CHAPTER XX
Brucellosis
R. A. Kelser, D. V. M., Ph. D.
Over a period of years, brucellosis, or undulantfever, has gradually become a disease ofincreasing 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 Brucellaorganisms, each capable of causing diseasein both lower animals and man. The original Malta fever factor (MicrococcusMelitensis), nowcommonly termed Brucella Melitensis, is still looked upon asprimarily a caprine strainproducing disease in goats, sheep, swine, and also man. Brucellaabortus is the common cause ofinfectious abortion in cattle, of brucellosis in man, and occasionallyof disease and diseaseprocesses in other species of animals. In addition to the caprine andbovine types of Brucella, aporcine variety (Brucella suis) has also become well known.This type, while not as commonlyprevalent as the bovine species, is ordinarily even more virulent forman 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 ofbrucellosis would be encountered in the military forcesduring World War II, the incidence was relatively veryminor.Provisional data based on sampletabulations of primary and secondary diagnoses taken from individualmedical records show atotal of 1,305 cases of brucellosis in the United States Army duringthe 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 strengthin the total Army, during 1942-45combined, was 0.05, the rate in the United States (0.06) being twicethe rate experiencedoverseas (0.03). In one year (1941), the rate reported from overseasareas was considerablyhigher (0.09) than for subsequent years either in the United States orabroad.
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.-Incidenceof brucellosis in the U. S.Army, by area andyear,1942-45
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brucellosis was in the Mediterranean theater. This coincides withthe wellknown occurrence ofthe 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 commonlyclassified as an acute, subacute, or chronic disease.Those cases which do not extend over a period greater than 10 to 12weeks or thereabouts andwhich do not relapse are generally considered in the acute category.The subacute cases are thosein which the acute stage is followed by one or more exacerbations,which may be more or lesssevere than the primary attack, but in which the patient finallyrecovers completely within a fewweeks. The chronic type of the malady may extend over a period of anumber of years withintermittent 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 inthe morning and those in the afternoon mayvary only a degree or two in their peaks, while in other cases theheight of the afternoontemperature may exceed that of the morning by 4 or 5 degrees.Characteristically, the daily peaksrise gradually, in a wavelike manner, to a peak which may persist for aday or two and then dropto a low point. These wavelike temperature rises may be repeated atintervals varying fromseveral days to several weeks. All patients do not manifest typicalfever reactions. In some cases,the fever is low grade in character and may persist over a prolongedperiod with intermittentintervals of normal temperature; in others, the fever may be wellmarked in the relatively earlystages of the disease and then drop rapidly and remain substantiallynormal or of littlesignificance.
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 commonlyare debilitating and disabling, fortunately thecase fatality rate is low (about I percent in the United States).Fatalities are often due tosecondary factors and conditions rather than the specific brucellarinfection.
Sources of Infection
Brucellosis in man may be acquired in one of severalways. It is an occupational hazard in someinstances, occurring among farmers, dairymen, livestock raisers andhandlers, and stockyard andpackinghouse employees. Laboratory infections are not uncommon, and atleast four cases werethus contracted in the Army during the war. In other individuals,infections more commonlyoccur as a result of consuming milk or dairy products containing viableBrucella organisms. It isa well-established fact that in dairy cows Br. abortus, whichhas a predilection for embryonictissues, does not remain in the female genital tract long afterparturition or abortion but migratesto the udder where it establishes itself without appreciable damage tothe udder tissues. In suchlocality, where it will often remain for years, the Brucella organismmultiplies and is shed withthe milk. Such milk, if unpasteurized, may well infect man.
Preventive Measures
During World War II, no raw milk was authorized forthe use of the United States Army troops.Furthermore, precautions were taken early to protect military personnelfrom infection throughother dairy products such as cheese. With the great demand for cheesefor soldiers' rations, lend-lease commitments, and civilian use, theVeterinary Division of the Surgeon General's Officeinitiated action early in the war to assure that no inadequatelyripened cheese was supplied fortroop consumption. Specifically, this was accomplished through thepromulgation of orderswhich required that all cheese purchased by the military establishmentbe held in quartermasterdepots or warehouses at least 60 days before shipment to militaryorganizations. The wisdom ofthis action was attested by the fact that both brucellosis and typhoidfever outbreaks did occuramong civilians in several areas as a result of eating "green" orinadequately ripened cheese.Although the Army received several lots of cheese which early tests bythe Food and DrugAdministration and Army laboratories proved to contain viable Brucellaorganisms shortly afterpurchase, subsequent extensive tests, following the prescribed 60-dayholding 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 confirma tentative clinicaldiagnosis 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 abilityof the polymorphonuclear leukocytes fromsuspected cases of brucellosis to phagocytize Brucella organismsis compared with the normal,has been utilized to a considerable extent. The results with this test,however, have not beenentirely satisfactory. An allergy test, utilizing an agent(Brucellergen) which is comparable totuberculin and which is administered intradermally, has been of somevalue in the diagnosis ofbrucellosis in man. Experience has shown, however, that it is sometimesnegative in casesproved 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 ofthe bacterium were commonlymade, recovery of the organism was obtained in only a relatively smallpercentage of the cases.
Treatment
When the sulfonamides became available and with thedevelopment of the various antibiotics,hopes were entertained that one or more of these agents would provespecific in the treatment ofbrucellosis. In general, the results from the use of all of theseagents have been disappointing. Inoccasional cases, the use of some form of sulfonamides or antibioticsor combinations of themappeared to influence favorably the course of the disease. On the otherhand, in similar cases, noappreciable favorable effects were achieved with such therapy.With somepatients, rest in bedwith little or no treatment has often given results comparable to thoseseemingly obtained withsome of the therapeutic agents which have been employed. The combineduse of sulfadiazine andstreptomycin gained considerable favor in the treatment of brucellosisafter expectations frompenicillin failed to materialize. Then, since the advent of aureomycin,it has been considered bysome that it is of distinct value. In view of all of the evidence,however, it must be concludedthat, while certain beneficial results may be obtained from the use ofsome of these agents inindividual cases, there is as yet no specific therapeutic treatmentwhich can be relied upon in themanagement of brucellosis.
