THE INFECTING AGENT OF EXANTHEMATIC TYPHUS

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Annotations.

THE CENTENARY OF THE LANCET.

"Ne quid nimis."

THE dinner in celebration of the completion of thehundredth year of THE LANCET will be held in Londonon Wednesday, Nov. 28th, 1923. Sir DonaldMacAlister, President of the General Medical Council,will take the chair, supported by the President ofthe Royal Society, the President of the Royal Collegeof Physicians of London, the President of the RoyalCollege of Surgeons of England, the Chief MedicalOfficer of the Ministry of Health, the President of theRoyal Society of Medicine, and the President of theMedical Society of London. Dr. J. H. W. Laing andMr. H. D. Gillies (7, Portland-place, London, W.) areacting as Honorary Secretaries to the DinnerCommittee.

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THE INFECTING AGENT OF EXANTHEMATIC

TYPHUS.

Prof. W. Barykin and Dr. N. Kritsch, of Moscow,have announced the discovery of what they claim tobe "with very great probability" the cause ofexanthematic typhus. Prof. Barykin has for fouryears been investigating typhus. He early foundthat the typhus process so altered the blood-vesselsas to facilitate infection of the blood-stream withmyriad micro-organisms, all of whom the blood oftyphus cases agglutinated. It was in consequence ofthese very various infections that complications wereso frequent, occurring as they do in 30 or even 60 percent. of the cases. Secondary infections being so

frequent, he concluded the true cause could only bediscovered in the body in the early days of the disease,in the pre-eruptive stage, and that he could hope for nohelp from agglutination ’reactions. So he investigated23 cases of pre-eruption typhus, finding nothing then inthe blood but some small elements (0’4-1-5), closelyresembling Rickettsia prowazeki (064.) or young formsof Plotz’s bacillus (0.9-1.9,u); to these he gave thename Microbion typhi exanthematici. He andAfanassieff proceeded then to seek for it in 150 cases ofhuman typhus, in 200 typhus-inoculated guinea-pigs,and in specimens from 11 early post-mortem examina-tions. They found that in the early days of the stageof invasion the bacterium (there seems no occasion forthe term microbion) is so constantly present in theblood of the guinea-pig that, by its presence or

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absence, diagnosis can be definitely made even in thepre-eruptive stage, but the search may last for hours,and many films may have to be examined. It was inthe blood that the bacterium was first found, but itoccurs in far greater numbers in the cells of the brain,the spleen, and the suprarenals, growing within thecells into clusters, and in time killing the cells. Thebacterium is not discoverable during the stage ofincubation, and it could not be found in the organs ofa hundred uninfected guinea-pigs and men. Theinvestigation next concerned itself with lice ; thebacterium was found in the intestinal epithelium andintestinal contents of 1050 of 1500 infected lice ; itcould not be found in lice from uninfected men.Further, in the intestinal contents of 280 infected lice,the bacterium was found in 192 ; it was found in theepithelium in 14 of the infected, in only one of thecontrols. It was difficult to make cultures of thebacterium until Kritsch hit upon the idea of making amedium out of the tissues in which the ., microbion"is, customarily, most plentifully found. A pancreatised,sterile broth being prepared, small portions of brain orspleen were rapidly removed under aseptic precautions,at early post-mortems of men or guinea-pigs dead in thefirst stage of the disease ; these portions were mincedvery finely, mixed with the broth, and tubed. Thetubes were over-layered with paraffin and incubated

1 Archiv flit Schiffs- und Tropen-Hygiene, 1923, Nr. 2.

at 37° C. During the first ten days, the bacteria whicnhad at first appeared, had gradually died out, and thenthe " microbion " might appear ; it begins to grow inthe tissue cells, only later spreading to the fluid. Itbegins as clusters of Gram-negative cocci, very small;later they increase in size and begin to stain withGram. It is non-motile. At 37° C. they remain alivefor 4-6 weeks, but die in an hour at 50° C. ; ; once

established it can be grown on pancreatised spleen-or brain-broth agar, on which it grows, aerobically, inround, glistening colonies. The growth is difficult toemulsify in normal saline ; it will not grow in broth.Lastly, of 22 guinea-pigs inoculated with thesecultures, 14 became infected; their disease, clinically,closely resembled typhus ; few of them died, but inthe ten that were killed at the close of the pyrexialstage there were found—hyperasmia of the spleenfollicles with hyperplasia, hyperaemia of the supra-renals, hyperaemia and oedema of the brain ; in otherwords, the histo-pathology of the infection producedby the bacterium in the guinea-pig is identical withthat originated by typhus in man. On the strengthof these observations Prof. Barykin and Dr. Kritschmake the claim that the bacterium is " very probably "the cause of typhus fever. We call attention to theirinteresting and suggestive observations. In spite ofall the work which has been done upon it, the Rickettsiais not yet firmly habilitated as the cause of typhus.That the blood in typhus patients is invaded by otherorganisms needs confirmation. But the Russianauthors have found a ready means of cultivating theinfecting agent which will pave the way for furtherinvestigation.

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ACID-FASTNESS.

, ALTHOUGH acid-fastness has always been associated: with the fatty constituents of the bacillus, this property, cannot be removed from the organism by extraction

with fat solvents alone. This fact may be consideredwell established, as Dr. J. A. Shaw-Mackenzie remindsus in his letter in another part of this issue. Aronson 1it was who showed that if the organisms are treatedwith an acid in addition to fat solvents the acid-fastness can be completely removed by prolongedextraction. This important piece of work was

confirmed by many workers, including Bulloch andMacleod, Much and Deycke,3 3 and others. Thelatter observers also showed that any organic acidsuch as lactic would answer the purpose. Prof.Dreyer finds that he can remove the acid-fastness bythe action of formalin and fat solvent extraction. Noexplanation is advanced for the action of formalin inplace of the usual acid treatment, but it seems

probable that it may act by virtue of the appreciableamount of formic acid always present in 40 per cent.formalin. If this is the case the action would beanalogous to the reaction of Much and Deycke withlactic acid. The bacilli obtained by this combinedformalin and fat extraction treatment are made intoan antigen apparently possessing valuable therapeuticproperties. Since the discovery and preparation oftuberculin by Koch a large amount of literature hascollected on the methods of preparation of tubercularantigens. By varying the technique each worker hashoped to produce an antigen more sensitive for bothdiagnostic and therapeutic purposes. Gabrilowitsch 4

was probably the first to work on fractional antigens.In 1891 he described a " tuberculum purum," obtainedby extracting bacilli with xylol, ether, chloroform, andalcohol. This preparation was used for therapeuticpurposes. Armand-Delille,s in 1902, worked withether- and chloroform-extracted bacilli, whilst Leberand Steinharter, in 1908, used an antigen prepared’from chloroform-extracted bacilli on 350 patients.

1 Aronson: Berlin. klin. Woch., 1898, xxxv., 484; also 1910,xlvii., 1617.

2 Bulloch and Macleod : Jour. Hyg., 1904, iv., 1.3 Much: Beitr. klin. Tuberk., 1911, xx., 345; also 1911,

xx., 353.4 Gabrilowitsch : Wien. med. Woch., 1891, No. 4.

5 Armand-Delille: Arch. Exp. Path., 1902.6 Leber and Steinharter : Munch, med. Woch., 1908, No. 25.