CHAPTER XV
PROTECTIVE VACCINATIONS
Vaccinations against I. Small-pox.—II. Sheep-pox.—III. Rabies.—IV. Rinderpest.—V. Anthrax.—VI. Symptomatic Anthrax.—VII. Swine Erysipelas.—VIII. Pleuropneumonia in the Bovidae.—IX. Typhoid Fever.—X. Plague.—XI. Tetanus.—XII. Diphtheria.
In the preceding chapters I have attempted to present to the reader a general view of the phenomena of immunity against infective micro-organisms and against their toxic products. I shall now attempt to give a review of the facts acquired in connection with the prevention of the infective diseases of man and of the chief domestic animals by means of vaccination. Vaccinations as we know can be carried out either with viruses the constituents of which have not as yet been recognised, with micro-organisms grown on various nutrient media, with virulent or attenuated micro-organisms, or with microbial products deprived of the micro-organisms by which they have been built up. In addition to these methods we may vaccinate with protective or antitoxic serum and other body fluids, with normal serum, or with a whole series of fluids not excepting water.
I. Vaccination against small-pox.—We naturally commence the series with vaccination against small-pox, which is one of the oldest and one of the best known, having been practised in every country in Europe for more than 100 years. Small-pox, a very contagious and fatal malady, was very rife in the 18th century. Large cities like London and Paris were severely affected. One-tenth of the total mortality was due to this disease. According to statistical information, very exact for that epoch, the deaths from small-pox in London during the course of the second half of the century (1751–1800) numbered more than 100,000 (102,112) persons. During the first half of the same century this disease caused great ravages in France, especially in Paris, where, according to certain statistics (Haeser), about 14,000 persons died in 1716.
Variolisation or “inoculation” coming to Europe from the East, had come into extensive use when, at the end of the 18th century, the discovery was made that cow-pox, the varioliform disease of the Bovidae, produced in persons who milked cows suffering from this eruption an immunity against small-pox. This idea, popular in origin, was known to breeders in England, France, Germany, and Holland; we have thus an indication that this knowledge must date from a fairly distant period. Jenner gave the question a scientific and experimental basis, and it was only after his intervention that vaccination by the contents of the pustules of cow-pox began to spread more generally. During the 19th century an immense amount of material bearing on this question was collected; we have thus been enabled to attain absolutely exact results, and that in spite of the very imperfect state of our knowledge on the etiology of small-pox and of cow-pox. Long ago Chauveau[765] demonstrated that the virus of these diseases must be organised, because that of the vaccine would not pass through a filter. This organism has been carefully sought, but sought in vain in spite of all improvements in microbiological methods. It was thought that the cocci so often found in the contents of the vaccinal pustule was the specific micro-organism of cow-pox. Such was the opinion of the illustrious botanist Cohn[766]. It was soon shown, however, that this was not the case. The cocci, principally staphylococci, are “secondary” micro-organisms which may be absent from the vaccine without its losing anything of its action. A search was then made for the micro-organism of the vaccine among the protozoan organisms. L. Pfeiffer[767] announced the discovery of a species of vaccinal Amoeba. Guarnieri[768] has even described various stages in the reproduction of this hypothetical parasite; but Salmon[769] demonstrated, in a work carried out in the Pasteur Institute, that we had here to deal merely with leucocytes which had entered epithelial cells and had there undergone marked degeneration. Funck[770] thought that he was able to confirm the discovery of the sporozoon of vaccinia, but his error was easily demonstrated (Podwyssozki and Mankowski)[771]. Up to the present, then, we have no knowledge of either the micro-organism of small-pox or of that of vaccinia. We still employ, as formerly, the virus taken from the vaccinal pustule. Even the relations which exist between the two viruses and the two diseases which they have set up have not yet been settled. Several authors believe that the bovine disease is only a modified and attenuated form of human small-pox; whilst others maintain that we have two very different exanthemata, one of which—cow-pox—is capable of setting up immunity not only against itself but also against small-pox.
For a long time, in order to vaccinate against small-pox, the contents of the vaccinal pustules which formed on the human subject after an original inoculation of the virus of cow-pox were employed. But a number of cases of infection by syphilitic virus and certain other accidents caused this method to be abandoned. A number of years ago, however, there spread throughout Europe and into several countries of other continents another method, which consists in vaccination by “animal lymph,” that is to say, by the contents of pustules developed on the skin of the calf. This method was first carried out at Brussels in 1868, under the direction of Warlomont, at the Institute founded by the Belgian Government for the preparation of vaccine. The original virus came from a genuine case of cow-pox and has since been kept up by uninterrupted passage from calf to calf. The virus is introduced into the shaved skin of the region between the groin and the udder as far forward as the umbilicus. It is inoculated superficially into the epidermis by cuts one centimetre long. At the points of inoculation characteristic pustules develop; from these the vaccinal content is withdrawn, on the fifth day in summer or the sixth in winter. The contents are removed by pressure and by scraping the pustules. The scrapings are mixed with water and glycerine. The vaccine thus prepared is put into small glass tubes which are sealed at both ends. This method, with slight modifications, has extended to many other countries, and is carried out either in private establishments or in State institutions as in Germany. For the purpose of purifying the vaccine it is diluted and then allowed to sediment or it may be subjected to centrifugalisation. The object of these measures is to rid the “lymph” of the micro-organisms which accompany it. This object is, however, only imperfectly attained and is moreover accompanied by an attenuation of the vaccinal action. On the other hand, precautions are taken to ensure all possible cleanliness during the operation of inoculation and whilst the calves are under treatment. Thus, great care is taken to disinfect the area of inoculation with alcohol or some other antiseptic and to dress the pustules during the course of their development. Similarly the arms of the patient to be vaccinated are well washed; following in this the rules of asepsis rather than of antisepsis for fear that the vaccinal virus might be destroyed by antiseptic substances. Various instruments are made use of for vaccination and care is taken to sterilise these before they are used. Sometimes the lancet is used, sometimes “plumes à vaccin” or vaccinostyles, or a bistoury of iridio-platinum (Lindenborn) etc.
When the vaccine is of good quality and the operation of vaccination is well done, there is no doubt as to the protective result obtained against small-pox. The observations that have been collected for a great number of years past, in many countries, place this beyond doubt. There are, indeed, statistics from which it is impossible to draw any precise conclusions because they are founded upon too scanty figures or deal with conditions that are too complex. This is the case with the Swiss vaccinations. Certain cantons (such as Zug and Uri) have made vaccination obligatory, whilst others (Bern, Zurich, Lucerne, etc.) some years ago abolished the law which compels the vaccination of all children in infancy. It happened that for some years small-pox had more victims in the cantons of the first group than in those of the second. The opponents of antivariolic vaccination attempted to use this as an argument against the utility of this method. But a more detailed study of the facts clearly shows that it is impossible to draw from it any conclusion whatever. Even in those cantons where vaccination is supposed to be compulsory this law is not carried out rigorously, and the number of persons vaccinated often does not exceed that in the cantons where it is not obligatory.
In order to gain some idea of the utility of vaccinations we must collect statistics on a much larger scale than are those obtainable from the Swiss cantons. Germany furnishes such statistics. Compulsory vaccination was introduced there more than a quarter of a century ago (1874), and statistical information has been collected with great care. With the exception of a slight increase during the period from 1879 to 1885 small-pox has diminished progressively since the proclamation of the new law, and has become so rare that in 1897 there were only 5 fatal cases in the whole German Empire. In the space of 13 years (1886–1898), in a population which embraces two-fifths of the total inhabitants of the German Empire, there were altogether five fatal cases of small-pox occurring in persons who had been successfully revaccinated. Moreover, the majority of the cases of small-pox occurred in the maritime towns or in the vicinity of the frontier of the Russian Empire.
Specially favourable results have been obtained in the German army, in which, even before the law of 1874, vaccination was compulsory. In 25 years there occurred in the Prussian army only two cases of death from small-pox. In summing up the statistical data on vaccination Kübler[772], from whom we have borrowed the above statements, expresses himself as follows: “The history of small-pox must in all cases register the fact that this dreaded disease has, as the result of general vaccination, not only become rare in the German Empire but that it has almost completely disappeared” (p. 365). The example of Germany encouraged several other countries to introduce compulsory vaccination, and Roumania, Hungary, and Italy have in turn promulgated similar laws. Here also it was not long before satisfactory results were obtained. In Italy especially the mortality from small-pox has largely decreased in recent years.
In England, where compulsory vaccination was introduced some time ago, it was abolished in 1898. As the opposition of the people became more manifest, the law, although it continued to exist formally, was carried out very imperfectly. The number of unvaccinated children had gradually increased in such a fashion that in London itself in 1897–1898 it attained the proportion of 24·9%, whilst in certain provincial districts it has oscillated between 78·4 and 86·4%. Under these conditions, the abolition of the law of compulsory vaccination was only the legal sanction of an accomplished fact. According to the details which have been supplied to me by the Jenner Institute in London (which has taken in hand the distribution of vaccine), vaccinations since they are no longer compulsory have become more frequent in England, and the quantity of vaccine distributed has increased considerably. This quantity, however, is not adequate because small-pox has again made its appearance in London in the form of a pretty serious epidemic[773].
In France a law is being framed which will render infant vaccination compulsory. Up to the present this has not been the case, and small-pox from time to time causes considerable ravages, as we may see at this moment in Paris. During recent years the mortality from small-pox in France has been from 90 to 100 times greater than in Germany. It is greater amongst the female population than amongst males; this constitutes a fresh argument in favour of vaccination. Although not compulsory for the whole of the French population, it is so for soldiers and for children who carry on their studies in schools, and it is for this reason that small-pox is rarer amongst males. The most complete demonstration of this is found in the incidence of small-pox in the French army. In spite of a less numerous contingent of troops (451,941–457,677) the mortality from small-pox was greater during the period when vaccination was not yet carried out generally (1885–1887) than during the period (1889–1896) when it was rigorously enforced on a much larger number of soldiers (524,733–564,643). From 13·6 fatal cases per year in the first period the annual figure fell to 6.
It follows, when we take into consideration the whole of the very numerous data at our disposal, that the usefulness of vaccination followed by revaccination after some (5–7) years cannot be seriously called in question. As to the inconveniences that may be caused, they are observed in very rare cases, and then most frequently when impure vaccines are used, or when the vaccinated skin becomes contaminated. According to the German statistics there were registered in the space of 13 years (1885–1897), in 32 millions of vaccinations, 113 fatal cases as the result of infection of the wounds. In forty-six of these it was proved that the small wound had been contaminated by impurities introduced by those attending on them. The remaining 67 fatal cases could be ascribed to the vaccines themselves. We must, however, still regard these cases as too numerous and as being readily avoidable by the adoption of rigorous asepsis. To sum up, the anti-variolous vaccination by the virus of cow-pox constitutes a method of very great value in the prevention of one of the most dreaded of infective diseases, but it is evident that improvement can still be made in this branch of practice. If science should succeed some day, as we may be permitted to hope it will, in finding the micro-organism of vaccinia and of small-pox, and it should succeed in growing it in pure media, it might react very beneficially on the practical application of vaccination. The more simple the methods, the less chance will there be of the occurrence of those unsuccessful cases which, even now, are rare exceptions.
II. Vaccinations against sheep-pox (la clavelée).—Sheep-pox, being a disease very similar to human small-pox and very serious from an economic point of view, the idea was conceived of fighting it by methods similar to those used against small-pox. Since the 18th century there has been practised on a large scale the artificial immunisation of sheep by the inoculation of the virus of the sheep-pox (clavelisation) just as the variolisation of man was practised before the discovery of cow-pox. For this purpose it was necessary to have a considerable quantity of virus; this was obtained by inoculating sheep-pox into the skin of sheep. This inoculation was effected either with a lancet or, according to Soulié’s method[774], by means of a Pravaz syringe. The pustules, developed under these conditions, were generally of large size and capable of furnishing a considerable quantity of the virulent lymph (claveau) used for immunisation. This fluid, when gathered pure, and kept in a closed vessel protected from light and heat, retains its virulence for a long time: unlike what is observed in the case of vaccine, the addition of glycerine destroys the virulence of the lymph pretty quickly. For use, the lymph is diluted with ten times its volume of 2% borated water; the fluid thus obtained is inoculated into the extremity of the tail or of the ear; usually a pustule, which remains single, is formed at the point of inoculation. Clavelisation rarely sets up a generalised eruption which is always serious and sometimes fatal.
In France the law ordains the clavelisation of flocks in which sheep-pox appears; but it interdicts its practice in unattacked flocks;—it is easy to understand the reason for this; in infected flocks all, or almost all, the sheep, gradually become ill and the illness lasts for some time; clavelisation diminishes both the duration and the gravity of the disease; the mortality that it causes, although sometimes very great, the French sheep being very susceptible to sheep-pox, is always much less than that due to a natural contagion;—on the other hand, the clavelisation of a healthy flock, beyond the fact that it may cause considerable losses, is attended by the special danger that it creates centres from which the contagion may invade all the flocks of the district.
But there are countries in which protective and general clavelisation does not present these inconveniences—the countries where the disease is endemic and where the sheep are very resistant to the action of its virus. This is the case in Algeria; sheep-pox exists there permanently without doing much damage; but the Algerian sheep, which take sheep-pox without suffering any apparent illness, communicate to French sheep amongst which they are introduced a very malignant sheep-pox which sometimes kills as many as 50 per cent. of the flock. This explains and justifies the measures recently taken by the Minister of Agriculture, forbidding the importation of Algerian sheep into France unless they have been vaccinated at least a month previously.[775]
In many other countries clavelisation is likewise enacted, being authorised in cases where it may be very useful and interdicted in other cases. In certain countries, e.g. Germany, Holland, and Denmark, clavelisation can be put into force by the Government, which alone has the right to authorise it under certain circumstances.
III. Antirabic vaccinations. Vaccination against rabies has this point in common with those against small-pox and sheep-pox, that it is effected with a virus whose micro-organism is as yet unknown. On the other hand, it is distinguished by its efficacy during the incubation period. When persons are vaccinated during the incubation period of small-pox, or sheep during the same period of sheep-pox, the vaccinations by vaccine and claveau are incapable of arresting the disease and the infections continue to follow their normal course. When, on the other hand, we vaccinate men or animals that have been bitten by mad animals or inoculated with the rabic virus by other means, the antirabic vaccination, with rare exceptions, prevents the development of rabies. This vaccination, taking advantage of the length of the incubation period of rabies, constitutes, therefore, a special type, intermediate between protective vaccination, properly so called, and a therapeutic method of treatment.
It is to Pasteur that science and humanity owe the invention of this method. Aided by his collaborators, especially by Roux, he established in the first place a whole series of important facts on the subject of the rabic virus and of experimental rabies. He then set himself to elaborate a practical method capable of preventing the manifestation of the disease in dogs inoculated with rabic virus and in men bitten by mad animals. He succeeded in solving this problem in 1885.
Pasteur’s antirabic vaccines are prepared from the spinal cords of rabbits that have died of experimental rabies as the result of the inoculation of the virus bearing the name of “fixed virus.” Prepared in the laboratory, this virus presents the characteristic feature that when inoculated under the dura mater of rabbits it sets up in them the first rabic manifestations after an incubation period of six or seven days. The disease soon assumes the typical paralytic form which lasts several days. Whilst the period of incubation presents only very limited variation, the time of death is subject to much greater variation, especially according to the season of the year. Sometimes the rabbits will die on the eighth day after the inoculation of the virus: but death may be delayed one or two days, rarely more.
It is necessary to wait for the natural death of the mad rabbits before the spinal cord is extracted, and not to kill them before this term, for it is only during the final moments of life that the rabic virus is abundant and is distributed uniformly through the whole substance of the organ. After removal from the vertebral canal the cord is suspended in glass vessels containing solid potassium hydrate at the bottom. A whole series of cords so prepared are then kept in a dark chamber heated to 23° C. or thereabouts. The progressive desiccation which the cords undergo under these conditions diminishes their virulence. At the end of several days of this treatment the desiccated cord, instead of producing rabies in 6–7 days in rabbits inoculated under the dura mater by trepanning, induces it after longer periods of incubation. Finally, the cords do not produce even the slightest symptoms of the disease.
The fundamental basis of the Pasteurian method consists in the fact that the desiccated cord, inoculated as an emulsion below the skin of animals, produces in them a complete and permanent immunity against inoculation of the most powerful rabic virus beneath the dura mater. This experiment, frequently repeated on rabbits and dogs, justified Pasteur in 1885 in attempting the first vaccinations of persons bitten by rabid animals, especially dogs. The encouraging results of these early attempts led to the foundation of the Pasteur Institute in Paris, devoted, in part, to antirabic vaccinations. Shortly afterwards, antirabic Institutes were founded in many other European towns, and later in North and South America, in Indo-China, the East Indies, and in Africa. At present there are in France six such Institutes (Paris, Lille, Marseilles, Montpellier, Lyons, Bordeaux), in Russia 9, in Italy 6, etc. The last of these institutions founded in Europe is that of Berlin, where it forms a branch of the Institute for Infective Diseases carried on under the direction of Robert Koch. The foundation of an antirabic institute in Berlin had a very important significance from several points of view. In the first place, it indicates the definite acceptance of the Pasteurian method, a method which has been discussed so long and so keenly. Secondly, it proves that even in a State where there is a highly organised sanitary police, antirabic vaccinations may still be of great service.
Seeing that it was in the Pasteur Institute of Paris that the method of antirabic vaccinations was first elaborated and that it has undergone a very prolonged ordeal, the method there used serves as a model for the practice of almost all other institutes. Although in some of them methods which differ more or less from the original may have been introduced, the fundamental principle upon which they are based remains the same.
According to the Pasteurian method properly so called the vaccinal inoculations are commenced with cords that have been dried for 14 days and have thus lost their virulence. A piece five millimetres long is pounded up with very weak veal broth. Up to 3 c.c. of the emulsion thus prepared is injected below the skin of the flank. The same day a second injection of the same quantity of an emulsion of a cord which has been drying for 13 days is made at the corresponding position on the opposite side. Each day an advance is made by injecting emulsions of cord which are increasingly fresh and the treatment is concluded by the introduction of virulent cords, which have been kept at 23° C. for 3 days only. The ordinary medium treatment lasts for 15 days. On the first 5 days two vaccine injections a day are made. On the last 10 days, when gradually fresher and more virulent cords are employed, only a single injection is made each day. The injections are made with syringes of the Pravaz type and are carried out under conditions of rigorous cleanliness.
If the bites are numerous, or if they are situated on exposed parts, the treatment is prolonged for 18 days and is further distinguished in that the cords of 4 and of 3 days are injected much more frequently.
In especially grave cases, when the bites are on the face and head, the treatment extends over 3 weeks. A more rapid progress is made by making four injections instead of two during the two first days; in this way a greater quantity of the virulent cords is injected than in the first two types of treatment.
The effect of the antirabic vaccinations is usually very good. During the early years of their application the results were fully discussed from all points of view, and no efforts were neglected of seeking out objections of every kind. For the purpose of obtaining rigorously accurate statistics a separate division was made, at the Pasteur Institute, for the cases of persons treated after bites inflicted by dogs whose rabic condition had been demonstrated experimentally (by the injection of an emulsion of the bulb below the dura mater or into the anterior chamber of the eye of the rabbit or guinea-pig). A second and special set of statistics was drawn up of cases where the bites had been inflicted by animals whose rabic condition had been recognised by veterinary examination. Individuals bitten by animals that were simply suspected to suffer from rabies were kept separate.
Thanks to this systematic classification we were able, at the Pasteur Institute of Paris, to establish the fact that the antirabic vaccinations performed on persons bitten by animals that were undoubtedly mad resulted in an extremely low mortality from rabies. Finding it impossible to attack these results, demonstrated with the precision of a laboratory experiment, the adversaries of the Pasteurian method alleged that, quite apart from any vaccination, the percentage of cases of rabies in persons bitten by mad animals is not greater than amongst the vaccinated. A hitch in the application of the new vaccinal method soon demonstrated how entirely unfounded was this objection. At the Bacteriological Institute of Odessa, founded in 1886, that is to say almost immediately after the Paris Institute, the first attempts at vaccination were followed by a mortality from rabies of 5·88 per cent., a figure incomparably higher than that of the Paris Institute. Analysing the probable causes of this want of success it was found that the Russian rabbits, being much smaller than the French ones, furnished far too small an amount of vaccinal matter. This being the case, the introduction of a more intensive treatment was sufficient to cause the mortality to drop suddenly to 0·8 per cent. This fact, added to so many other proofs, finally convinced the most sceptical and brought about a general acceptance of the Pasteurian method.
In course of time the number of cases observed has become very considerable and the experience gained in the manipulation of this method very wide. The improvements made in the details of the vaccinal practice have brought about a progressive diminution in the mortality amongst the persons treated. From 0·94 per cent. in 1886 the mortality (counted from the 16th day after the completion of the vaccinations) fell in 1897 to 0·39 per cent., in 1900 to 0·28 per cent. In the space of 15 years (1886–1900) there have been treated in Paris 24,665 persons, of whom 107 died from rabies, giving an average of 0·43 per cent.[776]. The greatest mortality was registered during the early years of the application of the method, and the rate of the later year’s (1896–1900) oscillated between 0·39 per cent. and 0·20 per cent.
The results obtained in the majority of the other antirabic institutes corroborate those of the Pasteur Institute of Paris. Thus, according to the latest statistics of the St Petersburg Institute[777], the mortality, in 1899, among persons who had completed their vaccinations, was about 0·5 per cent. At Berlin[778] there were treated during the same period 384 persons, of whom 2 died from rabies during treatment, whilst a third succumbed on the 14th day after the close of the vaccinations. Only this latter case ought, according to the principles generally accepted, to be counted as an unsuccessful case, this would give a mortality of 0·26 per cent.
Quite recently, the antirabic treatment has been so reinforced that the treatment terminates with the injection of cords desiccated for two days or even one day only. The results of this intensive treatment have not yet been reported upon.
According to the statistics of the Berlin Institute rabies is far from being so rare in Germany as was, at one time, generally supposed. During the year 1899 its presence was demonstrated, by the experimental method, in 206 dogs coming from various districts. It is in Silesia, Western Prussia, and Posen that rabies in dogs has been observed most frequently.
Antirabic vaccinations have also been performed on herbivorous animals (sheep, goats, cattle, and horses) which are immunised by means of injections of the rabic virus into the veins, according to the method suggested by Nocard and Roux[779], as the result of experiments made by Galtier[780].
IV. Vaccinations against rinderpest. For some time attempts were made to find a means of immunising the Bovidae and other ruminants, susceptible to rinderpest, against this terrible disease, which causes great ravages in regions where it is endemic and greater still in those regions where it only appears in epidemic form. The good results obtained from “clavelisation” suggested the idea of immunising against rinderpest by the inoculation of the rinderpest virus, but all such attempts gave unsatisfactory results, the inoculation setting up a rinderpest as grave, and often as fatal as the natural disease. Only in recent years have we succeeded in elaborating methods of vaccination really capable of coping effectively with rinderpest. Koch[781] went to Cape Colony, where this disease had recently appeared and had caused enormous losses, with the intention of finding a practical method of arresting the scourge. In spite of his technique and incomparable skill he was as unsuccessful in finding the parasite of rinderpest as had been other investigators. The micro-organism of this disease remains unknown. It was necessary, however, to seek a remedy against it. Koch, studying the properties of the bile of animals that had died from rinderpest, recognised that the injection of this bile into normal animals conferred upon them a fairly certain immunity, and this fact served as the basis on which to work out a practical method of combating rinderpest on a large scale. At first this method was received with much enthusiasm, but experience soon demonstrated the inconveniences it often presented. Kolle and Turner[782], who continued the researches on rinderpest in Cape Colony, extolled Koch’s method at the commencement of the epidemic with the object of establishing around the original disease centre an unaffected zone which would interfere with the propagation of the disease. They recognised, however, that this method could not be employed generally, for the reason that it does not set up immunity until the end of eight days, during which period the animals may contract the disease. Further, it demands the sacrifice of a large number of animals in order to provide the vaccinal bile required for the vaccinations; finally, it confers an immunity of short duration only (four to six months).
It was necessary, therefore, to find some method that was more generally applicable. With this object Koch himself began to study the blood serum of animals that had recovered spontaneously from rinderpest. He was able to assure not only himself, but several other observers, that this serum was capable of rendering normal animals into which it is injected refractory. Bordet and Danysz, who studied rinderpest in the Transvaal in 1897, made many experiments in this direction and devised a method which gave good results in practice. But it was left to Kolle and Turner to work out a method at once simple and easily applied, one which soon came into general use. This method is known by the name of “simultaneous vaccinations.” It consists in the injection of a protective serum simultaneously with the virulent blood. To prepare the former the authors just mentioned made use of animals that had recovered spontaneously from rinderpest or of Bovidae that had been immunised by bile or by some other method. It was recognised that the protective power of the serum of animals that have recovered is very small and cannot confer immunity on normal animals, except when injected in large doses. Kolle and Turner showed that if Bovidae that have recovered spontaneously are injected with very large quantities of virulent blood coming from animals fatally attacked, the protective power of the serum of the former is markedly increased and a serum is obtained which is active in small doses and which gives good results in practice. This serum may be kept for a long time by the addition of a small quantity of carbolic acid. The immunity conferred by this serum upon normal animals is immediate, but of short duration; it is completed by making a simultaneous injection of virulent blood; we thus obtain a double immunity, one part immediate, the other permanent; to get this result, however, the serum must not be mixed with the virulent blood, for when this is done the immunity conferred is trifling or nil. On the other hand, it is complete and persists for several months when the protective serum is injected separately on one side of the body and the virulent blood on the other.
Kolle and Turner had to defend their method against many ill-founded objections and attacks, but they succeeded in getting it accepted, not only in Cape Colony but also in many other parts of Africa, and in many countries in Europe and in Asia. In 1898 it was decided at a conference which met in Cape Town to use the method of simultaneous vaccinations to the exclusion of all others. This method has since been applied on a very large scale and it was not long before favourable results were obtained. The same method has proved to be very successful with Nicolle and Adil Bey[783] of Constantinople, who now prepare large quantities of the antirinderpest serum, and combat this disease with great success in the Ottoman empire. Yersin[784] adopted the same method to fight the cattle plague in Indo-China, where it causes great ravages, especially among buffaloes. His Institute at Nha-Trang has become a centre for the preparation of the specific serum, which he distributes over a vast territory. In the East Indies the simultaneous method has been applied by Rogers[785]. In Russia, where rinderpest is endemic in many regions, the Institute of Experimental Medicine at St Petersburg furnishes the serum destined to prevent the propagation of this epizootic disease[786].
In a few years this method of simultaneous vaccination has been extended to all the countries ravaged by rinderpest and has already rendered immense services to agriculture.
V. Anti-anthrax vaccinations. In the first four sections of this Chapter we have brought together the methods which have as their basis the vaccination by viruses whose nature is as yet unknown. Since we cannot obtain them by artificial culture, we have to introduce them with animal fluids:—either the contents of vaccinal or clavelar pustules, or matter from rabic nervous centres, or again the blood of animals attacked by rinderpest. In the case last mentioned, in order to prevent the too serious effect of the injection of the virus, it is combined with a simultaneous injection of protective serum.
In the case of the vaccinations against anthrax we pass to the group of viruses whose organised nature is well known and which can be injected in pure culture grown on artificially prepared media. This method constitutes one of Pasteur’s most brilliant discoveries, made in collaboration with Chamberland and Roux. Before they had found a satisfactory method of vaccinating against anthrax these observers had to solve the problem in connection with a less complicated and less difficult case. From the first, in his studies on pathogenic micro-organisms, Pasteur had devoted his attention to finding a means of communicating immunity against these parasites. With the aid of Chamberland and Roux he was not long in discovering a method by which it was possible to attenuate the virulence of the micro-organism of fowl cholera and to vaccinate fowls against this terrible disease by inoculating them with this attenuated micro-organism. Guided by these results Pasteur, Chamberland and Roux set to work to find the vaccine against anthrax; they were soon confronted by a serious obstacle in the formation of spores which prevented the attenuation of the bacilli. This obstacle they overcame by submitting cultures of the bacillus to a temperature of 42°·5 C. Under this condition spores do not develop, and the bacilli become attenuated at the end of a longer or shorter period. Although in possession of these attenuated viruses, it still needed very laborious investigations to adapt them to the vaccination of various species of animals susceptible to anthrax, especially sheep. In this they were also successful, and in 1881, over 20 years ago, Pasteur and his collaborators demonstrated the efficacy of their method on a large number of animals. This demonstration was made at Pouilly-le-Fort before a large commission. We may affirm that this celebrated experiment opened a new path to science and to the practice of vaccination. It was performed on 50 sheep, half of which were vaccinated twice with twelve days’ interval, the other 25 sheep serving as control animals. Fourteen days after the vaccination by the second vaccine all the 50 sheep were subjected to a test inoculation of a very strong anthrax virus. Two days later the vaccinated animals remained unaffected, whilst the control animals had all succumbed to anthrax.
Similar experiments, undertaken in France, Hungary, Germany, Russia and elsewhere, confirmed the efficacy of anthrax vaccinations and led to their extension into all the countries where bacterial anthrax was rife. From the year 1881 the method came into regular use, and before the end of that year there had been vaccinated, in France alone, 62,000 sheep and 6,000 Bovidae. Since these first attempts, made on a large scale, gave such good results, the anti-anthrax practice was not long in spreading through France, then into Hungary and several other European countries. Later, it extended into other continents, especially into South America (Argentina)[787] and Australia. Vaccinations against anthrax were also applied to horses with the same good results[788].
In France the anti-anthrax vaccines are prepared at and sent out from the Pasteur Institute of Paris. These vaccines consist of broth cultures of attenuated bacilli, of which the weakest, the first vaccine, is fatal to the mouse and small guinea-pigs. The bacilli of the second vaccine are less attenuated, and are capable of killing not only adult guinea-pigs but even a certain number of rabbits, when inoculated subcutaneously. The two vaccines are races of the anthrax bacillus, capable of producing spores which present the same degree of virulence as the filamentous bacilli which gave them birth.
The anti-anthrax vaccines are sent out in tubes containing the quantity necessary for the vaccination of a large number of animals. The vaccinations are made especially in spring in order that the animals may be protected during the hot season, which is usually more favourable to the development of anthrax epidemics.
In the sheep the vaccines are injected below the skin on the inner aspect of the thigh. One-eighth of a c.c. of the first vaccine is injected with a somewhat modified Pravaz syringe. Twelve or fifteen days later a similar injection is made on the opposite side with the second vaccine. In the Bovidae the vaccines are injected behind the shoulders, where the skin is thinnest. In the horse the injections must be made on the sides of the neck and shoulders. In large mammals double the amount (¼th of a c.c.) of each vaccine is injected.
The tubes of vaccine, once opened, should not be employed a second time. Care must be taken to use the whole of their contents at one series of vaccinations.
The vaccinal injections produce tumefaction at the point of inoculation and are followed by a slight rise of temperature. But these symptoms are of little importance and soon disappear. Serious complications and fatal results from the vaccinations are very rare. The loss due to these accidents is estimated at one-half per cent. in sheep and a quarter per cent. in the Bovidae.
The refractory condition resulting from the vaccination requires for its development a period of about a fortnight. The immunity is then very substantial and lasts for a fairly long time. According to Chamberland 60% of the sheep retain their immunity a year after they have been vaccinated. But as a great number of animals then become susceptible, it is usual to revaccinate annually.
According to the statistics furnished by the vaccine department of the Pasteur Institute there have been vaccinated, up to the 1st of January 1900, a total of 4,971,494 sheep, and 708,980 cattle. Abroad the corresponding figures are 3,831,948 and 1,869,445. Altogether, the number of animals vaccinated amounted to 11,381,867, of which 3,626,206 have been treated with the vaccine furnished by the Budapest Laboratory.
The results of the anti-anthrax vaccinations were found to be so favourable that it was unnecessary to introduce any improvements in technique. Attempts have certainly been made to prepare anti-anthrax serums, and these have been successful, but up to the present such serums have not been introduced into practice.