Brill's Disease Research Articles

Serologic Studies of Primary Epidemic Typhus and Recrudescent Typhus (Brill-Zinsser Disease)

Summary and Conclusions The major Rickettsia prowazeki antibody present in sera obtained from primary epidemic typhus patients between 11 and 58 days after onset of illness is 19 S. This is illustrated by the facts that a) the R. prowazeki agglutination titers of such sera are markedly reduced by contact with the sulfhydryl compound 2-mercaptoethanol and b) when such sera are subjected to electrophoresis and then diffused against a sonic vibrated R. prowazeki antigen, they form typical 19 S γ-globulin precipitin lines. The major R. prowazeki antibody present in sera obtained from Brill-Zinsser disease patients between 8 and 24 days following onset of illness is 7 S. This is illustrated by the facts that a) the R. prowazeki agglutination titers of such sera are unaffected by the sulfhydryl compound 2-mercaptoethanol and b) when such sera are subjected to electrophoresis in agar and then diffused against the supernatant of a sonic vibrated R. prowazeki antigen, they form typical 7 S γ-globulin precipitin lines. Various relationships of 19 S and 7 S antibodies to typhus immune responses are discussed.

Brill–Zinsser disease; the possibility of its occurrence in Britain

1. Of 318 Polish refugees now living in this country 30% gave a history of typhus fever; nearly half of these had complement-fixing antibodies to a titre of 1–5 or more to epidemic typhus. A further 12% without such a history similarly had these antibodies making a total of 22% of 318 refugees. None of the 174 British born controls had antibodies up to this titre.2. Brill-Zinsser disease may occur from time to time among immigrants or visitors from typhus endemic areas to this country, but it is unlikely to be a serious problem.3. The clinical diagnosis of Brill-Zinsser disease may not be easy because the characteristic rash is not always to be seen. Any patient of Eastern European origin or who has a history of typhus complaining of fever and severe headache should be examined serologically by the rickettsial agglutination or the complement-fixation test for specific epidemic typhus antibodies. The Weil-Felix reaction may be positive, but a negative result will not exclude a diagnosis of Brill-Zinsser disease.We acknowledge with gratitude the help, interest and advice of Dr E. S. Murray, of the School of Public Health, Harvard University and Dr Janet Niven and also the technical assistance of Mr J. P. Brooks, FIMLT. We have to thank Messrs Lederle for their kindness in supplying the rickettsial antigens and in addition those who helped us to obtain the specimens and the volunteers who supplied them.

Cutaneous leishmaniasis: confusion with histoplasmosis; report of a case.

When exotic diseases are encountered, they often are unrecognized and ineffectively treated. Leprosy, plague, and epidemic typhus or Brill's disease are well-known examples. In recent years, epidemic hemorrhagic fever, schistosomiasis, and leishmaniasis¹have attracted attention in this respect in military personnel and others who return from endemic areas. The index of suspicion is low, and diagnosis may be difficult when months or years elapse between the time of infection and the appearance of signs or symptoms, as may happen in typhus, leprosy, or leishmaniasis. This time interval often is called the incubation period.²However, it is more likely that the microbes lie dormant in the body until some precipitating cause favors their multiplication, pathogenicity, and the beginning of an incubation period. A healthy girl, aged 14, noticed a pimple on her chin that slowly grew larger. She requested its removal, but her physician demurred. After three months it

ANOTHER CASE OF BRILL-ZINSSER DISEASE IN BRITAIN

ANOTHER CASE OF BRILL-ZINSSER DISEASE IN BRITAIN

The incidence of epidemic typhus antibodies in individuals born in Eastern Europe.

Excerpt Since Brill's original paper1in 1910, and the definitive work by Zinsser2that followed, many cases of Brill's disease have been reported in the medical literature.3-8With the increased infl...

Typhus fever (Brill's disease) complicated by diabetes insipidus: report of a case.

Typhus fever (Brill's disease) has been reported only sporadically from areas other than the coastal region of the northeastern United States. As suggested by Brill 1 and Zinsser 2 and established by Murray, 3 cases of recrudescent epidemic typhus would be expected to occur in all localities to which persons from foci in the Old World have migrated. To our knowledge, this is the first case of typhus fever reported from the Middle West despite the presence in this region of a large population of eastern European origin. This patient also showed unusual features including a transient diabetes insipidus. A 51-year-old white male machinist was brought to the Henry Ford Hospital by his family on April 18, 1953. Five days prior to admission there was sudden onset of chills, fever, sweating, malaise, muscular aching, and a nonproductive cough. He was given penicillin by his family doctor for three successive days

Epidemic-typhus antibodies in human subjects in Boston, Massachusetts.

WHEN a clinician is consulted by a patient who formerly lived in an epidemic typhus zone and who now has fever, headache and possibly a rash, he must include Brill's disease in his differential diagnosis.1 , 2 The confirmation or elimination of the diagnosis of Brill's disease depends on the use of the complement-fixation test with epidemic typhus antigen.1 , 3 The interpretation of the results of the complement-fixation test is influenced by Zinsser's concept,4 which postulates that a patient with Brill's disease has previously suffered an attack of louseborne typhus fever. This hypothesis has been considerably strengthened by recent studies.1 2 3 Anyone suspected of . . .

Undiagnosed or subclinical Brill's disease?

Undiagnosed or subclinical Brill's disease?

Brill's disease. IV. Study of 26 cases in Yugoslavia.

IN 1934 Zinsser defined Brill's disease as sporadic typhus occurring in the absence of lice among immigrants to the United States from the typhus-ridden areas of southeastern Europe.1 Subsequently, physicians in Switzerland,2 France,3' 4 England,5 and Portugal6 reported occasional cases of Brill's disease among immigrants and displaced persons from the typhus regions of Europe. There are no reports, however, that Brill's disease has been recognized as such in any area where typhus fever actually occurs in epidemics among the local population. If Brill's disease is indeed a recrudescence of typhus in individuals who previously have had the disease, as postulated by Zinsser,1 then it should be occurring at the present time in those parts of the world where typhus epidemics have been widespread in the past 25 to 50 years. To investigate this possibility, we undertook a search for Brill's disease in Bosnia, Yugoslavia, where we know from

A CASE OF BRILL'S DISEASE IN LONDON

A CASE OF BRILL'S DISEASE IN LONDON

BRILL'S DISEASE

Brill's disease has been defined as a typhus-like illness occurring chiefly among the immigrant populations of the Northeastern coastal cities of the United States.1In this paper and one which is to follow2attention is directed to recent clinical and laboratory studies of Brill's disease which emphasize that: (1) the present diagnosistic criteria must be revised; (2) the reported incidence of Brill's disease may be expected to increase; (3) Brill's disease may indeed be important in initiating new epidemics of louse-borne typhus, and (4) the etiologic agent, isolated from 7 patients, is indistinguishable from that of classic epidemic typhus. HISTORY During an epidemic of typhoid in Mount Sinai Hospital, New York, in 1896 Nathan Brill became convinced of the specificity of the Widal test, which had just been described. Brill's curiosity was aroused when he observed sporadic cases of an atypical typhoid-like disease in which the Widal reactions

Aureomycin Employed Locally in Painful Mouth Ulcerations: (Stomatitis Aphthosa or Periadenitis Mucosa Necrotica Recurrens)

Aureomycin, the antibiotic derived from cultures of the mold known as Streptomyces aureofaciens, has shown promise of being an effective chemotherapeutic agent in many diseases produced by gram negative, gram positive and Rickettsial organisms. There have been encouraging reports in the recent literature to show that Aureomycin may even prove to be of value in the treatment of some viral diseases. Wong and Cox (1) in their experiments found Aureomycin to have therapuetic activity orally, as well as parenterally, for mice infected with psittacosis or lymphogranuloma venereum virus. Wright (2) et al., corroborated this clinically in a preliminary report on the treatment of lymphogranuloma venereum. The encouraging results they obtained may be even more significant, for because of their laudably cautious approach with a new drug, their dosages (10-20 mg. daily) were low according to more recent schedules. Braley and Sanders (3) in a preliminary report showed effective results of Aureomycin against staphylococci, pneumococci, influenzal and inclusion conjunctivitis. In a later report (4) infections produced by the diplococci of Morax Axenfeld and E. Coli were also found to respond very favorably to treatment. The work of Braley and Sanders is also of great interest as it is the first to show the possibilities of local therapy with Aureomycin. Crooke (5) found Aureomycin effective against the Rickettsia of Rocky Mounted Spotted Fever in a proven case. This was later corroborated by Ross (6) et al., in a larger series of cases. Schoenbach (7) found Aureomycin to exert a beneficial influence on the course of epidemic typhus (Brill's disease), another disease of Rickettsial etiology. Spink (8) et al., found that brucellosis produced by Br. Melitensis underwent dramatic remission while under Aureomycin therapy. Schoenbach and Bryer (9) found that atypical non-bacterial pneumonia gave results which were promising. Finland, Collins, and Paine, Jr. (10) showed beneficial results in treating a wide range of bacterial infections, especially those produced by cocci, and most recently Woodward (11), et al., found that Bacterium tularense was susceptible to Aureomycin. Thus the scope and efficacy of therapy with Aureomycin is ever increasing as the reports continue to be published.

AUREOMYCIN THERAPY OF RECRUDESCENT EPIDEMIC TYPHUS (BRILL'S DISEASE)

The nonepidemic occurrence of typhus among residents of New York City was first reported by Brill in 1898.1A singular selection of persons who had been born in Eastern Europe was described. Later investigations conducted by Maxcy in the Southeastern United States of what was believed to be Brill's disease revealed that endemic typhus in this country was caused by a murine strain of Rickettsia transmitted by the rat flea and was not the louse-borne epidemic type.2In 1933 and 1934, Zinsser, through careful epidemiologic analysis of data assembled in New York and laboratory studies on cases observed in Boston, postulated that Brill's disease was probably a recrudescence of epidemic louse-borne typhus and not the endemic flea-borne type observed in Southeastern United States.3The strains isolated by Zinsser from 3 patients behaved like the European type and supported the belief that Brill's disease represented the classic European

Brill's Disease

THE name Brill's disease is usually given to the isolated cases of typhus fever that occur in the coastal towns of the northeastern United States.1 In 1934 Zinsser2 showed that these cases develop almost exclusively in immigrants from areas where there have been epidemics of louse-borne typhus fever. He demonstrated that the rickettsias that he was able to isolate from a few of these patients resembled the causative agent of epidemic or louse-borne typhus fever but that the disease was not associated with louse infestation. He came to the conclusion that Brill's disease represented a recrudescence of a latent infection . . .

Diagnosis of Brill's disease (American form of European typhus fever) by skin biopsy

1. 1. In the United States at present there seem to be three distinct types of rickettsial disease. Brill's disease (the American form of typhus fever) is found in the northeastern part of the country, murine (flea-borne) typhus occurs mainly in the southeastern part of the United States while Rocky Mountain spotted fever (mite-borne) occurs throughout all parts of the country. 2. 2. The pathological changes caused by Rickettsiae are essentially similar. These characteristic vascular changes consist of vasculitis and perivasculitis. If carefully looked for, the Rickettsiae may be found in the endothelial cells lining the blood vessels. The vessels usually affected are the smaller ones of the brain, lungs, skin and heart. 3. 3. Successful treatment of the typhus group of fevers for the present depends upon starting therapy within the first week following the onset of the disease. Because of the difficulties in carrying out specific complement fixation and agglutination tests for Rickettsiae, a simple method of early diagnosis by skin biopsy is described. 4. 4. Two patients with Brill's disease with characteristic clinical and pathological changes in the skin are presented. In one of the subjects, the rickettsial organisms were identified.

Seminar on Rickettsial diseases

Tropical typhus bears a close clinical resemblance to mild typhus fever, but it does not spread from man to man, nor does it give rise to epidemics. Lice are not the vectors of the virus.There are two kinds of tropical typhus, the W. form and the K. form. In the W. form, the serum agglutinates the ordinary strains of B. proteus X. 19, and Wilson's B. agglutinabilis, but it does not agglutinate the non-indologenic strain, Kingsbury.In the K. form the serum agglutinates the non-indologenic strain, Kingsbury, but it does not agglutinate the ordinary strains of B. proteus X. 19, or B. agglutinabilis.The W. form of tropical typhus is a disease of the house and the town; the majority of those affected are indoor workers, such as clerks and shopkeepers, particularly those who deal with foodstuffs. Maxcy has found that the “endemic typhus” or Brill's disease of the United States, which is clinically identical with tropical typhus, has a similar distribution. The like is true of the typhus-like fever described by Hone in Australia which is probably the same disease as the W. form of tropical typhus.The distribution of the K. form is very different, it is essentially a disease of the open country and affects outdoor workers. It has a patchy distribution and outbreaks occur particularly in areas which, after being cleared of jungle, are allowed to grow up in weeds and scrub. For this reason, we propose the name scrub-typhus for the K. form of tropical typhus. Some of the cases of typhus-like diseases described in India are probably the same as scrub-typhus.An account is given of an outbreak of sixty-one cases of scrub-typhus on an oil-palm estate where cases of the tsutsugamushi disease had occurred among the European staff. This outbreak illustrates the limited distribution of the disease. Five adjacent estates, served by the same hospital, were unaffected, and the outbreak was confined almost entirely to one of the three Divisions of the oil-palm estate. This Division differed from the other two in being overrun with weeds and undergrowth, with which scrub-typhus is always associated. An attack appears to confer immunity. The cases occurred among the newly recruited labourers, those who had been on the estate for a long time escaped infection. Coolies recruited in the Federated Malay States were as susceptible as those from India, from which it appears that the Indian population of Malaya has not been generally exposed to infection. The outbreak consisted entirely of the K. form of tropical typhus (scrub-typhus); there were no cases of the W. form (? endemic typhus).Attention is drawn to the relationship of scrub-typhus and the tsutsugamushi disease by the occurrence of the latter on the same estate. The tsutsugamushi disease of the East Indies and scrub-typhus both occur in circumscribed areas which are covered with undergrowth, and their symptoms are much alike There are, however, the following points of distinction: (a) The fever of tsutsugamushi does not end abruptly at the end of the second week as it does in scrub-typhus, nor is convalescence so rapid. (b) A primary sore and bubo are present in tsutsugamushi, but absent in scrub-typhus. (c) The titre of agglutination with B. proteus, Kingsbury, is low in the tsutsugamushi disease but very high in scrub-typhus. In some cases of the tsutsugamushi disease, the serum agglutinates B. proteus, Kingsbury, in higher dilutions than that of normal persons, but not to titres nearly so high as in scrub-typhus.It is suggested that the two diseases have a similar ˦tiology and that scrub-typhus, like the tsutsugamushi disease, is carried by trombicul˦.

Medical Members' Monthly Meeting

A Meeting of the Medical Members was held in the Reid-Knox Hall of the Institute on March 17, 1939. Dr. J. F. Brailsford was in the Chair, and about 40 members were present. The following cases were discussed: Dr. Barrington Prowse: A case for diagnosis. ? Brill's disease. The patient, a woman of 72 years, developed a slight cough about nine months previously. In December of last year she was debilitated, complained of indigestion, and an increase of the cough. She was rather pale, and had dyspnoea on exertion. Dullness and other signs of fluid at the right base of the right lung were found. Except for a slight leucopenia there were no significant changes in the blood. The radiograph of the chest showed a right pleural effusion and an apparent pericardial effusion. The electrocardiogram was normal. Ten ounces of pleural fluid were aspirated, and the exudate showed a deposit of leucocytes (98 per cent, lymphocytes) and erythrocytes. The organisms were cultured, and tubercle bacilli were excluded after inoculation of a guinea-pig. In February 1939, forty-five ounces of pleural fluid were aspirated, but no organisms were isolated. The radiograph, taken at that time, threw doubt on the existence of the pericardial effusion. There was then the appearance of a solid tumour displacing and rotating the heart towards the right. During screen examination, apical pulsation was visible below and to the right of the tumour.

Endemic Typhus Fever in Texas

Summary Endemic typhus fever in Texas shows but few differences from the same form of the disease in the southern states. It is characterized by its fourteen-day duration, its freedom from complications and sequellae, and its low mortality rate. It apparently spares infancy, childhood, and old age. The majority of the cases occur among workers of the middle class. Its preponderance in this group, particularly in males, appears to be concerned with the occupational background of the disease in that a great majority of the cases originate in shops, grocery stores, grain depots, and warehouses where rat infestation is quite high. At the same time, a considerable number of cases occur among members of the lower social strata whose homes and places of employment show the same degree of rat infestation. Endemic typhus fever in Texas seems to be almost identical with the clinical manifestations of tropical (Malayan) typhus. At the same time, certain distinctions obtain: difference in vector; and failure of the serum of Texas cases to agglutinate the anindologenic strain of Proteus. In addition to the exhibition of established differences between this, the endemic and the epidemic form of typhus, the disease in the American southwest appears to show certain very definite clinical and epidemiological differences from Brill's disease however similar the two are immunologically. A summary of these differences is presented to support an argument for a complete distinction between Brill's disease and endemic typhus fever.

A case of endemic typhus fever (Brill's disease) in a three-and-one-half-year-old child

Summary The first case of endemic typhus fever occurring in a Connecticut child is reported. A three and one-half-year-old white boy developed an attack of acute tonsillitis and pharyngitis followed by lobar pneumonia, and simultaneously developed a rather typical case of typhus. The Felix-Weil agglutination test and the new slide test confirmed the diagnosis.

Studies on the Mechanism of Immunity in Typhus Fever

Summary The sera of guinea pigs infected with or recovered from either variety of typhus (Mexican and European) possess opsonins for Rickettsia prowazeki (Mexican type). The opsonizing properties have been observed in the blood of guinea pigs as early as 96 hours after the inoculation of Mexican typhus virus. In the convalescent and recovered guinea pigs the opsonizing properties of the serum have been found to persist as long as 3 months after the infection. The sera from patients and human convalescents from Mexican typhus, possess opsonizing properties for rickettsial bodies. This property is still apparent in the sera of persons who had had typhus or Brill's disease from 2 to 6 years previous to the date of the present studies. Following vaccination with the formalinized Mexican rickettsiae, opsonins appeared in the blood of a normal man. Anti-proteus X-19 sera fail to opsonize the rickettsiae of Mexican typhus fever.