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GLANDERS Glanders or farcy is a widespread communicable disease of horses, mules, asses, and other animals, and is readily communicated to man. Cats may become infected by eating the flesh of glandered horses. Goats also have the disease. Cattle are immune. Guinea-pigs and field mice are very susceptible by experimental methods; white mice have a natural immunity. In both man and horses it is remarkable for its fatality. The disease is characterized by the formation of inflammatory nodules either in the mucous membrane of the nose (glanders) or in the skin (farcy). The nodules break down, leaving crater-like ulcers. On the skin the farcy buttons break down and discharge an oily material. The mortality is about 50 per cent. Glanders occurs both as an acute and chronic disease.

Glanders is caused by the Bacillus mallei, which corresponds to the spore-free bacteria so far as its resistance is concerned. In gen eral the bacillus of glanders is killed by the same agents used against the tubercle bacillus, which it resembles in some particulars.

The infection may be introduced into the system either through the skin or mucous membrane, and is usually communicated directly from the horse to man by contact with the infected discharges. The disease is sometimes communicated from man to man. Washerwomen have be come infected from the clothes of a patient.

The bacillus of glanders does not have a spore. It is comparatively frail and readily destroyed by the usual physical and chemical germi cidal agencies used against spore-free bacteria. The bacillus, however, is frequently protected by albuminous matter or buried in the dirt of stables, water troughs, harnesses, and other objects. While the naked germs of glanders are readily destroyed, they are frequently hard to get at; cleanliness is, therefore, imperative.

The prevention of glanders in man depends primarily upon the sup pm.sion of the disease in horses. The only difficulty in controlling the disease in horses lies in the early diagnosis and recognition of mild or missed cases, which are very common. Horses affected with occult or latent glanders are important factors in the propagation of the in fection, especially in the crowded parts of cities. The clinical diagnosis in the frank cases usually is made without difficulty from the character istic symptoms and the lesions, but laboratory aid is necessary to discover the mild and atypical cases.

Diagnosis. The diagnosis of glanders may be made by : (1) the mallein test, both subcutaneous and ophthalmic; (2) the agglutination tat; (3) the Strauss reaction; (4) isolation of B. mallet in pure culture; and (5) complement fixation. All these tests serve a definite purpose. However, the mallein test, the agglutination test, and the Strauss re action have certain limitations. The isolation of the glanders bacillus in pure culture is definite and final, but time-consuming. There is no absolute relation between complement fixation, agglutination and mal lein tests in horses. An apparently healthy horse should not be con demned because one of these tests is positive but the animal should be studied further.

The Mallein Test. Mallein is a product of the glanders bacillus corresponding to tuberculin. The injection of mallein into normal ani mals produces no reaction, whereas the injection into glanderous ani mals causes a rise in temperature and a local reaction about the lesions. With the mallein test a large proportion of latent and occult cases of glanders can be diagnosed, but the test must be made and interpreted by an experienced veterinarian, else the results may be unreliable. The mallein test fails to give a typical reaction in a considerable number of glanderous animals; on the other hand, a reaction may follow the injec tion of mallein in the absence of active glanders. Thus mallein is not an entirely reliable diagnostic agent and has never been considered as specific in the detection of this disease as tuberculin for the diagnosis of tuberculosis.

The ophthalmic test for glanders is reliable, and has a great advan tage over other tests on account of its very simple application. It is only necessary to drop into one of the eyes of the animal three drops of con centrated mallein, or to dip a camel's-hair brush into mallein and intro duce this into the conjunctival sac. The reaction usually commences in fire or six hours after the introduction of the mallein and lasts from twenty-four to thirty-six hours. A positive reaction is manifested by swelling of the eyelids and a purulent secretion from the tested eye. Irritation of the conjunctivae due to cold weather, dust and other ir ritating influences must not be confused with a positive reaction.

The Agglutination Test. The agglutination test is of value in all cases of recent infection, the blood serum possessing a very high agglutinating powcr-1-1,000 and higher. In chronic glanders the ag glutinating power of the blood may be very low-1-400 or less; in some cases even lower than that of normal blood serum—which may be 1-800 and even higher. It is, therefore, plain that,agglutination tests alone do not constitute an entirely satisfactory diagnostic method for glanders. It may be used as an adjunct to other tests.

The Strauss Reaction. The Strauss 28 reaction for the diagnosis of glanders consists in inoculating material containing virulent B. mallei into the peritoneal cavity of male guinea-pigs, which causes an enlargement of the testicles, involving the scrotum; the testes become glued to their sheaths. A positive reaction associated with organisms resembling those of glanders, and typical cultures obtained from the lesions, are unfailing evidence of the presence of the specific virus. Failure to obtain the reaction is not proof that a suspected specimen may not have come from a horse or animal with glanders. Arms 29 recom mends that it is better to use more than one guinea-pig in testing suspected material, and that, before inoculating, it is well to make a microscopic examination as a guide to the dosage. A culture made from the swab often aids in the early diagnosis. Guinea-pigs should be kept under observation for a month, and if a lesion of any kind is present an autopsy should be made and cultures taken.

The Isolation of B. Mallei in. Pure Cu.lture. The bacillus of glanders may be isolated by introducing some of the suspected ma terial subcutaneously and also intraperitoneally into male guinea-pigs. In this way pure cultures may be obtained from the pus or necrotic foci in the spleen, which follow subcutaneous inoculation; or from the characteristic enlargement of the testicle which is observed in animals inoculated intraperitoneally. The organism isolated must be studied for cultural, morphological, and biological characters. The isolation of the bacillus in pure culture gives positive information of unquestioned character in any critical case. The method is not generally applicable to the diagnosis of glanders because it requires too much time and may occasionally fail to discover the bacillus. One of the chief difficul ties is that the material is usually grossly contaminated with other pathogens.

Complement Fixation. In 1909 Schatz and Schubert" published the results of their important work on the application of the method of complement fixation for the diagnosis of glanders. The splendid results obtained constitute, without doubt, the most reliable method for the diagnosis of glanders which we have at our command at the present time. The complement fixation test is, in fact, one of the most specific of the biological tests in immunity. It is readily applicable to the case of glanders. It has, however, less value in testing the blood of mules than horses because of the larger percentage of false positives in the former. The essential elements used in the test are as follows: The hemolytic mixture consists of the washed red blood corpuscles of a sheep and the blood serum of a rabbit which has been injected with the washed red blood corpuscles of a sheep. For preparation see raze 583.

Complement. The complement is contained in the fresh blood serum cf a healthy guinea-pig. For preparation see page 581.

Antigen..—This is an extract obtained by shaking glanders bacilli in salt solution. The bacillus is grown in pure culture on 2 per cent. acid, 6 per cent. glycerin agar. A luxuriant growth upon the surface of the medium is usually obtained in 48 hours. This is sus pended in 0.5 per cent. carbolized normal salt solution, heated to 60° C. for four hours in order to kill the bacilli. After heating, the dead bacilli are shaken in the salt solution in a special apparatus for eight to twelve hours. The bacilli are separated in the centrifuge and the dear supernatant liquid is drawn off and preserved with 0.5 per cent. phenol. The strength and specific quality of each extract must be de termined by suitable methods of titration, by control tests.

Technic. The test is carried out by adding together, in proper proportions, the following: (1) The blood serum of the horse to be tested; (1) the antigen (extract of glanders bacilli) ; (3) complement (fresh guinea-pig serum) ; and (4) the hemolytic system. If the blood serum of the horse to be tested contains the specific amboceptors, these will unite with the bacteria, fix the complement, and thus prevent hemol ysis. If the blood serum of the horse to be tested does not contain these specific amboceptors, this fixation of the complement cannot take place and hemolysis results. Therefore, the absence of hemolysis means the presence of glanders, and vice versa. The tests must always be carried out with controls and carefully conducted as to the amount of each substance used, the temperature and time.'' The technic and interpretation is precisely that of the Wassermann reaction (page 583), except that the antigen is an extract of the glanders bacilli.

Prevention. When glanders is discovered or suspected among horses in a stable, the horses in the infected stable should be tested in the manner above described. All animals with glanders should be destroyed without further consideration. After these animals have been killed and properly disposed of, the stable should be thoroughly cleansed and disinfected. All other horses which have in any way been associated with the infected animals should be carefully watched and tested again after three weeks, and, should there be no indication of the disease in the second test, the stable may be considered free from the infection; otherwise the infected animals should be destroyed and the tests repeated every three weeks until the disease has been eliminated.

The eradication of glanders from a stable often means considerable loss and sometimes a sacrifice valuable animals, but it is only through vigorous measures that the disease may be controlled. In the disin fection and cleansing, special attention should be paid to the stalls, harnesses, water troughs, bits, food containers, curry combs, sponges, and other objects exposed to the infection, which is eliminated mostly in the secretions from the mouth and nose. The common drinking trough for horses spreads the infection. The bacillus of glanders is lery susceptible to bleaching powder, and it therefore is a cheap and reliable germicide for this purpose.

The personal prophylaxis of glanders in man depends upon the education and care of those who have to handle horses. In working with horses known to be infected rubber gloves, disinfection, and other methods of protection should be employed. Special care should be taken to prevent the spread of the disease through the discharges or by infected fomites from human cases. Fatal accidents have occurred in laboratories in research workers handling pure cultures of B. mallei.

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