Causes of Vaccinia.— Since the discovery of the disease many observations have been made from time to time on vaccinia, with a view to determining its specific cause. Nearly all such were made from a bacteriologic standpoint and numerous investigations have described various bacteria as being specific. Pfeiffer (1889) ap proached the subject in another way. He noted that smapox and vaccine lesions contained bodies which, to all appearances, resembled that form of cell-life known as protozoa (a higher type than the bacteria), and later Guarnieri made a more comprehensive study of the lesions. He chose for his field of observation the cornea, where he was better able to observe the various changes occurring in the evolution of the vaccinal lesion, and in the life history of the parasite. He found that soon after the inoculation of the cornea with vaccine virus a certain number of epithelial cells at the point of inoculation began to undergo a change. These cells began to show small round bodies which highly refract the light, lying in the protoplasm of the cell, are surrounded with a clear zone. These bodies are usually spherical and vary in size, some occasionally attaining the size of the nucleus of the cell, while others are minute points. They vary considerably in their shape and appear to be endowed with arnceboid movements. The organism was pro toplasmic, having no limiting membrane, nor does it contain a nucleus. The mode of pro duction is by direct division. "The parasite has a circular evolution; it develops from around a central point— concentrically from within outward— hence the lesion of variola and vaccinia is circular° (Guarnieri). The an nouncement of this discovery excited no little interest among those who were devoting their attention to this subject. Since then much has been added to our knowledge regarding the nature of both smallpox and vaccinia. Guar nieri's work has been carefully reviewed by many, among whom that of Wasielewski has been of great service in bringing forward addi tional proofs, as well as adding no little to our knowledge of the parasite found in vaccinia and smallpox. He demonstrated beyond ques tion that a parasite was always found in the epithelial cells of a vaccine or a smallpox lesion, that these parasites are never found in any other lesion, nor in the healthy tissues. At tempts failed to produce these in the cornea by inoculating it with material from skin scrapings, from measles, scarlet fever, chicken-pox, foot and mouth disease, bacteria or matter from non-specific postules on the teats and udder of the cow. Nor are such bodies present when irritating substances, such as cantharides, cro ton oil, silver nitrate, glycerin, osmic acid, India ink, or bacteria are applied to the cornea. Further, that if vaccine virus be deprived of its activity by filtration through porcelain, it loses its power to produce these bodies. Lim ited quantities of vaccine virus have been inocu lated in the cornea of a rabbit and passed suc cessfully from one rabbit to another for as many as 130. It would not stand to reason that any quantity of the original would be transferred to the animal last in the series, yet the lesion in the cornea is identical with the first, and the parasites are present in number, and have the same form and location in the cells. The fil tration experiments also demonstrate that the bodies are larger than the bacteria, as virus sub jected to this process loses its power of pro ducing the vaccinal lesion. It would, therefore, appear that since these bodies are constantly present in the lesions caused either by smallpox or vaccinia, and are not observed in any other disease process, nor caused by physical or chem ical agents, that they are actual parasites and are not simple changes produced in the cells by any other than these bodies. "The 'vaccine) bodies are the only characteristic structures which can be found in the skin mucous mem brane in smallpox and vaccinia. They are ab sent in normal and other pathological condi tions of the skin. These vaccine bodies appear with certainty and constant regularity when an actual vaccine virus is applied to a lesion of the skin or cornea.° All attempts to cultivate the virus outside the body have so far been unsuc cessful. It appears that the living body cells are required for its development. Some multi plication of the bodies have been observed to occur in the epithelial cell containing these bod ies when the cell is placed under artificial con ditions; but these have not been transmitted to other cells which have not been naturally in fected.
All persons or animals of a given species do not contract vaccinia alike; some are quite refractory, and others so for the time being, but may be inoculated after repeated trials. In sonic
the vaccinal lesion develops poorly, being small yet typical and is often delayed in its evolution. Instances like these are not infrequently ob served where a group is vaccinated under prac tically the same conditions. Particularly is this so with animals used for the propagation of the vaccine virus. In those cases where the lesion is undeveloped, typical immunity, however, as a rule follows, and is more or less permanent. It is believed that such immunity is not so great as that following a fully developed lesion. The same insusceptibility to smallpox has also been observed. All persons exposed do not contract the disease, nor do all attacked suffer alike. However, those persons who resist the infec tion at first, if continuously or repeatedly ex posed, will sooner or later succumb. It is a current belief that a successful vaccination con fers a lasting immunity to smallpox. While a greater proportion of those successfully vacci nated are rendered refractory for a long time, there are some who will at some time or other contract smallpox. Such cases are, however, very rare. The most of them are among per sons who have either been vaccinated in their infancy, or in whom vaccinal lesion was atypi cal. Vaccinated persons who contract smallpox, as a rule, have it mildly, running a shorter course, with none of the usual complications. This modified form is designated as varioloid. Immunity conferred by vaccination does not last as long as that following an attack of smallpox. It was once considered so, particu larly during the time when arm-to-arm vaccina tion was practised. Jenner himself states that he deemed it advisable to revaccinate from time to time, in order to insure a full protection. It cannot be gainsaid that a single inoculation will be followed by a typical lesion, and that this will protect against smallpox, but for just how long it cannot be said. By comparison with the method of making multiple insertions (three or more), the cases of modified smallpox (vario loid) occurring among those vaccinated by a single insertion are found to be more frequent than among those vaccinated by multiple inser tions. In Sweden the multiple insertion method has been practised for many years; the cases of smallpox are few, revaccination is not the rule. It would seem, therefore, that multiple inser tions afford a greater protection than the single insertion. With regard to revaccination, two important facts are demonstrated: That many persons who were successfully vaccinated dur ing infancy again become susceptible to vaccinia later, and that revaccination produces the strongest kind of immunity to smallpox. In Germany all children are required to become vaccinated during their first year and again be tween the 11th and 13th. The percentages of successful revaccinations range from 69 to 91 per cent. The number of cases of smallpox developing are practically nil. There is no nat ural immunity to vaccinia any more so than there is a natural immunity to smallpox. The only immunity is a previous attack of smallpox or a successful vaccination. There may be a resistance of some degree which may vary with the individual, but repeated vaccinations will demonstrate their susceptibility by a successful vaccination.
Source of Vaccine The usual method of obtaining a supply of humanized virus was to make two or more insertions on the arm, and when the lesions reached the vesicular stage, to open one or more of these vesicles; the serum was taken directly from the arm and transferred to another person, or it was pre served by drying on pieces of glass, ivory or threads. Some employed a small capillary tube, into which the fluid contents of the vesicle were drawn and the ends sealed in a flame or closed with wax. The usual custom, however, was to vaccinate direct from arm to arm; especially so was this in cities where vaccination was being done continuously. The dried crust, or scab, was also used, particularly by those who could not always obtain fresh material. These crusts were often active for several months, and there were instances in which they produced the typi cal vesicle even after a year or more. Great care was exercised in obtaining a crust from a typical lesion, and extra precautions were taken to keep this as dry as possible, it often being sealed in wax. At the present time humanized virus in any form is little employed, save in some of the Latin-American countries, where it is still the custom to use it; the bovine virus having superseded it in almost every civilized country.