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Chapter 20 - Brucellosis

Contents

CHAPTER XX

Brucellosis

R. A. Kelser, D. V. M., Ph. D.

Over a period of years, brucellosis, or undulant fever, has gradually become a disease of increasing importance in the human family.

Prior to 1918, the malady in man was thought to be limited to infection with the organism responsible for Malta fever in goats and, therefore, more or less restricted to areas where goat raising was well developed and goat's milk more commonly consumed. With the discovery by Alice Evans in 1918 that, the causative agent of infectious abortion (Bang's disease) in cattle was a species closely related to the Malta fever organism, the possibility that the bovine bacterium might be capable of producing disease in man became apparent. Subsequent studies and experience have made this early supposition a well-established fact.

There are recognized today three species of Brucella organisms, each capable of causing disease in both lower animals and man. The original Malta fever factor (Micrococcus Melitensis), now commonly termed Brucella Melitensis, is still looked upon as primarily a caprine strain producing disease in goats, sheep, swine, and also man. Brucella abortus is the common cause of infectious abortion in cattle, of brucellosis in man, and occasionally of disease and disease processes in other species of animals. In addition to the caprine and bovine types of Brucella, a porcine variety (Brucella suis) has also become well known. This type, while not as commonly prevalent as the bovine species, is ordinarily even more virulent for man than the cattle variety.

While more cases of brucellosis have been definitely diagnosed in recent years than previously, it is very likely that there are a great many brucellar infections which are not diagnosed. Since the end of World War II, some 4,000 to 7,000 cases of brucellosis are diagnosed annually in the United States. These figures are, without doubt, far too low.

WARTIME INCIDENCE

While it was anticipated that cases of brucellosis would be encountered in the military forces during World War II, the incidence was relatively very minor.Provisional data based on sample tabulations of primary and secondary diagnoses taken from individual medical records show a total of 1,305 cases of brucellosis in the United States Army during the years 1942 through 1945. Of this total, 956 cases were in the United States and 349 overseas.


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The annual incidence rate per 1,000 average strength in the total Army, during 1942-45 combined, was 0.05, the rate in the United States (0.06) being twice the rate experienced overseas (0.03). In one year (1941), the rate reported from overseas areas was considerably higher (0.09) than for subsequent years either in the United States or abroad.

Table 76 indicates the number of cases and incidence rate of brucellosis in the United States Army at home and in foreign areas. Of the 250 cases reported among troops in the United States in 1945 (the only year for which a distribution by service command is presently available), 40 cases were in the Fourth Service Command, 70 in the Ninth Service Command, and 45 in the Eighth Service Command. Thus, approximately 62 percent of the cases was reported from 3 of the 9 service commands during this year.In considering the incidence in these three service commands, it should be remembered that in locating training camps and distributing soldier trainees the Fourth, Eighth and Ninth Service Commands were favored areas because of climatic conditions well suited for year-round training.In overseas areas, the highest incidence of

TABLE 76.-Incidence of brucellosis in the U. S. Army, by area and year,1942-45


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brucellosis was in the Mediterranean theater. This coincides with the wellknown occurrence of the disease in that particular part of the world.

When one considers the brucellosis cases reported by the Army during the period of World War II, it must be realized that while some of the cases, from their history, epidemiology, et cetera, without doubt originated in the military service, not all of them had their origin in the Army. The history and evidence in many cases clearly pointed to the acquisition of the infection in civil life at some earlier period. Of the 370 cases in which brucellosis was the primary cause of admission to medical treatment in 1945, the individual medical records on 70, or about 19 percent of the cases, characterized the disease as having existed prior to the time the individual entered the service. Some were probably inapparent infections, and others with appreciable symptoms were undoubtedly not identified as brucellosis. It is also possible that there were some cases in the Army during the war which were not recognized either because of their minor character or because they were classified as something else.

Brucellosis, as it occurs in man, is commonly classified as an acute, subacute, or chronic disease. Those cases which do not extend over a period greater than 10 to 12 weeks or thereabouts and which do not relapse are generally considered in the acute category. The subacute cases are those in which the acute stage is followed by one or more exacerbations, which may be more or less severe than the primary attack, but in which the patient finally recovers completely within a few weeks. The chronic type of the malady may extend over a period of a number of years with intermittent exacerbations and variable degrees of symptoms.

The period of incubation in brucellosis is quite variable. In some instances, it may be as short as 3 or 4 days, and at the other extreme it may extend over a month or more. In general, the average case will develop within 10 to 16 days.

In some cases of brucellosis, the temperatures in the morning and those in the afternoon may vary only a degree or two in their peaks, while in other cases the height of the afternoon temperature may exceed that of the morning by 4 or 5 degrees. Characteristically, the daily peaks rise gradually, in a wavelike manner, to a peak which may persist for a day or two and then drop to a low point. These wavelike temperature rises may be repeated at intervals varying from several days to several weeks. All patients do not manifest typical fever reactions. In some cases, the fever is low grade in character and may persist over a prolonged period with intermittent intervals of normal temperature; in others, the fever may be well marked in the relatively early stages of the disease and then drop rapidly and remain substantially normal or of little significance.

In addition to the generalized, febrile disease, brucellosis occasionally manifests itself as a local or focal infection in which the lungs, spleen, lymph nodes, eye, brain, bony structures (vertebrae), heart, or skin may be involved.


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While the apparent cases of brucellosis commonly are debilitating and disabling, fortunately the case fatality rate is low (about I percent in the United States). Fatalities are often due to secondary factors and conditions rather than the specific brucellar infection.

Sources of Infection

Brucellosis in man may be acquired in one of several ways. It is an occupational hazard in some instances, occurring among farmers, dairymen, livestock raisers and handlers, and stockyard and packinghouse employees. Laboratory infections are not uncommon, and at least four cases were thus contracted in the Army during the war. In other individuals, infections more commonly occur as a result of consuming milk or dairy products containing viable Brucella organisms. It is a well-established fact that in dairy cows Br. abortus, which has a predilection for embryonic tissues, does not remain in the female genital tract long after parturition or abortion but migrates to the udder where it establishes itself without appreciable damage to the udder tissues. In such locality, where it will often remain for years, the Brucella organism multiplies and is shed with the milk. Such milk, if unpasteurized, may well infect man.

Preventive Measures

During World War II, no raw milk was authorized for the use of the United States Army troops. Furthermore, precautions were taken early to protect military personnel from infection through other dairy products such as cheese. With the great demand for cheese for soldiers' rations, lend-lease commitments, and civilian use, the Veterinary Division of the Surgeon General's Office initiated action early in the war to assure that no inadequately ripened cheese was supplied for troop consumption. Specifically, this was accomplished through the promulgation of orders which required that all cheese purchased by the military establishment be held in quartermaster depots or warehouses at least 60 days before shipment to military organizations. The wisdom of this action was attested by the fact that both brucellosis and typhoid fever outbreaks did occur among civilians in several areas as a result of eating "green" or inadequately ripened cheese. Although the Army received several lots of cheese which early tests by the Food and Drug Administration and Army laboratories proved to contain viable Brucella organisms shortly after purchase, subsequent extensive tests, following the prescribed 60-day holding period, demonstrated that the cheese was safe for use.

Diagnostic Tests

The clinical diagnosis of brucellosis is not easy. In cases where the disease is suspected, laboratory tests and procedures must be resorted to in order to confirm a tentative clinical diagnosis or to rule out the possibility of brucellosis.


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The agglutination test is the simplest and most commonly employed diagnostic aid. Agglutination values, however, in actual cases of the disease vary considerably, and difficulty may be encountered in interpreting agglutination reactions when they occur in relatively low serum dilutions. Agglutination in serum dilutions as low as 1:100 may be diagnostically significant when considered together with clinical manifestations. On the other hand, serum from some cases of chronic brucellosis may give negative agglutination reactions. Some cases of brucellosis will give agglutination reactions in relatively high serum dilutions (one to several thousand). High agglutination titers and those cases in which a rising titer is found in a series of tests are the easiest to evaluate. In some, of the chronic cases of brucellosis, the agglutination test gives negative results. It also must be borne in mind, in interpreting agglutination reactions, that cross agglutination reactions with a brucellosis antigen may be encountered in cases of tularemia and also in serum from individuals who have been vaccinated against Asiatic cholera.

The complement fixation test may be used as a diagnostic procedure in brucellosis, but since it is more complicated than the agglutination test it is not utilized as frequently. It, however, is perhaps positive earlier in the disease than the agglutination test, and it may persist for a longer period.

The opsonocytophagic test, in which the ability of the polymorphonuclear leukocytes from suspected cases of brucellosis to phagocytize Brucella organisms is compared with the normal, has been utilized to a considerable extent. The results with this test, however, have not been entirely satisfactory. An allergy test, utilizing an agent (Brucellergen) which is comparable to tuberculin and which is administered intradermally, has been of some value in the diagnosis of brucellosis in man. Experience has shown, however, that it is sometimes negative in cases proved culturally to be brucellosis.

Naturally, the most positive evidence of brucellosis is the isolation of the Brucella organism from the patient. The bacterium is usually present in the blood in the initial stages of primary attacks of the disease but commonly is there only in relatively small numbers. Repeated blood cultures, therefore, are made at frequent intervals in attempting to isolate the organism.

Where the organism is isolated in pure culture, typing to determine species is not particularly difficult. Bacteriologic procedures involving tests for CO, requirements, the production of H,S, and growth or failure of growth in the presence of certain dyes such as basic fuchsin, thionine, pyronine, and methylene-violet, are commonly utilized in typing Brucella organisms. Agglutinin absorption tests are likewise very valuable in determining Brucella species. All of this is relatively easy when the specific organism has been isolated from a case of brucellosis. Much greater difficulty is encountered if blood serum from the patient is the only thing available for typing.

The precise incidence of the different specific types of brucellar infections among those cases of brucellosis identified in the Army was not determined. Most of the cases in the Army were diagnosed on the basis of clinical symptoms and agglutination tests. In some instances, in addition, the opsonocytophagic


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and skin tests were used.While blood cultures for the isolation of the bacterium were commonly made, recovery of the organism was obtained in only a relatively small percentage of the cases.

Treatment

When the sulfonamides became available and with the development of the various antibiotics, hopes were entertained that one or more of these agents would prove specific in the treatment of brucellosis. In general, the results from the use of all of these agents have been disappointing. In occasional cases, the use of some form of sulfonamides or antibiotics or combinations of them appeared to influence favorably the course of the disease. On the other hand, in similar cases, no appreciable favorable effects were achieved with such therapy.With some patients, rest in bed with little or no treatment has often given results comparable to those seemingly obtained with some of the therapeutic agents which have been employed. The combined use of sulfadiazine and streptomycin gained considerable favor in the treatment of brucellosis after expectations from penicillin failed to materialize. Then, since the advent of aureomycin, it has been considered by some that it is of distinct value. In view of all of the evidence, however, it must be concluded that, while certain beneficial results may be obtained from the use of some of these agents in individual cases, there is as yet no specific therapeutic treatment which can be relied upon in the management of brucellosis.