For many years investigators have been searching for the cause of measles. Hektoen in 1905 did some very interesting work in this field. He showed that blood of an early case of measles, after being transferred to ascitic broth and kept in an incubator for twenty-four hours, was still able to transmit measles to a person who had never had the disease. He also noted that no growth appeared in the culture fluid and therefore concluded that the virus was too small to be seen by the microscope. A number of other investigators studied this subject and apparently proved that the virus was readily filterable. They also proved that monkeys could be infected, and that they then frequently showed fairly characteristic symptoms of measles.
In our laboratory rabbits were also shown to develop a rash after an injection of throat secretion taken from early cases of measles. Some two and one-half years ago work done in the Research Laboratories of the Department of Health showed that the culture fluid, inoculated with the filtrate of the nasal secretion of an early case of measles, developed a toxin which, when injected subcutaneously, seemed to be somewhat diagnostic of the absence or presence of immunity. A green streptococcus similar to that studied by Tunnicliff was found. On further study, however, the results of skin tests were not found to be consistent. For this reason these findings were not published, especially as we thought that the germ causing the disease was ultra microscopic.
Early in 1926 Tunnicliff published an article citing more strains of green streptococci in all cases of measles. These she had already drawn attention to several years ago. She noted in tests that the culture fluid containing the dead streptococci when injected into the skin of non-immunes was toxic, but it was not toxic to those who were immune and there therefore diagnostic of immunity.
Those children who had had measles very seldom showed any effect from the intracutaneous injection of a 1:40 dilution of the culture fluid, while those who had not had measles as rule did show effects. Later in the year Ferry, of Detroit, added further information by showing that a culture, obtained from the blood of an early case of measles, made a soluble toxin, which, after separation from the streptococci and injection into animals, produced an antitoxin. Cultures obtained by us from Dr. Tunnicliff and Dr. Ferry proved to be strains of practically the same organism. At the present time they make the following claims:.
These organisms are constantly present in the earliest stages of the disease. By using the toxin or the toxin and culture of these strains for the skin test, the immunes can be differentiated in almost all cases from the non-immunes. Antitoxic and antibacterial antibodies are produced by injections of the culture and its toxin. An injection of this antiserum acts as a preventive against measles in those who have not been exposed for more than four days. Just as convalescent human serum there are some failures.
The serum from the treated animals, when injected into the skin of a developing case of measles before the rash has appeared, will prevent the development of the rash so that an unchanged area of the skin remains surrounded by the rash.
Owing to these findings, chiefly to Tunnicliff but also of Ferry, the Research Laboratory has again applied itself to an intensive study of the etiology of measles. The special study now in progress was made possible through a grant of money from the Milbank Memorial Fund. Our investigations have developed certain findings which make it difficult to accept the conclusions of Tunnicliff and Ferry. It is only fair to state that we were skeptical of these findings before any of our experimental work was done; it was difficult for us to believe that measles could be due to one of the strains of the streptococcus viridans in the same way that scarlet fever is due to one of the hemolytic strains. Soon after a child is exposed to scarlet fever, if he is to become infected, signs of inflammation appear in the throat and the disease is communicable.
A child exposed to measles, however, is entirely well and free from danger of transmitting the disease for about eight days. After this period the first signs of the disease develop and it becomes extremely communicable. When the rash has disappeared the communicability disappears. A case of scarlet fever, however, may still spread infection during convalescence; and we know that there are scarlet fever carriers. Measles, on the other hand, almost immediately after the completion of the rash, ceases to be communicable.
We therefore tried not only to corroborate the findings as to the presence of streptococci, which indeed we already knew from our previous work to be correct, but we tested cases for the presence of the streptococci during the height of the disease, during convalescence, and after recovery. We found the streptococci practically always present. During the height of the disease they were present in enormous numbers. They were, however, also present in fairly large numbers during convalescence and after recovery. Also, we found that the streptococci were of many strains just as is the case with influenza bacilli in different cases of so-called influenza. These findings seemed to us to offer very serious objections to considering these organisms as the true cause of measles.
We found, just as Tunnicliff and Ferry had found, that we could produce an antitoxin and other antibodies effective against the toxin produced in these organs. We have tried the diagnostic skin test not only with our toxins and our mixed toxins and organisms, but also with those we got from Dr. Tunnicliff ad Dr. Ferry. The results were similar to those we had obtained two years ago from the culture that we had isolated at that time. The skin reactions gave no significant difference between the immune and those not immune. It seemed to us more likely that the moderate immunity to these toxins frequently developed during an attack of measles was due to an incidental reaction caused by the growth of these organisms in the tissues whose resistance had been lowered by the true virus of measles.
Unfortunately we were unable to properly test the use of the anti-measles goat serum supplied by Dr. Ferry and by Dr. Tunnicliff respectively as a preventive of measles in young children who had been exposed. We had one special opportunity for observation in New York in which a number of children were believed to have been exposed. One-third of this group of children were given preventive inoculations of convalescent measles serum, one-third were given the goat serum and one-third were not given any serum.
As none of these cases developed measles the test was valueless. We sent some of the serum to Syracuse where there had been a very definite exposure. Unfortunately the exposure was over four days in duration and that in itself might have been a reason why the goat serum did not prevent the development of measles.
Degwitz of Germany has reported recently that he has been able to obtain from the blood an ultra microscopic virus which can be transferred from one culture fluid to another for many generations, and that even after the enormous dilution of fifteen transfers it has transmitted measles to monkeys and to several human beings. The culture fluid in which this virus grows is free of all visible micro-organisms.
To sum up, therefore, Dr. Tunnicliff, and to a less extent Dr. Ferry, have claimed to find strong evidence that measles is due to a special type of streptococcus just as scarlet fever is; that the toxin can be used in skin tests to differentiate the immune from the non-immune, and that the serum from animals immunized against this streptococcus is as potent as the serum from the convalescent cases of measles to prevent the development of infection in exposed children. Our own work has corroborated many of their findings, but has also discovered certain facts which make it difficult to accept their views as to the relation of the organism to measles without further corroboration.
We are therefore at present extremely doubtful as to whether the Tunnicliff organism is the cause. Degwitz, who is well known because of his wide use of convalescent measles serum, believes, on the other hand, that he has demonstrated that an invisible virus which can be cultivated is the true cause. It is hoped that the physicians of this city will refer to the Hospitals of this Department a number of cases of measles in the first stages of the disease, so that we can more rapidly reach a final decision on these debated points. Request is also made by the Bureau of Laboratories for notification of children that have been exposed to measles so that the anti-toxic serum may be tried as a preventive, as to which very favorable reports have been received from Chicago.
WILLIAM H. PARKS, M. D..
City of New York, Department of New York.