the tuberculin test
Embed Size (px)
68 EDITORIAL ARTICLE~.
Som~ interesting examples of this indirect. spread Qf.the contagion are mentioned in the report regarding the occurrence of foot-andmouth disease in Saxony in the year 1899" from which we have already quoted. In one outbreak the introduction of the disease appeared to have been brought about by intercourse between the girl who attended to. the animals and the wife of a man who was engaged at a farm where foot-and-mouth disease existed. In another case a cattleman carried the infection to the animals under his charge in consequence of his having sat for a short time in a shop beside the servant from another farm on which the disease had previously 'broken out. In a third case the first animals attacked were the cows milked by one particular milkmaid, and it was ascertained that some days previously she had been in company with a servant from an infected farm. So convinced were some of the local authorities in Saxony of the possibility of the disease being spread in this way that the children from infected farms were not allowed to attend school, and in some cases restrictions were placed on the movements of all the persons residing at places where outbreaks had occurred.
If the contagium is as easily carried as these cases would appear to show, it is in no way surprising that the disease should be occasionally introduced from abroad by travellers who have been in districts in which it is prevalent, and it is obvious that no efficient precautions can be taken against such a risk. Finally, a correct appreciation of the many subtle ways in which the agents of infection may be carried suggests that it would be very unwise to attempt to deal with any of the outbreaks occurring in this country at the present time by any other plan than the wholesale slaughter of all the animals on the affected premises.
THE TUBERCULIN TEST.
The present occasion appears to be opportune for taking stock of the position with regard to the practical applications of tuberculin as an aid to the diagnosis of tuberculosis in the lower animals, and especially in cattle. It is true that so much has already been written regarding the tuberculin test that any further contribution to the subject must be largely of the nature of a repetition; but our main motive in reverting to the question is to comment upon some rather important additions that have recently been made to our knowledge by two independent, though almost simultaneous, sets of experiments.
The first of these is the series of experiments with regard to the reliability of the tuberculin test which was carried out by the Royal Agricultural Society of England. These experiments were begun in
the summer of 1899, and completed in July last, and the report regarding them appeared in the last number of this journal (p. 368). For the most part the experiments consisted in infecting presumably healthy cattle with tuberculosis, and afterwards testing them at intervals with tuberculin in order to ascertain how soon, if at all, they would react. It was hoped in this way to add to the already existing knowledge regarding the general question of the accuracy of tuberculin as a diagnostic agent, and also to obtain information concerning a point which at that time was very obscure, viz., the period which elapses between infection and the earliest moment at which an injection of tuberculin will provoke a reaction. At present we desire to call attention only to the information with regard to this latter point which the results of the experiments provide. In this respect the results were somewhat remarkable, or at least different from what most people would probably have expected. Briefly stated, the experiments indicated that with different methods of infection, and even when animals are infected in the same way, the period which elapses before a distinct reaction to tuberculin can be obtained is very variable, and may be anything from eight days to over seven weeks. The actual periods observed were from eight to twenty-three days when the animals were infected by intravenous injection, from eight to fifteen days with subcutaneous inoculation, and from eight to fiftyone days when the infective material was administered by the mouth. It ought to be observed that it is possible, though it cannot be said that it is at all probable, that what for the sake of brevity may be called the period of incubation, may have been modified by the preliminary test with tuberculin to which the animals had been subjected in order to ascertain whether they were the subjects of naturally contracted disease or not, and by the repeated injections which were made after infection to discover the earliest moment at which a reaction could be obtained. This possible source of error could only have been avoided by using a very much larger number of animals for experiment, so as to permit of proportionally longer intervals between the tests. As already said, however, it does not appear to be at all probable that the injection of an ordinary dose of tuberculin, even when several times repeated, has any effect in preventing an ulterior reaction when it does not itself provoke a reaction. In some cases the animals were tested once a week after infection, but in the later experiments the interval between the injections was purposely made longer.
The second series of experiments throwing light on the length of the period which elapses between infection and the earliest moment at which the animal acquires the power of reacting to tuberculin, was carried out in France during the past year.' In that series several different methods of infection were employed. To four animals the
1 See page 80 of this nnm ber.
infective material was administered by the mouth; two were made to inhale air in which tuberculous material was suspended as a dry powder or dust; two were similarly infected by distributing in the air which they breathed a fine spray of water to which tubercle bacilli had been added; two cows had the tuberculous material introduced into the udder through the teat; and in two other experiments the animals were respectively infected by intra-venous and intra-tracheal injection.
As in the English experiments, the date at which the first reaction was obtained varied a good deal in different cases. In the conclusions placed at the end of the report the period of incubation is said to have varied from thirty-two to forty-eight days in the animals infected by way of the mouth, and from nineteen to thirty-two days in those infected through inhalation. In this statement, however, there appears to be a slight inconsistency, for in one of the animals infected by way of the respiratory passages the temperature rose to 39·5° during the test carried out on the thirteenth day; and in one of the two animals infected by feeding, and credited with a reaction on the thirty-second day, the highest temperature recorded was precisely the same, and in the other it was only one decimal point higher. The fact is that in none of these cases was the rise of temperature very decisive, and the only distinct reaction obtained from the animals infected by way of the alimentary canal was that which occurred on the forty-fourth day in one of them. In the animal infected by the intra-venous method, and in one of the cows infected through the teat, the temperature soon became so unsteady as to make the results of the tests with tuberculin uncertain. The first reaction from the other cow infected through the teat was obtained on the thirteenth day, and the animal infected by intra-tracheal inoculation reacted for the first time on the twenty-fifth day.
The results of these experiments are important from two different points of view. The one which may be noticed first furnished the principal motive for the French experiments. It appears that in r899 the French Senate passed a new project of law, the purpose of which is to give the purchaser of an animal the right to return it, or to have the bargain declared void, if it can be shown that the animal in question was affected with tuberculosis at the time of sale. Any claim under this law would have to be made within thirty days after purchase, and, naturally, doubts appear to have been entertained as to whether a reaction to tuberculin, or even the demonstrable existence of tuberculous lesions, thirty days after purchase, would constitute satisfactory proof that the animal in question had been diseased at the time of sale. The Committee who carried out the French experiments appear to have interpreted the results which they obtained as evidence that this law would not be likely to involve injustice to sellers, for one of the conclusions which they draw is, that" if a cow recently pur-
chased reacts to tuberculin within the thirty days following the sale, the veterinary surgeon who carries out the test is fully justified in concluding that, in all probability, the cow in question was infected before sale." The qualified form of this conclusion is worthy of note, and it ought to be stated that the italics occur in the original report of the Committee. Probably a good many people will think that the conclusion, even with the qualification" in all probability," goes further than the results of the experiments warranted. It is admitted that in one of the experiments an animal reacted as early as nineteen days after infection, and, as we have already pointed out, another animal had a slight reaction on the thirteenth day, but this difficulty is disposed of by concluding that" in the conditions of natural contagion the period of incubation would certainly be considerably longer." It appears to us that the qualifying phrase "in all probability" might with· advantage have been introduced into this conclusion also.
In this connection attention may be called to Experiment I 7 in the series carried out by the Royal Agricultural Society'S Committee. In that case the animal was infected by way of the mouth, and it had a pronounced and typical reaction when tested on the eighth day afterwards. It also reacted distinctly to no fewer than six subsequent tests, and the post-mortem examination revealed in the intestine lesions which could reasonably be ascribed to the experimental administration of infective material, and none there or elsewhere that appeared to have been in existence for longer than the duration of the experiment. In another experiment of the same series (No. 23) there was a pronounced and typical reaction when -the animal was tested with tuberculin on the twenty-fourth day after the infective material had been administered to it by the mouth.
I t, therefore, appears to be pretty well established that an animal which has been experimentally infected with tuberculosis, by a method which closely imitates one of the ways of natural infection, may react to tuberculin well within a month afterwards. In saying this the fact is not overlooked that the quantity of infective material employed in these experiments was very large-probably much larger than ever enters the body of an animal of the ox species in a single day in natural circumstances, unless, perhaps, when a calf is fed with the unmixed milk from a tuberculous udder; but it is not at all certain, indeed, scarcely probable, that the period which elapses between actual infection and the earliest moment at which a reaction to tuberculin can be obtained is greatly influenced by the quantity of infective material administered to, or naturally taken in by, the animal. The larger the number of tubercle bacilli administered at one time the greater is the likelihood that infection will be induced, but even when very large quantities are given by the mouth only a small number of bacilli may be concerned in the actual infection. In evidence of this it may be pointed out that, in spite of the unnatural character of the
experiments previously cited (Nos. 17 and 23), in respect of the quantity of infective material administered, the lesions induced were by no means extensive.
\Vhen all these points are taken into consideration, it would appear to be very doubtful whether a reaction to tuberculin thirty days after purchase justifies the veterinary surgeon who carries out the test in certifying that the animal in question was in all probability infected before the date of the sale.
The second conclusion drawn by the French Committee is, that" if the lesions are softened or calcified, whatever be their extent, and no matter how discrete or limited they may be, in future the veterinary surgeon may affirm with certainty that these lesions have been in existence for more than fifty days." We cannot help thinking that this conclusion is much too positive. There is reason to think that the date at which caseation, softening, and calcification take place varies a good deal in different cases, and it is far from certain that caseous lesions never soften in less than fifty days from their commencement, especially in young animals. Moreover, it is not impossible that calcification of tuberculous lesions may set in within fifty 'days after their inception.
In No. 14 of the experiments carried out by the Committee of the Royal Agricultural Society, the animal was infected by subcutaneous injection in the region of the flank, and it was killed on the sixtythird day afterwards. Not only was there softened caseous material at the point of inoculation, but the adjacent precrural lymphatic gland was in a similar condition. The latter lesion was, of course, a metastatic one, and probably it had been in existence for considerably less than sixty-three days. In another experiment of the same series (see p. 3 of this number) the lesion at the point of inoculation was found to be softened when the animal was killed on the thirtieth day after inoculation, and there were indications of commencing caseation in metastatic lesions which must have come into existence well within the month. We do not know of any experiment proving that calcification may occur within less than fifty days, but it seems to be a little rash to assert positively that such a thing is impossible because it has not been observed in a comparatively small series of experiments.
The other aspect of the results of these recent experiments is no less interesting. In both series it was found that a v.ery considerable period might elapse after infection before the animal had acquired the property of reacting to tuberculin. The maximum period in the French experiments was forty-eight days, and in the English experiments fifty-one days. In three of the six animals infected by way of the alimentary canal in the English series it was forty days. The important bearing of this discovery on the practical uses of tuberculin is obvious. In the first place, it indicates that in any herd of con-
EDITORIAL ARTICLES. 73
siderable size in which tuberculosis has existed for a considerable time an attempt to weed out the affected animals by the aid of the tuberculin test is very likely to fail unless the test is repeated at rather short intervals during the first year. Even in the absence of such proof as has now been provided, the probability that such was the case was on a former occasion pointed out in these columns. It must be pronounced distinctly unfortunate that for six weeks after infection an animal may pass for healthy when it is tested with tuberculin. No doubt this defect can be overcome by it more frequent application of the test, but that means a considerable increase in the trouble and expense of eradicating the disease from a herd.
It is a fairly safe prediction that the facts brought to light by the experiments to which we have referred will be not unwelcome to those who have all along industriously endeavoured to spread the notion that tuberculin is an agent of no value in the diagnosis of tuberculosis, and we may confidently expect to see the fact that the property of reacting is not acquired by an animal on the day on which tubercle bacilli enters its body put forward as a reason for entirely abandoning the tuberculin test. It need hardly be pointed out that there is neither logic nor reason in such an attitude. When the test is properly carried out its imperfections are almost entirely in the direction of failing to detect the disease, and very rarely in the way of incriminating an animal that is free from tuberculosis. At the present time the agitation against the employment of tuberculin is fostered mainly by those who are in no way anxious for the discovery of an infallible method of detecting tuberculosis in the living animals, and who, having animals for sale, sigh for the return of the days when good condition and the absence of a cough were nnhesitatingly accepted by a purchaser as satisfactory proof of freedom from the disease. I t deserves to be characterised as a stupid delusion on the part of the owners of tuberculous herds if they imagine that intending purchasers at fancy prices are likely to refuse the ass.istance which tuberculin can lend them when they desire to avoid coming into the possession of animals that are already diseased. Non-reaction, unfortunately, falls a good way short of being absolute proof of freedom from tuberculosis, but in the present state of knowledge it is by far the most conclusive evidence of that kind that is obtainable while the animal is still alive. In like manner, not every animal in which the temperature rises after an injection of tuberculin is tuberculous, but the exceptions are not sufficiently numerous to seriously weaken the weight of a reaction as evidence of infection.