it produces an acute disease of a relapsing type and is THE USE OF ARSPHENAMIN IN self-limiting. Spironema morsus muris {Spirochaeta morsus- NONSYPHILITIC DISEASES - muris), the organism of rat-bite fever, produces a local MATHEW A. REASONER, M.D. lesion at the point of entrance and passes through the Major, Medical Corps, U. S. Army lymph nodes and invades the blood stream and tissues. AND It produces an acute disease of a relapsing type and is HENRY J. NICHOLS, M.D. self-limiting. Major, Medical Corps, U. S. Army Treponemp. pertenue, Castellani, 1905 {Spirochaeta WASHINGTON, D. C. pertenuis), begins its invasion by a local lesion, invades the blood stream, then localizes and produces surface It has been shown by Bronfenbrenner and Noguchi,1 and occasionally deep lesions. It also and may spread by Akatsu,2 Akatsu and Noguchi3 that the spiro- autoinoculation. It is self-limiting. Yaws is not a chetes, especially those parasitic to the higher animals, congenital disease. have many characteristics to a greater or less degree Treponema pallidum, Schaudinn, 1905, {Spirochaeta in common. This is noted in their to be morphology, pallida), produces at first a local lesion, invades the motility, cultural peculiarities and methods of growth, blood stream and involves all tissues and may be trans¬ their reaction to certain compounds especially those mitted to the next generation. The disease does not sometimes known as spirocheticides, and their thermal tend toward recovery. death point. While between some of the various spe- In considering the effect of arsphenamin in non- cies of spirochetes there is quite a little difference in syphilitic disease, it should be remembered that the morphology, there seems to be a sufficient number of original work which led to the production of ars¬ characteristics in common to justify our placing them in phenamin was done not only with Treponema pallidum a single group. but also with Spironema recurrentis of relapsing The following examples will serve to illustrate grada- fever, Spironema gallinarum of a disease in fowls and tions in pathogenicity: Treponema pertenue of yaws. Ehrlich and Hata's a free first monograph on salvarsan is called "The Experi¬ Spirochaeta plicatilis, Ehrenberg, 1833, living mental organism found in stagnant water. Chemotherapy of Spirilloses (Syphilis, Relaps¬ Cristispira balbiana, Certes, 1882 (Spirochaeta bal- ing Fever, Chicken Spirillosis and Yaws)."4 The favorable action of is to be con¬ bianii), has developed parasitic properties for a cold arsphenamin blooded animal and is found in the of sidered as a group effect due to a chemical affinity crystalline style between the and the vital structure of the oyster. drug the organ¬ ism. It was dentium, Koch, 1887 den- logical to expect that other affinities, to a Treponema (Spirochaeta greater or less would be found others is a found com¬ degree, among tium), ordinarily saprophytic organism of the and in the normal human mouth. It invade spirochetes that when present, they could be monly may demonstrated Erom the but its exact rôle in such invasion is not therapeutically. beginning, damaged tissue, the action of as known. therefore, arsphenamin was studied a effect on diseases rather R. 1906 group spirochetal than from Spironema vincenti, Blanchard, (Spirochaeta the of alone. It has been in is the cause of local lesions on the standpoint syphillis given vincenti), probable almost every pathologic condition to which human flesh human mucous membrane, and it invades the underly¬ is heir, but for effect, its tissues but is not believed to invade the specific proper therapeutic ing regularly field would seem to be limited among dis¬ blood stream. nonsyphilitic eases to those caused and in a few 1874 by spirochetes Spironema recurrentis, Lebert, (Spiroschaudin- instances in lesser degree to certain protozoal and nia recurrentis, Spirochaeta recurrentis), invades the bacterial infections. Favorable results had also been human blood stream but does not local produce lesions, observed in one disease of unknown etiology, in rat- bite fever. the cause the was Read before the joint meeting of the Section on Pharmacology Later, of disease found and Therapeutics and the Section on Dermatology at the Seventy-First to be a An should not be made Annual Session of the American Medical Association, New Orleans, spirochete. attempt April, 1920. to carry the group effect too far as there are appar¬ Because of lack of space, this article is abbreviated in The Journal. some diseases, such as Weil's disease The complete article appears in the Transactions of the Section and in ently spirochetal the author's reprints. A copy of the latter will be sent by the author and yellow fever, in which arsphenamin has no benefi¬ en receipt of a stamped addressed envelop. cial effect. 1. Bronfenbrenner and Noguchi: J. Pharmacol. & Exper. Therap. 4: 333 (March) 1913. 2. Akatsu: Arb. a. d. k. Gsndhtsamte 25: 494, 1907. 4. Ehrlich and Hata: The Experimental Chemotherapy of Spirilloses, 3. Akatsu and Noguchi: J. Exper. Med. 25: 363 (March) 1917. Berlin, Julius Springer, 1910. Downloaded From: http://jama.jamanetwork.com/ by a Northeastern University Libraries User on 05/26/2015 CONSIDERATION OF SPECIAL SPIROCHETAL of 10 per cent, arsphenamin in glycerin. This form of DISEASES treatment is probably more essential in military than Vincent's is a form of in civil practice. Ordinarily, this treatment will suffice ; Angina.—Vincent's angina it if have ulcération of the mucous membrane by a but if fails to control the disease, the lesions produced become it spirochete known as Spironema vincenti (possibly extensive or if serious complications exist, is neo- Spironema buccalis, which has for some reason advisable to give intravenous injections of in become pathogenic), in connection with a fusiform arsphenamin medium-sized dosage. bacillus. The relationship of these two organisms to Pulmonary Spirochetosis; Fetid Spirillar Bronchitis ; the disease has not been entirely worked out, as some Pidmonary Gangrene.—From a number of widely sepa¬ observers attribute the lesions to the fusiform bacillus, rated sources, different observers have described a form Tunnicliff,5 however, an excellent of a of spirochetal lung involvement. From Uganda, Tay¬ gives description 13 phase of the pathology, showing the zone of spirochetes lor describes a condition with pneumonic symptoms in advance of the fusiform bacilli in the affected tissue. and termination by crisis. Loygue, Bonnet and Peyre 14 This disease is ordinarily located in the pharynx, but found many organisms in fourteen of twenty-seven may occasionally involve other portions of the body. grave cases of influenza and in four fatal cases. In In civil practice it is not a very common disease, it one case the spirochetes were also found in the urine. is generally susceptible to treatment with local anti¬ Ribeyro15 describes a prolonged case in Peru. A septics and rarely assumes epidemic form. In the mili¬ series of cases was reported from Egypt by Farrah.16 tary service, conditions are different and this disease Castellani1T found two types of spirochetal pulmonary must receive serious consideration as a cause of con¬ involvement in soldiers of the Italian army, the one siderable invalidism and occasional deaths. Bouty ' lasting only several weeks and appearing as an acute states that Vincent's angina forms from 2 to 3 per bronchitis ; the other as a chronic bronchopneumonia of cent, of throat troubles in the French army in peace months' or years' duration or becoming malignant with times. Recent statistics in a British in France irregular fever, emaciation and death. hospital 18 hemoptysis, show the proportion to be as high as 23 per cent. Violle described a mild type with good prognosis. Campbell and Dyas 7 give a very adequate description Nolf and Spehl19 described a condition which they met of the epidemic among the English soldiers at Bram- during the war, similar to a baronchitis or a broncho¬ and detail the different and forms pneumonia, and always characterized by a fetid breath. shott, England, types 20 of manifestations. They note that syphilitics seem The causative organism is described by Nolf and to react worse to this affection. They advise that in seems very similar to what Noguchi has termed Trep¬ mild cases, any of the numerous recommended applica¬ onema macrodentium. It is also to be found in pul¬ tions will about a cure, but con¬ monary gangrene, which may be a termination of this frequently bring they 20 sider the most useful remedy to be arsenic in the form condition. Nolf states that arsphenamin exercises of arsphenamin or neo-arsphenamin, as a local appli¬ a decidedly curative effect if given early. If delayed, cation. the prognosis is not so favorable, or it may be necessary Tixer and Tobe8 discuss the disease as found to administer repeated doses over a period of several among the French soldiers. They advise various local weeks. In such a case it will be noted that, coincident applications, giving first place to neo-arsphenamin. with the treatment, there is a diminution of the spiro¬ They advise the intravenous administration of neo- chetes and a disappearance of the fetid odor of the arsphenamin when the lesions of stomatitis or angina breath. are particularly extensive or when they are accom¬ Pyorrhea alveolaris.—Little is known of the etiology panied by complications. Bouty ° describes the serious of the several conditions resulting in this disease. In results which may follow the appearance of Vincent's some cases, arsphenamin has a decided effect (which angina in the military service. He recommends the use many not be permanent,) and in others, no results are of neo-arsphenamin either in solution or powder noticeable. Where improvement is shown, the spiro¬ applied locally to the affected portion. Renon and Des- chetes are probably responsible, either primarily or bouis * report a series of cases treated in this same secondarily.