A system of practical medicine. By American authors. Vol. 1

by Unknown

VACCINIA.

BY FRANK P. FOSTER, M.D.

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SYNONYMS.—Vaccina, Variolæ vaccinæ (Jenner), Cow-pox, Cow-pock, Kine-pox, Kine-pock; Fr. Vaccine; Ger. Kuhpocken, Schutzpocken, Impfpocken, Schutzblattern; It. Vaccina; Sp. Vacuna.

DEFINITION.—An eruptive disease characterized by a cutaneous lesion closely resembling that of small-pox, going through the stages of papulation, vesiculation, pustulation, incrustation, and cicatrization; differing from small-pox in the mildness or almost total absence of the constitutional symptoms, by being communicable only by inoculation, and by the fact that the lesions, as a rule, are developed only at the points of inoculation and in their immediate neighborhood.

This definition holds good for the great majority of cases, but in each of its parts we must take account of exceptions. For example, the lesion does not always follow the regular sequence of changes described. It may stop short at the stage of papulation, constituting the so-called raspberry excrescence, which will be further referred to hereafter; it may pass directly from the stage of vesiculation into that of incrustation, without any such change in its liquid contents as can properly be said to form a pustule; desquamation may take the place of incrustation; and, after an evolution otherwise normal, there may be no formation of a scar, simply because the destructive effect of the lesion has not extended deeper than the epidermis. The constitutional symptoms are sometimes severe, but they are always of very short duration. The disease is said to have been communicated otherwise than by inoculation in the case of some of the lower animals. Thus, Chauveau succeeded in producing some of its phenomena in the horse by causing the virus to be inhaled in the form of spray. It is doubtful, however, if it is possible to eliminate all sources of fallacy in such experiments. Finally, a generalized eruption is occasionally observed, although with great rarity. In stating these exceptions no reference is intended to cases in which complications occur.

NATURE OF THE DISEASE.—Many considerations warrant us in classing cow-pox among the varioliform diseases—chiefly its general resemblance to variola, and the fact that individuals who have been affected by it are thereby more or less fully protected against small-pox. It has been thought, indeed, that cow-pox was in reality but a modified form of small-pox; and this idea has been the basis of one of the theories that have been held as to the origin of vaccinia. Before enumerating and discussing those theories it will be well to mention that cow-pox is spoken of as spontaneous, casual, or inoculated, according to its mode of origin, known or assumed, in individual instances.

Spontaneous or original cow-pox is the name commonly applied to the disease as it is met with in the cow in instances in which its mode of origin is unknown. Strictly interpreted, this expression implies a belief that the affection is capable of being developed in a cow independently of contagion or infection—a notion that seems to be held by many physicians, but not, so far as the writer is aware, by those whose study of the subject has been such as to lend any considerable weight to their opinions. Ordinarily, however, the term spontaneous cow-pox is employed simply as a convenient expression to denote the disease as it occurs naturally in cows, without implying any belief or theory as to its mode of origin.

Casual cow-pox is the term applied in cases that have been contracted by accidental inoculation, whether in the cow or in man. It is manifest that the so-called spontaneous cases are really casual, unless we accept the doctrine that infection is not necessary to the development of the disease.

The term inoculated cow-pox implies that the affection has been produced by intentional inoculation. Here, again, we are confronted with an illogical expression, for a disease that is inoculated accidentally is still inoculated, as much as if it had been conveyed purposely. It may be said, indeed, that the casual disease is due to some other form of infection than inoculation, but for such an assertion there is not a particle of proof.

Passing from this unsatisfactory nomenclature to a consideration of the theories that have been held as to the nature of cow-pox, we are first met with that of its being a disease sui generis, like small-pox, measles, scarlet fever, and the like, and, like them, originating only by its own specific contagion, not being capable of development by a modification of any other contagion, however closely it may thus be counterfeited. This seems the most rational theory of the nature of cow-pox, but it cannot be demonstrated except by disproving all opposing theories; and that has not yet been accomplished.

Another theory is, that cow-pox is really small-pox modified, as the phrase runs, "by passing through the system of the cow." It has been thought possible, indeed, to specify in what way the cow's system could impress such decided changes upon the virulent disease small-pox as to convert it into the mild affection that we know as vaccinia; in other words, it has been imagined that the function of lactation accomplished this remarkable result. This notion may have been due to the observation that so-called spontaneous cow-pox is met with only in cows that are in milk. The significance of this fact, however, is really nothing more than that cows in milk are more exposed to accidental inoculation than other bovine animals—namely, at the hands of the milkers. The fact that in such cases the lesions are almost always confined to the teats and the udder, far from affording any ground for the notion that there is some mysterious connection between cow-pox and the function of lactation, is but another proof that the disease is the result of inoculation. The lesions appear at the points of inoculation, the teats and the udder being the parts handled by the milkers. Moreover, there is no difficulty in inoculating young calves or adult bulls, and the lesions so produced do not vary in a single particular from those observed in so-called spontaneous cases.

Men have been so carried away with this milk theory, however, as even to believe that the virus of small-pox might be shorn of its dangerous properties, so that it would produce only the vaccinal lesion when inoculated simply by mechanical mixture with milk. During the late Civil War one of the Confederate Army surgeons actually put this notion to the test of practice on quite a large scale, inoculating large numbers of persons with a mixture of small-pox virus and milk, terming the practice mitigated inoculation. We can scarcely suppose that he did anything else than variolate these persons, just as he would have done had he used variolous lymph without the addition of milk. His experiments show nothing new; they merely furnish a recent confirmation of the well-known fact, familiar to the old inoculators, that inoculated small-pox is sometimes exceedingly mild in a series of cases.

This theory of the variolous origin of cow-pox, and of the practicability of converting small-pox into cow-pox at will by "passing it through the system of the cow," has taken deep root in the minds of men, especially in Great Britain, where the late Mr. Ceely's experiments and Mr. Badcock's experience seemed to give it some color. Some years ago, however, the question was investigated most practically and thoroughly by a commission appointed for the purpose by one of the medical societies of Lyons, Chauveau being the recorder. Their conclusion was—and their reasoning seems to the present writer incontrovertible—that small-pox and cow-pox were wholly distinct from each other under all circumstances, and that it was impossible to convert the one into the other. But the doctrines of the English investigators, reinforced as they were by the ingenious arguments of the late Dr. Seaton, were not easily to be overturned in their own country or in America; consequently, the practice of variolating cows has been resorted to from time to time for the purpose of obtaining a stock of vaccinal virus of unquestionable authenticity—the so-called variola vaccine. This practice is utterly fallacious, and it is also dangerous, since the disease so produced, however mild it may seem to be, is nothing more nor less than small-pox, with its infectiousness by effluvium and its liability to prove serious even when carefully inoculated.

Quite recently the experimental investigation of the question has been undertaken de novo by a well-known English veterinarian, Mr. Fleming; and, since his conclusions coincide with those of the Lyonnese commission, it is to be hoped that we have seen the last of this rough-and-ready method of improvising a case of genuine cow-pox—a method that, in the light of our present knowledge, can only be characterized as downright malpractice.

The third and last theory we have to consider is that which ascribes the origin of cow-pox to infection from the horse. So far back as Jenner's time it was conjectured that cow-pox was due to the accidental conveyance of the virus of the grease (the eaux-aux-jambes of the French) by reason of the cows being milked by persons who were also employed in the care of horses affected with that disease. Grease is an eruptive disease of horses' heels. Doubtless it has often been confounded with a mere eczematous affection by those who have repeatedly failed in their persistent attempts to inoculate cows with it, and, on the other hand, a localized eruption of horse-pox may have been mistaken for it by those who have supposed themselves to have succeeded in producing cow-pox by inoculating cows with the virus of grease, and have consequently given in their adhesion to the grease theory of the origin of cow-pox. At all events, so far as the writer is aware, that theory is not now held by any well-informed writer.

Still regarding the horse as the originator of cow-pox, we must turn our attention to horse-pox (equinia). Several years ago Depaul of Paris took great pains to establish the fact that horse-pox (an affection totally distinct from grease) was an eruptive febrile disease of horses, an exanthem; that the eruption was generalized, and, being for the most part concealed by the hair, generally overlooked; and that it was capable of being conveyed by inoculation, the lesion being indistinguishable from that of cow-pox. He believed himself to have demonstrated also that it was the contagion of horse-pox that gave rise to cow-pox in the cow.

Depaul's investigations were very keen and his conclusions were exceedingly plausible, but they cannot be called convincing, notwithstanding the fact that Constantin Paul succeeded for a time in popularizing a stock of horse-pox virus as material for vaccination. At about the same time the Beaugency case of cow-pox was discovered, and the perfectly satisfactory use that has been made of that stock may have thrown Depaul's theories and Paul's practice undeservedly into the background.

We can only say, in summing up, that the small-pox theory is utterly untenable, that the horse-pox theory has not been disproved, and that the theory that regards cow-pox as derived neither from small-pox nor from horse-pox, but as a disease sui generis, although not proved, is the most rational of all, and the most in keeping with known facts.

ETIOLOGY.—Nearly everything that could be said under this head has already been considered. It may be added that meteorological conditions have been supposed to favor the prevalence of the disease among cows. More precise observations are needed to enable us to determine whether or not there is any truth in this supposition. It has been said that the affection is most apt to prevail during warm and moist seasons. This is contrary to what we might have imagined, as warmth and moisture are quite destructive of the vaccinal virus. Under ordinary circumstances, however, the contagium often proves wonderfully tenacious of life, and the disease, once introduced among a herd of cows, is prone to linger for months, or even years, attacking animals recently added to the stock and young cows during their first lactation. As has already been stated, age, sex, and parturition can be regarded as etiological factors only in so far as they favor the occurrence of accidental inoculation. In the human subject vaccinia occurs generally as the result of intentional inoculation, as will be more fully referred to when we come to the consideration of vaccination. Insusceptibility is occasionally met with, both in the cow and in man, but it is very rare. Perhaps it may be explained in some instances by the subject having really had the disease, or indeed small-pox, either before or after birth, in so mild a form as not to have left the characteristic marks. Certain it is that the lesion does not always leave a permanent scar, especially in the cow.

GENERAL COURSE OF THE DISEASE.—This is best studied in cases that have followed intentional inoculation, for here we know the chronological sequence of events. Depending somewhat upon the method of inoculation, and perhaps also to some extent upon the state of the skin at the site of the inoculation, or even upon a systemic condition (since some vaccinators hail it as a harbinger of success), at the time of the operation a ring-like erythema may be seen surrounding the inoculation. This is exceedingly evanescent, being doubtless due to vaso-motor action, and is not often witnessed.

Ordinarily, no effect whatever is observed until after the lapse of two or three days, when a red papule is formed. This papule increases in superficial area, but not in height, and gradually loses its redness. It assumes a circular form, or, in the case of a compound pock (for that is the proper name for the lesion), a configuration representing segments of several circles, and as it increases in area it becomes more and more raised at the border (the bourrelet of French writers), while the central portion, which also increases in size pari passu with the peripheral annular vesicle, does not become more elevated, but remains depressed, giving the pock as a whole the peculiar shape termed umbilication. Up to the eighth or tenth day, inclusive, the marginal elevation contains a limpid fluid termed lymph, and consequently presents a pearl-like lustre. At this period a rather sudden increase takes place in the corpuscular elements contained in the lymph, causing that liquid to become thick and opaque, so that the elevated margin of the pock, which before had shown the pearl-like lustre alluded to, now comes to look as if made of tallow.

At the same time what is known as the areola forms around the pock, and constitutional symptoms show themselves. The areola is a circumscribed redness of the skin, perfectly circular in form and of five or six times the diameter of the pock itself. It is sharply defined and of a vivid red hue. Usually it is a mere hyperæmia of the skin, but in some instances, especially where the process of pock-formation is decidedly pronounced, a few papillary elevations are to be seen in the immediate neighborhood of the pock, and at that situation there may also be some lividity. After a few hours' persistence in the form of a disc the areola begins to disappear, the redness fading first at the central portion, so that in its declining stage it assumes the shape of a ring which constantly grows narrower and narrower at the expense of its inner portion, and finally disappears altogether. In the cow the areola is only a faint line immediately around the pock.

Constitutional symptoms are invariably present in cases that follow the regular course. The temperature rises one or two degrees Fahrenheit, the appetite becomes impaired, and sleep is somewhat disturbed. In many cases, mostly those of secondary inoculation, the symptoms are more severe; the fever runs higher, and may be accompanied with transient delirium; nausea is experienced, perhaps with actual vomiting; and severe pain is felt in the head and along the spine, the latter being most marked in the cervical region. These symptoms usually last but a few hours, and they are apt to be accompanied by a modification of the areola whereby it loses its disc-like outline and becomes diffused irregularly, especially, if, as is usual, the inoculation has been done on the arm, in a downward direction toward the elbow.

Along with these phenomena intense itching is often felt at the situation of the pock, being an aggravation of the pruritus that in a mild form accompanies the greater part of the whole course of the lesion. Supposing the arm to have been inoculated, the lymphatic glands of the axilla now become swollen and tender, but their suppuration is unusual, and is to be regarded as a complication.

To go back to the pock: some time before the contents of the marginal elevation become opaque the central portion is converted into a crust of a brownish color, and finally, from the tenth to the fifteenth day, the bourrelet itself, having ceased to increase in size, takes part in the process of incrustation, the completed crust representing the form of the pock, having a circular ridge at the border, at which part its color is not so deep as at the centre. The crust usually falls off between the fifteenth and the thirty-fifth day. It is hard, translucent, and of a prune-juice color; thick at the centre and thin at the periphery; smooth on its attached surface and somewhat wrinkled on its outer aspect; surmounted at the centre by the epidermal débris produced by the operation of inoculation, mingled perhaps with more or less dried blood.

After the crust falls off a reddened surface is left of a cicatricial nature, usually somewhat depressed below the level of the surrounding skin, and frequently showing lesser pits, which latter appearance is termed foveolation. Instead of these pits, radiated striæ are frequently left. Gradually the scar loses its red color, and, like other scars, finally becomes paler than the surrounding skin. It is usually permanent.

IRREGULARITIES IN THE COURSE OF THE DISEASE.—Ever since cow-pox first became the subject of medical study deviations from its typical course have been noticed, and have been the theme of a good deal of speculation. The older writers, indeed, bestowed no little attention upon what they considered to be not irregular forms of vaccinia, but distinct affections with which it was liable to be confounded. Their descriptions of these diseases, which they termed spurious cow-pox, are, however, so vague as to possess but little more than an historical interest. In regard to affections met with casually in the cow, we can often determine their nature only by test-inoculations, and even that criterion is not always thoroughly convincing; for, on one account or another, we may fail in the attempt to propagate true cow-pox, and on the other hand, if we admit that there is a radical difference between cow-pox and small-pox, it is manifest, bearing in mind the errors into which experienced investigators have fallen, that we may propagate small-pox through a long series of experiments without once suspecting it to be anything but cow-pox. We may, nevertheless, always determine, provided we succeed at all, whether we are dealing with a disease that protects against vaccinal and variolous inoculation.

In the human subject we seldom meet with affections that counterfeit vaccinia, although, if we take only the lesion into consideration, there are certain contagious forms of herpes that may give rise to doubt, and possibly the same may be true of impetigo contagiosa.

Turning, then, to the irregularities properly so called, we have first to consider the absence of constitutional infection. This must not be confounded with the mere lack of obvious constitutional symptoms; what is meant by the expression is, that in certain instances the local lesion may appear typical, and yet no such impression be made upon the system as to render it proof against subsequent inoculation. Early in the century the possibility of this lack of systemic infection was insisted upon by Mr. Bryce of Edinburgh, who invoked it as an explanation of the occasional failure of vaccinia to protect against small-pox. The practical question was, how to decide, in a given instance, whether general infection had or had not taken place. In the opinion of many observers—and that notion has cropped out every now and then up to the present day—absence of the areola furnished at least presumptive evidence that the constitution had eluded infection. But, whatever may be held theoretically, it must be conceded either that the general system very rarely fails to feel the impress of the disease, or else that the criterion is fallacious. For in an experience of seventeen years the present writer has not known of a single instance in which a vaccinal lesion that pursued a regular course in other respects has failed to be accompanied by the areola. And certainly Mr. Bryce himself must have attached little if any importance to it, for he took great pains to establish a means of determining the presence or absence of constitutional infection—the so-called Bryce's test. This consists in repeating the inoculation at a certain period in the evolution of the disease, the theory being that systemic infection does not take place at once, but only after the lapse of a number of days from the time of the inoculation. Up to that time a repetition of the inoculation is possible, and, if systemic infection results from the first one, both lesions will mature at the same time, the second one following an accelerated course, reaching its acme rapidly, although dwarfed in size. If, on the other hand, the first inoculation failed to infect the constitution, the second one will pursue its course in the usual manner. Moreover, at a certain time, generally about the fifth day, a repetition of the inoculation will fail altogether if the original insertion has really infected the system. The present writer can testify that Mr. Bryce's statements are correct; he has applied the test in many cases, but in no instance has he been led to the conclusion that constitutional infection had failed to take place. He is inclined to think, therefore, that such failure is exceedingly rare.

Passing over the multiplicity of irregularities in the lesion that were described by the older observers, it seems that there are a few that are of practical importance. In the first place, there is a variety of pock to which it is not easy to give a definite name, but which is characterized by a lack of decided elevation above the surrounding skin (a deficiency for which it makes up in superficial area), by the early formation of a thin, flimsy, straw-colored crust, and by the utter failure of the characteristic firm brown crust of the typical variety to become developed. This form of irregular pock has not been seen by the writer of late years, but before animal vaccination came into general use he met with it frequently, mostly in cachectic children. Notwithstanding its sprawly, unsatisfactory appearance, it is undoubtedly genuine, for the typical lesion may be produced by inoculation with its contents.

Another irregularity of the pock is what is familiarly termed the raspberry excrescence. A red elevation forms at the seat of inoculation, and at first promises to follow the typical course, although it may be tardy in making it appearance; but it never advances to full development. It becomes indolent, and may last for several weeks, or even months, in the form of a hard, flat nodule of a bright-red color, not unlike a small nævus. In many instances it has a succulent look, but no lymph can be obtained on puncturing it. No areola appears at any time, and finally the lesion slowly disappears, leaving no trace of its existence. It is probably an abortive form of pock, in which only the papillary layer of the skin takes part, without any exudation into the epidermis. It is seldom, if ever, protective against small-pox, for it constitutes no bar to a subsequent vaccination. This irregular pock has been observed from time to time ever since the early days of vaccination, but for the past six years it has been seen more frequently in New York than for many years before. Now, however, it seems to be growing less common. The writer is not aware of any satisfactory explanation of its occurrence. It is seen in all sorts of subjects, and seems to follow the use of one variety of virus as much as the employment of any other.

What has been termed generalized vaccinia is another form of irregularity. The expression is a vague one, covering as it does not only the very rare cases of true eruptive vaccinia, in which a general eruption of pocks takes place as a consequence of constitutional infection, playing the part of an exanthem, but in addition those instances, not very uncommon, in which pocks are formed here and there on the body, probably as the result of the accidental transfer of the virus from the pock by scratching. Under such favorable conditions—the immediate transfer of lymph from a pock in which the specific evolution is going on vigorously—the slightest penetration of the epidermis with the nails is enough to secure self-inoculation. In view of this facility with which it may be effected, we should be very careful not to jump hastily to the conclusion that in any given case of generalized vaccinia the supplementary pocks are truly eruptive; as a matter of fact, the present writer has never seen an instance in which he was convinced that such was the case. Where the pocks are very numerous, especially in subjects with an irritable skin, much distress may be caused by the itching and by the consequences of scratching, and marked febrile reaction may accompany the process; so that, in view of the great similarity of the lesions to those of the variolous eruption, much doubt is sometimes entertained as to whether the disease is not really small-pox. This question cannot always be definitely settled at first, but the failure of the secondary fever of small-pox, together with the fact that the disease does not spread by infection, will generally suffice to decide it.

Concerning those cases of generalized vaccinia that are manifestly not eruptive, it sometimes happens that the cutaneous receptivity is not exhausted for several weeks, or even months. Such cases set Bryce's test at defiance, in consequence, probably, of an idiosyncrasy. In some of these instances the pocks appear in clusters of successive formation, looking not unlike patches of zoster. Small supplementary pocks in the immediate neighborhood of the original lesion are not at all uncommon.

PATHOLOGICAL ANATOMY.—Avoiding the minute histological details for which the prescribed length of this article gives no scope, but little is to be added to what has already been said in the section on the clinical features of the disease. The lesions of vaccinia are wholly cutaneous. Confining ourselves to cases that follow a regular course, there is, indeed, but one, the pock—a term that seems preferable to vesicle and pustule, since the latter apply only during certain phases in the development of the lesion.

A pock may be regarded as essentially a lesion of the epidermis, for it is in that structure that its most striking features are developed, and in some cases, although doubtless the papillary layer of the derma is congested, there is no permanent alteration of tissue below the Malpighian layer of the epidermis. These are the catarrhal pocks of Rindfleisch, and it is in such cases, if in any, that no scar (even of temporary duration) results. The term catarrhal pock, however, is not vitiated by an extension of the morbid process deep enough to produce a permanent cicatrix, and it is probable that in most cases the catarrhal type predominates. By the term diphtheritic pock the same author refers to cases in which the congestion of the papillary layer is so intense as to block the supply of blood to the apices of the papillæ, as a result of which they become exsanguinated and necrosed, forming a white pultaceous layer on the floor of the pock, which is undoubtedly what Ceely referred to when he spoke of a false membrane. In some cases even the subcutaneous tissue undergoes necrosis, a sort of core being included in the substance of the crust that ultimately forms.

Whichever of these forms of pock we take into consideration, always excluding irregularities and complications, we find certain definite changes in the epidermis. The dome of the pock is formed by the unbroken transparent horny layer of the epidermis, unaffected by the morbid process. The cavity of the pock is formed by the squamous cells of the epidermis being forced out of their normal relations by an exudation of lymph between them, some of them being tilted up edgewise while still retaining their connection with the surrounding cells, thus accounting for the multilocular structure of the pock; for it is a fact that the circular bourrelet consists not of one ring-like cavity, but of many separate chambers. The result of this structure is, that the liquid contained within the pock—the lymph—escapes only partly through a puncture made in the wall of the vesicle. In order to evacuate the pock thoroughly it is necessary to make a great number of punctures or a circular incision following the ring-like ridge of the bourrelet.

The lymph contained within the cells of the pock is a liquid which in its gross physical properties differs but little from the lymph which exudes from any traumatic surface shortly after the injury has been inflicted, as in the glazing process that takes place in wounds. Examined microscopically, however, it is found to contain not only the fibrin, the salts, the corpuscular elements, and the débris that ordinary tissue-juice presents, but also certain minute spherical bodies—termed microspheres, microzymes, vaccinads, etc.—that give it its characteristic infective quality and justify the title of virus commonly applied to it. That these minute bodies really constitute the virulent element of the lymph, or at least that they are the vehicle of the contagium, is not a mere matter of conjecture, but has been demonstrated abundantly, notably by Chauveau and Sanderson's diffusion experiments. Inoculation with the supernatant liquid, containing none of these bodies, always fails to convey the disease, but it is not absolutely essential that they should be present in large proportion in the lymph to render the latter virulent, for Chauveau found that lymph diluted with thirty times its bulk of water was not without infective power. It scarcely need be said, however, that the greater the proportion in which they are present, the greater is the probability that the lymph will prove infective on inoculation. These bodies have been supposed to be of a vegetable nature, and Hallier, Kohn, and others have bestowed no little study upon their botanical characteristics. Under favorable circumstances they retain their virulent properties for a long time, especially if kept perfectly dry and not subjected to a high temperature. The present writer has met with success in the use of vaccinal virus seven years old.

The lymph differs somewhat in its gross appearances according as it is produced in man or in the bovine animal. In the former it is clear and limpid, and exudes freely in great drops when the pock is punctured in its peripheral portion; in the latter it is more straw-colored and more viscid, exuding sluggishly, or even refusing to flow without the aid of pressure. Moreover, the vaccinads seem endowed with different properties in the two cases: in man they have a tendency to remain equably diffused through the liquid, while in the cow they tend to separate from it and to be deposited upon any solid surface at hand.

The phenomenon termed umbilication, common to the vaccinal pock and to that of variola, has given rise to some differences of opinion as to the mechanism of its production. The term implies a depression at the centre of the pock. This appearance is not invariable, but it is constant enough to have met with general acceptance as a characteristic feature, notwithstanding the undoubted fact that it is found in lesions that have nothing whatever to do with any of the varioliform diseases. Not to waste space in discussing the various theories that have found supporters, it may be said that they have all been proved to be defective, save only the simple explanation that as the process of evolution advances the centre of the pock undergoes desiccation, whereby that portion of the tissue involved is so glued and drawn together as to become incapable of the swelling that is still going on in the growing peripheral portion of the lesion.

The crust into which the pock ultimately becomes converted is not, as is commonly supposed, mere dried lymph and nothing else; it is dried tissue enclosing concrete lymph. It generally includes also various sorts of débris—broken-down epithelium, blood-corpuscles, pus-corpuscles, and even, in rare cases, a core of sphacelated tissue like that of a furuncle.

As has already been said, the cicatrix is to a certain extent peculiar in that it is usually depressed and foveolated. Too much stress has been laid upon these features, however, and the truth is that some traumatic scars cannot be distinguished readily from that of vaccinia, while, on the other hand, many a genuine pock leaves no permanent trace behind it. Indeed, in the cow it is the exception for a noteworthy scar to form.

SEQUELÆ AND COMPLICATIONS.—The most important sequela of vaccinia is the fact that it protects the subject against small-pox, and on that circumstance hinges the chief practical interest of the disease. This leads us at once to the subject of vaccination, and therefore under that head we shall pursue our consideration of this curious affection.

Vaccination.

SYNONYMS.—"The new inoculation;" Fr. Vaccination; Ger. Kuhpockenimpfung, Schutzpockenimpfung; It. Vaccinazione; Sp. Vacunacion.

HISTORY.—Before giving the history of vaccination itself (meaning by that term the intentional inoculation of vaccinia for the purpose of protecting the subject against small-pox), it may be well to devote a few words to a practice that preceded it—that of the intentional inoculation of small-pox (or simply inoculation, latterly called variolation). In very early times various Oriental peoples became aware of the fact that small-pox might be very decidedly mitigated by inoculation. This was practised in various ways, all of which may be reduced to the process of inserting small-pox virus into a solution of continuity. Lady Montagu, the wife of an English ambassador to Turkey, brought the practice back to England with her, where it soon made its way into popular favor, and whence it spread rapidly over Europe and America. Thus contracted, small-pox was shorn of a great part of its terrors; the eruption was usually trifling in amount, and in every way the disease was mild as a rule. Still, the mortality was something worth considering, and, worse than that, the inoculated disease was communicable by effluvium, so that an inoculated person had to be secluded carefully for fear of spreading the disease in the ordinary way. In all cases, too, careful medical treatment was thought necessary. On the whole, then, while inoculation was undoubtedly a boon, it was fraught with many grave perils. So great, indeed, were these perils, and so thoroughly were they appreciated, that the practice was interdicted by law in most civilized countries so soon as vaccination had become established in popular favor.

In several European countries the common people—at least those of them who had much to do with dairies—gradually became aware of the existence of the disease termed cow-pox, and of the fact that those individuals who had accidentally contracted it were rendered proof against the infection of small-pox. There is even fair testimony to show that some of these people, particularly the English farmer, Benjamin Jesty, relying on their observation to this effect, employed intentional cow-pox inoculation as a protective measure. These facts, however, do not detract in the least from the credit that all Christendom has awarded to a man who subjected the popular impression in question to the test of scientific investigation, proved its truth, and demonstrated its value to the world. That man was Edward Jenner, an English country physician. It was in the last quarter of the eighteenth century that he entered upon his course of inquiry, and on the eve of the present century he published his demonstration to the world. It was not a discovery; it was not an invention: it was more than either, "a matchless piece of induction," to quote the words of Mr. John Simon. Filled as he must have been with the consciousness of his great achievement, Jenner set this good example to all investigators: that he did not make haste to convert the world; he first convinced himself. It may almost be said, indeed, that, like Minerva from the head of Jove, the rational and perfected practice of vaccination sprang complete from Jenner's hands. Doubt and ridicule he had to encounter at first, and afterward envy and detraction; but the force of his facts and the symmetry of his deductions were such that the new inoculation soon spread through the broad world, and has ever since maintained its sway, save with a few fanatical scoffers.

That vaccination really does protect against small-pox observation has taught the whole civilized world, if we leave out of account the few conscientious and intelligent doubters (made such, doubtless, quite as much by the extravagant statements often put forth by those who from time to time think it incumbent on them to defend vaccination, as by their own misinterpretation of facts) who are to be found associated with the noisy little body of actual opponents of the practice. One of the most injurious statements ever made in the advocacy of vaccination is, that it always protects if properly done. When one of these illogical defenders of that proposition is confronted with an instance that disproves his assertion, he falls back on the allegation that in that instance the vaccination was not properly done. The manifest absurdity of such an argument strikes the doubter most forcibly, and inclines him to say to himself, Falsus in uno, falsus in omne. Unbelief founded on this ground would never have arisen if the plain truth had always been adhered to: that the protection afforded by vaccination is not invariable, and that very often it is not permanent. In the infancy of the practice these facts were not known, but it is now many years since they became obvious to every fair-minded observer. The misapprehension of facts lies chiefly in the false deduction from the circumstance that the great majority of cases of small-pox occur in persons who have been vaccinated. But the explanation of this is very simple. Suppose that, of one hundred persons vaccinated, twenty fail to be protected permanently; that all persons not vaccinated are unprotected; and that throughout the civilized world the proportion of vaccinated to unvaccinated persons is as ninety to ten. Making no pretence of arithmetical accuracy, it may certainly be said that all these suppositions are well within the truth. It follows from them that in a community of ten thousand persons there will be nine thousand who have been vaccinated, and one thousand who have not. Of the former, eighteen hundred will have failed to secure lasting protection. Therefore in case of an epidemic there will probably be a proportion of eighteen cases of small-pox in the vaccinated to ten in the unvaccinated; and yet this should not obscure the fact that of the nine thousand vaccinated more than seven thousand were absolutely protected, whereas of the one thousand not vaccinated not one could escape the disease if exposed to it. When we add the further observation that of the eighteen hundred cases of small-pox among the vaccinated not more than thirty or forty would probably prove fatal, while of the one thousand cases in the unvaccinated about two hundred would end in death, we have a striking demonstration of the efficiency of vaccination. As a matter of fact, statistics show that the figures here given err rather in allowing too little than in asserting too much in favor of vaccinal protection.

The question naturally arises, Why it is that vaccination protects some persons and does not protect others?—reference being had, of course, to permanent protection, for it is exceedingly rare for temporary immunity to be attained if we exclude those instances in which the variolous infection has taken place before the operation is resorted to. This question cannot be answered with any certainty, but various theories have been brought forward, some of which call for notice.

In the first place, it has been thought that the revolution of the system termed puberty was fraught with such a radical change as to do away with the mild modification due to vaccination. While this theory has an air of plausibility, it seems to lack proof and not to be upheld by analogy, for we do not find that children who have had scarlet fever, measles, and the like often undergo those diseases a second time on arriving at the age of puberty.

The only remaining theory that our limits will allow a consideration of is that put forward by Marson of London, that the degree and duration of vaccinal protection are proportionate to the perfection of the vaccinal lesion and to the number of insertions made. In a large experience with small-pox Marson found that the disease was more fatal among those whose vaccinal scars were imperfect or few in number than among those who bore evidence that several pocks had been produced and had run a typical course. As to the influence of a perfect evolution of the lesion, but little doubt can be entertained, for we have already seen that in some instances its course is so different from what it should be that no protection whatever seems to result. When we come to consider the number of the pocks as affecting the degree or the duration of protection, however, an obvious source of fallacy arises in the fact that we cannot always be sure that some of the scars on a person having a number of them were not the products of a repetition of the operation several years after the first—that is to say, a revaccination, the efficiency of which in restoring lost immunity is now well established. Nevertheless, as long as the doubt remains the best course to pursue seems to be to act as if Marson's theory were in all respects correct, and vaccinate by multiple insertions.

We have, then, no positive means of ascertaining who those persons are that are likely to fail of lasting protection, or how long a time will elapse before the cessation of their immunity will take place. The only safety lies in revaccination. But after how many years should revaccination be resorted to? It has been thought that this question might be settled by noting at what age, or at what period after primary vaccination, large numbers of people became susceptible of revaccination. This test, however, is not altogether trustworthy, for a renewed susceptibility to vaccinia by inoculation does not necessarily imply that the liability to take small-pox by effluvium has been regained. If it did, modified small-pox (varioloid) would be far more common than it is, for it is certain that revaccination can be made to succeed in a very large proportion of children long before they have reached the age of puberty. The fact is, contrary to the notions of the last generation, that success in revaccination is the rule, not the exception. Formerly it was not expected to succeed, and therefore no special pains were taken to ensure success.

Definite rules cannot be laid down as to the time that should be suffered to elapse before vaccination is repeated, but in the great majority of instances safety may be attained by revaccination every five or six years, and always in the presence of an epidemic, regardless of the lapse of time; also whenever one's mode of life is to undergo a noteworthy change, as in emigrating to a foreign country, on entering the military service, and the like.

To sum up, then, vaccination almost invariably protects against small-pox for the time being; generally for a long term of years; sometimes for a lifetime. Often the protection is absolute; as a rule, it is very nearly so; in rare instances it is trifling. In general terms, it may be said that it is scarcely less protective than variolous infection itself, for death from a second attack of small-pox is by no means rare. Here the question comes up: Is vaccination less protective, either in degree or in duration of effect, than it was at the time of its adoption? Given a typical vaccinia, we may unhesitatingly answer, No; but do we now so invariably produce the disease in all its essential features as was done in Jenner's time? Yes, provided we use proper virus and employ as much care as was taken by the older physicians, who, trained to the practice of variolation (the inoculation par excellence of bygone days), did their work with a gusto now seldom witnessed. But there was a time, now happily at an end, when it was not easy to obtain thoroughly good virus, and when, therefore, the result was apt to vary materially from the standard. This may be conceded without entering upon the vexed question of the general deterioration of the Jennerian stock of vaccine.

Besides immunity from small-pox, there are one or two sequelæ of vaccinia that deserve mention before we proceed to consider what it is better to class as complications. In the first place, vaccination has been supposed to confer temporary protection against whooping cough. The writer is not aware, however, of any precise data going to prove either the truth or the falsity of this supposition.

Secondly, by virtue probably of the inflammation that attends the evolution of the vaccinal pock, vaccination practised in the immediate neighborhood of a small nævus often cures that blemish, and it has been done for that purpose in many cases. It has no advantage over many other measures, however, and there is the disadvantage that the nævus may so mask the pock as to give rise to some doubt as to the satisfactory character of the latter. The practice, therefore, is not to be urged.

COMPLICATIONS.—These are local and systemic. Those of them that are at all serious are rare, and can generally be traced to fortuitous circumstances.

Inflammatory complications are usually due to undue traumatism at the time of the inoculation, to injury of the pock, or to the previous existence of a cutaneous disease or of some dyscrasia. Dermatitis is the most common. It is usually a mere erythema, but in some instances lymphangitis, lymphadenitis, phlegmonous inflammation, with diffuse suppuration, may result. From injury of the pock ulceration and gangrene may take place, and septic absorption may follow in their train. These complications are to be treated as if they had occurred from any other cause. Generally, the mere vaccination is not responsible for them, but in some instances putrescent vaccine may be adduced as their source. In such cases the complications, if they can still be called so, are apt to make their appearance long before the pock matures, even within forty-eight hours of the vaccination. Inflammatory complications supervening on the full development of the pock may invariably be set down as due to some cause not connected with the quality of the virus employed.

An undue amount of dermatitis is best treated with some mildly astringent and anodyne application. The following liniment is excellent for the purpose: Rx. Unguenti Stramonii oz. j; Liquoris Plumbi Subacetatis fl. drachm ss; Olei Lini fl. oz. iv.—M. fiat linimentum. As a rule, it is best to avoid poultices applied over the pock itself, for they soften the tender structures that make up its dome and render it prone to rupture, with all the consequences that may follow its conversion into an open sore. When the latter accident has occurred, dusting powders will ordinarily suffice to absorb the discharge, and thus prevent putrefaction—either the ordinary toilet powder or salicylized or carbolized powders, the basis of which may be starch with a small proportion of the oxide of zinc. Besides the antiseptics mentioned, iodoform, boric acid, etc. may be used to advantage. Liquid applications are not usually so appropriate, but the writer has known the proprietary preparation termed Listerine to answer admirably.

Circumscribed collections of pus are to be treated as under other circumstances, and burrowing is to be guarded against. It is only in the worst cases that constitutional treatment of any sort is demanded, and in these it should be of a supporting nature.

Passing from the simple inflammatory complications to those of a specific character, we will first mention erysipelas. Genuine erysipelas following vaccination is quite rare, but when it does occur it is prone to prove serious. The writer believes that it always depends on secondary infection—i.e. that the vaccinal wound becomes the nidus of an erysipelatous contagium already existing in the patient's surroundings, just as any other traumatic surface might, and that the vaccinal virus has nothing whatever to do with it. Admitting that improper virus is apt to give rise to dangerous inflammatory complications, the latter are not really erysipelatous, whatever guise they may put on. Erysipelas following vaccination calls for no other treatment than what is proper for traumatic erysipelas under ordinary circumstances.

We now come to the subject of vaccinal syphilis. The question of the possibility of conveying constitutional taints along with vaccinia was raised long ago, but, partly relying on certain theoretical tenets, and partly because of the rarity of well-ascertained facts to shake the blind confidence felt in the utter harmlessness of vaccination, the profession fought the suggestion without properly investigating it. In regard to syphilis, the broad assertion was maintained that two infectious diseases could not affect an individual at one and the same time: either syphilis would be communicated alone or vaccinia alone; moreover, it was affirmed that the juices of a syphilitic person were not capable of giving rise to the disease by inoculation unless they happened to proceed from a syphilitic lesion. There was never sufficient basis for the former of these two doctrines, and the latter received a rude shock when it was shown by Pallizzari and the anonymous physician of the Palatinate that the blood of a syphilitic subject was capable of conveying the taint. Meantime, certain horrible outbreaks of syphilis were reported, chiefly in Italy, that could not reasonably be imputed to the ordinary occasions of syphilitic infection. Even these occurrences, however, failed to shake the general incredulity, especially in Great Britain, where until quite recently men's orthodoxy in medical matters was gauged by their obstinacy in refusing to investigate, far less believe, the slightest proposition unfavorable to vaccination, and where, also, observations from beyond the limits of the empire were looked upon as in all probability fallacious.

To a Frenchman, M. Viennois, we are indebted for the first systematic and fair-minded study of the subject of vaccinal syphilis. This writer demonstrated that the Rivalta cases and those of other like outbreaks were certainly due to vaccination, but he concluded that they owed their occurrence not necessarily to the use of lymph from syphilitic subjects, but to the fact that that lymph contained blood. By this time it had come to be recognized that syphilis was inoculable by the blood. But even Viennois's masterly essay, and the facilis descensus it offered to those English authors who found themselves confronted with proof positive of their error, failed to make any noteworthy impression beyond the concession that syphilis might possibly be communicable in vaccination, but that, if it were, the catastrophe might easily be escaped by avoiding the use of lymph contaminated with blood, and that, therefore, the danger was practically no danger at all, for no one in England would think of using bloody lymph! In all this the English were slavishly followed by our own countrymen. It is proper to add, however, that Ballard of London did his best to present the matter in a proper light to the British profession, and that it is largely due to his labors and to those of Jonathan Hutchinson (the latter of whom supplemented Ricord's discovery that vaccine lymph is never free from blood with abundant clinical evidence of the existence of vaccinal syphilis unavoidable by the mere observance of Viennois's safeguard) that we are now freed from the clog of error in this matter. Nor was it the English alone that so long baffled the recognition of the truth; in the French Académie de Médicine, Jules Guérin and his adherents fought desperately against it.

At the present day we know that syphilis is liable to be communicated in vaccination, and that, too, without regard to visible blood in the lymph employed. There are two ways of avoiding it. One is, to use non-humanized lymph, since the lower animals are insusceptible to syphilis.¹ This is simple. The other is, to select a human vaccinifer that is free from syphilis. This is difficult. Too great reliance, however, should not be placed upon the vaccinifer; it is possible to convey syphilis even in the use of bovine virus. Suppose two persons, A and B, are to be vaccinated at one sitting, A being syphilitic. If A is vaccinated first, and the same lancet, imperfectly cleansed, is used on B, it is plain that B will be inoculated not only with vaccine lymph, but also with A's blood. It is of the first importance, therefore, that this form of vaccinal inoculation of syphilis should be carefully guarded against; and that can be accomplished most certainly by using a fresh instrument for each patient.

¹ Practically, this is certain, although there is some reason to believe that the disease may be conveyed to monkeys.

From a medico-legal point of view it is important to note that constitutional syphilis may follow vaccination, and yet have nothing to do with it. Suppose an infant to be born syphilitic, but with no visible manifestations of the taint. Let that child be vaccinated, and let the syphilitic dyscrasia afterward break forth. The ordinary inference would be that the syphilis was due to the vaccination; and in most instances this view would certainly be urged by the syphilitic parent, since it would free him from suspicion. It is always easy to disprove such an allegation, however, for syphilis communicated in vaccination always shows itself first in the form of a chancre at the site of the vaccination. Therefore in any given case, unless this mode of onset can be proved, the syphilis is manifestly not of vaccinal origin. Some observers, it is true, are of the opinion that vaccination may evoke a pre-existing syphilis, to use Lanoix's term—i.e. that it may hasten the appearance of the characteristic manifestations, and even determine their localization at the site of the vaccinal inoculation. But, even allowing the truth of that proposition, in such a case the lesion would be constitutional, not chancrous.

It is well, nevertheless, to take precautions against being placed on the defensive in this way; and it may commonly be avoided by declining to vaccinate infants under three or four months old, since inherited syphilis generally manifests itself by that time. This prudence on our own behalf should not be carried so far, however, as to lead us to deny the benefit of vaccination to very young infants whenever the prevalence of small-pox is such that they are in obvious danger of exposure.

As regards its management, vaccinal syphilis does not differ from the ordinary form of the affection, and hence demands no other treatment than what is proper for the disease contracted in the usual way. It simply originates in an extragenital chancre.

Concerning the conveyance of other constitutional taints in vaccination our knowledge is very limited. The present tendency of pathological investigation is, however, to accord inoculability to many diseases that formerly were not imagined to possess that quality, so that in regard to other affections than syphilis it is prudent to use the utmost care in the choice of lymph. There is one supposed safeguard that does not seem to have the slightest title to be so regarded—namely, the notion that a typical pock cannot be developed on a person affected with a specific cachexia. There is no truth in the doctrine. Over and over again the writer has seen perfect vaccine pocks on persons whom he knew to be syphilitic.

Cutaneous affections of a non-specific character are sometimes observed to result from vaccination; that is to say, they follow close upon its performance, without any other known exciting cause. It may fairly be supposed that in many instances they would have shown themselves even if the vaccination had not been performed, for it is often the case that we are unable to speak positively in regard to the exciting cause of an eruption. Several years ago a striking case in point was related to the writer by a well-known physician of this city, S. S. Purple, in whose practice it occurred. Purple had engaged to vaccinate a child on a certain day, but for some reason the vaccination was not done. In about a week from the appointed day, however, erysipelas made its appearance, beginning on the left arm at the usual site of vaccination, and pursued its course to a fatal termination. To be sure, we are now speaking of non-specific affections, but erysipelas illustrates the proposition perfectly, notwithstanding its specific character.

Children with a tendency to eczema are prone to suffer an outbreak of that disease as the result of vaccination. In Jenner's time, indeed, it was considered not only that there was great risk of causing an aggravation of any slight eczematous eruption by vaccination, but that the mere existence of the eczema, even in the most trivial form, was likely to interfere with the success of the vaccinal inoculation. This has been the general feeling of the profession. Quite recently, however, many observations have been recorded tending to show that the old dread of vaccinating an eczematous child was not altogether warranted. The question needs further study, and, while it is probably best to postpone the operation under ordinary circumstances, nothing should induce us to withhold its protective influence where there is any manifest danger of actual exposure to small-pox.

Although eczema is the most common of the cutaneous affections called forth or aggravated by vaccination, there are various forms of skin disease, some of them difficult to classify, that occasionally result. They are usually vesicular, pustular, or furuncular—that is to say, irritative. In the majority of instances it will be found either that the pock itself has followed an irregular course, being whitish, diffuse, and ending in an exaggerated although superficial incrustation, or that it has been subjected to injury. Still, in some cases neither of these conditions is the precursor of the skin affection. In many instances the latter can only be called nondescript. There seems to be some occult connection between vaccination and the curious skin disease described by the late Tilbury Fox of London under the name of impetigo contagiosa; and, indeed, Piffard of this city has found certain microphytes to be common to the crusting period of vaccinia and that of contagious impetigo. What the relation of the two affections is to each other, however, it is difficult to say.

Apart from impetigo contagiosa, the cutaneous complications that follow in the wake of vaccination possess no distinctive features, and their management differs in no wise from that of the same manifestations due to other causes.

THE TECHNICS OF VACCINATION.—This aspect of our theme involves a number of separate considerations. It will be convenient to give our attention first to the matter of the choice of virus. The question arises at once as to the selection between animal vaccine and the humanized variety. In a broad sense the term animal vaccine includes—1. Virus derived directly from a case of so-called spontaneous cow-pox. 2. Variola vaccine—i.e. the virus of an affection of the cow resulting from variolation. 3. The virus of horse-pox (not strictly vaccinal). 4. Retro-vaccine—i.e. the virus of an affection produced in the cow by the inoculation of vaccinia from the human subject. 5. The virus of a disease (true vaccinia) propagated through a series of bovine animals from the so-called spontaneous cow-pox, being the virus now commonly understood by the term, and the variety here referred to when it is not stated to the contrary.

By humanized vaccine we understand that which is obtained from the human subject, no matter how short or how long its descent from the cow. As regards animal vaccine, we may practically exclude from consideration all but the last variety mentioned, that being the one to which, in the great majority of instances, the term is now restricted. This narrows the question down to the choice between virus that has been propagated through a number of bovine animals (practically, calves) from the spontaneous disease in the cow, and that which, whatever its original source, has already passed through the human system.

The variety first mentioned, sometimes called primary vaccine, is generally spoken of by authors as not very trustworthy as regards its infective power (that is, not to be counted on to take), and as prone to give rise to undue inflammatory complications when its use does prove successful. These unpleasant qualities might be explained by the supposition that primary vaccine is not apt to be at its best when it is now and then obtained. Practically, however, it may be dismissed without further consideration, for it is seldom to be had.

The second form—variola-vaccine—is manifestly improper to be used whenever genuine vaccine is to be obtained, unless, indeed, we shut our eyes to the accumulating evidence that variola-vaccine, so called, is not vaccine at all. Furthermore, it is a question whether its use, as well as all attempts to produce it, should not be forbidden by law.

The third variety, if such it may be called, it does not seem legitimate to use in the present state of our knowledge, since it is not yet proved satisfactorily that horse-pox possesses the full protective power of cow-pox, or is free from objections that do not arise in connection with the latter.

As to retro-vaccine, while the writer is unable to see any positive reason against its use, neither can he see any reason why it should be superior to humanized vaccine, as such, save that during the period of its bovine propagation it is not liable to become contaminated with the poison of syphilis. The idea that an enfeebled stock of humanized vaccine can have new life infused into it by passing through the system of the cow is not reasonable primâ facie, and there are no particular facts to support it. By ensuring freedom from the danger of communicating syphilis retro-vaccination doubtless served a good purpose at one time, but now, since the remarkable and enduring excellence of the Beaugency stock is so well established, there seems to be no excuse for a further resort to the practice.

The last of our five forms of animal vaccine, that produced by the continued propagation of spontaneous cow-pox through calves, is what is now known as animal vaccine par excellence. Its advantages over the other forms are so obvious that it alone should figure in any comparison between animal and humanized vaccine. That being understood, what are the relative merits of animal and humanized vaccine? It should be stated, in the first place, that bovine virus should be compared with virus that has long been humanized, for lymph of but a few removes from the bovine animal does not show any noteworthy differences from animal vaccine itself.

In behalf of humanized virus it is maintained—1, that it is a more trustworthy preventive of small-pox; 2, that it is superior in its infective property, so that it is surer to take; 3, that it is more prompt in its action, thereby affording more speedy protection to persons who have actually been exposed to small-pox; 4, that its virulent property is easier of preservation, wherefore it is more to be depended on when it is necessary to keep it on hand for a long time or to transmit it to great distances; 5, that its use requires less skill, or, rather, less special knowledge of the peculiarities of the animal virus; 6, that it is less violent in its effects; 7, that it is less apt to give rise to irregular, and therefore more or less abortive and non-protective, forms of pock.

The first of these propositions, which asserts that humanized vaccine confers greater protection against small-pox than the animal virus, was warmly maintained by those who opposed animal vaccination on its first introduction into this country; but now the record of the past thirteen years, during which period bovine virus has more and more borne the brunt of the fight against small-pox, has disproved it in the judgment of all competent and fair-minded observers. So far, indeed, as the facts have been analyzed, they go to show that the reverse is the case—that bovine virus confers a more complete and a more lasting protection. Direct observation on this point is strengthened by the collateral fact that revaccination became at once astonishingly successful when the use of animal vaccine first gained currency, whereas now it is again declining in success; the explanation of which latter circumstance is, that it is now found difficult to revaccinate those whose primary vaccination was done with bovine virus—a striking indication of the permanence of the protection accomplished with the latter.

The second assertion—that humanized virus succeeds more readily than the bovine variety—is still maintained by many, but, it may confidently be said, by few if any whose experience with good animal vaccine has been large. The truth is, that every large public vaccination service in the country is now carried on almost solely with bovine virus, and that results are thus achieved that were not dreamed of in former times. Individual experience cannot weigh against this fact, but may be explained, rather, by what modicum of truth there may be in the fifth proposition, or by the assumption (surely a legitimate one, in view of the number of irresponsible and ignorant purveyors of animal vaccine that have thrust themselves before the profession since the advantages of the practice were established by the labors of others) that those whose observation leads them to a conclusion at variance with that reached by the great majority of trained observers have really been unfortunate in the quality of the virus with which they have been supplied. Whatever the explanation may be, however, there is nothing more certain than that the use of animal vaccine, properly carried out, is daily furnishing results that have never been excelled, if they have been equalled, in the employment of humanized virus on a like scale.

The third suggestion—that the humanized virus acts the more promptly of the two, and is therefore to be preferred for immediate protection—is plausible, since the areola (the alleged sign of systemic infection) forms somewhat later around a pock produced by animal virus than around one that is the result of vaccination with the humanized variety. The difference is one of a few hours only at the most, and it is not by any means a general occurrence; still, we may concede that in this respect the use of humanized virus is to be preferred under certain circumstances.

As to the fourth statement—that humanized virus is more tenacious of its infective property—strictly speaking, there is not a particle of truth in it. In the case of liquid lymph preserved in capillary tubes it has the semblance of truth, but, for reasons that will be more fully set forth hereafter, that is because it is difficult to get the virulent portion of bovine lymph out of the tube. In the form of dried lymph (the only form that ought to be used) animal vaccine may be sent to all parts of the world, and may be kept any reasonable length of time and without special care, without undergoing sensible deterioration, if tested by one who is familiar with its peculiarities and aware of the care that should be taken in using it. Under ordinary circumstances there is no difficulty about preserving animal vaccine with its energy practically unimpaired.

The statement that the use of humanized virus demands less special knowledge than that of bovine virus is conceded at once. That special knowledge is easily mastered, however, and no man fitted to practise medicine will look upon its acquirement as a bugbear or a hardship.

The impression, almost universal thirteen years ago, that humanized vaccine is less severe in its local and constitutional effects than the animal virus has been eradicated from the minds of all but those who still follow the teachings of the older writers rather than yield to what daily experience has been teaching during these thirteen years, or those who reason from exceptional cases rather than from a general drift. The truth seems to be this: with revaccinated adults animal vaccine acts somewhat more severely than the humanized virus; in infants, on the other hand, its action is not so violent as that of the humanized variety.

Concerning the seventh and last claim put forward in behalf of humanized vaccine—that it is less apt to give rise to irregular or spurious pocks—we may say that no form of irregularity has been observed by those who have lately used the bovine virus that was not well known to the older writers, who founded their observations wholly, or almost wholly, on the use of the humanized virus; nor is there any proof that such irregularities are more common now than formerly. The truth seems to be, that these irregular forms of pock seem to prevail at certain times, and not at other times, regardless of the particular stock of virus used, other things being equal. Why this should be so we do not know, but the fact is beyond dispute.

To sum up, then, we can only say that in barely one particular—that of promptness of action—can humanized virus justly be credited with any superiority, while in every other essential respect it is inferior, so far as any difference is to be observed.

What, on the other hand, are the points of superior excellence attaching to bovine virus? Setting aside certain extravagant assertions that have sometimes been made in its behalf, such as that it far exceeds the humanized virus in its protective virtue (which may be true, but is not yet proved), they may be put in general terms in the form of a denial of all the particular claims that we have enumerated as having been put forth for its rival. Such a denial, it has been seen, seems to the writer to be justified, save in the one particular that perhaps we should accord to humanized virus the merit of speedier action, and consequently greater certainty of protection, in cases of actual exposure to small-pox.

Besides these negative points in its favor, the foremost advantage of animal vaccine is the guarantee it gives that, properly used, no syphilitic contamination will result. On this point no argument is needed, for the cow is insusceptible to syphilis.

A second consideration in its favor is, that it can always be had in large quantities at short notice. The young practitioner of the present day can scarcely appreciate the importance of this fact, but whoever remembers the comparative helplessness in which, in past years, he has found himself in the face of a sudden outbreak of small-pox, not knowing which way to turn for an adequate supply of vaccine, will at once concede its force.

On the whole, then, it must be said that bovine virus is entitled to the preference as a rule, but that possibly it is well to resort to humanized lymph of early removes under the special circumstances above referred to. On no account should long-humanized vaccine be used so long as our present stocks of animal virus maintain the excellence they have thus far preserved, nor should humanized virus of any sort be preferred in the general run of cases.

Passing now to a consideration of the various forms of vaccine, disregarding its source, there are practically these three: the crust, liquid lymph preserved in capillary tubes, and dried lymph.

Until recently the crust, or scab, was much used in this country. Its capability of being preserved unimpaired for a long time was a valid excuse for this, especially in regions remote from the great channels of communication, and it was in such districts that the use of the crust was chiefly practised. That excuse scarcely exists now, for there are few physicians who cannot obtain a better form of vaccine within a very short time. The objections to the crust are two: 1. Most crusts are inert. Especially is this true of bovine crusts, which are wellnigh worthless. It must be confessed, however, that when once a crust has proved itself active it may be trusted to retain its infective property for a very long time. The writer has made successful use of crusts seven years old that had made the voyage to Japan and back; and they were bovine crusts too. Still, the rule is, that crusts are untrustworthy. 2. Their use is apt to be followed by undue inflammation, probably of septic origin, for they almost invariably contain putrescent or readily putrescible elements. It has even happened to the writer to cut open a crust that to all appearance was typical and innocent, and to find in its interior a cavity occupied by a pulpy, stinking slough. Manifestly, such material is unfit to be introduced into the system of any human being.

In regard to liquid lymph in tubes, it is not much used in this country, and its employment elsewhere is on the decline. At first thought, it would seem to be the best form of all, but experience does not bear out this view. In this form humanized lymph is vastly superior to animal lymph, but with every possible care in charging and sealing the tubes it is not uncommon to find their contents putrid. There are low vegetable organisms that are supposed to prey on the vaccinad. If there is any truth in this supposition, those organisms are certainly favored in their destructive luxuriance by keeping the lymph liquid, thus furnishing them with the best possible culture-fluid. Be this as it may, the fact is well ascertained that tube-lymph does not keep well. It has been mentioned already that bovine lymph stored in tubes is decidedly inferior to the same form of humanized lymph. This was long ago recognized by propagators of animal vaccine, but the cause remained a mystery until Warlomont of Brussels suggested that it was due to one of the physical peculiarities of animal lymph—that, namely, as already hinted at, by virtue of which its formed elements tend to attach themselves to any surface presented to them, leaving the supernatant liquid a mere inert compound of water, albumen, and salts; so that in the case of tube-lymph the virulent elements remain attached to the glass, and only the inert constituents are really used. This theory is exceedingly ingenious and plausible, but the writer is not aware that it has been proved. He does know, however, that in some South American countries, where calf lymph in tubes is used with success, the custom is to grind the tubes to powder, and inoculate with the resulting magma, glass and all. This practice is certainly not to be commended.

Dried lymph is the most efficient of all forms of vaccine, and, kept as it ought to be, it retains its infective power long enough to answer all ordinary requirements. The writer has used it three years old with success. It may commonly be counted on for six weeks. One fact should be borne in mind, however: the longer dried lymph has been kept the more care is necessary in its use, for by long keeping it becomes very hard, so that it is a work of patience to dissolve it off from the surface on which it was deposited. Failure to accomplish its solution is the most common cause of a lack of success in its employment.

The various forms of stored vaccine are esteemed by the writer in the following order: 1, dried bovine lymph; 2, dried humanized lymph; 3, humanized tube-lymph; 4, humanized crusts; 5, bovine tube-lymph; 6, bovine crusts.

The age and other circumstances under which it is best to vaccinate children constitute a point for practical consideration. It may first be mentioned that pre-natal vaccination has been advocated by some authors; that is to say, the vaccinal infection of the foetus in utero by vaccinating the mother during gestation. There seems to be respectable testimony going to show that the end may thus be accomplished, but a weighty objection arises in the fact that this mediate vaccination of the foetus produces no physical sign of its success, so that doubt must always be felt as to whether or not the procedure has been efficacious. Moreover, it is seldom indeed that a child needs protection before its birth, provided we protect the mother, for it is well known that vaccinia will overtake and destroy the variolous infection, even when the latter has had two or three days' start. The practice has been chiefly urged by Bollinger. It is not likely to come into general use.

There is no special objection to vaccinating an infant at any time after birth, but usually it is well to defer the operation until the child is about three months old, unless there is actual danger of exposure to small-pox. Yet it is not well to postpone vaccination until the period of dentition, for the combined irritation of the two disturbing elements may prove decidedly uncomfortable if not serious.

Something is to be said as to the time of the year to be chosen. In New York the bad custom prevails, especially among the poorer classes, of having children vaccinated only in April, May, or June—just the part of the year in which erysipelas is most rife. The hot months should not generally be chosen, for any source of irritation is apt to be felt more severely by infants during the summer heat. However, no circumstances should be looked upon as a positive bar to vaccination in case of actual danger of exposure to small-pox, and in large towns children should never be taken into public conveyances or carried into any promiscuous assemblage until they have been protected by vaccination.

The next question is as to the part of the body that should be selected for the inoculation. The region of the insertion of the left deltoid muscle is usually chosen—the left rather than the right, because most nurses habitually carry an infant on their own left arm, so that the child's left arm is uppermost, and hence less exposed to injury. The region of the deltoid insertion is comparatively free from the irritation of muscular contraction, and it is easily accessible. If two insertions are made, it is well to make one of them over the deltoid insertion and the other at a point about an inch distant on the line of the posterior border of the same muscle, for there the lymphatic connection with the axillary glands is less free, so that adenitis is not so much to be feared. To avoid a scar in a locality that may be exposed to view on certain occasions some mothers prefer that their daughters should be vaccinated on the lower limb. To this there is no special objection, further than that the lower limb is rather more exposed to rough handling than the arm. If the leg is chosen, the point of junction of the two heads of the gastrocnemius is an eligible situation.

The actual operation is performed in various ways. The old inoculators generally made an incision through the whole thickness of the skin, so that a pellet of subcutaneous fat rolled up into the little wound. This is wholly unnecessary; furthermore, it is objectionable, for it decidedly increases the risk of inflammatory complications. Still more to be avoided are the methods by inserting a seton imbued with the virus and by hypodermic injection or other like procedures. The best way is, simply to remove the horny layer of the cuticle, so as to expose the succulent portion of the epidermis. This surface is somewhat red, and from it a slight exudation of lymph will be observed, but there need not be the least flow of blood. By this procedure it is not uncommon to vaccinate a sleeping child without waking it. It is not only admissible, but preferable, not to wound the derma at all. Such an abrasion is easily made with an ordinary lancet, which, contrary to the advice sometimes given, should be very sharp; but no cutting or scratching should be done with it, only scraping with the convex part of its edge, precisely as in using an ink-eraser. Scratching instruments (such as the rake-like vaccinator often used or a row of needles set in a handle) are not easy to adapt to varying degrees of plumpness of the arm, and are apt to make too deep scratches, one at either side, while the skin between the two is scarcely touched. Whatever instrument is chosen, it should not be used again until it has been thoroughly cleansed—made chemically clean—which can be accomplished only by heating it or by wiping it off and then dipping it into a strong disinfectant solution.

Some individuals are refractory to vaccination, but complete insusceptibility is exceedingly rare. Various expedients have been resorted to in rebellious cases, such as vesication with ammonia-water, maceration of the skin for some hours with glycerine, and the like. The writer has known these devices to succeed, but he has not seen the slightest advantage in the plan recommended by Ceely, that of using a wound some hours old rather than one just made, although he has tried the experiment many times. It is not necessary to make a large abrasion; one as large as the little finger-nail is ample.

The next step is to apply the virus, and it should be so applied as to bring it into contact with every part of the denuded surface. In what is known as arm-to-arm vaccination, or its equivalent, calf-to-arm vaccination (by all means the most successful method, although not often practicable in this country), the liquid lymph, fresh from the vaccinifer's pock, is simply applied, when it will at once become diffused over the abraded surface without any special pains being taken to accomplish that end.

If dried lymph is used, particular care should be taken to see that it is actually dissolved and transferred from the substance on which it was dried to the abraded surface. Failure to accomplish this is the cause of almost all the lack of success that inexperienced vaccinators meet with. The lymph should be moistened with water, or, if it is quite old, with glycerine, before the abrasion is made, so that it may have time to dissolve. It should then be rubbed upon the abraded spot vigorously, and at least for the space of a full minute.

In the use of tube-lymph no other precautions are necessary than in arm-to-arm vaccination, but, simple as this method is, its results are unsatisfactory.

Crusts should be reduced to a powder, and then made into a thin paste with water or glycerine. A convenient way of powdering a crust is to rub it on a file or between two files. The paste is to be well rubbed upon the abrasion. The insertion of a solid piece of crust into a valvular incision is not to be recommended.

When the operation is finished it is well to keep the arm bare for about five minutes, but not necessarily until the spot has become dry. It is not well to apply any sort of plaster, but means should be taken to prevent the underclothing from sticking to the abrasion. For this purpose there is no objection to the shields that are furnished by the surgical instrument-makers. Usually, however, nothing of the sort is necessary.

THE STORAGE AND PRESERVATION OF VACCINE VIRUS.—Lymph should usually be taken on the eighth day, inclusive—never after the areola has formed. On the other hand, the writer's experience does not lead him to coincide with those who state that the earliest lymph that can be obtained is the most energetic. If it is to be dry-stored, the substance to be coated with it (slips of quill, ivory, wood, whalebone, glass, and the like) should be laid gently in the pool of lymph that exudes on puncturing the pock, and allowed to dry, preferably without the aid of artificial warmth. The layer of lymph should be plainly visible after it has dried. A second coating is advisable, as it serves to preserve the first.

Capillary glass tubes are either cylindrical or furnished with a bulbous expansion at the middle, the latter form being most commonly used. To charge a tube make sure that both ends are open, and then submerge one end in the pool of lymph. Capillary attraction will cause the tube to fill, and the process may be facilitated materially by inclining the tube toward a horizontal direction, so that the capillary attraction is not opposed by that of gravitation. Care should be taken to keep the applied end of the tube constantly submerged, or bubbles of air will enter it. The sealing may be done with a blowpipe, by simply holding the ends in a flame, or by means of sealing-wax or some similar substance. The satisfactory charging of tubes demands some practice, but a little patience will enable any intelligent person to succeed.

In regard to crusts, they should never be removed until the surface beneath has become cicatrized and they have been partially detached by the natural process. A crust torn off prematurely should never be used, and the same may be said of secondary crusts—i.e. those that form by the desiccation of the discharge from the raw surface left when the primary crust has been removed forcibly.

For the preservation of vaccine in these various forms tubes need only be kept in a cool place. Dried lymph and crusts should be guarded against dampness even more than against warmth. Their preservation may be decidedly favored by over-drying, either in an exhausted receiver or by keeping them in a closed vessel in the presence of sulphuric acid, chloride of calcium, or some other substance having a strong affinity for water. It is needless to say, however, that they should not come into actual contact with any such agent. While this artificial desiccation tends powerfully to preserve dried lymph, it makes it more difficult to use. When dried lymph or a crust is to be sent by mail or other conveyance, it should be wrapped in some impermeably envelope, for which purpose gutta-percha tissue is very convenient. Both these forms of virus should be kept in a cool place. There is no objection to keeping them on ice, provided they are well protected against moisture.

In conclusion, the writer wishes to say that the limited space at his command has compelled the assumption of a dogmatic rather than an inductive form in the construction of this article. To the reader who may wish to pursue the subject further—and it will well repay thorough study—he would recommend the following bibliography:

Ballard: On Vaccination: its Value and Alleged Dangers, London, 1868.

Bousquet: Nouveau traité de la vaccine et des éruptions varioleuses, Paris, 1848.

Bryce: Practical Observations on the Inoculation of Cow-pox, Edinburgh, 1809.

Ceely: Observations on the Variolæ Vaccinæ, Worcester, 1840.

Chauveau et al.: Vaccine et Variole, Paris, 1865.

Depaul: Nouvelles recherches sur la véritable origine du virus vaccin, Paris, 1863; De l'origine réelle du virus vaccin, Paris, 1864; et al.: De la syphilis vaccinale, Paris, 1865.

Hardaway: Essentials of Vaccination, Chicago, 1882.

Hering: Ueber Kuhpocken an Kühen, Stuttgart, 1839.

Jenner: An Inquiry, etc., 2d ed., London, 1800.

Sacco: Trattato di Vaccinazione, Milano, 1809.

Seaton: A Handbook of Vaccination, London, 1868.

Steinbrenner: Traité sur la vaccine, Paris, 1846.