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and state institutions. But unfortunately, this is only a temporary procedure, for when the disease is again introduced, the susceptible individuals contract the disease.
To prevent such recurrences, newer methods have been instituted. These methods, the Schick testing and the giving of toxin-antitoxin to the susceptibles, have been tried out extensively in the schools of New York for a number of years. The purpose of this new method is to produce an immune population.
Newer Methods—Schick test and Toxin-antitoxin Immunication. The Schick test is a simple clinical test devised by Dr. Schick, who in 1913 presented it to the profession as a very convenient clinical method of determining the susceptibility of various individuals to diphtheria. The test is local skin test and not a general reaction. It is performed by injecting a very minute amount-.2 of a cubic centimeter of diluted diphtheria toxin, into the superficial layers of the skin of the forearm. Some individuals have a susceptibility to the protein in the material and have a pseudo or false reaction which does not mean that the person is susceptible to diphtheria. To rule this out, the control injection of heated toxin is given with the non-heated toxin, and by comparing this with the other injection the pseudo or false reaction can be definitely determined. So we use .2 c. c. of diluted diphtheria toxin heated to 75° C. for 10 minutes, injected into the superficial layers of the skin of the forearm for this control. If the individual has enough antitoxin in the body, or in other words is immune, the site of injection of unheated toxin will show no redness or induration. But if the individual has no immunity, a red area 3 or 4 cm. in diameter will appear at the site of injection in 48 hours and persist for 96 hours. The Schick test is read as a preliminary at 48 hours and final at 96 hours; positive if the test is red, and there is no redness on the control. It is called negative if there is no redness on either the test or the control; pseudo or false if in 48 hours there is the same amount of redness and induration on the test and the control. Both of these reactions fade to the same extent in 96 hours. Combined positive if in 48 hours the control shows less or about the same amount of redness and induration as the test, but in 96 hours it fades while the test does not fade in this length of time.
The susceptibility as shown by this Schick test varies considerably among various individuals and ages; Drs. Park and Zingher(2) found in the Brooklyn schools among 30,000 children from 6 to 12 years of age, that 16 to 72 per cent were susceptible and the average susceptibility was 41.5 per cent. In the Manhattan schools, they found among 52,000 children from 6 to 12 years of age, th at 13 to 67 per cent were susceptible with an average susceptibility of 30 per cent. By age group they found that
for the first 3 years 60 per cent were susceptible; for the 4 and 5 years, A0 per cent were susceptible; 6 to 10 years, 35 per cent were susceptible; 10 to 20 years, 25 per cent were susceptible; 20 to 40 years, 18 per cent were susceptible, and over 40 years, 12 per cent were susceptible.
A few years ago it was discovered that the mixture of diphtheria toxin when combined with a certain amount of antitoxin and administered to guinea pigs, made them after a certain length of time, immune to diphtheria. Continuing this experimentation, the present day immunizing agent of toxin-antitoxin, has resulted. Toxin-antitoxin is a combination of toxin and antitoxin which is given in 1 c. c. doses subcriarccus; at veekly intervals, for three doses. The immunity produced by this toxin-antitoxin is not immediate, as in the case with antitoxin, but rather takes a variable length of time ranging from twelve weeks to one year,
The first injection of toxin-antitoxin gives immunity to about 50 per cent of those taking it; the second injection, 70 per cent and the third injection, 80 per cent. This immunity develops in from 8 to 12 weeks, and at the end of three months, 20 per cent of those who have received the injection are still susceptible. But during the year following this injection, half of this 20 per cent develop immunity without further toxin-antitoxin. Thus one series of toxin-antitoxin injections gives, in three months, im munity to 80 per cent, and in one year, immunity to 90 per cent. There is left then, 10 per cent of these susceptibles who need second injection of toxin-antitoxin. This cent may be detected by means of the Schick test, given one year after the toxin-antitoxin injections. And all of those found to be susceptible can be definitely immunized by the second series of toxin-antitoxin injections. The immunity so produced lasts about six years, and perhaps for the rest of the life of the individual.
The reactions accompanying the injection of toxin-antitoxin are dependent to a large extent upon the age of the individual, slight local reactions are present in the young children, moderate local in the older children, while about 10 per cent of the older children have severe local and constitutional reactions; adults have slight, moderate or quite severe local, or slightly moderate or severe constitutional and local reactions. These reactions are less severe than typhoid innoculation and are not due to the toxin or antitoxin but rather the protein in the material.
5,175 patients in eight state institutions in Iowa have had the Schick test. In this number 1,605 were found to be susceptible. Up to the present date, 1,012 of these have received the three injections of toxin-antitoxin. Thus, as far as we know, there are around 593 susceptibles who have not been immunized.
We have been somewhat disappointed in that these 593 have not received the toxin-antitoxin immunization.
The susceptibility as found in each institution, varied considerably, not only due to difference in group, but also due to difference in the patients themselves. One striking thing brought out in the work this past one year and a half, is the fact that the female patients showed a higher susceptibility than the male patients. At the Mount Pleasant State Hospital, where 1,000 insane received the Schick test, the female susceptibility was 27.5 per cent while the male was 20.8 per cent; at Independence State Hospital, where 1,197 insane were tested, the male showed 24 per cent while the female, 35 per cent. At the Training School for Girls at Mitchellville, where 204 girls were tested, the susceptibility was 55 per cent while at the Training School for Boys at Eldora, where 331 boys were tested, the susceptibility was found to be around 27 per cent. The age range of each of the groups that are compared are about the same.
One peculiar reaction complained of by a superintendent of one of the state institutions was that accompanying a positive Schick test which he had. He was aware of a general malaise which lasted for a day or so. This malaise was also complained of by a few patients at this same hospital. The Schick test in this superintendent gave a local and constitutional reaction and at times now the area where the test was given will burn and itch. This is the only instance among the 5000 Schick tests in which a general reaction has been complained of by anyone.
The reactions obtained from the injections from the toxinantitoxin have been slight as a whole and even in adults the reaction has not been great. From the 90 given toxin-antitoxin at the Soldiers' Orphans' Home, about 15 children had local and constitutional reactions enough to warrant bed rest for a day or so; at Mount Pleasant State Hospital of the 237 insane, mostly adults, who received the injection, only 7 had very severe local and constitutional reactions. At Woodward, of the 110 epileptics, only 8 had severe local and constitutional reactions.
There have been no disastrous results from these 1,000 immunized. One child had a flare-up of a chronic nephritis immediately following the injection, but it quieted down very nicely under appropriate treatment.
In carrying out the work the following institutions have been visited and all the patients have received the Schick test. The susceptibiles have been given toxin-antitoxin in all but three of the institutions.
Soldiers' Orphans' Home, Davenport,
Juvenile Home, Toledo, Iowa,
The work was begun at the Soldiers' Orphans' Home at Dav. eport in the summer of 1921, followed by work at Independence State Hospital in June, 1922, and all the other institutions were visited during the summer of 1922.
Several important facts have been brought to our attention during the course of the work. In performing the Schick test to be sure that the test will be absolutely accurate, and also in carrying out the toxin-antitoxin immunization, certain points must be borne in mind.
1. The toxin for the Schick test must be reliable, not only
(b) .2 cubic centimeters of the solution, no more and no
and to rule out the possibility of reading a test positive when it really is a pseudo or false test. 4. Great care should be taken in reading a test and if in doubt, it is much safer to err on the safe side and call a doubtful test positive, rather than negative. 5. To protect patients arriving in the institution for the first time, they should have the Schick test as soon as possible or if it is not practical to use this test, they should receive the three injections of toxin-antitoxin. 6. Due to the fact that the first series of toxin-antitoxin gives immunity to 90 per cent insde of one year, it is very inportant that the 10 per cent who are still susceptible should be detected by means of the Schick test. All those who have received the toxin-antitoxin should, one year from that date, receive the Schick test, and the susceptibles, receive the second series of toxin-antitoxin immunization. 7. Care should be taken in the giving of toxin-antitoxin to those patients with chronic lesions such as chronic nephritis for this may cause a flare-up of the old condition.
(1) Mortality statistics 1920, Department of Commerce, Bureau of the 21st Annual Report.
(2) Park W. H. Toxin-antitoxin Immunization against Diphtheria. J. A. M. A. 79 1584 (Nov. 4) 1922.