THE MODE OF INFECTION AND ETIOLOGY OF SIMON FLEXNER, M. D. Member, Public Health Council and Director of Laboratories, Rockefeller Institute for Medical Research I The two problems of uppermost interest in respect to epidemic poliomyelitis are: first, the mode of infection, and second, the nature of the specific microorganism causing the disease. I propose to deal briefly with these two aspects of the subject. Two views are entertained regarding the mode of infection; according to one, the infectious agent of the disease is communicated by personal contact; according to the other, it is conveyed by the stable fly. The differences involved in these two conceptions are fundamental, and hence the practices looking toward prevention of the malady based on them must be wholly different, if they are to achieve the result desired. For that reason it is imperative that the validity of the two doctrines be carefully scrutinized and appraised. Let us examine first the evidence available bearing on the insect conveyance of the disease. This notion was suggested, in the first place, by the seasonal prevalence of epidemic poliomyelitis, which is predominantly a disease of midsummer and early autumn. However, it is not strictly speaking thus narrowly limited in incidence, since cases occur in the spring and even in the winter months, although they are few in number. In the second place, the notion is supported by the rural character of some epidemics, as well as by the relatively wide distances which separate many of the cases. In these instances, however, the peculiarities are of degree rather than of kind. Epidemics of poliomyelitis prevail also in towns and cities, and cases may be closely associated as well as widely separated. The notion of insect carriage received for a time the support of experimental evidence, without which it would have remained merely a suggestive possibility; and the wide currency which this notion has obtained among the laity depends wholly on an imperfect experimental foundation which has now been largely disproved. At the Congress of Hygiene and Demography held in Washington in 1912, Dr. M. J. Rosenau of the Harvard Medical School announced, as will be recalled, that he had succeeded in communicating experimental poliomyelitis to several monkeys by permitting stable flies to feed first on monkeys inoculated intracerebrally with the poliomyelitic * Reprinted from the Journal of Diseases of Children, May, 1915 virus, and then on normal monkeys. Although the studies which he reported were then incomplete and he made his announcement in a judiciously tentative fashion, he expressed the opinion that the flies might carry the infective agent, and also that in conveying it from one human being to another an intervening period of time was necessary, during which the virus underwent some change of development within the insect host. This announcement was followed very quickly by a confirmatory one emanating from Anderson and Frost of the U. S. Public Health laboratory in Washington. No satisfactory explanation of the successful experiments performed. by Rosenau and by Anderson and Frost has thus far been offered, since in no other instance have confirmatory results been obtained. The great importance of the subject led immediately to a repetition of the experiments in several laboratories in this country and in certain laboratories abroad, without yielding a single instance of positive infection. Moreover, Anderson and Frost themselves a little later announced that they had failed subsequently to repeat their earlier successful experiments. Without pursuing this topic further, we may now turn our attention to the other conception, namely, that infection in poliomyelitis is conveyed through personal contact. In considering that view of the mode of infection it is necessary at the outset to have an understanding of the clinical types of poliomyelitis. So long as the affection was conceived of as a frankly paralytic disease in all instances, it was impossible to trace the connection of cases one with another, but once it was determined as was done by Wickman — that epidemic poliomyelitis assumes nonparalytic and ambulant forms, the subject of the mode of infection was opened up to restudy and to a wholly new interpretation. The proof of the existence of abortive and ambulant forms of poliomyelitis is not clinical merely, but depends also on laboratory findings. The several laboratory findings may be stated briefly to be the following: the detection of changes in the cerebrospinal fluid; the demonstration of neutralizing immunity principles in the blood; and the determination of the presence of the virus of poliomyelitis on the upper respiratory mucous membrane. The changes in the cerebrospinal fluid consist of increased cellular content and the presence of globulin; the two conditions may coexist. The new cells are chiefly lymphocytes. The neutralizing properties of the blood depend on the appearance in the serum of immunity principles absent from the normal blood, which correspond to similar immunity principles arising after a frank attack of paralytic poliomyelitis. The virus of the disease has been detected on the nasal and pharyngeal mucous membranes in such quantity and quality as to make possible the communication of poliomyelitis to monkeys. The unmistakable demonstration, both by clinical observation and laboratory tests, of the existence of abortive and ambulant cases of epidemic poliomyelitis - many of which may and do escape detection indicates how wide, indiscriminate, and unsuspected the distribution of the virus by personal contact may readily become. - But the facts now in hand carry us beyond the distributing power exercised by the frank and abortive ambulant cases, since it can now be affirmed that epidemic poliomyelitis is one of the diseases in which both healthy and chronic carriers of the microbic agent of infection arise. The few healthy carriers thus far detected consist of persons who have been in very close and intimate contact with persons acutely ill with poliomyelitis; for example, the parents of a paralyzed child. The few instances of chronic carriers now known consist of persons who have recovered from an acute attack, but in whom at the expiration of several months the virus has been detected, by animal inoculation, on the upper respiratory mucous membrane. The two classes of potential carriers of the infectious agent last mentioned add materially to the possibility of wide dissemination of the virus. It is very important, now that the existence of healthy and chronic carriers of the infectious agent of epidemic poliomyelitis is established, that there should not arise undue concern regarding the dangers of conveying the disease, while the fact should be taken into account in devising measures for the prevention of the conveyance. Possessing as we do at present only the imperfect means of animal inoculation for detecting the virus of poliomyelitis, still it appears that the healthy and chronic carriers are not more numerous in this disease than in many other infections of more common occurrence. Given, therefore, the possibility of the distribution of the virus being effected by, first, the frankly ill, second, the slightly ill, third, healthy, and fourth, chronic carriers, the striking discrepancy noted between the prevalence of cases in small, sparsely populated rural communities and the more thickly populated towns and cities at once disappears. To sum up the aspect of the subject concerning the mode of infection, we may now state emphatically that the indications are all in favor of personal communication of the virus. Hence the measures which we seek to put into effect against the introduction and spread of epidemic poliomyelitis should now be based on the conception of the personal factor as paramount, and not on the notion of insect carriage. II I turn now to the question of the nature of the virus or microorganism causing epidemic poliomyelitis. You will recall that the virus is filterable, that is, it passes through the pores of earthenware filters which exclude under similar conditions the ordinary bacteria. We are now acquainted with a score or so of diseases in man and animals definitely proved or believed to be caused by parasites belonging to this filterable class. It is self-evident that these parasites are very minute; and because of their minuteness it has until recently been doubted whether they had actually been viewed under the microscope. About two years ago, Dr. Noguchi and I announced that cultures of a very minute organism had been obtained which might be regarded as the possible microbic agent of epidemic poliomyelitis. The cultures were derived from the central nervous organs of human beings and monkeys who had had poliomyelitis. As evidence of the nature of the cultures it could then be stated that experimental poliomyelitis had been produced in monkeys by inoculation of the cultures. We have recently confirmed. this result in an interesting manner. The culture employed for inoculation had been isolated about eighteen months before and had gone. through a number of generations in artificial mediums. It was cultivated finally in a mixture of ascitic fluid and broth, and the fluid carrying large numbers of the micro-organisms which are of extremely minute size was injected, in some cases intraspinally, in others intraperitoneally into rhesus monkeys. The injection produced no immediate effect; indeed, a single injection caused no effect whatever. But when the intraperitoneal and intraspinal injections were repeated three or four times, the animals developed paralysis, and the paralyzed animals showed the peculiar histologic changes of the central nervous system indicative of poliomyelitis. In other words, these experiments showed that a culture of the micro-organism mentioned, long removed from the nervous tissues, is capable of causing infection of monkeys, and that by this means the symptoms and lesions of epidemic poliomyelitis are produced. The fact that several inoculations of the culture were required to cause infection agrees with observations previously made by Lewis and myself, that when a subminimal dose of the usual virus of poliomyelitis is injected into monkeys, no effect is produced; but when the subminimal injections are repeated, paralysis may suddenly supervene. The two sets of observations are, therefore, in accord. SUMMARY The data which I have had the pleasure of laying before you have led me to believe, first, that the microbic agent of epidemic poliomyelitis is present in the nasal and buccal secretions and is carried by persons, not insects, and communicated by them in such manner as to gain access to the upper respiratory mucous membranes of other persons, among whom a portion, being susceptible to the injurious action of the virus, acquire the infection and develop the disease. The clinical variety or form of the disease which they develop may be the frankly paralytic, the meningitic, or the abortive and ambulatory in which no severe symptoms whatever appear. But however the persons may be affected, they become potential agents of dissemination of the virus of poliomyelitis, as do a number of healthy persons who have been in intimate contact with those who are ill, and another group of persons who have recovered from an acute attack of poliomyelitis. These several classes of infected or contaminated persons constitute the active means through which the virus is spread and to the control of which sanitary measures designed to prevent epidemics must be directed. Finally, the virus or microbic agent of epidemic poliomyelitis appears now to have been cultivated and to consist of minute globular bodies, capable of being distinctly viewed under the high powers of the microscope. THE DEVELOPMENT OF THE LABORATORY SERVICE OF THE STATE* A. B. WADSWORTH, M.D Director, Division of Laboratories and Research The laboratory of the Department of Health at Albany has been established for twelve years. It was organized to prepare and distribute antitoxins and for the past five years diagnostic examinations for diphtheria, tuberculosis and typhoid fever have been undertaken. In 1906 chemical and bacterial examinations of water samples were made for the first time. Within the past year this work has been completely reorganized and extended in scope, with the object of bringing to physicians and health officers, wherever they may be located in the State, the advantages of a modern laboratory. A year ago last February, on taking charge of the work, I found a brick stable and an adjoining two-story frame structure with numerous lean-to additions and sheds, in which were housed a dozen or more horses and a laboratory staff of seventeen workers. The buildings leaked badly, the street was not paved and for two months during the spring the laboratory was almost inaccessible. Everything had to be carried to and from the laboratory by hand. With the accumulation of refuse and the complaints of neighbors on all sides and chaos within and without, the outlook was not altogether encouraging to a newcomer. The toxins were prepared, the horses bled and the antitoxins concentrated, all in these narrow quarters. The stablemen looked after the horses, inoculated them *Abstract of a paper read at the meeting of the New York Academy of Medicine, May 6, 1915 |