the second class in smaller numbers, but finds the conditions of growth better because of the depth of the wound.

The severity of the wound has nothing whatever to do with the occurrence of tetanus, pin-pricks, nail punctures, insect stings, vaccination, and a variety of other mild injuries sometimes being followed by it.

An interesting fact has been presented by Vaillard and Rouget,* who found that if the tetanus spores were introduced into the body freed from their poison, they were unable to produce the disease because of the promptness with which the phagocytes took them up. If, however, the toxin was not removed, or if the body-cells were injured by the simultaneous introduction of lactic acid or other chemic agent, the spores would immediately develop into bacilli, begin to manufacture toxin, and produce the disease. This suggests that many wounds may be infected by the tetanus bacillus though the surrounding conditions rarely enable it to develop satisfactorily and produce enough toxin to cause disease.

In very rare cases tetanus may possibly occur without the previous existence of a wound, as in the case reported by Kamen, who found the intestine of a person dead of the disease rich in Bacillus tetani. Kamen is of the opinion that the bacilli can grow in the intestine and be absorbed, especially where imperfections in the mucosa exist. It is not impossible, though he does not think it probable, that the bacteria growing in the intestine can elaborate enough toxin to produce the disease by absorption.

A peculiar observation has been made by Montesano and Montesson,* who unexpectedly found the tetanus bacillus in pure culture in the cerebro-spinal fluid of a case of paralytic dementia that died without a tetanic symptom.

Immunity. All animals are not alike susceptible to tetanus. Men, horses, mice, rabbits, and guinea-pigs are susceptible; dogs much less so. Cattle suffer chiefly after accouchement, and after abortion. Most birds are scarcely at all susceptible either to the bacilli or to their toxin. Amphibians and reptiles are immune, though it is said that frogs can be made susceptible by elevation of their body-temperature.

* See "Centralbl. f. Bakt., Infekt., u. Parasitenk.," vol. XVI, p. 208. "Centralbl. f. Bakt. u. Parasitenk.," Dec., 1897, Bd. xxII, Nos. 22, 23, p. 663.

The injection of the toxic bouillon or of the redissolved ammonium sulphate precipitate, in progressively increasing doses, into animals, causes the formation of antibodies (antitoxin) by which the effects of both the tetanospasmin and the tetanolysin are destroyed. The purely toxic character of the disease makes it peculiarly well adapted for treatment with antitoxin, and at the present time our sole therapeutic reliance is placed upon it. The mode of preparing the serum and the system of standardization are discussed in the section upon Antitoxins in the part of this work that treats of the Special Phenomena of Infection and Immunity.

Antitoxin. Numerous cases of the beneficial action of antitoxin are on record, but, as Welch* has pointed out, the antitoxin of tetanus has proved a disappointment in the treatment of tetanus. Moschcowitz,† in his excellent literary review of the subject, has shown that its use has reduced the death-rate from about 80 to 40 per cent., and that it therefore cannot be looked upon as a failure. The result of its experimental injection, in combination with the toxin, into mice, guinea-pigs, rabbits, and other animals is perfectly satisfactory, and affords protection against almost any multiple of the fatal dose, but the quantity needed, in proportion to the body-weight, to save an animal from the unknown quantity of toxin being manufactured in its body increases so enormously with the day or hour of the disease as to make the dose, which increases millions of times where that of diphtheria antitoxin increases but tenfold, a matter of difficulty and uncertainty. Nocard also called attention to the fact that the existence of tetanus cannot be known until a sufficient toxemia to produce spasms exists, and that therefore it is impossible to attack the disease in its inception or to begin the treatment until too late to effect a cure. At this point it is well to recall Nocard's experiment with the sheep, in whose blood so much toxin was already present when symptoms first appeared that the amputation of their infected tails could not save them.

The explanation of this inability of the antitoxin to effect a cure when administered after development of the symptoms of tetanus is probably found in a ready fixation of the *"Bulletin of the Johns Hopkins Hospital," July and August,

"Annals of Surgery," 1900, XXXII, 2, pp. 219, 416, 567.

toxin in the bodies of the infected animals. This is well shown by the experiments of Dönitz,* who found that if a mixture of toxin and antitoxin were made before injection into an animal, twelve minimum fatal doses were neutralized by I c.c. of a 1 : 2000 dilution of an antitoxin. If, however, the antitoxin was administered four minutes after the toxin, I c.c. of a 1: 600 dilution was required; if eight minutes after, I c.c. of a 1 : 200 dilution; if fifteen minutes after, I c.c. of a 1:100 dilution. He found that similar but slower fixation occurred with diphtheria toxin.

It was found by Roux and Borrel † that doses of tetanus antitoxin absolutely powerless to affect the progress of the disease, when administered in the ordinary manner by subcutaneous injection, readily saved the animal if the antitoxin were injected into the brain substance.

Chauffard and Quénu, ‡ who injected the antitoxin into the cerebral substance, found that such administration brought about an apparent cure in one case.

Their observations were followed by an attempt to apply the method in human medicine, and patients with tetanus were trephined and the antitoxin injected beneath the dura and into the cerebral substance. The results have not, however, been satisfactory, and as the method cannot be looked upon as itself free from danger, it has been abandoned.

The only means of treating the disease that can be recommended at present is by intravenous and subcutaneous injection of large and frequently repeated doses of the antitoxic serum. There can be little doubt but that the administration must be so free as to load up the patient's blood with the antitoxin in hopes that its presence there may be able to detach the toxic molecules from their anchorage to the nerve cells and form an inert union.

Prophylactic Treatment.-While tetanus antitoxin is extremely disappointing, in practice, for the cure of tetanus, it is most satisfactory for its prevention. "An ounce of prevention is better than a pound of cure," and if the surgeon would administer a prophylactic injection of tetanus antitoxin in every case in which the occurrence of tetanus was at all likely, the disease would rarely develop.

* Reference 18, in "Jour. of Hygiene," vol. II, No. 2, in Ritchie's article.

"Ann. de l'Inst. Pasteur," 1898, No. 4.
"La Presse méd.," No. 5, 1898.

Bacilli Resembling the Tetanus BACILLUS.

*

Tavel has called attention to a bacillus commonly found in the intestine, sometimes in large numbers in the appendix in cases of appendicitis, and looked upon by one of his colleagues, Fräulein Dr. von Mayer, as the probable common cause of appendicitis. He calls it the "Pseudo-tetanusbacillus."

The bacillus is slender and measures 0.5 by 5-7 μ, is rather more slender than the tetanus bacillus, and its spores are oval, situated at the end of the rod, and cause a slight bulging rather pointed at the end. The bacillus is provided with not more than a dozen flagella,-usually only four to eight, thus differing markedly from the tetanus bacillus, which has many. The flagella are easily stained by Löffler's method without the addition of acid or alkali. The organism does not stain so well by Gram's method as the true tetanus bacillus. The bacillus is a pure anaerobe.

The growth in bouillon is rather more rapid than that of the tetanus bacillus. It will not grow in gelatin. The growth in agar-agar is very luxuriant and accompanied by the evolution of gas. Upon obliquely solidified agaragar the colonies are round, circumscribed, and often encompassed by a narrow, clear zone, which is often notched. The organism grows in serum only in a vacuum. The spores are killed at 80° C.

The organism produced no symptoms in mice, guineapigs, and rabbits even when 2-5 c.c. of a culture were subcutaneously introduced.

Sanfelice † and Lubinski ‡ have observed a bacillus in earth and meat-infusions that is morphologically and culturally like the tetanus bacillus, but differs from it in not possessing any pathogenic powers.

Kruse § has also described a bacillus much like the tetanus micro-organism that grows aerobically. It is not patho

genic.

* "Centralbl. f. Bakt.," etc., March 31, 1898, XXIII, No. 13, p. 538. "Zeitschrift für Hygiene," vol. XIV.

"Centralbl. f. Bakt. u. Parasitenk.," XVI, 19.

§ Haggis, "Die Mikroorganismen," vol. II, p. 267.

CHAPTER IV.

ANTHRAX.

BACILLUS ANTHRACIS (KOCH).

General Characteristics.-A non-motile, non-flagellated, sporogenous, liquefying, non-chromogenic, pathogenic, aërobic bacillus staining by the ordinary methods and by Gram's method.

The disease of herbivora known as anthrax, "splenic fever," "Milzbrand," and "charbon," of infrequent occurrence in this country and England, is a dreaded and common malady in France, Germany, Hungary, Russia, Persia, and the East Indian countries. In Siberia the disease is so common

and malignant as to deserve its popular name, "Siberian pest." Certain districts, as the Tyrol and Auvergne, in which it seems to be endemic, serve as foci from which the disease spreads in summer, afflicting many animals, and ceasing its depredations only with the advent of winter. is not rare in the United States, where it seems to be chiefly a disease of the summer season.