J&r>- (7^^^ c^tA^ <*, J^X^V V: ; ' ,.,.''.■*. \ilifTillM iWt^Xl- ■+ I902.-N0. 1. DEPARTMENT OF THE INTERIOR. j j. BUREAU OF GOVERNMENT LABORATORIES. BIOLOGICAL LABORATORY. Preliminary Report of the Appearance in the Philippine Islands of a Disease Clinically Resembling Glanders. BY R. P. STRONG, M. D. MANILA: BUREAU OF PUBLIC PRINTING. 419 |L_ I902.— No. I. DEPARTMENT OF THE INTERIOR. BUREAU OF GOVERNMENT LABORATORIES. BIOLOGICAL LABORATORY. Preliminary Report of the Appearance in the Philippine Islands of a Disease Clinically Resembling Glanders. iY R. P. STRONG, M. D. MANILA: H'KK.W" OF ITI'.LU' I'KINTIN'c; 1902. LETTEB OF TRANSMITTAL. Department of the Interior, Bureau of Government Laboratories, Office of the Superintendent of Laboratories, Manila, P. L, July 19, 1902. Sir: I have the honor to transmit herewith a preliminary report of the appearance in the Philippine Islands of a disease clinically resembling glanders, by Richard P. Strong, M. I)., Director of the Biological La horatory. I am, very respectfully, Paul C. Freer, Superintendent Govern ment Laboratories. Hon. Dean C. Worcester, Secretary of the Interior, Manila, P. I. 3 PRELIMINARY REPORT OF THE APPEARANCE IN THE PHILIPPINE ISLANDS OF A DISEASE CLINICALLY RESEMBLING GLANDERS. By R. P. Strong, M. D. Veterinarians and owners of horses are advised that an infec- tious disease which may clinically at times closely simulate farcy (the nodular, cutaneous form of glanders) has been found to exist in the Philippine Islands. My attention was first called to this malady by Dr. J. GL Slee, veterinarian of the Board of Health, Manila, who sought aid from the Laboratory in the diagnosis of the disease with which several horses were afflicted, and requested an examination of these animals for glanders. That this malady sometimes closely resembles the cutaneous form of glanders may be evidenced from the fact that in the first case encountered a diagnosis of farcy had already been made by three veterinarians. Upon a microscopical study of material removed from the pseudo- farcin ous buds, however, it has been possible to show that the disease under discussion is of an entirely different origin from glanders. Indeed, while farcy is an affection which owes its origin to one of the schizomyeetes or fission fungi (bacillus Mallei) the malady under consideration, it seems, is not due to bacterial infec- tion at all, but to a parasite of an entirely different group, namely, one of the budding or yeast fungi (a blastomyces). CLINICAL MANIFESTATIONS. The disease starts as a small nodule situated in the cutis and frequently in the neighborhood of some slight abrasion. The primary node usually appears upon one of the extremities or in the cervical or abdominal region, but may be situated on the shoulders or chest. From the first nodule the infection spreads, apparently along the course of the lymphatics, and eventually many buds form. Frequently the adjacent lymphatics become swollen and arranged in a row presenting somewhat the appearance of beads on a rosary. The nodules vary in size from about 5 mm. to 3 cm. in diameter. 5 6 The hair is preserved over the younger tumors, which at first are hard, hut usually soften later and form larger abscesses. If left to themselves, they generally finally open and leave ulcers with mar- gins which {ire usually irregular. When the abscesses are incised in their early stages they are found to contain a bloody, purulent, tenacious material. . The contents of the older tumors is yellowish white, gelatinous, and very tenacious. When the cervical region is affected, the submaxillary glands are not uncommonly swollen, and the lymphatic glands near the other parts involved are usually enlarged, soft and freely movable. The disease extends gradually, and in neglected cases may spread over almost any part of the body and even invade 1 the nasal mucosa. A mucous dis- charge from the nose then appears, and the picture now more closely resembles glanders. We, however, have not yet seen the primary nodule situated in the nares. In the cases observed there seems to be no tendency for the process to invade 1 the scrotum, testicles, or penis. Indeed, though there have been nodes very near these organs, there has so far been no involvement of them. In the fairly severe cases there may be some general disturbances, such as slight fever and loss of appetite. In the severe ones anemia and cachexia appear in addition. The mild cases may run an almost afebrile course. While glandular metastases occur, metastases in the internal organs have not as yet been, observed. Occasionally sinuses form in the subcutaneous and deeper muscular tissues. The disease runs a chronic* course and may last for months, but the prognosis is usually favorable and a very large majority of the animals eventu- ally recover. Catlle are sometimes affected with this malady, but it is not so common in these animals as in horses. ETIOLOGY. As has been referred to above, upon microscopical examination it was very soon seen that the disease had an entirely differ- ent origin from glanders, (-over slip preparations and cultures made from many early and late nodules showed no bacteria. In a few instances micrococci were found present, but it seemed likely that these organisms had invaded the lesions secondarily from the skin, as it was particularly in the older and more super- ficial abscesses that they were encountered. In no case have bacilli been met with either in cover slip preparations or on the various culture media employed. In fresh microscopic prepara- tions made from material of the nodes, while the absence of bacteria is noticeable, what is still more striking is the presence of numerous oval glistening bodies measuring from about 4 to 5 v* long by about o\ m wide^ and presenting a double contour. These bodies are found lying both free and inside the cells. In specimens of the pus stained with Ehrlich's triacid solution, the cell- which contain the parasites arc 1 seen to be generally of two varieties, namely, large endothelial phagocytes and polymorphonuclear neu- trophiles. Inside the cells these oval bodies generally appear in the hardened specimens as clear, glistening spots somewhat re- sembling vacuoles. Often from three to five may be seen in one cell. Frequently they do not stain with the aniline dyes. Fven after prolonged, treatment with earbol-fuehsin, most of them re- main clear, though some show a deeply staining point which is usually placed eccentrically, or others inclose several deeply stained granules. Occasionally then* is some staining at the periphery of the body while the central part remains clear. A smaller number may, however, uniformly color a fairly deep red or assume a pinkish tinge. In. specimens of the pus carefully hardened at a low tem- perature, treated with carbol-fuchsin and mounted in water, while one still finds a large number of clear ovals, many others are stained a deep red and some of an eosin color. It can not be said that the age of the blastomyces is the only factor which determines this atlinitv for the i\\i\ as many young cells stain poorly, while occasionally older cells color intensely. From these preparations, however, it is easy to see tlurt the glistening, oval bodies observed in specimens, hardened in alcohol and ether or hardened without certain precau- tions, are the empty capsules of the blastomyces from which the protoplasm has in some way escaped. In the specimens moulded in water it is x^vy common to find one or several deeply colored stain- ing granules situated inside of the clear capsule and endowed with very active Brown ian movement. We have not been successful in staining the empty capsules with the methods employed m coloring the capsules of bacteria, nor have we been able to obtain anv apparent reaction with the iodine stains. Frequently there is the appearance surrounding the oval bodies of a ragged envelope which stains faintly. The capsules may be made 1 very distinct bv treating them with dilute acid or alkaline solutions. The exudate from the nodules is very rich in cells and consists 8 chiefly of large phagocytic cells and polymorphonuclear neu- trophiles. In addition to red blood corpuscles, there are a fair number of small round mononuclear cells, some eosinophiles, and a few plasma cells. A few of the neutrophiles show iodophilia with Ehrlich's stain. The exudate also contains a large amount of fibrin. CULTURAL PROPERTIES OF TILE BLASTOMYCES. The organism does not grow well on bacteriological media, such as plain agar, glucose, maltose, saccharose, and beer- wort agar or bouillon and potato. After from seven to ten days, on glucose or wort agar, sometimes a very delicate growth may be observed along the track of the needle on the surface of the media. Cover slips show that the organism is living and slowly reproducing itself. Small portions of the material removed from the nodule and mixed with a small quantity of bouillon or agar in a hanging drop show numerous budding forms after from forty-eight to sixty hours in a moist chamber. After a still longer time jointed hyphse may be noted, and later formations of lateral and terminal conidia. In the protoplasm of the cells may be frequently ^am vacuoles and bodies resembling oil drops. No fermentation of any of the sugars has as yet been observed. We have been successful in producing small nodules in one monkey by subcutaneous injection of material containing the blastomyces. DIFFERENTIAL DIAGNOSIS. The disease briefly reviewed above is not to be confused with that termed "Bursattcc/' in India, as described by F. Smith as being due to a "mould fungus," or with that known as "farcin