plete persistence of the distal portion of the right aortic arch associated with the disappearance of a greater or less portion of its proximal part, the result being the apparent origin of the right subclavian artery from the descending aorta, whence it passes to the right behind the trachea and esophagus. Variations of this condition depending on the portion of the right arch, may modify the relations of the right vertebral and subclavian arteries. Thus, in some cases the vertebral may arise as in the

Dovener

normal arrangement from the subclavian, or it may, as it were, change positions with the subclavian, arising from the descending aorta, while the subclavian arises in common with the right carotid from an innominate stem; or the vertebral may arise with the right common carotid from the innominate stem, the subclavian alone coming from the descending aorta."

Dr. D. S. Lamb said that the anomaly was no doubt dependent upon a developmental cause; such abnormalities of origin and course of blood vessels are always interesting from an anatomical standpoint. From the surgical viewpoint, a condition such as existed in the specimen might prove embarrassing.

BACTERIAL INOCULATIONS IN THE PROPHYLAXIS AND TREATMENT OF TYPHOID FEVER.*

BY JOHN BENJAMIN NICHOLS, M. D.,

Washington, D. C.

HISTORICAL.

As early as 1893 Fraenkel tried the injection of bouillon cultures of typhoid bacilli, killed at 61-63 C., in the treatment of typhoid fever, and reported the results in fifty-seven cases. General improvement was noted as being produced by the treatment, but the method was not followed up.

Haffkine's methods of preventive inoculation against cholera, by injecting killed and living cultures of cholera spirilla, first suggested the idea of employing similar methods for prophylaxis against typhoid fever, and about 1896 Pfeiffer experimented along this line with injections of killed typhoid bacilli. The present development of antityphoid inoculation is mainly the outcome of the work of Sir Almroth E. Wright, who began his investigations in 1896, as the result of personal suggestions from both Haffkine and Pfeiffer. Wright made his first typhoid inoculations in two men in July and August, 1896, recording the fact incidentally in an article on another subject published in the Lancet for September 19, 1896. Pfeiffer and Kolle made the first report on their investigations of the blood changes following injection of typhoid bacilli in animals and men in the Deutsche Medicinische Wochenschrift for November 12, 1896. In the British Medical Journal for January 30, 1897, Wright made a more definite report on his investigations.

Preventive inoculations were soon afterward made in the British soldiers in India, and in the Boer War-1899-1902-the method was employed on a large scale, about 100,000 inoculations being made, with a claimed reduction of the incidence of the disease of about one-half. Opposition developed to Wright's inoculations, and in the latter part of 1902 they were discontinued in the British army. Wright at this time resigned his connection with the British Army Medical School at Netley. The subject was further investigated by another commission, under Read before the Medical Society, November 3, 1909.

Lieut. Col. W. B. Leishman, of the British Royal Army Medical Corps, which confirmed Wright's methods, and since 1904 the antityphoid inoculations have been practiced on a large scale in the British Colonial army. Wright was knighted in 1906 in recognition of his services. The inoculations were also practiced on a large scale in the German army in Southwest Africa from 1904, and in 1908 were introduced in the United States army. Much more attention has been given to typhoid inoculations for prophylaxis than for treatment of the developed attack; but the therapeutic use of the vaccine has recently been attracting attention, and during 1909 a number of contributions on this phase of the subject have been presented.

The subject of antityphoid inoculation may be considered under three aspects, namely, its diagnostic, its prophylactic, and its therapeutic use.

DIAGNOSTIC TYPHOID INOCULATION.

Ocular and cutaneous tests with extracts of typhoid bacilli, entirely analogous to the corresponding tests with tuberculin, have been tried for diagnostic purposes in typhoid fever.

An ocular test was introduced by Chantemesse in 1907, and further reports on its use have been made by a number of obThe method consists in introducing into one eye a drop of a watery extract of typhoid bacilli, or of the alcoholic precipitate therefrom; the appearance of congestion or inflammation in the inoculated eye in 6 or 8 hours, and continuing for 24 to 72 hours, is an indication of the existence of typhoid fever. The observers in general in a large number of typhoid cases obtained positive reactions in nearly every instance, while in non-typhoid cases only an occasional reaction developed.

During the past summer I prepared a watery extract of typhoid bacilli (not from a strain of proven virulence), of a strength of 2,000 million to the cubic centimeter, and applied the test in a few cases. While I obtained a positive result at some stage of the disease in most instances, the difference between the two eyes that constituted a positive reaction was usually so slight that the method seemed of little reliability for diagnosis. The most marked reaction of all was given in a case of miliary tuberculosis.

The cutaneous test for typhoid fever is performed after Von

Pirquet's method, by applying a typhoid-bacillus extract or suspension to a slight abrasion of the cuticle. The reports of the few who have tried the method are not very encouraging as to its usefulness.

THE VACCINE.

The typhoid "vaccine" or bacterial suspension used for subcutaneous injection for prophylactic and therapeutic purposes consists of either a 24 to 48-hour bouillon culture of typhoid bacilli, or a suspension in about 0.85 per cent. NaCl solution of the bacilli grown for 24 to 48 hours on the surface of agar. The bacilli and any contaminations are killed by heating for one hour at 53 to 60 C., after which 0.25 per cent. of liquor cresolis compositus, or "lysol" (practically equal parts of cresol and soft soap), is added. As the cresol alone will kill all bacteria and spores within five days the heating could be dispensed with, probably with advantage to the efficiency of the vaccine. Sterility is tested and assured by cultures and animal inoculations. The bacteria in the suspension are then counted and the preparation made up to some standard strength, conveniently 1,000 million germs to the cubic centimeter.

The strain of typhoid bacilli used for making the vaccine appears to be a matter of indifference, virulent strains not having been found to yield results more efficient than attenuated strains. For therapeutic purposes autogenous vaccines might in some cases be advantageous. The time for which the vaccine retains its potency unimpaired has been variously estimated at from three months to two years.

PROPHYLACTIC ANTITYPHOID INOCULATION.

The technic of preventive inoculation against the development of typhoid fever consists in the subcutaneous injection, in the arm or other convenient locality, of two doses of vaccine, ten days apart, the first of about 500 million, the second of 1,000 million killed typhoid bacilli. A third inoculation of 1,000 million, after another interval of ten days, is sometimes given, and undoubtedly augments the protection conferred. Three doses are apparently sufficient to confer the maximum protection. The dosage employed by Wright is 750 to 1,000 million for the first and 1,500 to 2,000 million for the second dose.

The injection of the vaccine in the doses mentioned usually

produces local and general symptoms, sometimes quite severe. At the site of injection appears in a few hours a diffuse area of swelling, induration, redness, and tenderness. This increases, reaching a maximum in 24 to 48 hours. These local phenomena are accompanied by constitutional symptoms, such as fever, pains, vomiting, malaise, prostration, etc. In the course of a couple of days more the symptoms, both local and general, subside and disappear. The reaction varies in intensity in different cases, ranging from slight soreness at the point of injection to a generally swollen arm, exquisitely tender, presenting the appearance of an angry case of cellulitis, which, however threatening, usually promptly subsides.

Following the injections the specific antibacterial properties of the blood are developed or augmented to a high degree. The agglutinative, bactericidal and bacteriolytic activities of the blood serum against the typhoid bacillus are very greatly increased, partially after the first injection, much more after the second. These antibodies begin to appear most markedly about seven to nine days after the injections. Leishman found agglutination developed to a potency manifested in a dilution as high as I to 4,000; bactericidal power trebled or quadrupled; bacteriolytic power increased up to ten times normal. He found an increase

of the stimulins, but was unable (by the methods employed by him) to demonstrate any effect on the opsonic power. Wright found an increase of the opsonic index from the injections.

These demonstrable antibodies are often developed to a greater degree and persist for a longer time from the bacterial injections than from an attack of typhoid fever itself. As the protection conferred by an attack of the disease is greater than that derived from the inoculations, it would appear that there are other essential factors involved in acquired immunity against the disease than those capable of determination by present laboratory methods.

Wright and others claim to have demonstrated the occurrence, for a few days after the injections, of a negative phase, during which there is increased susceptibility to the disease. Leishman and others have been unable to find evidence of such a phase. This is an important practical point, as, if there is a negative phase, inoculation at a time of exposure to the infection might increase the liability of contracting it.