CHOLERA, PLAGUE, SMALLPOX, TYPHUS FEVER, AND YELLOW

FEVER-Continued.

Reports Received from June 30 to July 27, 1923-Continued.

CHOLERA, PLAGUE, SMALLPOX, TYPHUS FEVER, AND YELLOW

FEVER-Continued.

Reports Received from June 30 to July 27, 1923—Continued.

PUBLIC HEALTH REPORTS

VOL. 38

AUGUST 10, 1923

No. 32

THE CURATIVE ACTION OF SULPHARSPHENAMINE IN EXPERIMENTAL SYPHILIS.

BY CARL VOEGTLIN, Professor of Pharmacology, C. ARMSTRONG, Passed Assistant Surgeon, and HELEN A. DYER, Assistant Pharmacologist, Hygienic Laboratory, United States Public Health Service.

In a previous paper by Voegtlin, Johnson, and Dyer (1922), experiments were reported which showed that treatment with single doses of sulpharsphenamine (15 to 50 mg. per kilo) leads to a prompt disappearance of Treponema pallidum from the scrotal lesions in rabbits and causes a marked improvement of these lesions. From the practical standpoint of the efficacy of sulpharsphenamine in the treatment of human syphilis, it is, of course, important to know whether this drug is able to sterilize the animal, i. e., to cause the death of all the parasites. The question is, What shall be the criterion of sterilization? Clinical relapse usually occurs after a sufficiently long time has elapsed following treatment with subcurative doses, but this criterion alone furnishes insufficient proof, and, furthermore, requires a very long period of observation.

Pearce and Brown (1922) have recently shown that Treponema pallidum has a strong tendency to localize in lymph glands, and in the experience of these investigators, transplantation of macerations of lymph glands into the scrotum of normal rabbits yields fairly good evidence as to the presence or absence of syphilitic infection in the donor. We have, therefore, used this method on some of our rabbits treated with sulpharsphenamine and neoarsphenamine. The control numbers of these rabbits are the same as those given in the previous paper. Unfortunately, three of the animals (Nos. 4, 6, and 7) died of intercurrent infections before transplants could be made. However, in none of these three animals was there any recurrence of syphilitic lesions before death occurred. The history of these three rabbits is, briefly, as follows:

Rabbit No. 4.-October 23, 1922: Scrotal lesions completely healed. November 29 sixty-fifth day following treatment with 27 mg. neoarsphenamine per kilo): Animal has developed an infection of the respiratory tract, causing a purulent nasal discharge; chloroformed. Necropsy: Both testicles normal; infectious process of upper respiratory tract; mucous membrane of trachea congested and hemorrhagic; no other gross lesions.

Rabbit No. 6.-October 23, 1922: Scrotal lesions healed. November 29 (sixty-fifth day after treatment with 36 mg. sulpharsphenamine per kilo): Found dead. Necropsy: Purulent discharge from nostrils and ears; both testicles normal; no other gross lesions.

Rabbit No. 7.-December 1, 1922 (sixty-seventh day after treatment with 15 mg. sulpharsphenamine per kilo): Found dead. Both testicles normal; far advanced post mortem changes.

We may conclude from these observations that the three rabbits did not develop a clinical relapse for a period of 65 to 67 days following treatment.

The histories of the remaining four animals used for lymph node transfer are given below. In addition, there is described an experiment with an untreated animal which was infected the same day (July 17, 1922) as the other animals of this series with the same suspension of the Nichol's strain of Treponema pallidum.

Rabbit No. 2.-October 23, 1922: Scrotal lesions completely healed. April 9, 1923, (one hundred and ninety-sixth day following treatment with 27 mg. sulpharsphenamine per kilo): Has shown no evidence of recurrence of any syphilitic lesions to date. Lymph gland and testicular material transferred to left scrotum of rabbit No. 2a.

Rabbit No. 3.-October 10, 1922: Scrotal lesions healed. April 9, 1923 (one hundred and ninety-sixth day following treatment with 36 mg. neoarsphenamine per kilo): Has shown no evidence of recurrence of any syphilitic lesions to date. Lymph gland and part of testicle transferred to right scrotum of rabbit No. 3a.

Rabbit No. 5.-April 9, 1923 (one hundred and ninety-sixth day following treatment with 50 mg. sulpharsphenamine per kilo): Has shown no evidence of recurrence of any syphilitic lesions to date. Lymph gland and piece of scrotum transferred to

right scrotum of rabbit No. 5a.

Rabbit No. 8.--April 9, 1923 (one hundred and sixty-ninth day following treatment with 15 mg. neoarsphenamine per kilo): Has shown no evidence of recurrence of syphilitic lesions to date. Lymph gland and part of testicle transferred to rabbit No. 8a.

Control rabbit X.--Inoculated July 17, 1922. Never developed well-marked scrotal lesions. April 9, 1923: Lymph glands and testicular material transferred to scrotum of a normal rabbit, Xa.

Result of transplantations.-At the time that this is being written, i. e., on the seventy-first day following transplantation of the lymph nodes, none of the animals, except control rabbit Xa, has shown any signs of syphilitic infection. The glands are normal, except one of rabbit 3a, which shows a small nodule (scar tissue (?)), free from spirochetes on three different days (June 2, 4, and 19). Rabbit Xa showed a well-developed chancre on June 4, and dark field examination revealed the presence of numerous spirochetes. On June 19 the chancre had reached very large size.

It is evident, then, that in none of the treated animals was it possible to establish any evidence of infection by means of lymphgland transfer. This fact is all the more significant in view of the long time (196 days) intervening between treatment and lymph-node transfer, which should have given the infection a chance to reestablish itself in the lymphatic system. These observations on a small series of animals suggest that treatment with a single injection of sulpharsphenamine is sufficiently effective to prevent a clinical relapse and to produce sterilization of the lymph glands, which,

according to Pearce and Brown, always harbor spirochetes during the latent stages of the disease. Work is now in progress on a large number of animals which it is hoped will yield absolutely conclusive. evidence of the relative curative action of sulpharsphenamine, neoarsphenamine, and arsphenamine in rabbit syphilis.

REFERENCES.

Pearce, Louise, and Brown, W. H. (1922): J. exp. Med. xxxv, 55. Voegtlin, Johnson, and Dyer (1922): Public Health Reports, 37, 2783. Reprint No. 797.

PAROLED LEPERS FROM KALIHI HOSPITAL, HAWAII.

The following report of leper patients paroled from Kalihi Hospital, Hawaii, was furnished by Surg. H. E. Hasseltine, director of the Kalihi Leprosy Investigation Station.

While favorable results are shown in the treatment of leprosy with the ethyl esters of chaulmoogra oil, a longer period of time will obviously be required for an exact determination of the value of this therapeutic agent.

Report of paroled cases of leprosy from Kalihi Hospital which have been returned to the hospital.

Crude chaulmoogra, or emulsions of crude oil, used prior to July 1, 1916. Derivatives of chaulmoogra (esters, salts, etc.) used on some patients July, 1916, to July 9, 1919; others took crude oil. Mixed esters used since July 9, 1919, except in five groups, aggregating 25 patients, who received single esters.