Chapter XI: Front Matter (11)

_Infection Atria._ Inoculation on a skin wound or abrasion, is a most effective mode of transmission, but the virus undoubtedly enters in certain cases with the air, food or water, or by accidental lodgment of a speck of the virus on the mucosa of the nose or eye or other natural opening. Through the healthy mucosa the bacillus may enter by penetrating the soft epithelium, or entering the mucous follicles, but it will find the way smoothed for it, if there has been friction, abrasion, desquamation or congestion. The skin in its healthy state is usually resistant, but Babes has conveyed infection by rubbing on the virus mixed with vaseline, and without displacing the epithelium. The channel of entrance was the hair follicles. Injected into the blood, intravenously, or into a serous cavity, the bacillus infects with great certainty and promptitude.

There is ample evidence that primary lesions appear not only in the skin and nasal mucosa, but also in the bronchia, intestines, and other parts. Much time and ink have been wasted in attempts to prove that pulmonary lesions are always secondary, and doubtless many are so, but the cases in which the lesions are confined to the bronchia or parenchyma, and the many parallel cases of direct infection of the lungs by other diseases (tuberculosis, lung plague, contagious pneumonia, influenza, etc.,) furnish conclusive enough evidence that the germ may be inhaled and colonize this part first. Cases of inhalation bronchitis, are equally corroborative, and not only may the grosser solids be aspired, but infection droplets can easily gravitate down when from congestion or inflammation the action of the tracheal and bronchial cilia, is suspended.

FORMS AND LESIONS OF GLANDERS IN SOLIPEDS.

Glanders appears in two primary forms—_acute_ and _chronic_, and each of these is further divided according as the lesions are exclusively or mainly seated in one part of the body or another. The generic term _glanders_ is habitually used to designate that form in which the lesions are situated in the nose, the nasal sinuses, and the submaxillary lymphatic glands—_nasal glanders_. When the principle lesions are situated in the lungs and lymph glands of the chest, the case is one of _pulmonary glanders_. When the skin and subcutaneous lymphatics are most prominently affected it is known as _farcy_ or _cutaneous glanders_. When the skin and nose are simultaneously affected the name _farcy glanders_ is sometimes applied. But as the bacillus may enter by very varied channels the primary lesions may appear in still other organs. Thus in stallions the first symptom is often a glanderous orchitis. In other horses it may be a glanderous arthritis, and in still others infected by ingestion it may be an abdominal infection.

_Symptoms of Nasal Glanders in Solipeds._ _Acute._ After an incubation of three to five days the subject shows prostration, weariness, stiffness, erection of the hair, and even tremor or shivering, inappetence, thirst, hyperthermia, rapid pulse, weeping eyes, the discharge becoming purulent, snuffling breathing, and a discharge from the nose, at first serous, with a remarkable viscidity which tends to glue together the long hairs or even the margins of the nostrils. This discharge may be reddish, greenish, or brownish and may become distinctly purulent and opaque. The _alæ nasi_ are swollen, hot and painful, and the mucosa red, congested, thickened, with a blackish or violet tint especially along the median part of the _septum nasi_. On these, violet patches appear on the second or third day, pronounced elevations of very varying size indicating the centres of active hyperplasia. They are usually yellowish or grayish, surrounded by a deep violet areola, and may become confluent forming patches. The centre of each undergoes rapid degeneration, forming a rounded ulcer with salient edges, a yellowish base, more or less pointed or streaked with red, and a viscid seropurulent or bloody discharge which may concrete in crusts or scale. The whole septum may become one continuous ulcer with excavations of various depths surrounded by hyperplastic elevations, and involving not only the mucosa, but even the cartilage and leading to perforations.

From an early stage of the attack the submaxillary lymphatic glands and the investing connective tissue become swollen, forming a mass of firm bean- or pea-like nodules, with no excessive heat nor tenderness, and with little disposition to suppurate and discharge. If this has lasted for some time the glands often become more firmly attached to adjacent parts (maxilla, tongue) by the contraction of the exudate.

The swelling of the alæ nasi also often extends to the skin of the face, and firm, rounded cords formed by the swollen lymphatics stretch upward toward the eye, or the submaxillary glands. Upon the turgid lymphatics may appear more or less rounded nodules from the size of peas to hazel nuts, which, unlike the submaxillary glands, tend to soften, burst and discharge a viscid, glairy, sanious liquid.

At the same time the morbid process is liable to show itself in the cutaneous lymphatics of one limb, usually a hind one, in the form of firm cords, with degenerating or ulcerous nodules (farcy buds) and pasty patches. Or the throat or lungs may become involved, with local swellings, violent cough, dyspnœa and fever. The swellings of the cutaneous lymphatics usually follow the course of the veins, in the hind limbs the branches of the saphena, and extend from below upward, and the first nodules may be on the fetlock or hock.

_Symptoms of Chronic Nasal Glanders in Solipeds._ The chronic form of the disease follows an indolent course, and local symptoms are often so slight or equivocal that the true nature of the malady is unsuspected. If the patient is well fed and cared for and not overworked, the malady may run a course of three, five or seven years, and the victim may pass through many hands leaving infection in every stable it occupies. Diagnostic symptoms, more or less clear, may be obtained from the discharge; the lesions of the mucosa and the submaxillary glands.

The _nasal discharge_ may be bilateral, but if confined to one nostril is strongly suggestive of glanders. It may be profuse or scanty, continuous or intermittent, of a yellowish, purulent tint, or greenish, or grayish and with a special tendency to viscidity. In some indolent cases the nostrils may be clean but if there is any matting of the long hairs, or adhesion of the alæ nasi, the case is specially suspicious. If it is sanious, flocculent, or bloody it is all the more characteristic, and suggests the supervention of an acute attack.

The _lesions of the pituitary membrane_ are varied. Hyperæmia of a purple or violet color is common, especially along the septum, and the mucosa is liable to be somewhat tumid or œdematous. Nodules the size of a pin’s head, a pea or larger appear inside the inner ala, or on the septum or turbinated bones, and at first red from extravasation and, as it were vesicular, become grayish, whitish or yellow with points of red and surrounded by a deeply congested areola. Larger nodules forming in the submucosa approach the surface and stand out the size of the tip of the finger and with the same general character as the smaller. Sooner or later these degenerate and form ulcers which bear a resemblance to those of acute glanders but are less angry, and when small and solitary may be taken for simple erosions. In other cases they become thickened and indurated with sharply defined projecting margins, and a yellowish base with points or lines of red. The presence of red, black, green, or brown crusts may also be noted.

Another lesion frequently observed in indolent cases is a cicatricial white spot or patch in which the hyperplasia has become partially developed into tissue and shows no tendency to ulcerate. The mucosa may even be drawn or puckered around the cicatrix, making the illusion all the more complete.

The _submaxillary swelling_ is even less sensitive than in acute glanders and produces the same sensation as of an aggregation of small, hard, pea-like, masses with no tendency to ulcerate.

_Symptoms of Cutaneous Glanders (Farcy) in Solipeds._ Acute cutaneous glanders has been already referred to under nasal glanders. The chronic type is often less characteristic, yet may be detected by careful observation of the symptoms. The main symptom may be the swelling of a joint with more or less engorgement of the limb from attendant lymphangitis. There can usually be detected around the margins of such swellings firm, tender cords representing the larger lymphatic vessels and often branching in their course. In the absence of the engorgement, or when it is slight, these _cords_ may be the main evidence of the disorder, and in the hind limb usually follow the course of the flexor tendons on the inner side of the digit, metacarpus and thigh. At intervals along the line of the _cords_ appear nodular masses (farcy buds) varying in size from a pea to a hen’s egg, and showing a great disposition to soften and discharge a glairy, sanious or more or less bloody liquid. The inner sides of the fetlock and tarsus are favorite seats of these nodules but they may form at any point. On the trunk also the corded lymphatics and nodules follow the lines of the veins and lymphatics, and here there may be the complication of large intermuscular abscesses often in connection with the groups of lymphatic glands.

_Latent or occult glanders_ is often met with, the indolent, specific lesions being confined to some internal organs, like the larynx, lungs or womb, or to the testicles, the nasal diagnostic symptoms being absent. A chronic cough, with a slight purulent discharge from the nose, a chronic leucorrhœa, a swollen testicle, or simply a persistent low condition or weakness without apparent cause, may be the only indications, and special means of diagnosis are demanded.

_Special Means of Diagnosis._ In occult cases, the disease may be identified by inoculation, or by the mallein test.

_Inoculation_ is best performed on a very susceptible animal. If the suspected discharge from the nose, vagina, open sore or preferably from a freshly incised nodule is inoculated subcutem in the flank of a male Guinea pig, or better in the peritoneum, there develops a local ulcerous sore and on the second or third day a violent orchitis in which pure cultures of the bacillus can be obtained. The caseous and purulent centres are found not only in the testicle but along the line of the spermatic cord, affecting the tunica vaginalis and connective tissue. Death usually follows in four to fifteen days. The cat and dog can also be utilized, inoculation being made on the forehead. Old wornout, but otherwise healthy asses, and even horses make very available subjects, inoculation in the nose speedily developing acute glanders. In the absence of a good subject the suspected animal is sometimes availed of, scarifications being made in the nose and the morbid product rubbed in freely. The rapid development of ulcerous wounds is characteristic. If, however, the case is chronic, and if a fair measure of immunity has been acquired this test may prove misleading.

_Test by Mallein._ Mallein is the sterilized and concentrated toxic product obtained from a pure culture of bacillus mallei in a peptonized glycerine bouillon. When injected hypodermically in a small physiological dose this has no effect on a sound horse, but in one affected with glanders it develops in several hours an extended swelling in the seat of inoculation, hot, tense and painful, which continues to enlarge for 24 to 36 hours and does not subside for 4 or 5 days. From the margin of the swelling, swollen lymphatics may often be traced running toward the adjacent lymphatic glands. There is also decided dulness, prostration, inappetence, staring coat and tremors. The body temperature rises 1.5° to 2.5° and upward from the eighth hour after inoculation attaining its maximum from the tenth to the eighteenth hour and subsiding slowly to the forty-eighth to the sixtieth.

Mallein must be used under precautions like tuberculin. It must be obtained freshly prepared from a reputable maker. If preserved for months its force may be largely lost. The animal to be tested should be in his customary environment, and not just arrived from a railroad journey nor other cause of excitement. He must not be fevered as any rise of temperature is then equivocal, and a fall of temperature, which sometimes occurs in the febrile system under mallein, is no sure evidence of glanders. Reaction sometimes fails in advanced cases of glanders, but in such a case other symptoms are usually diagnostic so that mallein is superfluous and should not be misleading. The greatest care should be taken to prevent infection from the syringe, nozzle, skin, hands, etc., as other infections may give rise to local swelling and hyperthermia (see tuberculin test). If a first test leaves the matter in doubt, the animal should be secluded and tested again in a month (some prefer 3 months).

_Pathological Anatomy._ The colonization of the bacillus mallei in a tissue usually determines a concentration and multiplication of leucocytes, so as to form rounded nests of small lymphoid cells in a scanty fibrous network. These may be miliary or by aggregation they form masses the size of a pea or larger, which bear a close resemblance to the neoplasms of tuberculosis. As in tubercle the central cells of the group, degenerate, forming a granular fatty debris, and constituting an ulcer or abscess. In certain cases with a proliferation of fibrous tissue a cicatricial material is developed. Another characteristic lesion is the occurrence of hyperplasia in the walls of the lymph vessels so as to constitute firm tender cords, and the infiltration of the adjacent lymphatic plexus.

In the _nasal mucosa_ the bacilli form prolific colonies at different points of the membrane and submucosa with the active production of lymphoid cells, followed by granular fatty degeneration and ulceration. Hence may be found different lesions representing the different stages. First there may be miliary deposits with clear contents and standing out like grains of sand. Then there are the larger pea-like nodules with congested vessels and minute hæmorrhages, but made up largely of the nests of lymphoid cells. These may bear on the surface a distinct blood extravasation, or the epithelium may be raised from the corium layer by a liquid exudation. The more advanced nodules show the centre light colored, grayish or yellowish with a distinct granular degeneration of the cells. Later still the degeneration involves the superficial layers and epithelium and an open ulcer is formed with a strong tendency to extend in depth and width. The formation and degeneration of numerous foci of cell proliferation gives the ulcer a very uneven outline. The continuous growth of fresh centres of proliferation may cause marked elevations between the ulcers, constituting extended patches, or the entire nasal mucosa may be thickened as the result of the morbid deposit. The cicatrices resulting from the apparent healing of deep or extensive ulcers or from a fibroid, transformation of the neoplasm consist of condensed connective tissue with small scattered nests of lymphoid cells and bacilli. In chronic cases the bacilli are very scanty.

The mucosa of the _Eustachian pouches and tubes, the larynx, trachea and bronchia_ often present lesions similar to those of the pituitary membrane.

The _lungs_ are usually marked in chronic cases by circumscribed lobular pneumonia, interlobular and peribronchial inflammations and miliary or larger areas of degeneration resembling tubercles. These may begin as a minute congestion and ecchymosis, which later shows in the centre a translucent or gray mass of lymphoid cells, with a surrounding area of congestion. Later still this central mass becomes yellowish and caseated from granular and fatty degeneration and this gradually extends so as to involve the whole area of the nodule. The peripheral portion may condense into a fibroid envelope, but usually this is less smooth and evenly rounded than in the case of an inspissated abscess or bladder-worm. The bacilli are found in the affected tissue but not always abundantly.

In _cutaneous glanders_ the lesions may begin in the papillary layer by active congestion and infiltration and proliferation of lymphoid cells which cause an eruption of rounded papules like small peas that degenerate and soften and form superficial ulcers. When the derma is mainly involved the inflamed area becomes the seat of larger hard nodules which are at first deeply congested, with capillary thrombi, minute extravasations and rapid cell proliferation; later on section they show numerous caseated centres with a dense fibroid framework and surrounded by an area of active congestion and capillary hæmorrhage; later still the caseation and softening has caused rupture of the investing epithelium and the discharge from the ulcerous cavity of a yellowish, glairy, grumous liquid (open farcy buds). Sometimes the nodule undergoes fibroid induration and fails to ulcerate, becoming the counterpart of the cicatrices in the nose. When the infective inflammation extends to the subcutaneous connective tissue, diffuse engorgements and extensive swellings occur from the general infiltration of the abundant lymph plexuses. Lymphoid cells accumulate in the perivascular sheaths and lymph plexuses, the walls of the lymphatic trunks running out of these swellings become swollen and indurated and at intervals, mostly on the seat of the valves there is the proliferation of small round cells to form farcy buds. In chronic cases the fibroid thickening involves the skin, subcutaneous connective tissue and walls of the lymph vessels binding the whole into one dense resistant mass, more or less studded with corded lymphatics, firm nodules, and ulcerous sores.

The _lymphatic glands_ in the line of circulation from the infected centres are constantly involved. Hypertrophy, congestion, serous infiltration, and rapid cell proliferation are present and a section will usually show caseated or caseopurulent centres confined by the outer dense fibrous envelope. Exceptionally, these necrosed contents will escape through an ulcerous opening, forming a deep cavity which is slow and difficult to heal. In the vicinity of these glands and in the loose intermuscular connective tissue abscesses of the size of an egg or an orange or larger are sometimes met with.

Nodules and ulcers are found on the pharyngeal and intestinal mucosa, similar to those of the larynx.

The spleen, and less frequently the liver, may be the seat of caseating nodules exactly comparable to those of the lungs. Glanders of the kidney is rare.

Nodules have been seen on the ventricular endocardium and one case of nodules of the choroid plexus (Boschetti).

In stallions, glanderous, caseating foci in the _testicle_ and dropsy of the scrotum are common, while mares may have similar formations in the mammary glands or ulcers of the vaginal or uterine mucosa.

Infiltrations of the joints and other synovial cavities are not uncommon and glanderous infiltration of the bones with caries is also found. In chronic cases, fragility of the bone is marked, and the blood contains an excess of leucocytes. These may be traced to disease of the bone marrow, as well as of the spleen and lymphatic system.

GLANDERS IN SWINE.

The healthy, vigorous pig is practically immune. Experimental inoculations have uniformly failed to produce the disease. Exception must be made when inoculation is made into the aqueous humor, in which there is comparatively little resistance by leucocytes. Sacharoff succeeded in giving the disease in a fatal form to a young pig in this way. To weak and debilitated pigs, on the other hand, the disease may be conveyed as shown by Spinola, and Cadeac and Malet. The symptoms were engorgement of the tissues in the seat of inoculation with the formation of glanderous nodules, which undergo molecular degeneration and ulceration; swelling of the lymph vessels extending from the infected point, and of the adjacent lymph glands; the formation of glander nodules in the lungs, liver and spleen, and of nodules and ulcers on the nasal mucosa.

GLANDERS IN SHEEP AND GOAT.

Casual glanders is uncommon in the small ruminants, yet it has been seen in goats that fed on the soiled provender left by glandered horses (Ercolani, Trasbot, Mesnard). Sheep have suffered after inoculation (Renault, Bonley, Gerlach, Bollinger, Croker, Peuch, Galtier) showing nodules and ulcerous swellings in the seat of inoculation, with extension in some cases to the nasal mucosa and lungs, and a fatal result. In other cases the lesions remain localized and the disease progresses to recovery.

GLANDERS OF RODENTS: RABBIT, GUINEA-PIG, MOUSE, RAT.

The _Guinea-pig_ is especially susceptible, and like the rabbit and mouse may contract the disease by eating the soiled fodder of glandered horses. It is usually selected for inoculation for diagnostic purposes, because in the male, the insertion of the virus in the peritoneum determines a rapid swelling of the testicle and cord, with a glistening, violet engorgement and tension of the scrotum, suppurative adenitis and death in three to six days. In other situations the inoculated part swells rapidly and ulcerates, the adjacent lymph glands become swollen and tender, similar lesions form in other parts and notably in the nose which discharges profusely a whitish, sticky fluid, the breathing is hurried, and emaciation is marked. Death occurs in a few days and ulcers, and abscesses are found in the lungs and other internal organs, as well as in the nose. In less susceptible subjects or under smaller doses of the virus the local swelling and ulceration in the seat of inoculation are slight, but there persist engorgements of the adjacent lymph glands, swelling (cording) of the lymph vessels adjacent, and nodules and abscesses, (cutaneous, subcutaneous, intermuscular, intravisceral), arthritis, emaciation, dyspnœa and death in two to four months. In some cases with a very small dose of the poison, there is no local swelling, and no generalization nor subsequent manifestation of the disease.

In the _rabbit_ the lesions are less certain and often less marked. There is sometimes no swelling in the seat of inoculation, in the neighboring lymph glands, nor elsewhere, and the rodent might have been supposed to have escaped, only that successful inoculation of the ass may be made from the tissues inoculated (Galtier). In such a case a certain immunity of the rabbit must be inferred. In less resistant rabbits, or with a larger dose, an ulcerous swelling forms in the seat of inoculation, the adjacent lymph glands become engorged or even purulent, corded lymphatics intervene, and nodules and caseous degenerations appear in the lungs, nose, spleen, liver, and other organs.

The _hedgehog_, _ground squirrel_, the _field mouse_, _house mouse_, _mole_ have been successfully inoculated.

The _frog_ immersed in water at 30° C., forms a good culture ground for the bacillus which may be found in its blood, in pure cultures, from the second to the fifty-fifth day. These cause no local lesion, nor obvious, constitutional disorder. It seems possible that, in summer, the infection may be propagated by frogs in the drinking water.

GLANDERS IN CARNIVORA.

All carnivora are liable to contract glanders by eating the flesh of glandered horses, asses and mules, and this has been noted especially in menageries. _Lions_, _tigers_, _bears_ and _wolves_, have shown the ulcerous lesions in the nose, and the nodules in the lungs, spleen, liver, kidneys and elsewhere. The carcass of the diseased horse is, however, often devoured without evil result, and even when the carnivora become affected the disease is not always fatal.

In the _dog_, experimental glanders has been closely studied by many observers. Casual glanders has been contracted by living with the glandered horse; by licking his nasal or other discharges, and by eating his flesh. The disease has also been conveyed from dog to dog by licking each other. In many cases even inoculated glanders produces only a local ulcerous inflammatory lesion with or without hard swelling of the adjacent lymphatics, and engorgement of the lymph glands. After a rather tardy granulation and cicatrisation, the symptoms subside and the animal is restored to health. Yet such benignity does not depend on any lessened virulence of the bacillus, for an inoculation of the discharges on the ass produces acute and fatal glanders.

GLANDERS IN MAN.

Recognized by Lorin 1812. Causes: infection from soliped, man less
susceptible; infection from man, clothing, stable bucket, inhalation,
etc.; industrial disease; native immunity. _Symptoms_: incubation;
mistaken for carbuncle, small pox, measles, erysipelas, anthrax;
anamnesis; anthrax focus has darker center, no caseation, no corded
lymphatics; nodules and ulcers in nose, swollen submaxillary glands
and lymph vessels, general illness, diarrhœa, vomiting, dyspnœa,
mental derangement, stupor, coma, internal deposits, bloody sputa,
fœtid breath, hepatic pain, icterus, muscles, bones, bowels, typhoid,
pyæmic, osteo-myelitic, or acute tuberculous symptoms. Death in 3 days
to 4 weeks. Chronic cases, cutaneous, muscular, osseous, skin nodules
in group or chain, glandular swellings. Diagnosis from pyæmia by lack
of chills, and the sanious pus; from syphilis by futility of potassium
iodide, and history; inoculate ox or white mouse; find bacillus.
Lesions: as in horse, more early coagulation necrosis, ulceration,
abscess; pus more viscid than in pyæmia, walls of abscess more
irregular, lymphoid cell proliferation more abundant and extended
(glands, spleen, liver, lung, nose, etc.), history; distinguished from
variola, rötheln, and erysipelas by the many miliary or pea-like
neoplasms with cellular caseating centres; lymphoid deposits in bone
marrow, with friability.

Until the early part of the present century glanders in man was not traced to its origin in the soliped. Lorin in 1812 recorded a case in which the human hand had been accidentally inoculated from handling a horse suffering from farcy. Soon other cases were put on record by Waldinger and Weith, Muscroft, Schilling, Rust, Sedow, and a host of followers. Later Rayer, Tardieu, Virchow, Leisering, Gerlach and Koránye have thrown much light on the subject.

_Etiology._ Man is manifestly less susceptible than the soliped, considering the great number of exposures relatively to the victims. Yet the infection of man is altogether too common to be lightly passed over. The infection is almost always derived directly or indirectly from the horse, yet a number of cases have been derived from the human being through handling the dishes, towels or handkerchiefs of a patient, dressing his wounds, or performing a necropsy. Other cases like that of Dr. Hoffmann of Vienna, came from handling artificial cultures of the bacillus mallei.

Glanders is preëminently an industrial disease, attacking persons of the following occupations: hostlers 42, farmers and horse owners 19, horse butchers 13, coachmen and drivers 11, veterinarians and veterinary students 10, soldiers 5, surgeons 4, gardeners 3, horse dealers 2, policeman, shepherd, blacksmith, employe at a veterinary school, and washerwoman, 1 each.

The modes of transmission are essentially the same as in the animal. In the great majority of cases there has been the direct contact of the infecting discharges with a wound of the human victim. Handling the diseased horse with injured hands, giving him a bolus and scratching the hand on the teeth, examining the nose, sleeping under a blanket which has been used on a glandered horse, removing the dressings of such an animal or performing a post mortem examination on him are familiar examples. The particles scattered by the diseased animal in snorting, will infect the mucous membrane of the eye or nose, and all the more readily if these are already sore or abraded. Infection of man by ingestion has been discredited mainly because the carcasses of glandered horses have often been eaten with impunity; but this may be largely accounted for by cooking, the bacillus being destroyed by a temperature of 131° F. Carnivora such as dogs, cats, lions, polar bears and prairie dogs have been infected by feeding. Men also have been infected through drinking from the same bucket after a glandered horse. After making full allowance for the inimical action of the gastric juice, we must admit that this has often failed, and there is the added danger of abrasions of the lips, mouth and throat and of the entrance of the microbe into the tonsillar follicles and gland ducts. Still other cases are recorded of men sleeping in stables, but not handling horses, who contracted glanders, presumably, through the dust borne bacillus inhaled. The bacillus, is however, so readily destroyed by thorough desiccation that this mode of transmission is exceptional. Some men are immune to glanders, and suffer only when predisposed through a course of ill health, and yet a large proportion of the cases on record have been in strong hearty men.

_Symptoms of Glanders in Man._ In man as in the horse, glanders occurs in the _acute_ and _chronic forms_. In the _acute_ supervening on an external inoculation, _incubation_ is from one to four days. When it enters through other channels it may seem to extend to a week or more.

When a skin abrasion has been inoculated it will show in a few days a soft inflammatory swelling or a firm nodule with a puffy reddish areola, and it may be mistaken for a carbuncle. In not a few cases the small nodule has been mistaken for small pox. In my experience a horsemen on a ranch on which over a hundred horses showed glanders, died of an ulcerous skin affection which was variously supposed to be a malignant small pox and measles, though neither malady was known to exist in the district. Other cases are confounded with gangrenous erysipelas. The absence of these other affections from the locality, and the fact that the patient was employed about glandered horses, should go far to correct such mistakes. The early supervention of ulceration is further diagnostic, and discovery of the bacillus mallei in the products will be conclusive. From anthrax it is easily distinguished by the absence of the dark centre of the sore in the early stages, and of the large sized bacillus anthracis. The caseation or liquefaction of the necrotic centre further distinguishes it from the characteristic anthrax slough, and the thickening and induration of the lymphatic walls are not present in anthrax. Sometimes the inoculated case proves mild and recovers in two or three weeks with healing of the ulcer, but in other cases there is an extension to adjacent tissue and a general infection with the supervention of nasal glanders.

There is a spread of the erysipelatoid inflammation and swelling, and the formation in such newly invaded tissue of nodules and ulcers in successive crops. In acute cases too, the nasal mucosa becomes involved with the formation of the nodules and ulcers that are so pathognomonic in the horse. The discharge is then somewhat sticky and often tinged with blood. In acute cases according to Senn, the nose may be completely destroyed and deep facial ulcers may be formed in a week. The submaxillary glands are enlarged and painful and the facial lymphatic vessels leading from these to the nose may be red, thickened and tender. Suppuration and ulceration of the glands may ensue. Headache, prostration, nausea, inappetence and vomiting with diarrhœa usually supervene. Then follow dyspnœa, wakefulness, troubled dreams, anxiety, nocturnal delirium, stupor and coma. The pulse may rise to 120 and the temperature to 104° F.

There may be various complications as deposits in the lungs with pain in the chest, weak cough, aphonia, bloody expectoration and offensive breath; or the morbid process may take place in the liver or spleen with pain in the hypochondrium and much prostration and even icterus; or the muscles, bones, joints or testicle may suffer and the symptoms may suggest typhoid fever, pyæmia, osteomyelitis, or acute general miliary tuberculosis. The bacillus can usually be detected in the blood.

Acute glanders may prove fatal in three days or it may be prolonged for two, three or even four weeks.

_Chronic glanders_ in man usually confines itself to the cutaneous muscular and osseous systems. It may take on an indolent type with the formation of skin nodules in groups or chains which remain hard and show no tendency to soften nor ulcerate. The adjacent lymphatic glands may become enlarged and indurated and the affection strongly resembles tuberculosis of the skin. Later when the nodules have softened and formed irregular and obstinate ulcers with swollen lymphatic glands, the disease is easily mistaken for syphilis. From pyæmia and septicæmia it is usually to be distinguished by the comparative absence of chills, and by the more sanious character of the pus. From syphilis it may be distinguished by the futility of a course of potassium iodide, and the general history of the case and probable exposure of the patient, and for tuberculosis the same principles will apply. In case of uncertainty, inoculation may be resorted to on the horse in suspected syphilis and on the pig when there is suspicion of tuberculosis. Or conversely the ox may be employed for the latter disease as he is altogether insusceptible to glanders. As a last resort the discovery of the bacillus may be made or the mallein test may be adopted with the concurrence of the patient.

_Pathological Anatomy and Diagnosis._ This is fundamentally the same as in the horse. The bacillus and its toxic products act on the infected tissues to produce clusters of lymphoid cells in a fibrous stroma after the manner of tuberculosis. Like that disease it also tends to affect primarily the lymph channels and glands, showing a particular tendency to the respiratory mucosa and has a great disposition to early coagulation, necrosis, ulceration, suppuration and abscess. The giant cell of tuberculosis is not a prominent feature in glanders, and the disposition to suppuration is greater especially in the human being so that the disease often resembles pyæmia. As in solipeds, however, the glander abscess has somewhat more sanious or glairy contents and the investing wall is not smooth and regular, but uneven and ulcerous from the successive softening and discharge of the clusters of degenerating lymphoid cells in the adjacent tissue. The pallor of the adjacent tissues from exudation and from the presence of numerous nests of lymphoid cells, the thickening of the efferent lymphatics, and the presence of numerous lymphoid neoplasms in the adjacent glands, and tissues, and often in the internal organs such as the liver and spleen and in the nasal mucosa or lungs together with the history of the patient’s exposure to glanders serve to diagnose from pyæmia. From smallpox and rötheln the skin lesions are distinguished by the presence of a central coagulation necrosis bathed in a glairy seropurulent fluid, and by the infiltration and thickening of the efferent lymphatic trunks. It differs from erysipelas in the same way by the presence in the affected tissues of the small hard lymphoid masses of embryonal tissue, and in a more advanced stage by the granular fatty debris resulting from their fatty degeneration. The presence in the affected tissue of these miliary or pea-like neoplasms in all stages of development from the primary congestion, through the embryonal tissue to the coagulation necrosis and caseation or softening is characteristic of the lesions of glanders. The sanious, sticky or glairy pus is especially noticed in the newly opened abscess, as after exposure to the air it is speedily infected with pus microbes, and the discharge becomes less serous and more creamy. Another characteristic of glanders in man is the frequent implication of the bone marrow, and the formation of the lymphoid deposits in the cancellated tissue until the bone may be reduced to a mere friable shell. Even when the disease is localized in the nasal mucosa it extends rapidly, not only to the skin and muscles, but also to the cartilage and bones of the face, so that deep, wide, perforating and destructive ulcers are common. The enlarged ends of the long bones of the limbs are favorite seats of the lesion, and the synovial membrane of the joints and the articular cartilage often bear centres of lymphoid proliferation. Though usually small the intermuscular neoplasms may form abscesses as large as a hen’s egg. The affected muscle appears pale, degenerated and granular with foci of lymphoid cell growth. The swelling of the lymph glands is usually less than in the soliped though the same in character. The pulmonary neoplasms are histologically almost indistinguishable from tubercle, though the comparative absence of the giant cell, the different staining qualities of the bacillus, and the coincident lesions in the upper air passages, with the cord like infiltration of the walls of the lymphatics may assist in diagnosis. Diagnostic inoculation may be made on the basis of the susceptibility of the ox and white mouse to tuberculosis, and their insusceptibility to glanders; also the partial insusceptibility of the soliped to tuberculosis and his marked susceptibility to glanders.

The characteristic nodules and abscesses may be found in different internal organs such as the stomach, intestine, liver, spleen, kidneys, testicles and brain, especially in acute cases, whereas the lesions of the skin and nose are more common in chronic cases.

PROPHYLAXIS AND TREATMENT OF GLANDERS.

Extinction. Exclusion, in Australia, New Zealand, English army.
Occision of infected, and disinfection of stables, harness, vehicles,
utensils, manure and other infected things, mallein diagnosis;
attendants should avoid handling suspicious horses, except with sound
hands, and disinfect latter. Sheep living in horse stables, tested
before slaughter, or inspected after. Malleinization on Plains and in
high, dry air, in secluded herds: less hopeful elsewhere. Mallein test
for all solipeds from glanders districts, and imported horses.
Treatment illegal in many states, so that justice would require
extinction with indemnities. Successful on high tablelands and
mountains. Demands careful segregation and disinfection. Acute cases
always hopeless: chronic skin cases more promising. Antiseptic
injection of unbroken nodules (carbolic acid, potassium permanganate),
also of open sores (mercuric chloride, iodized phenol, cupric
sulphate, saturated, zinc chloride), excise nodule. For delicate
mucous surfaces Lugol’s solution of iodine or iodized phenol diluted.
Tonics: arseniate of strychnia, copper biniodide, baryta nitrate, iron
sulphate, sulphites, bisulphites, hyposulphites, phenic acid, open air
life at pasture, or thorough ventilation, sunshine, moderate exercise,
generous, partly grain diet. Mild cases in separate herd, in secluded,
wide pasture with rich diet, including grain, and shelter in clean,
comfortable shed at will, under tonics and antiseptics, tested by
mallein at intervals, to be restored individually to work after two or
more tests without reaction. Serum of immune animals subcutem.
Treatment in man: surgically as in the horse, excision, curetting,
antisepsis, abscesses opened and disinfected; iodoform insufflations,
antiseptic gases, sprays and solutions. Internally: tonics,
sulphocarbolates, iron muriate, iodides, phenic acid, quinia,
strychnia, arsenite, stimulants, serum treatment, pure air, out door
life, rich, digestible food.

Radical efforts at prevention must look to the extinction of the disease in the soliped, and its complete exclusion from Australia and New Zealand shows that such a result is not unattainable. In the English army where every glandered horse is at once killed and all pertaining to him disinfected, the disease is now virtually unknown except in the case of newly purchased horses or regiments operating in the field. In the French army which formerly lost 9 per cent. per annum from glanders, now under similar precautions loses but .5 percent. A law providing for the prompt destruction of every glandered soliped and the safe disinfection of carcasses, stables, harness, vehicles, utensils, fodder, litter and manure that have been exposed to contamination, if enforced, would soon eradicate the disease. But this law should provide efficient machinery for its enforcement, and, under suitable safe guards, an appropriate indemnity for the owner. With the use of mallein in all infected studs, as a diagnostic agent, the campaign can be made sharp, short and effective, instead of waiting as in the past for the slow development of occult cases.

The greatest and most fundamental error in veterinary sanitary legislation is the lack of a guarded indemnity for the animals killed. I strongly urged this fact on the committee of the N. Y. legislature in 1898 but to no purpose. A bill was passed forbidding all indemnity for glandered horses, and an impetus thus given to the spread of the disease is daily bearing fruit in our great cities especially, disastrous to the health of the horses, and a constant menace to that of humanity as well. The law makes it the duty of veterinarians to report all cases of glanders, but in great horse establishments such a report would stop the use of the whole stable, at a loss of thousands of dollars per diem, and put a sudden end to the employment of the reporting practitioner by the firm or corporation in question. The owner of one or two horses can afford to report, the loss of these and their work does not mean absolute ruin, but the owner of hundreds can not safely report. For owner and practitioner alike the alternatives are presented of obedience to the law with personal ruin on the one hand, and the surreptitious dealing with cases of glanders and the preservation of their livelihoods on the other. Whatever may be said as to the constitutionality of the law which destroys private property without compensation under the right of eminent domain, this is certain, that, as applied to animal plagues, this course is unjust, oppressive, and not only useless, but positively injurious, in that it drives the owners of animals to such courses as favor the spread of the plague in place of restricting it. To-day in New York City glanders is extensively prevalent, but large horse owners dare not adopt the legal measures for its extinction, with the certainty of great loss or ruin staring them in the face as the result. It should be further considered that any law is at once bad and vicious in its tendency which places before the citizen the alternatives of disobedience with profit, and obedience with loss or ruin. Such a law is the worst possible economy because in preserving the infection, it not only perpetuates the disease and its attendant losses for all time, but perpetuates forever the official expenses of keeping it in check, when a prompt extinction of the infection would once for all time abolish all loss and all outlay for surveillance.

Until provision can be made for the enforcement of our laws against glanders, all who handle horses should be warned of the danger of working about strange solipeds, or those that show suspicious symptoms, while they have any sores on the hands, and in case they must run any risk of contact with infection, to promptly wash hands and face in a solution of hydrargyrum chloride (1:2000), or carbolic acid (2:100). Animals of susceptible races (sheep, etc.) which have lived with glandered horses should be made to pass the mallein test before they can be put upon the market for human food.

In the high, dry altitudes of the Plains and Rocky Mountains, where most cases of glanders are mild and the majority recover, resort may be had to malleinization provided the patients are kept safely secluded from all other horses. In some horses with a native tendency to immunity, the oft repeated inoculation with 0.5cc. of mallein will render the animal refractory to the infection. Animals that have recovered from casual attacks show the same immunity. Among those who have experimented with mallein may be named: Straus, Schneidemuhl, Semmer, Bonome, and Vivaldi, Mowry and Michel, Schweinitz and Kilborne. Sacharoff apparently secured immunity in the horse by inoculation with virus modified by passing through the cat. Straus found that dogs which had received mallein intravenously could be made immune against intravenous inoculations, but, as Galtier had already pointed out, were still susceptible to cutaneous inoculations. Finger, experimenting on the rabbit, found that immunity only resulted after a long series of inoculations. The frequency of successful auto-inoculations in chronic cases of glanders in the horse would tend to discredit the alleged value of single injections of mallein, so that a long series is necessary if we would aim at good results.

Altogether attempts at immunizing the equine population generally, are not hopeful where it is dense, where they must be kept stabled, where the climate is moist and where glanders is deadly, or tends to persist in the chronic form for years in the same animal.

Considering the prevalence of the disease in a mild form on many of the western breeding ranches it is well to test all horses arriving from the west. The same applies to solipeds imported from abroad.

TREATMENT OF ANIMALS.

In the majority of the states the treatment of a glandered horse is prohibited by statute. Yet without providing definite machinery for the administration of the law, and without indemnities for horses disposed of, such laws are largely inoperative. On the other hand treatment is quite successful on the pastures of our dry table lands and mountains. It can, however, be sanctioned only when careful segregation and disinfection are provided for. Acute cases of glanders are hopeless in any region, but chronic cases and especially such as have the lesions confined to the skin are much more hopeful.

The unbroken nodules may be injected with carbolic acid solution (1:200), or permanganate of potash (1:60). The open sores on the skin may be treated with the same solutions, with mercuric chloride (1:2000 to 1:5000), with iodized phenol, with cupric sulphate (saturated solution), or with chloride of zinc. A primary nodule may be excised and the sore treated with antiseptics. When the lesions are very extensive the less poisonous agents should be made use of, or tincture of iodine may be substituted. The nose lesions may be treated by the weaker solutions of iodine or of iodized phenol.

Benefit also comes from a course of tonics the most successful of which have been arseniate of strychnia, binodide of copper, sulphate of copper, nitrate of baryta and sulphate of iron. The sulphites, bisulphites and hyposulphites and phenic acid are desirable adjuncts. An open air life at pasture is the ideal condition. Otherwise thorough ventilation, sunshine, moderate exercise and nourishing easily digestible food including grain are very important.

When conditions are favorable and an absolutely secluded pasture can be secured, with shelter from storms, and where civic or state authorities do not take effective measures to stamp out glanders, nor compensate owners for animals killed, mild, chronic and cutaneous cases and occult ones that have reacted to mallein without showing any other symptom, may be subjected to treatment. They should have an open air life, a generous diet, including grain, perfect cleanliness and pure air in the shelter-shed, an antiseptic and tonic medication (sulphites, tonics) may be given, and every three months a new mallein test may be applied. If the individual horse passes two successive tests without reaction, and shows no other indication of glanders, if his general health appears perfect and his condition good, he may be returned to work as a sound animal. With effective measures of extinction in force on the other hand, and indemnity for the slaughtered animal, any such measure would be entirely unwarrantable.

Treatment by injecting the serum of immune animal subcutem has given encouraging results. Helman, Semmer and Itzkovitch, Pilavios, Bonome and Vivaldi, Johne, Schindelka, Prieur and others record recoveries in recent cases and there need be no doubt of its value in subjects that are naturally somewhat refractory to the germ. Babes introduced the blood serum of the ox, which is naturally immune, and Prieur speaks with confidence of the treatment of cutaneous glanders in man and certain cases of pulmonary glanders in the horse.

TREATMENT IN MAN.

The surgical treatment of glanders in man does not differ materially from that given for animals. It is more frequently possible to deal with the local lesion in its early stages and then a thorough cauterization of the infected sore, and a little later the complete excision of the primary nodule, or the limited regional infiltration, the curetting of the adjacent parts and the maintenance of thorough disinfection by irrigation, sponging and compress will often be followed by success. Where such radical measures are inadmissible the infected parts should be excised and curetted as far as safe and the adjacent parts subjected to carbolic injections (1:200). Abscesses should be evacuated, fistulæ slit open, and thorough disinfection applied. For the affected air-passages, iodoform insufflations and antiseptic gases, sprays, and solutions should be freely used.

Internally, antiseptics such as sulphocarbolates and tincture of muriate of iron, iodides, and carbolic acid have been largely employed. Whitla recommends 5 grains of quinia in 15 grains of tincture of muriate of iron every four hours. Tonics (arsenate of strychnia), and stimulants, ammoniacal or alcoholic, may be called for. Special symptoms such as pain, rigors, nausea, vomiting, diarrhœa and profuse perspirations must be met by suitable remedies. Finally blood serum from healthy cattle or from immunized animals may be employed subcutem. Pure air and nourishing, easily digestible food are very essential. Every effort should be made to check the disease at its outset, as generalized acute glanders is speedily fatal, and recoveries in chronic cases usually leave a broken down constitution.

LYMPHANGITIS SACCHAROMYCOTICA (FARCINOIDES: EPIZOÖTICA:ULCEROSA.) FARCY
IN CATTLE.

Geographical distribution and nature: Japan, Northern Europe, France,
Guadaloupe; caseating nodules in skin, subcutem, in mucosæ and
internal organs. In _horse_ skin nodules, and glandular abscesses,
with thick ovoid refrangent bacterium; saccharomyces (Hitt); swellings
first local, then multiple, and general, extending along lymph vessels
to glands (Hitt); along air-passages to lungs, from prepuce or scrotum
to peritoneum (Hitt), or from conjunctiva to other parts in the orbit
(Caparini and Ferner). In _cattle_, multiple, subcutaneous,
nodules—hazlenut to walnut, isolated, hard, painless. Suppurate
slowly. Same saccharomyces (Tokishige, Nocard). May invade lungs with
fatal result in a year. Mallein test gives no reaction. Treatment:
actively antiseptic; open, curette, pack with antiseptic gauze,
sublimate bandages; internally, tonics, antiseptics.

Horses and cattle in certain countries (Japan, Sweden, Finland, France, Guadaloupe) are subject to a chronic lymphangitis resembling cutaneous glanders, but associated with the development of bacilli or fungi in the nodular, caseating swellings in the skin, subcutem, in mucosæ and in internal organs.

Nocard describes the affection in the horse as characterized by skin nodules (buttons, boils), which burst and discharge a thick, grumous, or thin, oily, yellowish or bloody pus. The surrounding lymph plexus swells up into corded lines, with at intervals nodules or abscesses. The infection extends to and implicates the lymph glands and general pyemia may follow. The thick ovoid refrangent, pathogenic, bacterium stains in Gram’s solution.

In Northern Europe and Asia, Southern Europe and Guadaloupe an analogous affection is described by Rivolta, Claudio-Fermi, Aruch, Tokishige and Nocard and Leclainche. Hitt attributes this to saccharomyces. The infection attacks horses and cattle, entering by sores and abrasions of the skin of the limbs, or under the harness (back, breast, rump, head). Confined at first to the point of infection it becomes multiple, being conveyed from place to place, through the soil, floor, stall, harness, blankets, brushes, combs, straw, etc., and may extend on the mucosæ. The wounds fester, forming pus and crusts over a more or less considerable swelling. In a variable time, (one to twenty weeks) the surrounding lymphatics become swollen and tender (corded), and nodular swellings appear on their course which fluctuate, burst and discharge a whitish or yellowish pus, sometimes oily or slimy. The disease extends along the lymphatics, invading the lymph glands and even the internal organs.

Tokishige describes cases in which it extended along the respiratory mucosa, causing constriction of the nasal passages and larger bronchi, with dyspnœa, and finally, invading the lung. In other cases it spread from the prepuce, or scrotum, upward along the tunica vaginalis, spermatic cord and testicle. Caparini and Ferner describe it in the orbit, affecting the lids, nictitans, conjunctiva and adjacent parts, with nodules and abscesses. Mazzanti describes the case of a filly which died with pea-like nodules on the colon, and ulceration, with dirty, black, purulent centres, and indurated borders. Tokishige describes the affected cattle as showing a vast number of subcutaneous, hard, painless nodules, varying in size from a hazel nut to a walnut and covered by light colored skin. The nodules were isolated and not connected by swollen, beaded lymph vessels. They encrease and suppurate much more slowly than in the horse. In three cows microscopically examined he found apparently the same branching fungus (saccharomyces), as in the horse cases. The mortality is about 10 per cent.

In the _farcy of the ox_ of Guadaloupe there form subcutaneous nodular abscesses, with cordiform swelling of the lymph plexus and trunks, often proving fatal in a year through extension to the lungs. The abscess breaks, discharging a whitish, creamy or caseous, or grumous contents, containing a bacillus (Nocard). The abscesses usually appear under the sternum or belly and later extend to the thighs and legs. In all such cases the mallein test is inoperative.

The _treatment_ of such cases should be actively antiseptic to destroy the germ while still local. After opening and evacuating the abscesses, excise or curette the diseased tissue, or destroy with the actual cautery, pack the cavities with pledgets soaked in tincture of iodine, iodized phenol creolin, lysol, mercuric chloride, zinc chloride, or copper sulphate, or dusted with aristol, iodoform, or iodized starch. The surrounding swelling, if any, may be painted with tincture of iodine, or covered with cloths wet with a sublimate lotion or other antiseptic. Internally, tonics and antiseptics may be given: arsenite of strychnia, quinia, iron or copper sulphate, sulphites or hyposulphites of soda or potash.

RABIES AND HYDROPHOBIA.