inhabitants of the Fiji Islands. The disease was introduced by the King of the Fiji Islanders and his escort, upon their return from New South Wales. The entire population of the islands was estimated at 150,000 and it is officially stated that there were 40,000 deaths from measles in the ensuing period. In certain islands and villages where more exact information was secured, it was found that from twenty-seven to twenty-eight per cent. of the people died. Panic, insanitary conditions and ignorance of how to care for the sick resulted in this high mortality. V. C. Vaughan has remarked that when measles is introduced into a population with a susceptibility of 100 per cent. “it strikes down so many at practically the same time that adequate care for the sick is impossible.” The rapidity with which the population is invaded is practically as great as it is during influenza epidemics.

It is the opinion of the author that the phenomenon which contributes chiefly to the occurrence of influenza in epidemics and pandemics, and which causes the characteristic curves of a primary influenza wave, is the absence of any permanent immunity. We have shown in our discussion that no immunity is proven to exist after a year and a half or two years at the most. Measles occurring in a non-immune population spreads through that population with the same high rate as does the influenza. In Charts XXVIII and XXIX we find the curves of incidence of measles in certain of the United States Army camps in the fall and winter of 1917–18. The simplest curve is that for Camp Wheeler. Here the type is similar to that found in the primary wave of influenza. There is a quasi-symmetrical evolution and the concentration is closely grouped around the maximum. The total duration of the epidemic is short, not being much over eight weeks. The troops at this camp were predominantly rural. The disease starting in this group of relatively non-immunes spread rapidly until presumably all susceptible material was exhausted. Compare Camp Wheeler with those camps where the population was chiefly urban. Here the wave is of longer duration, is not as high, the increase is slower, the decrease is more gradual and the concentration is not grouped so closely about the maximum. In the case of the other camps with chiefly rural population, the curve is not as simple as is the case with Camp Wheeler, and there are at times secondary curves as in the case of Camp Bowie, but the essential similarity to the curve at Camp Wheeler and the difference from the curves at Devens, Dix, Custer and Grant is striking. It may be that the double waves are explained by acquisition of new bodies of troops, by the introduction of new susceptible material. On this question we have no exact information.

CHART XXVIII.

CHART XXIX.

This experience was equally true during the Civil war. Although there are no exact reports, it appears that measles prevailed in the Confederate army and was much more highly fatal than in the Union army.

A recurrent influenza epidemic usually takes the form of a secondary wave, particularly so if it follows the primary wave within a short period of time. The difference in the character of the wave is due to the fact that there is still a comparatively large concentration of immune individuals, immunized by having had the disease during the primary spread. The secondary type of the influenza wave corresponds with the measles curves for the urban camps. There are all gradations in influenza from the typical primary wave down to a very much flattened wave of relatively long duration, and even on to the stage of endemicity, with no discernible wave. In 1920 the recurrent epidemic partook more of the form of a primary wave, because in most individuals the period of immunity had been completed by January and February, 1920.

If we could, by some means, induce an immunity which would last for long periods of time, pandemic influenza would disappear from the earth and the disease would be relegated to the comparatively minor position now occupied by measles. The disease would be constantly endemic, frequently breaking out in small epidemics, but never becoming pandemic. This is one object that should be held in view by the immunologists and bacteriologists. But it is not so simple. Even were a successful vaccine discovered, it is doubtful whether any considerable group of the population could be persuaded to take it as often as would be necessary. Universal vaccination against small pox has never been carried out. The same would be true at the present time with regard to influenza.

There is another similarity between measles and influenza. Measles is as infectious as is influenza. It is as readily transmitted and the mode of transmission is probably the same or very similar. In both diseases we are made poignantly aware of the great contagiousness of the disease, and yet in neither disease has there ever been conclusive evidence of experimental transmission from man to man. Several have reported attempts to transfer measles, but in each case the evidence of infection has been incomplete. The work of Hektoen has been quoted in particular, but Sellards, after carefully reviewing his work, concludes that the evidence of infection is insufficient. Moreover Hektoen’s patients were not exposed subsequently to measles infection in the natural way.

SECTION VIII.

THE PREVENTION AND CONTROL OF INFLUENZA.

Dr. Hamer has visualized the present state of our knowledge of epidemic influenza in a manner which can scarcely be improved upon. We, therefore, quote him at length: “It seems to me that, during the last thirty years or more, we have been making fairly steady uphill progress along the road which constitutes the boundary between the county of epidemiology and the county of bacteriology, and that we have at length reached, at a height considerably above sea level, the foot of the mountain, on the very top of which lies hidden the secret of an ‘epidemic constitution,’ and now we are face to face with a parting of ways. Straight ahead is the frowning height, its summit in cloud. On the right hand stretches away a fine road skirting the base of the mountain. Along this road we have recently seen Dr. Brownlee whirled away in his new car ‘periodogram.’ We are all hoping to hear more from him, but as he is still insisting upon the primary, if not the exclusive, importance of continuous variation in the virulence of the germ, we have to realize that for the time Dr. Brownlee’s road is going down-hill. On the other hand, on the left, there swerves away, through the territory of the old epidemiology, another fine road, which has been explored more particularly by believers in ‘skiey influences.’ So far as it has been traced this road is as flat as flat can be, but of course there is always the possibility that after a while it will begin to rise, as it skirts round the mountain, and leads to a good vantage point from which to start climbing. At the risk, however, of being laughed at, I venture to bring under notice the very rough and at first sight unpromising ground directly in front of us. Along this can be seen two obscurely marked sheep tracks proceeding at any rate onwards and upwards. One diverges slightly towards the left hand and it has been followed at various times by De Schweinitz and others, naturalists bent on collecting ‘ultravisible viruses;’ the second track, directed rather more to the right, has been explored by Reiner, Müller, Massini, Penfold, and others, workers at the problem of discontinuous variation by ‘mutation.’ As a matter of fact I have reason to believe that two travellers, each of whom follows one of these tracks, will keep in sight of and after a while will find that they are approaching one another, and will ultimately meet at a small and retired upland farm; then after passing some dogs and following the track until clear of all stone walls, they will come right out in open ground on the face of the mountain and can start straight up the steep. But it must here be pointed out that there remains to be considered a fourth method of approach to the mountain, the most direct of all; but that is by aeroplane and is of course only open to those trained in metaphysics and statistical methods. Investigators thus equipped are able to rise in the air, to survey with careful scrutiny the whole of the ground beneath them and to make the best use of details of information obtained by scouting parties below. It is to be hoped that at no very distant date a survey of the top of the mountain will thus become an accomplished fact. Meantime, those who cannot fly may find useful employment in examining the track beyond the farm. There is the chance there of picking up facts relating to such questions as the ‘parasites associated with a parasite,’ symbiosis, and the like; take, for example, a suggestion made fourteen or fifteen years ago that the influenza organism may at one time live in association with Pfeiffer’s bacillus, at another with the Micrococcus catarrhalis, and so on; or the throat distemper organism may be yoked now with the diphtheria bacillus and now with the Streptococcus conglomeratus. (Is that, I wonder, now to be regarded as a concept or as an occurrence or happening?)”

At best our knowledge of the cause and manner of spread of influenza is fragmentary and insufficient. Attempts to outline a system of control and prevention based upon present concepts are met with many discouragements. The next pandemic will not be prevented. The disease will surely return. If the interval be sufficiently long it may find us quite as unprepared as we were in 1918. Discouraging as the outlook is there are many bright points upon which we must base our hopes for future results.

The difficulties are many: First the _diagnosis_ of influenza is difficult either in the individual case or in the form of a mild epidemic. Even in 1918 the identification was often not definitely made until after weeks had elapsed. Second, we know little concerning the _mode of transmission_ of the disease. We speak of “respiratory infection.” We believe that the transmission is by a mechanism similar to that for measles, but we have never experimentally transmitted either disease. The _short incubation period_ places us at a great disadvantage. Were the interval between the occurrence of the first case and the development of additional cases as long as it is in measles, the problem of isolation and quarantine would be simplified. As in measles the disease is probably _very early infectious_, presumably before acute symptoms develop. The majority of cases of influenza are _ambulatory_. Many individuals do not take to their beds, but continue about their work, spreading the disease wherever they go.

Again, we are ignorant of the _period of infectiousness_. Dr. Meredith Davies has made observations indicating that a patient becomes non-infectious within one week after the temperature has become normal. How many influenza patients remain isolated throughout this period?

A _carrier state_ probably exists and plays a most significant part in the spread.

Yet another drawback is the _apparent wide susceptibility_ to the disease. Were individuals definitely immunized by one attack the proportion of susceptibles would be lessened, their concentration in a population would be decreased, and the probability of their being exposed would be proportionately diminished.

An additional difficulty is that after an epidemic has once become prevalent, we must combat not only the virus causing the disease but also the _secondary invaders_.

Epidemiologic work has shown that _crowd gatherings_ are instrumental in the spread of influenza. The density of population has not been as definitely proven to be a factor. Crowding, however, does play a part. Close crowding in communities must facilitate the spread, but pandemics of influenza were known before the great metropoleis existed. _Hygienic conditions_ play their part in the etiology. Finally, in the presence of every serious epidemic we must also combat the _tendency to panic_ in the population.

_Anticipatory or preventive measures._—It is erroneous today to speak of measures for the prevention of influenza in a community. We cannot prevent the disease. At most, we can anticipate the occurrence of an epidemic and take precautionary measures by which the spread and the severity of the disease may be minimized.

First and foremost comes _education_. Education of the public, of the medical profession and of health authorities. “Scare headlines” in the newspapers during epidemics should be discouraged. Health cartoons are of value, but when they express only partial truths they cannot but do some harm. General education in hygienic methods and in a knowledge of the spread of contagious diseases has already been most productive. Many methods by which the public intelligence could be reached are as yet untried. A daily paper in Boston devotes two columns a week to a discussion of public health problems, under the title of “The Clinic.” The statements appearing in these columns are nearly always the truth and are not exaggerations. There are discussions of recent scientific work of interest to the reading public. As has been emphasized by Carnwath, a page devoted to methods of maintaining the health of the community would probably be of more immediate value than are the many pages devoted to financial statements, “such as the price of Mexican Eagles or of Peruvian Corporation Preference.”

The _organization of health services_ to combat unexpected epidemics would be of great assistance. In times of peace, prepare for war. In all but the largest cities the health authorities are generally so free from contact with epidemics and are so pressed with routine that they do not organize in readiness for an epidemic which may not come. There should be a closer co-operative organization between health officials and practising physicians, so that the latter may aid to a greater extent in the public health work. The physician co-operates in furnishing information required by the health officer, but too frequently takes little interest in what further is done with this information. The medical profession should be made to understand the importance of public health work, should have a general comprehension of the methods used in its execution and should particularly develop a sympathetic and co-operative mental attitude.

The medical societies of the country should be so organized that at a moment’s notice their membership can be mobilized for the defense of the community. There is much that the practising physician does not know about influenza. One of the leading internists in one of our largest cities, during the 1920 epidemic, refused to call his cases influenza and treated them as mild “grip.” It is stated that he lost an unusually large number of his patients. There are still many who believe that the two diseases are not identical. Not only is this detrimental to the patient, but as it results in failure to isolate the sick, it is detrimental to the community.

Nursing groups should be organized to aid at a moment’s notice.

Much work has been done and great experience gained by both the physicians and the nursing organizations during the last epidemic. Now is the time to prepare for the next epidemic or pandemic. With the remembrance of 1918 fresh in our minds we can establish a working system, while if we delay until the expected arrival of another epidemic much of our painfully acquired knowledge will have been forgotten.

Opinion differs as to whether influenza should be made a _reportable disease_. The added expense would be not insignificant. This particular malady presents the additional complication of being difficult of diagnosis. The records would at best be inaccurate. The author believes that certain experiments in reporting the disease even in interepidemic times should be carried out. This should be done by competent epidemiologists who could later formulate plans for the permanent reporting of the disease. We will discuss this further under the heading, “Constructive Research.”

The use of _vaccines_ has been tried. In 1918 it was almost universally begun too late—after the epidemic had become prevalent. Prophylactic vaccination should be inaugurated before the disease actually becomes epidemic. Vaccination, particularly against the secondary invaders, is entirely rational. It may not prevent influenza, but it may protect against the serious complications in individuals and may prevent to an extent the spread of secondary invaders in the community.

Greenwood aptly remarks that, “In estimating the total effects produced upon morbidity and mortality by disease, the non-specific secondary invaders are as important as the specific causes. The camp followers of an army may do more damage than the regular soldiers, and the same camp followers may ravage in the wake of different armies.”

At a conference held at the London War Office, October 14, 1918, the subject of vaccination for influenza was discussed. It was decided that only three organisms should be employed in each case in the preparation of the vaccine; that these races should be recently isolated from cases of the disease developing during the course of the epidemic and that the microorganisms should be submitted to a rigorous study as to race and type. The first dose should include 30,000,000 of Bacillus influenzae, 100,000,000 pneumococcus, 40,000,000 streptococcus; the second dose 60,000,000 Bacillus influenzae, 200,000,000 pneumonococcus, 50,000,000 streptococcus. The vaccine should be sterilized at 55° C. and one-half per cent. phenol should be added. The administration should be at ten days’ intervals.