Chapter XV: Protective Vaccinations (3)

As regards vaccination against diphtheria of persons who are in good health but are especially exposed to infection, the question must be accepted as settled in the affirmative.

[Sidenote: [522]]

From the commencement of our attempt to cure diphtheria by means of a specific serum, the necessity was seen of protecting children who were in contact with the sick persons against this disease. Small quantities of serum were injected into such children for protective purposes. The first results communicated in 1894 by Roux to the Congress at Budapest being very encouraging, an attempt was made to give the greatest possible extension to the system of vaccination by antidiphtheria serum. In the following year, 1895, fairly numerous statistics had been collected, and Torday[824] at Budapest, Kurth[825] at Bremen, and Rubens[826] at Gelsenkirchen were able to publish a number of favourable statistics. Soon afterwards, however, a fatal case occurred in the family of a well-known Berlin doctor, Langerhans[827], an accident that started a violent controversy and stirred up an active campaign against serum. Langerhans’s son, a boy aged 2 years, in good health, was inoculated with a small dose (1·2 c.c. of this serum) and succumbed about a quarter of an hour afterwards with symptoms of suffocation. The post-mortem examination made by Strassman[828] showed the cause of death to be suffocation in consequence of the aspiration of food into the respiratory passages during the act of vomiting. An examination of the serum used by Langerhans did not reveal any toxic action on animals or any contamination by micro-organisms. All to no purpose, the serum was held answerable for the death of the child, and an attempt was made to demonstrate at almost any cost that its use in human practice was extremely dangerous. Gottstein[829] joined in chorus with the over-excited opinion and published a denunciation of vaccinations by antidiphtheria serum. He collected from the literature of both hemispheres four cases, in all, in which death had occurred some time after the injection of this serum into children not suffering from diphtheria. A perusal of the description of these cases is sufficient to convince one that the death could in no sense be attributed to the serum, and that it could be explained much more easily by the fatal action of the streptococcus, the cause of the non-diphtheritic affections of the children that died.

[Sidenote: [523]]

The ineptitude of this denunciation must have done much to calm public opinion, and in September of the same year, 1896, C. Fränkel[830], in a report presented to the German Association of Public Hygiene, was able to give a review of the state of the question of vaccination against diphtheria, summing up in favour of the use of the specific serum. “Taking into consideration the data collected,” he remarks, “it is scarcely possible to doubt the value of immunisation by serum, so that we may say positively that we are now treading a path which will lead us to great and important results.” This very favourable opinion was due in great measure to the vaccinations carried out in the wards of Heubner’s Clinic at Berlin[831]. At first, injection of the antidiphtheria serum as a protective into patients who were found in the immediate vicinity of the children attacked with diphtheria (contacts) was deemed to be sufficient: but in consequence of the results obtained by this method it was decided (starting from January, 1896) to inject all children who came into the hospital. During the first period there still occurred a few cases of diphtheria contracted in hospital, but from the moment systematic and general vaccinations were introduced not a single new case occurred.

The immune condition of the vaccinated children is maintained for three to four weeks. After this lapse of time some of them contracted diphtheria. But it was sufficient to introduce revaccination at the end of this period to prevent the outbreak of any further case of diphtheria in Heubner’s wards. Results quite as favourable and as convincing were obtained in the department for children attacked by scarlet fever.

[Sidenote: [524]]

The amount of serum injected varied, but it was usually given in doses of 1 c.c. containing from 200 to 250 I.E. (immunising units of Ehrlich). The serum was always found to be innocuous except in certain cases where it set up erythemata of greater or less extension. In 460 injections 20 cases of these exanthemata were produced, that is to say 4·34%. The frequency of these complications was not proportional to the amount of serum injected. According to the figures communicated by Löhr the largest doses of the serum employed did not produce exanthemata more frequently than did the smaller quantities. Thus 117 injections of 1 c.c. only were followed in five cases by these erythemata, which corresponds to 4·27 per cent. The hope of diminishing the frequency of the exanthemata by diminishing the amount of serum injected was therefore not realised. This fact lends support to the conclusion above formulated as to the exaggeration of the importance of the measurement of serum. If it could be established that small quantities of serum rich in antitoxin caused cutaneous eruptions less frequently than did stronger doses there would certainly be a great advantage in using serums containing a very large number of immunising units for vaccination. Perhaps serums having a great antimicrobial power but of comparatively low antitoxic potency might even render great service in protective treatment. Future researches undertaken in this direction alone can give us information on this subject.

In 1896 the vaccinations in Heubner’s wards were discontinued, but the reappearance of diphtheria in 1897[832] rendered their recommencement necessary. 500 children were vaccinated each with 200 immunising units. Following this no case of diphtheria broke out. The eruptions were rare and slight.

The increasing extension of the use of antidiphtheria serum for the cure of the disease after it has broken out has led to a greater development in its use as a preventive measure. Thus, in the countries where diphtheria is endemic, vaccinations by serum are now practised very extensively. In Russia, which is one of the great hotbeds of this disease, vaccinations by antidiphtheria serum are frequently practised.

[Sidenote: [525]]

At the Congress of Russian doctors at Kasan in 1896, Vissotsky communicated the result of 2,185 vaccinations which gave a morbidity of 1·3%, a morbidity that must be regarded as very low indeed. A well-known Russian physician for children’s diseases, Rauchfuss[833], who cites these figures, has collected several other facts concerning the prophylactic injections of antidiphtheria serum followed by good results. In the government of Woronetz, according to the statements of Ouspensky[834], out of 738 vaccinated persons diphtheria occurred in 2·2 per cent., which again may be considered a favourable result, especially if we take into account the great extension of diphtheria in this country. In Podolia, out of 537 children vaccinated in 1895, only four cases of diphtheria occurred, a morbidity of 0·74%. In the government of Kherson, one of the great centres of diphtheria in southern Russia, the results appear to be less favourable: out of 543 children which received a protective inoculation, 21 contracted the disease (or 4·6 per cent.), of which five died. If we study these statistics more closely[835] it will be seen that these results are far from being unfavourable. The protective inoculations were made only once and with somewhat small doses, nevertheless many of the cases of diphtheria broke out only at a late period, sometimes more than nine months after the injections had been made. Now, it is proved that these injections, although very efficacious, produce their action for a very short time only, for a few weeks at most. Of the five fatal cases, four did not occur until 2, 4½, 6, and 9½ months respectively after the protective inoculation. It is impossible to look upon these statistics as affording proof of the inefficacy of the serum. The fifth case is the only one that occurred within a short time (15 days) of the injection, and in this instance only 150 immunising units had been injected.

A detailed study of the other examples of antidiphtheria inoculations in the government of Kherson leaves a very favourable impression. Out of 90 children inoculated by Wecker[836] in the district of Elisabetgrad not a single one contracted diphtheria, which is the more remarkable as at the time of the inoculations there existed in the same families 14 cases of diphtheria; the chances of contamination were thus great.

[Sidenote: [526]]

Recently, on the occasion of the outbreak of a great epidemic in Paris, the question of vaccinations by serum was again raised and earnestly discussed at the Paris Hospitals Medical Society and at the Society for the Study of Children’s Diseases. Voisin and Guinon[837] communicated the history of an epidemic amongst the staff at the Salpêtrière Hospital in the wards of idiot children, “against which protective serum treatment was remarkably effective and absolutely innocuous.” The serum was injected, in the case of children more than 10 years of age, in 10 c.c. doses, and into the rest in 6 c.c. doses. This measure brought about first an abatement and then cessation of the epidemic. The immunity after a single injection lasted from two to three weeks, and the few cases of diphtheria which broke out amongst the infected children were distinguished by their great mildness. Erythemata and other post-injection complications were insignificant, so that the protective use of the serum was fully justified. Only a small minority of the medical men who took part in the discussion spoke against the antidiphtheria vaccinations; once, indeed, a reference was made to the case of Langerhans’s child, although its death was certainly not due to the serum. It is true that in families where it is possible to keep the children under careful observation and to intervene at the appearance of the first symptoms of diphtheria, the preventive injections may be dispensed with, but in practice these favourable conditions are rarely realised, and the prophylactic serum treatment is then of great service in preventing the outbreak of the disease.

Netter[838] communicated to the Society of Pediatrics a summary of 32,484 observations on the prophylactic injection of antidiphtheria serum. Of this number 192 cases were noted in which the diphtheria broke out in spite of the injections, corresponding to 0·6 per cent. of those treated. These figures, however, included all cases of the disease which occurred up to thirty days after the injection. Now, the immunity is often less durable than this, and it may disappear more or less completely twenty days and sometimes even fifteen days after vaccination.

Netter himself made great use of antidiphtheria vaccination. It was his custom to propose to the parents either a protective inoculation at once or a systematic precautionary bacteriological examination of the throats of the children not yet attacked. He regards the first method as preferable. According to the latest statistics which he was kind enough to communicate to me, of 152 children (in 50 families), 91 of whom received protective inoculations, not one contracted diphtheria: whilst in 239 other families where the children had not been inoculated there were 52 cases of diphtheria, with 10 deaths. Many practitioners in Paris have now pronounced themselves in favour of protective injections of the serum, and the Society of Pediatrics, at its meeting on 11th June, 1901, concluded the discussion of this question by proposing the following resolution: “The Society of Pediatrics, affirming that protective inoculations present no serious danger and confer a very considerable amount of immunity for some weeks, recommend their use when children are gathered together in numbers, and in families where a scientific supervision cannot be maintained.”

The large amount of evidence collected on this question leaves no doubt as to the real efficacy of vaccinations by antidiphtheria serum.

[Sidenote: [527]]

The summary of the results obtained by vaccination in the 12 diseases of man and of animals I have just placed before my readers cannot pretend to serve as a detailed guide to prophylactic practice. My object has been merely to concentrate into one chapter the principal data upon which this very important question rests, to bear witness to the progress which has already been realised, and at the same time to show that the scientific study of immunity is in very intimate relation with its practical application. It is evident that the road is far from traversed to its terminus, for there are many infective diseases in which vaccinations cannot be employed, but it is none the less certain that the path which has led to so many important and useful results should still be followed in studying problems which up to the present we have been unable to solve.