Vaccination consists in the inoculation of virus taken from the pock produced by vaccinia.

Vaccine Virus.—Virus has been taken from vaccine vesicles on almost all animals susceptible to vaccinia, but throughout the greater part of the last century the material used in the vaccination of human subjects was taken generally from a vaccine vesicle on the arm of a previously unvaccinated healthy child. Such virus when collected at the proper time was found to take with great regularity, and vesicles resulting from its use were uniformly well developed and typical. Humanized virus was, however, open to the objection that it could communicate disease if the child were not perfectly healthy, and as a matter of fact it did communicate syphilis in a certain number of instances. The possibility of this infection was so serious an objection to the use of virus from this source that in the last quarter of the century calf virus, recommended and used in Italy many years before, was gradually substituted for human virus, and at the present time the use of animal virus is general in Europe and in the United States. In the production of virus, calves are for commercial reasons generally preferred to other animals. Calves take typically, and a large amount of virus can be collected from them, whereas all other animals either are comparatively expensive, or take poorly, or are able to furnish but little virus. Cows also are more expensive, are less easily handled, and develop vaccine vesicles less typically.

In the practical production of vaccine virus calves are vaccinated much as human beings are vaccinated, but over a larger area. Usually the posterior abdomen and the insides of the thighs are covered with superficial linear incisions, and into these incisions the seed virus is rubbed. In the laboratory of the New York City Health Department all operations relating to the vaccination of the animals and to the collection of the virus are carried on in an operating-room provided with a cement floor, glazed brick walls, and equipped with enamelled metal operating furniture, such as would be used in a hospital. The attendants wear sterile gowns and the technique of the operations is aseptic. The seed virus is either humanized virus collected by touching sterile pieces of bone to the serum exuding from ruptured vesicles on the arms of children, or in the great majority of cases bovine glycerinated virus which has been preserved two months or longer.

It is found that the crust of the vesicle, the serum issuing from the vesicle after the crust is removed, the pulp which forms the semi-solid contents and base of the vesicle, and the serum which exudes from the base of the vesicle after the pulp has been removed by a curette, all convey material capable of producing the vaccine vesicle in a susceptible person, and are therefore all different forms of vaccine virus. It has been shown, however, that if any of this material is filtered, so that all the solid particles are removed, the filtrate is inefficient. In other words, the serum is efficient as vaccine virus simply by virtue of the solid particles which it contains. It is also found that the pulp is so rich in the active principle of vaccine virus that it may be mixed with several times its weight of glycerin or other diluent and still maintain its efficiency.

The different sorts of vaccine virus on the market are simply different ways of supplying this material coming from the vesicle. Most material is in one of three forms,—

(a) The pulp diluted with some excipient, such as glycerin, vaseline, or lanolin. The emulsion, made by mixture with glycerin, may be contained in a vial or in a capillary tube, or may rest on some holder, such as an ivory or bone point. In the latter case the point is usually protected by some form of cap. Mixture with vaseline or lanolin makes a paste, which is usually issued in a box. This is in use in parts of Italy and in India.

(b) The serum dried on a holder, as an ivory or bone point or a quill.

(c) The serum mixed with some excipient, usually solid or semi-solid, until it becomes a paste, and furnished like dried serum on a holder.

For a physician the choice among these three forms is governed by considerations of efficiency, safety, and ease of use. All the forms are under certain conditions efficient, but comparative tests show that the emulsion of the pulp issued by different laboratories is much more certainly efficient than the other forms, and the glycerinated emulsion is at present in most general use both abroad and in this country.

It is also true that all forms may be perfectly safe. All forms contain bacteria when prepared, and the majority of these bacteria die within a few weeks or months after preparation. On account of the mildly antiseptic quality of glycerin the bacteria in the glycerinated emulsion usually die sooner than those in the other forms of virus, and so far as bacteria are objectionable in the virus the glycerinated form may therefore be said to be somewhat preferable. It should be added, however, both that glycerinated virus is usually put in the market before the bacteria have disappeared and that the bacteria present in virus issued by well-conducted laboratories are not found to be pathogenic to persons when inoculated by the customary method of vaccination.

The ease of use of any form of virus depends largely upon the custom of the physician. In vaccinating a large number at one time there can be no question that the use of a liquid virus supplied in vials is more rapid than the use of a dried virus, as the latter has to be thoroughly moistened before it can be applied effectively.

Methods of Vaccination.—The usual method of vaccination is to scarify a spot on the skin and to rub the virus on that spot. The choice of place depends partly on Æsthetic reasons and partly on convenience. To avoid the formation of an unsightly scar on the arm, the leg may be used instead. If the arm is chosen, the insertion of the deltoid is the place of election on account of the small number of lymphatics there. If the leg is chosen, the area just below the head of the fibula presents the same anatomical advantage; but a spot a short distance above the knee on the outside of the thigh is often thought to offer less opportunity for injury and infection. Choice between the sides depends in an adult on the use to which the vaccinated limb is to be put, and in a baby on the advantage of vaccinating the side which is carried away from the nurse.

The size of the scarification is important. The vesicle is always somewhat larger than the scarification, and the larger the vesicle the greater danger that the surface may be broken, and the more opportunity there is for the introduction of extraneous infection. A spot as large as the head of a medium pin is about as small as can be easily scarified, and vesicles formed on such scarifications are least liable to have inflammatory complications. If, as certain evidence tends to show, a larger area of scar guarantees greater protection, and if a larger area is therefore desired, it is better to vaccinate in two or three small spots than in one large one. It is somewhat difficult to rub the virus from a bone point on a spot of the minute size described, and as this form of virus is usually more dilute than glycerinated virus, a larger area may safely be employed.

The scarification may be made with any sharp instrument, or with the point itself. The only precaution necessary is that the instrument should be free from infection. As a scarifier the ordinary cambric needle presents the advantages that it is usually clean, is easily sterilized, and is so inexpensive that a fresh one can be used for every operation.

It is not necessary that the scarification should draw blood, although blood is not objectionable unless it flows so freely as to wash away the virus, or unless the subject has hÆmophilia.

Although with a notably susceptible subject or with especially active virus it may be sufficient simply to smear the virus on the scarified area, it is usually necessary and always advisable to rub in the virus with a wooden slip or with the point firmly and thoroughly.

Other methods of introducing vaccine virus are by puncture, by deep injection, and by the mouth.

In the method by puncture either a grooved lancet or a hollow needle may be used. A shallow puncture is made and the virus is deposited in it. The resulting vesicle is usually small and nearly circular, and generally remains free from infection; but as the hole in which the virus is placed is small, it is possible that the issuing blood may wash it away completely, and the percentage of success with this method of inoculation is not quite so large, even in careful hands, as by the process of scarification with the same virus. Animal experiments with deep injection of virus through a hypodermic syringe and with administration of virus by the mouth show that there is no certainty of successful vaccination by these means, and that when success results there is no proof of it without a subsequent vaccination on the skin to test or to demonstrate the immunity.

Care after Vaccination.—As vaccination is a surgical procedure, it should be conducted aseptically with a sterile instrument on clean skin, and the wound should be guarded against extraneous infection. It is well therefore to put either a sterile gauze cover or a clean shield over the wound as soon as the virus has been sufficiently absorbed, and to leave the protection on until the natural crust has been formed,—i.e., for a few hours. If the guard could be kept in position without motion and also without injurious pressure, it might remain until the process ended with the formation of a scar and the exfoliation of the crust; but practically it is so certain that the guard will be moved that it is wise to remove it and to trust to the protection of a clean muslin or linen cloth attached to the loose sleeve or other undergarment. For a day or two at the time when the inflammation is at its height it may be well again to guard by a shield against injury from a blow or push, but the shield should always be regarded as itself a danger. If by any accident the vaccine pustule becomes infected, it should be treated like any other infected wound,—the crust removed, the ulcer cleansed with antiseptics and dressed surgically. The immunity given by the pock is not at all lessened by this treatment.

Normal Clinical Course.—After primary vaccination in man there is a stage of incubation lasting for from forty-eight to seventy-two hours; a papule then develops, and by the end of the third or fourth day this has begun to show umbilication and a vesicular structure. When fully developed, about the sixth day after vaccination, the vesicle is distended and pearly in color. On the seventh or eighth day the areola develops,—i.e., the skin about the vesicle becomes hard, sensitive, and red, the redness extending a variable distance, not usually more than two inches from the edge of the vesicle. In the course of the next day or two the vesicle loses its pearly appearance and becomes opaque and often slightly yellow. With the development of the areola and of the pustule the adjacent lymph glands may swell and become somewhat painful; there may also be constitutional derangement,—some fever, pain, anorexia, restlessness, and more or less prostration; there is usually a moderate leucocytosis. About the eleventh or twelfth day the areola begins to fade, the constitutional symptoms to subside, and the pustule to dry up. A dark crust is formed which drops off usually between the eighteenth and twenty-fifth days, leaving a rosy depressed scar on which not infrequently a secondary scab is formed, to be shed a few days later.

Variations in the Clinical Course.—The vesicles may appear on the second day, but it is more frequently delayed until the fourth, fifth, sixth, seventh, or even the eighth day, and cases have been observed in which the delay was even longer.

The areola, which should be bright red, may be purple, and may extend a long distance from the vesicle.

The pustule may be hemorrhagic or may be filled with greenish pus; in this case there is probably a mixed infection.

Sometimes instead of a vesicle there appears a hard elevated nodule, in color like a red raspberry. With this there is usually no areola, and no constitutional symptoms develop. The growth is usually an evidence of poor virus. It may persist for some time before absorption.

The course may be abortive,—i.e., the vesicle does not develop completely; pustulation comes early and the crust is shed and the scar formed before the end of the second week. This course is normal though not invariable in revaccinations.

The scar may be poorly marked, even when the vaccination has run a typical course.

Complications.—The most frequent complications are infections and eruptions. An infection may be, of course, of many sorts. It may be, for example, the streptococcus of erysipelas, or the bacillus of tetanus, but it is oftenest a skin coccus. These infections may be introduced with the virus, with the instrument, or later through wounds in the vesicle or pustule. Erysipelas and tetanus following vaccination are exceedingly rare, and it has never been shown that in a case of tetanus the germ was inoculated at the time of vaccination.

Eruptions are probably usually due to a chemical irritation produced by the development of the vaccinia; they are analogous to the eruptions following the injection of antitoxine and the ingestion of various drugs. They vary in appearance, sometimes resemble the eruption of measles or of scarlet fever, and again are urticarial; they are macular, papular, and vesicular.

When a moist eczema is present there may be auto-inoculation of the pock on the affected area and a general confluent vaccine eruption appear.

Immunity.—The immunity against smallpox, or vaccinia, produced by vaccination is of gradual growth, and is not complete until the period of suppuration, about the beginning of the second week. Natural immunity is said to exist, and is probable, but it is exceedingly rare. Vaccination of a pregnant woman rarely, if ever, confers immunity on the foetus.

Duration of Immunity.—Sometimes a single vaccination gives immunity for life. Usually, however, susceptibility returns at latest seven to ten years after vaccination, and the second vaccination may give immunity for the rest of the lifetime, or susceptibility may return again and again. Failure of active, properly inserted virus shows only that the person so vaccinated is at that time immune, but conveys absolutely no information about the condition a few months later. The appearance of the scar is not a trustworthy guide as to immunity. Susceptibility to vaccination returns frequently within one year, and has returned in three months from the time of a successful vaccination. Susceptibility to smallpox probably returns, as a rule, later than susceptibility to vaccinia. It is rare that a case even of varioloid occurs within five years of a successful vaccination.

Conclusions.—Every child should be vaccinated at the time of election during the first year of life, and should be revaccinated before beginning school-life with its possibility of exposure. Every person, no matter at what age, should be vaccinated at a time of possible exposure to smallpox unless he has been successfully vaccinated within three months.