Vaccinia

BY FRANK P. FOSTER, M.D.

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.