This disease has two febrile periods, which, it may be inferred, have different relations to the infective agent. There is the primary, fever which is accompanied by severe general symptoms, and is probably to be explained by the presence of the infective agent and its toxines in the blood. It is not a mere matter of inference that the agent is in the blood, as its subsequent presence in the skin all over the body can only be explained by its being carried by the blood. The secondary fever coincides with the appearance and development of the eruption in the skin. The infective agent, which is probably a protozoon, multiplies in the epidermic layer of the skin, and the fluid or lymph which is there produced is highly infectious. As the eruption occurs only in the skin and mucous membranes immediately continuous with it, such as the mouth and extreme lower extremity of the rectum, we may infer that oxygen is required by the contagium for its development. It is probable that the local multiplication in the skin is associated with the production of toxines, which passing into the blood produce the secondary fever and other general symptoms. The suggestion that the secondary fever is septic is not a tenable one, as the fever occurs where the eruption has not yet produced any breach of surface, and where no septic microbes are present in the lymph.
The nature of the infective agent in small-pox and vaccinia has been the subject of much investigation and discussion. The lymph from the characteristic pustules is undoubtedly the vehicle of contagion, and it contains multitudes of minute particles. The pustules themselves contain peculiar bodies which are largely within the epidermic cells at first, but, as the cells are destroyed, become free. Inoculation has been successfully performed, chiefly on the cornea of the rabbit, and here also peculiar bodies are found in the epidermic cells. These bodies, which are in a non-committal style, called "vaccine-bodies" or "variola-bodies," are of various sizes, and are rendered prominently visible by various methods of staining. Their nature is matter of serious difference of opinion. On the one hand they are accepted as parasitic, and if so they are protozoa. By those who accept this position the name cytoryctes vaccinise Guarnieri is adopted for the parasite, Guar-nieri being the author of the first reliable research on the subject. Those opposed to the parasitic view, while acknowledging the actuality of the bodies, regard them as products of the nuclei or protoplasm of the epidermic cells. The latest writer on the subject, whilst denying that these bodies are parasites, yet holds that they are the product of the contagium, and that the true, infective agent develops and multiplies in the epidermic cells, and more particularly in these bodies which he regards as derived from the protoplasm. The matter is, therefore, still sub judice, but seems on the way to decision. The author, from a survey of the subject and from personal observation in cases of small-pox and chicken-pox, is inclined to the belief that these bodies, so abundant and so characteristic, are no mere product of the cells, but are actual parasitic protozoa.
A full statement will be found in Huckel, Die Vaccinekorperchen, Supplement to Ziegler's Beitrage, 1898.