B74 191 55 IN MEMORY of Dr. Clement A, Whiting PRESENTED BY Dr. Lillian Burlier FIG. A. Spirochaeta pallida and Spirochaeta refringens. Smear from a primary syphilitic sore, fixed in osmic vapour and stained by Giemsa's method (leucocytes necessarily overstained) . I FIG. B. Spirochaeta pallida in liver of syphilitic foetus. Stained by Levaditi's silver method. UBF/iFY OF COLLEGE op GG F H Y s f r,f A f/s J& r I ROCHET ES 3 ,4 REVIEW OF RECENT WORK- ORIGINAL OBSERVATIONS I. BY W7 CECIL BOSANQUET, M. A., M. D. FELLOW OP THE ROYAL COLLEGE OF PHYSICIANS. LONDON; FORMERLY FELLOW OF NEW COLLEGE, OXFORD ILLUSTRATED PHILADELPHIA AND LONDON W. B. SAUNDERS COMPANY 1911 * UU O:n\<0 nO 303JJOO i/;KMcM-iS Copyright, 1911, by W. B. Saunders Company PRINTED IN AMERICA PREFACE HAVING had occasion to study the literature bearing on the subject of Spirochaetes in connection with obser- vations which I made on two species of this genus, I was struck with the voluminous and at the same time scattered mass of papers to which reference had to be made. I therefore thought it might be useful to others if, instead of merely laying aside the abstracts which I had made, I put them together in the form of a small book. The Spirochaetes present a problem of considerable interest. Their position in the scale of living things is still undecided, and there is a tendency to place them in a position between the bacteria and the protozoa. My own observations would lead me to regard them as much more closely allied to the former than to the latter. I have endeavored, in the first part of this work, to compare the statements of different writers on the morphology and behavior of Spirochaetes, with a view to establishing, if possible, the features characteristic of the genus. In the second part, I have dealt with the separate species described. I have confined myself to very brief descriptions of the various organisms and of the methods employed for examining them, as those who are interested in particular species or methods will in any case refer to the original papers. Their task will, I hope, be facilitated by the bibliography here appended. This is by no means exhaustive, as many papers are published in unattainable periodicals, and I 5 6 PREFACE. have included comparatively few references to articles which I have not myself consulted either in the original or in abstract. I hope, however, that the more impor- tant papers are included. My thanks are due to Mr. A. N. Leathern for the loan of specimens, and to Professor E. A. Minchin for the very kind loan of books from his library and of specimens in his possession, as well as for permission to use his laboratory for my own small researches. LONDON, ENGLAND, W. C. B. May, 1911. CONTENTS. SECTION I. GENERAL CHARACTERS OF SPIROCH^ETES. PAGB BIOLOGICAL POSITION OF SPIROCH^ETES - . . n MORPHOLOGY OF SPIROCH^TES 16 Large Spirochaetes 16 Shape . . . '. = .'... 18 Movements 19 Structure 19 Undulating Membrane 20 Nucleus 21 Small Spirochaetes ...*..- 25 Movements 25 Structure ..... 26 VARIABILITY OF FORM 29 HABITAT 31 CULTIVATION 31 MULTIPLICATION AND DEVELOPMENT 33 Conjugation 37 Encystment . , . - 38 Sporulation , 40 Coccoid Forms 40 ASSOCIATION WITH OTHER ORGANISMS 42 PATHOGENICITY 45 Relapsing Fever . 45 African Tick Fever 46 Other Forms of Current Fevers 47 Syphilis 48 Yaws (Pian, Frambcesia) 57 Lymphadenoma 57 Ulcerative Granuloma 58 Vincent's Angina 58 Other Diseases in Man 59 Diseases of Animals (Fowls, Cattle, Bat, Pig, Mouse) . . 60 SUMMARY OF PHENOMENA OF PATHOGENICITY OF SPIROCH^TES 62 8 CONTENTS. PAGE METHODS OF STAINING 63 Giemsa's Stain 63 Other Methods 64 Impregnation with Silver 65 Indian Ink Method 66 EXAMINATION OF LIVING SPIROCH^TES 66 Dark-field Examination 66 Intra-vitam Staining 67 PSEUDO-SPIROCH^TES 67 CLASSIFICATION ' 69 SECTION II. SYSTEMATIC DESCRIPTION OF SPECIES. LARGE SPIROCH^ETES . , 73 Spirochaeta Plicatilis 73 Spirochaeta Daxensis 76 Spirochaeta Balbianii 77 Spirochaeta Anodontae (Spirochaeta Spiculifera) .... 79 Spirochaetes in Various Molluscs 82 Spirochaeta Pinnae 84 Spirochaeta Mactrae 84 Spirochaeta Pectinis 86 Spirochaeta Interrogationis 86 Spirochaeta Polyspira 86 SMALL SPIROCH^TES OR SPIRILLA 86 Spirochaeta Obermeieri 86 Spirochasta Duttoni (Spirochaeta Novyi, Spirochaeta Carteri) 88 Spirochaeta Pitheci 90 Spirochaeta Anserina 90 Spirochaeta Gallinarum 91 Spirochaeta Lagopodis 93 Spirochaeta Lovati . 93 Spirochaeta Vesperuginis 93 Spirochaeta Lutrae 94 Spirochaeta Theileri and Allied Forms 94 Spirochaeta Suis 95 Spirochaeta Laverani . 96 Spirochaeta Muris 96 Spirochaeta Minor 97 Spirochaetes in Mouse-cancer 97 Spirochaeta Gondii 98 Spirochaeta Culicis 98 CONTENTS. 9 PAGE Spirochaeta Minei 98 Spirochasta Gadi 98 Spirochaeta Pelamydis 99 Spirochaeta Jonesii 99 Spirochaeta Hartmanni 99 Spirochaeta Bufonis , . . . . 99 Spirochasta Buccalis 100 Spirochaeta Dentium 101 Spirochaeta Vincenti 102 Spirochaeta Gracilis -..'.' 102 Spirochasta Schaudinni 103 Spirochaetes in Gangrenous Processes, Haemoptysis, etc. . 103 Spirochaeta Pseudopallida 104 Spirochaeta Bronchialis 104 Spirochaeta Microgyrata ....... 105 Spirochaetes in Small-pox .............. 105 Spirochaetes in Vaccine Lymph ....... ' . . .106 Spirochaeta Refringens 106 Spirochasta Balanitidis 107 Spirochaeta Pallida ...'... 108 Spirochaeta Pertenuis 112 Spirochaeta Obtusa 113 Spirochaeta Lymphatica 113 Spirochaeta Aboriginalis 114 Spirochaeta Interrogans 114 VARIOUS DOUBTFUL SPIROCHAETES AND SPIRILLA 115 BIBLIOGRAPHY 117 BIBLIOGRAPHIC INDEX 137 INDEX 143 SPIROCH/ETES. A REVIEW OF RECENT WORK. SECTION I. GENERAL CHARACTERS OF SPIROCH^TES. BIOLOGICAL POSITION OF SPIROCH/ETES. The name Spirochaeta was first invented by Ehren- berg in 1833 for the organism discovered by him and named Spirochceta plicatilis. It was regarded by him as a protozoon, but its relationship to other members of this order was not clearly determined; and while some writers considered that spirochaetes were members of the class Trypanosomidae, others regarded them as really bacteria. Indeed, in some of the earlier text- books of bacteriology the term spirochaete was applied to a number of spirillar forms. The great increase of interest which has recently been aroused in the spirochaetes dates from the discovery by Schaudinn in 1905 of the spiral organism associated with syphilis, which he assigned to this class. The attention thus directed to these minute organisms has resulted in the discovery of a large number of forms, some associated with conditions of disease, others living apparently as harmless saprophytes. Among the latter must be classed the large varieties present in several genera of shell-fish. The relationship existing between the larger and the smaller spirochaetes has not been thoroughly eluci- 12 SPIROCILETES. dated. Indeed, owing to the minute size and feeble staining properties of the latter organisms, it is difficult to recognise more than their shape and movements. Details of finer structure, which might throw light on their true nature, are as yet wanting. The type of the smaller spirochaetes may be seen in the organism associ- ated with the disease called relapsing fever, usually called Spirillum or Spiroch&ta obermeieri, after its dis- coverer, but perhaps more correctly on the basis of recent biological nomenclature, Spirochceta recurrentis, the spirochaete of recurrent fever. This organism was for many years regarded as a bacterium and placed in the same class as the spirillum or vibrio of cholera. It does not seem proved so far that this classification is incorrect, and the question is still at issue, names of weight being found on both sides in the controversy as to the protozoan or bacterial nature of the smaller spirochaetes. Even the larger spirochaetes have by some been assigned to the bacteria as, for example, by Schwellengrebel, who points out the close resemblance between an organism, such as Sp. balbianii and some of the larger spirilla, such as Spirillum giganteum (Spm. volutans) . I hope to show in subsequent pages reasons for thinking that this view is probably correct. With regard to the larger spirochaetes, it is certainly natural to anyone who observes the extreme activity of movement exhibited by such an organism as Sp. anodontcz, to regard it as prima facie an animal. This vigour of movement, however, does not by itself con- stitute an argument of appreciable weight, for among the spirilla, which are generally admitted to be bacterial, very active movement may be observed. Nevertheless, there is some difference between the two classes in this respect; for while the spirochaetes perform vigorous lashing movements in which the whole body is bent to- GENERAL CHARACTERS OF SPIROCTLETES. 13 and-fro like the lash of a whip, the spirilla confine them- selves almost entirely to a rapid "cork-screw" motion, with little alteration in the long axis of the body. A certain degree of the latter motion may, however, at times be observed in them, so that this difference is rather quantitative than one of kind. Failure to cultivate spirochaetes, large or small, in artificial media has been urged as a reason for regard- ing them as protozoa and not bacteria, but this argu- ment again is of little weight, since, not all known bacteria can be grown artificially (e.g., B. leprcs), and the quality of adaptability to cultivation in the labora- tory can hardly be looked upon as essential to this or any other class. Indeed, some of the protozoa can be cultivated; for example, some forms of amoebae and of flagellata. The curious arrangement of the staining material in the body of the larger spirochaetes, which has been regarded as constituting a special nucleus, has been held to prove their animal nature ; but there is at present too much uncertainty as to the constitution of this staining substance and its formation in these organisms to allow of any great weight being assigned to this peculiarity for purposes of classification. Schwellengrebel states that a spiral filament similar to that found in Sp. bal- bianii may be found in Spirillum giganteum, though his statement has not so far been confirmed. Certainly a resemblance exists between the form taken by the staining substance in this spirillum and that seen in some spirochaetes (Figs. 8,9,10). Other peculiarities of the large spirochaetes which are regarded as protozoan characteristics are the asserted existence of an undulating membrane, the lack of flagella, and the habit of longitudinal division for pur- poses of multiplication. With regard to the first of 14 SPIROCILETES. these, doubt has recently been thrown on the identity of the appearance seen in spirochaetes with the true undulating membrane of such organisms as trypano- somes. Consequently it is premature to regard this as a distinctive feature. Flagella have been described in some of the smaller spirochaetes, but with doubtful certitude ; they appear to be absent in the larger forms. Such absence does not seem to constitute an argument for or against their vegetable nature. The method of reproduction even in the larger spirochaetes is still dis- puted, but there appears to be a balance of authority in favour of longitudinal division as the usual occurence, and I have myself seen an instance of what appeared to be this procedure in Sp. anodonta. l The occurrence of encysted forms in such species as Sp. balbianii has also been held to prove them to be protozoa, but the real nature of the curled up forms is as yet uncertain, and it is not unknown for vegetable organisms to enter upon a resting stage. The strongest argument which could be brought for- ward in favour of the animal nature of the spirochaetes would be the occurrence of conjugation a distinctive protozoan characteristic. This phenomenon has been described as occurring in several species of spirochaetes (see p. 37), but the evidence adduced is unconvincing. The nature of the smaller spirochaetes is still more un- certain. The points about them which seem to place them in the same class as the larger spirochaetes are their general shape and movements, the occurrence of longitudinal division, the asserted possession by some of them (not by all) of an undulating membrane, and the absence of flagella. Their resemblance to the larger forms in the matter of general shape and movements is 1 If Schmeidlechner's observation of bacilli which divide lon- gitudinally is confirmed, this mode of multiplication cannot be considered a distinguishing feature of animal organisms. GENERAL CHARACTERS OF SPIROCILETES. 15 certainly striking, but is not in itself a strong argument for combining them in a single group. The possession of an undulating membrane by these minute organisms is certainly doubtful, and the presence or absence of flagella has little weight in this connection, except as an arbitrary ground of classification. The question as to the multiplication of these little organisms by lon- gitudinal or transverse division is still undecided; but the formation of a fine thread at the point of divi- sion seems to be established, whereas bacteria divide by means of a distinct septum. The argument from the possibility of cultivation on artificial media has just been noticed to be valueless, and indeed some of the small spirochaetes have, if the claims of various writers are to be believed, been successfully grown in the lab- oratory. The conveyance of some of the pathogenic spirochaetes by biting insects (ticks) has been used as a proof of their animal nature, but can hardly be re- garded as a conclusive argument ; for it has not been proved that they undergo any constant process of development within these hosts. A stronger argument has been drawn from the action of certain chemical reagents on small spirochaetes. Thus it is said that cobra-venom, taurocholate of sodium, saponin, and pancreatic extract destroy spirochaetes and protozoa, but do not affect bacteria. Spirochaetes are little affected, however, by distilled water or by concentrated salt-solution. It is also asserted that whereas bacteriolysins are thermostable (not destroyed by heat), the corresponding substances which act on spirilla (spirochsetes) are thermolabile, thus resembling the haemolysins. On the other hand, the action of immune serum in producing agglomeration or aggluti- nation of spirochaetes is like that exerted upon bacterial organisms; and Sp. pallida if this be really the cause 1 6 SPIROCILETES. of syphilis gives rise in the body of the human host to the formation of an antibody (copula or amboceptor) as do the pathogenic bacteria. This form of immune sub- stance has not been found in infections caused by protozoa. It is to be hoped that further study of the life-history and development of spirochsetes will throw definite light on their true biological position. If the observa- tjon of Leishman on the development of Sp. duttoni into coccoid forms be confirmed, and if a similar change can be shown to take place in other spirochaetes, as is suggested by my own experience, their close relationship to the bacteria will be manifest. 1 In attempting to assign the spirochastes either to the protozoa or the bacteria, it must be borne in mind that there are several other kinds of organisms known, about which there is equal uncertainty as to their correct classification. Indeed, it has to be con- fessed that there are no definite criteria, by which to draw a line of division between the lowest forms of animals and plants. This must be regarded as al- most inevitable, since both animal and vegetable kingdoms present to us as their lowest members uni- cellular organisms of very simple structure, while it is at least probable that at the beginning of things a single form of living matter gave origin to both the great divisions, animals and plants. MORPHOLOGY OF SPIROCHAETES. The minute structure of the larger spirochaetes has been carefully observed in the species Sp. balbianii and 1 The suggestion that spirochaetes are stages in the development of a bacterial organism is referred to on page 42. Schaudinn's original view that they constitute a stage in the life-history of a trypanosome is now generally supposed to have been based on a mistaken identification. (See Novy and MacNeal, Journ. Infect. Dis., 1905,11,256; Sergent, Edm. and M., Ann. d. VInst. Pasteur, 1907.) GENERAL CHARACTERS OF SPIROOELETES. 17 Sp. anodonta, which are easily obtainable, as well as, to a less extent, in the typical species Sp. plicatilis. De- FIG. i. FIG. 2. FIG. 3. FIG. i. Spirochaeta plicatilis : Schematic. (After Doflein.) PIG. 2. Spirochaeta balbianii, showing so-called "undulating membrane." (Perrin.) FIG. 3. Spirochaeta anodontae, with "undulating membrane." (Keysselitz.) scribed in general terms, they are elongated, vermi- form organisms, endowed with active movement. They are said to be flattened from above downward, thus l8 SPIROCILETES. resembling strips of ribbon rather than threads of cot- ton in form. They are further stated to be furnished with an undulating membrane and with a complicated nuclear apparatus (see Figs, i, 2, 3). Shape. The length of these organisms is usually not less than twenty times the breadth, Sp. balbianii for example reaching a length of TOO/*, while its breadth is usually less than 5/1. The length of Sp. plicatilis may reach 500^. I have found specimens of Sp. anodontcs nearly 130;* in length, without any signs of division at any point ; but unusually long forms are regarded by some writers as about to enter upon the process of fission. It is difficult to ascertain whether these organisms are naturally flattened in form, as during active move- ment, while they are alive, the exact contour cannot be made out, while some flattening might easily take place after death in the process of fixing. Sp. balbianii is said by Perrin to be round in section. Fantham and Gross have succeeded in obtaining transverse sections of spiro- Cn3etes > which suggest a form such as that chaete in trans- shown diagrammatically in figure 4 a verse section. .. , . . , .. , , rounded organism with a loose sheath which may project on one side. The organism might thus appear flattened in one direction, and round in another; and the opposing views might thus be har- monised. Gross regards the projecting portion as con- stituting a crest or comb. The ends of the organism may be either blunt or pointed (Figs. 2, 3). It is uncertain whether this fea- ture is always constant in the same species. Thus, in the case of Sp. anodonta Schellack would constitute the individuals with pointed ends 1 a separate species (Sp. *Cf. Castellani's distinction of Sp.obtusa and Sp. acuminata, page 113. GENERAL CHARACTERS OF SPIROCILETES. IQ spiculifera) . Certainly this form tends to be shorter on the average than the form with blunt extremities; but some overlapping may occur, and it seems prema- ture to make a specific division on this ground alone (see page 81). Movements. The movements of the large spirochaetes are very rapid under normal conditions, but become slower as vitality diminishes. They are of three main kinds: (i). Lashing movements, such as are performed by an eel suspended on a hook, the whole body being bent from side to side, taking the forms of a circle or an S or a figure of eight. These are most evident when the spirochaete is attached in some way by one extremity or hindered in its progression. (2). Undulating move- ments, which are compared to the flapping of a sail "in the wind," a wave passing from one end of the organism to the other and being rapidly succeeded by other similar waves in the same direction. It would seem that the direction may be reversed. (3). A rota- tory movement, like that of a cork-screw when pushed into a cork, the whole spirochaete turning on a longit- udinal axis passing through the centres of the spirals (the axis of the helix). Special forms of movement are described by Perrin as taking place in the process of encystment, one end of the organism gliding down the side of the body, to be followed by a similar movement of the other extremity, and finally by a continuous movement by which the creature is rolled upon itself. Structure. Examined microscopically, the structure of the spirochaete is seen to consist of an external coat or periplast, which contains an inner protoplasmic sub- stance or entoplasm. The periplast may be prolonged at one or both ends of the organism into an appendage, which some authors regard as a flagellum. This iden- tification seems incorrect. It has also been suggested 20 SPIROCILETES. that these appendages are formed in the process of division of the spirochaste, and thus may not be per- manent. Perrin speaks of the periplast retaining its form after the entoplasm has escaped from within it and become 'encysted. Attached to the periplast or forming part of it is the so-called undulating membrane (Figs. 2, 3). This is described as running round the body of the spirochaete in a spiral direction, and as being bounded at its external margin by a darkly staining fibril (randfibrille) , while other fibrils may be seen running in it parallel to the marginal one. The latter is said to be connected at its extremities with two darkly staining particles, situated at the ends of the spirochaete, called by Gonder bleph- aroplasts, on the analogy of the blepharoplast of trypanosomes. The nature of this undulating membrane has been called in question. Laveran and Mesnil regard the appearance thus named as produced by the existence of a loose sheath outside the spirochaste ; and a sheath has been described in several of the smaller spiro- chaetes by different writers (see p. 26). Schellack believes that the so-called undulating membrane is an artifact, produced in the process of fixation. My own ex- perience with Sp. anodontcs would seem to support this view, as I find that the better the specimen is fixed, the less frequent are individuals which appear to have undulating membranes. Nor does the appearance when present correspond at all closely with that seen in trypanosomes, the marginal fibril being often seen as a separate structure with no membrane visible between it and the body of the spirochaete, and often also appearing at only one or two points, not as a struc- ture continuous all along the organism. The appear- GENERAL CHARACTERS OF SPIROCILETES. 21 ance of this fibrillary structure at the outer margins of the curls presented by the spirochaste suggests that it may be a portion of periplast which has become fixed to the slide, and has thus remained fast, in a figure cor- responding with the curves in which the creature lay at the moment of death: then as drying took place and the body of the spirochaete shrank, the latter straight- ened out somewhat, while the adherent periplast re- mained. Sometimes, however, the "membrane" runs in a straight line between neighbouring coils, having apparently shrunk more than the body-substance. Borrel and Cernovodeanu, however, state that they have seen an undulating membrane in living specimens of Sp. anodontcB. Perrin thinks that the undulating membrane is not of much importance as an aid to locomotion in Sp. balbianii. With regard to the structure of the entoplasm and its contents an equal degree of uncertainty prevails. Perrin described in Sp. balbianii the existence of pecu- liar form of nucleus. It consists, according to this writer of a spiral band of achromatic substance (karyosome) on which appear at intervals masses of staining material (chromatin ?) . These latter usually, in resting organ- isms, take the form of rods arranged so as to lie trans- versely, more or less at right angles to the main axis of the spirochaete (Fig. 5) ; but when fission is about to occur, the rods assume other forms and undergo divi- sion. Fantham confirmed Perrin's statements. Keys- selitz described in Sp. anodonta balls and rods of chro- matic material (Fig. 6) , and thinks that there may be a spiral arrangement such as Perrin found, but did not himself observe it. Schellack confirms the existence of bands of chromatin, but denies that they are connected 22 SPIROCILETES. by any spiral thread. He regards the spirochaete as made up of a series of chambers, in which these rod- shaped nuclei lie, and thinks that the increase in length of the spirochaete is effected by a multiplication of these FIG. 5. FIG. 6. FIG. 5. Spirochaeta balbianii, showing nuclear (?) bands. (Perrin.) FIG. 6. Spirochseta anodontse, with irregular masses of staining substance. (Keysselitz.) chambers, taking place especially at the ends. In some cases the staining substance appears as a central continuous band or rod, running along the middle of the body of the spirochaete (Fig. 7). GENERAL CHARACTERS OF SPIROCILETES. 23 The appearances seen in Sp. plicatilis are some- what different (Fig. i). Here the organism appears to be furnished with a series of rounded nuclei, distributed FIG. 7. Spirochseta balbianii; rod-shaped "nucleus." (Perrin.) fairly evenly throughout its length. The general out- line of the spirochaete is also different, since it shows not only the large undulations seen in Sp. anodonta and balbianii, but also a series of smaller waves super- imposed upon the others. It has no undulating mem- FIG. 8. Spirochaeta anodontae, showing irregular granules of staining material. brane, as depicted in Doflein's illustration indeed, judged merely by a comparison of this with the illus- trations of Sp. balbianii, given by Perrin or Fantham, it SPIROCILETES. is difficult to believe that the two organisms belong to the same genus. So far as I can judge from my own observations, the peculiar aggregations of staining material seen in Sp. FIG. 9. FIG. 10. FIG. 9. Bacteria from rectum of ox for comparison with Fig. 8. FIG. 10. Spirillum volutans for comparison with Fig. 8. anodonta are not to be looked on as nuclei. They are irregular in shape and quite unlike the nuclei of pro- tozoa. They seem to occur for the most part in organ- isms which are degenerating (so-called "involution 9 FIG. ii. Filaments of algae: a, Resembling fusiform bacilli; b, showing central staining rod; c, with series of chambers; d, e, curved like spirochaetes. forms ") . In other instances they may point to a forth- coming developmental change (p. 40). The great majority of the organisms in my experience stain GENERAL CHARACTERS OF SPIROCH^TES. 25 homogeneously like bacteria. In some a vacuolated structure may be made out, resembling that seen in some of the larger spirilla. In the larger bacteria also granules or masses of staining material may be seen, not unlike those in Sp. anodontce (see Figs. 8, 9, 10). Fila- ments of algae may also show features bearing a close resemblance to some of those described in spirochaetes (Fig. n). In the case of the smaller spirochaetes the minute size of the organisms renders the investigation of their intimate structure almost impossible. The general shape is the same as that of the large varieties, accord- ing to most writers, but it is even more difficult to make sure of their flattened shape than in the larger organisms. Some are definitely stated to be round in section, e.g., Sp. pallida, but many authors follow Vuillemin and Schaudinn in placing this and a few others in a separate genus, Treponema, partly on this account. The movements of the small spirochaetes are the same as those described above. An additional form of movement is, however, described by Plaut in Sp. vincenti and called by him "euglenoid" movement: it consists in the appearance of a thickening at one point in the body of the organism and the gradual pas- sage of this swelling from one end to the other. Krzys- talowicz and Siedlecki describe a somewhat similar com- pression and extension of the body of Sp. pallida when it is in motion. It must be remembered that in these mi- nute thread-like organisms it is impossible to distinguish under the microscope between rotatory movement and undulation. Lashing movements are said to be less marked in treponema: indeed, the movements Sp. pallida (Trep. pallidum) are altogether sluggish. 26 SPIROCHjETES. Of the actual structure of these tiny organisms little can be said. An undulating membrane has been de- scribed in some species, as by Gonder in Sp. vesperu- ginis, by Prowazek in Sp. gallinarum, by Hoffmann in Sp. buccalis, and by Schaudinn in Sp. refringens. On the other hand, Levaditi denies that Sp. refringens possesses an undulating membrane, and this structure has never been seen or described in Sp. obermeieri, Sp. pallida, Sp. muris, the spirochaete of ulcerating cancer, etc. When it is borne in mind that one of the favourite stains for spirochaetes, Giemsa's, is deposited round, as well as in, the struct- ures which attract it, it is easy to imagine a FIG. 13. FIG. 14. FIG. 12. Spirochaetaduttoni; appearance of a sheath. (Stephens.) FIG. 13. Spirochaeta buccalis. Sheath. X22SO. (Prowazek.) FIG. 14. Anthrax bacillus, with appearance of a sheath. (Ascoli.) possible source of error in observing this point in a minute organism of spiral shape. Most of the illustra- tions of undulating membranes in these small spiro- chaetes are far from convincing. A definite sheath has been described in some forms, e.g., in Sp. duttoni by Stephens (Fig. 12), in Sp. pallida by Leuriaux and v. Geets, in Sp. buccalis by Prowazek (Fig. 13), in the spirochaste found by Baruchello and Pricolo in equine pneumonia, and in an unidentified spirochaete found by Kenrick in a case of fever. An appearance resembling a sheath, may be found in bac- teria, as is shown in the accompanying illustration of GENERAL CHARACTERS OF SPIROCH^TES. 27 Bacillus anthracis (Fig. 14), taken from a paper by Ascoli. 1 Terminal flagella are described in some forms, e.g., Sp. obermeieri (Reichert), and Sp. duttoni (Stephens), FIG.. 15. Spirochaeta pallida, with terminal filament; so-called autogamy stage. (Prowazek.) but these are generally regarded (as by Schaudinn and by Krzystalowicz and Siedlecki) as mere prolongations of the periplast (Figs. 15, 16, 17, 18). Lateral flagella have also been described (e.g., by Fraenkel in Sp. FIG. 16. FIG. 17. FIG. 18. FIG. 19. FIG. 1 6. Spirochaeta, media of stomatitis, with terminal fila- ment. X225O. (Prowazek.) FIG. 17. Spirochseta duttoni (terminal filament). (Schellack.) FIG. 18. Spirochaeta balbianii, with terminal "brush." (Schellack.) FIG. 19. Spirochaeta recurrentis; splitting of penplast. (Schellack.) obermeieri}, but are probably due to injury in fixation of specimens (Fig. 19). Small granules or nodules, appearing rather larger in diameter than the rest of the spirochaete, are commonly *Centralbl.f. Bakt., 1908, XLVI, 186. 28 SPIROCH^TES. seen. A single terminal nodule has been noted, for example, in Sp. duttoni (Button, Todd and Tobey), Sp. pallida (Dudgeon), Sp. pertenuis (Castellani) , and in FIG. 20. FIG. 21. FIG. 20. Spirochaete of ulcerating cancer (left) and Sp. refringens (right), with terminal nodules. (Schaudinn.) PIG. 21. Spirochaeta pertenuis with terminal granules. (Castellani.) many other forms (Figs. 20, 21, 22, 23). Two nodules may be placed toward the same extremity (e.g., Sp. aboriginalis, Bosanquet) . One or more of such dots or masses may also be seen (Figs. 24, 25), in the central FIG. 22. FIG. 23. FIG. 24. FIG. 25. FIG. 22. Spirochasta aboriginalis with granules and "loop." (Bosanquet.) FIG. 23. Spirochaeta duttoni. Injured specimen. (Schellack.) FIG. 24. Spirochaeta duttoni, with masses of staining sub- stance. Supposed to represent nuclei. X22oo. (Mayer.) FIG. 25. Spirochaeta lagopodis, showing dots resembling nuclei. (Fantham.) part of the organism. These have been supposed to represent nuclei, and Herxheimer has indentified a kineto-nucleus, a tropho-nucleus and centrosome a GENERAL CHARACTERS OF SPIROCILETES. 29 degree of refinement which at present seems fanciful. These little nodular bodies sometimes appear to be attached to the side of the spirochsete rather than to lie in its body (Fig. 26). It is not unusual to find spirochastes which resemble a chain of granules set like a string of beads (Fig. 27) : these are usually regarded as degenerated forms ("moniliform degeneration"), but the possibility that these organisms break up into FIG. 26. FIG. 27. FIG. 26. Spirochaeta gallinarum, with lateral nodule. (Pro- wazek.) FIG. 27. Spirochaeta obermeieri, showing breaking up of body into rods and granules (diagrammatic). minute bodies capable of growing into other individu- als, when placed in favourable circumstances, cannot be excluded. A loop has been described as present at one end of the spirochaete in certain forms, e.g., in Sp. pallida (Reuter), Sp. pertenuis (Castellani) . Masses of organisms may be found tangled together, as in Sp. pallida (Bandi and Simonelli), Sp. dentium (Miller), Sp. obermeieri (Zettnow), and Sp. duttoni (in the tick, Koch) . I have once seen a large number of Sp. anodontcz forming a tangle. VARIABILITY OF FORM. A very important question is that of the possibility of some degree of change of form in a single species, since upon the negative reply to this question must at present depend the possibility of accurately distin- 30 SPIROCIOETES. guishing and classifying these organisms. The exist- ence of somewhat different forms side by side has been already referred to in connection with Sp. anodontaz. It is remarkable that two forms also exist together in Tapes laeta (Sp. tapetos) and in other molluscs (Schellack) . The coexistence of the two forms, Sp. pallida and Sp. refringens, in syphilitic lesions is well known. Two forms are described by Loewenthal in ulcerated cancers , one larger and the other smaller, and two also by Branch in cases of haemoptysis, and by Moritz in decaying potato (5^?. polyspird). Castellani found four forms associated in his cases of haemoptysis. The question of change of form has been most care- fully studied in connection with S^. pallida. Bertarelli and Volpino describe intermediate forms between Sp. pallida and Sp. refringens, and Bosc suggests that refringens is a degenerative form of pallida. Schere- schewsky noted irregular forms of Sp. pallida in cul- tures, and was struck by the resemblance of some of these to refringens, and Sobernheim and Tomasoli also observed irregular forms. 5^. pallida is noted for the regularity of its curls and is indeed identified by this means; yet Schaudinn observed that almost straight forms might occur; Sobernheim and Tomasoli found specimens with straight portions toward the centre ; and Fouquet recorded the discovery of straight forms in tertiary syphilis. Krzystalowicz and Siedlecki noted changes in Sp. pallida by which individuals contracted and thus became shorter and plumper. Eitner, who observed living forms indistinguishable from Sp. pallida noted that some of these straightened out when dead and were thus differentiated. Krienitz studied the spirochaetes present in the stom- ach and found that they underwent a change of form according to alterations in their environment. He GENERAL CHARACTERS OF SPIROCH^TES. 31 consequently held that morphology does not constitute a valid test of species. These observations are sufficient to indicate that con- siderable doubt must be felt as to the constancy of form among the small spirochaetes ; and when it is remembered that the identification of such a form as Sp. pallida de- pends entirely upon its morphology, and that many forms have been described in conditions other than syphilis which can only be differentiated by experts from this spirochaete, the uncertainty that must continue to prevail as to relations of the small spirochastes to each other and to the morbid conditions with which they are associated, is undeniable. HABITAT. The only free-living spirochaetes at present known are Sp. plicatilis and Sp. daxensis which are found in fresh water. Sp. polyspira is a saprophyte found in decaying vegetable matter (potato). The rest of the large spirochastes are saprophytes or commensals in the alimentary canal of various shell-fish. Of the smaller forms many are apparently saprophytes on the surface of ulcerative lesions ; others are also saprophytic within the intestines of various animals. A few only are definitely pathogenic, being capable of multiplying within the living tissues of an animal host and there producing poisonous products. CULTIVATION. Spirochaetes have never been satisfactorily culti- vated; that is to say, they have never been isolated in artificial media and passed from culture to culture. Many authors have stated that they have succeeded in producing multiplication of spirochaetes on laboratory media. Thus Duval and Todd kept Sp. duttoni alive 32 SPIROCILETES. in a mixture of yolk of egg and decoction of mouse- flesh for forty days. They observed the formation of long chains under these conditions. Williams grew this organism in defibrinated blood, and Norris, Pappen- heimer and Flournoy cultivated Sp. obermeieri in cit- rated blood. Lebailly states that Sp. pallida multiplied when kept on pieces of infected liver, and Volpino and Fontana found that it even grew into pieces of normal liver placed in contact with the infected tissues. Bor- rel and Burnet cultivated Sp. gallinarum in blood. Levaditi cultivated Sp. pallida and also Sp. refringens in collodion sacs placed inside the peritoneal cavities of animals, but these cultures were not pure, being con- taminated with great numbers of bacterial organisms. Beer claims to have cultivated Sp. pallida, anaerobically like a bacterium on bouillon mixed with ascitic fluid. Leuriaux and v. Geets state that they cultivated Sp. pallida in a mixture of broth with cerebrospinal fluid taken from syphilitic patients; after incubation in this medium the precipitate formed was sown on pigs' se- rum, and colonies developed. Other writers state that they have obtained multiplication of these spirochaetes by incubating portions of infected organs ; and Levaditi, as previously mentioned, "cultivated" Sp. pallida in collodion sacs within the peritoneal cavities of mon- keys, but found the resulting "cultures" incapable of inducing infection. Recently successful attempts to cultivate Sp. pallida are reported by Schereschewsky and by Miihlens. The medium used was horse-serum, which was first heated to 58 to 60 C. a point at which it threatens to solidify and then kept at 37 C. for three days. A piece of infected tissue (e.g., a bit of a gland taken from a patient suffering from syphilis) is then inserted deeply into the medium and kept under anaerobic conditions for five GENERAL CHARACTERS OF SPIROCILETES. 33 days or so, when multiplication of the spirochaetes is found to have taken place. An odour of sulphureted hydrogen is evolved, which may be compared with the foetid odour produced by the organisms of Vin- cent's angina. Schereschewsky found that forms resembling Sp. refringens first developed and after- ward characteristic pallidce. Inoculation of animals with the cultures was unsuccessful. Levaditi and Stanesco also record successes in culti- vating Sp. gracilis and Sp. balanitidis in a somewhat similar way. In the case of the latter organism they first inoculated tubes of horse-serum and then made sub-cultures in collodion sacs containing this serum, placed in the serum tubes. They noted that multi- plication of the spirochaetes only occurred when the media were liquefied by the action of proteolytic bacteria an example of symbiosis which they compare with that needed for the cultivation of amoebae. 1 Most recently of all Bruckner and Galacesco have grown Sp. pallida on coagulated ascitic fluid and have successfully inoculated rabbits with sub-cultures made a month after the material had been sown on artificial medium. MULTIPLICATION AND DEVELOPMENT. Much controversy has centred round the question of the mode of division of spirochaetes, large and small. Perrin described longitudinal division in Sp. balbianii, and Keysselitz in Sp. anodontcs; and I have seen what appeared to be this process taking place in the latter. Schwellengrebel believes that transverse division is the rule in Sp. balbianii, and Schellack finds it in Sp. ano- dontcs (Fig. 28) and in other forms. Among the smaller 'The "symbiotic" bacteria probably serve as food for the amoebse, which need solid pabulum. 34 SPIROCILETES. spirochaetes longitudinal division is described in Sp. duttoni by Mayer and by Newstead; transverse by Duval and Todd, and by Koch. In Sp. obermeieri, (Fig. 29), both longitudinal and transverse division are found (Mackinnon; Nuttall, Fantham, and Porter). In Sp. pallida, longitudinal division is upheld by Beer and by FIG. 28. Spirochaeta anodontae; transverse division. (Schellack.) Krzystalowicz and Siedlecki (Figs. 30, 31); transverse by Levaditi and Yamamouchi. In Sp. vesperuginis, Nicolle and Compte observed transverse division, Gonder on the other hand longitudinal (Fig. 32). In Sp. gallinarum, Borrel saw transverse division, Prowa- zek, longitudinal (Fig. 33) ; the latter method is described GENERAL CHARACTERS OF SPIROCELETES. 35 by Gonder in Sp. hartmanni, the former by Martin in the spirochaete of the horse and by Wenyon in that of the mouse. Forked forms which are not infrequently Ji FIG. 29. FIG. 30. FIG. 31. FIG. 32. FIG. 29. Spirochaeta recurrentis (Sp. obermeieri); transverse division. (Schellack.) FIG. 30. Longitudinal division of Spirochaeta pallida. (Krzys- talowicz and Siedlecki.) FIG. 31. Spirochaeta pallida; multiple transverse fission. (Krzystalowicz and Siedlecki.) FIG. 3 2 . Spirochaeta vesperuginis; transverse division. (Gonder.) FIG. 33. FIG. 34. FIG. 33. Spirochaeta gallinarum, longitudinal division: a, First stage; b, second stage (transverse fission ?) ; c, daughter form after division. (Prowazek.) FIG. 34. Spirochaeta obermeieri; filamentary forms in the bug. (Klodnitzky.) observed are held to point to longitudinal division, forms with attenuated central strand, to transverse multiplication ; but the latter formation has been held by 3 6 SPIROCILETES. the supporters of longitudinal division to represent the final stage in this process, just before separation of the daughter individuals takes place (Fig. 33). Gross believes that spirochaetes become bent upon themselves before undergoing transverse division, the close apposition of the two limbs of the bent organism FIG. 35. FIG. 36. FIG. 37. FIG. 35. Spirochasta balbianii ; supposed conjugation. (Perrin.) FIG. 36. Spirochaeta vesperuginis; conjugation (?). X22$o. (Gonder.) FIG. 37. Spirochaeta anodontae; apparent conjugation, probably a stage in longitudinal fission. then giving rise to an appearance of longitudinal fission. He terms the process division by "incurvation." A development of the spirochaetes into long fila- ments has been described by Duval and Todd in culti- vations of Sp. duttoni, and by Klodnitsky as occurring in Sp. obermeieri within the body of the bug (Fig. 34). Koch also saw filamentary forms in ticks infected with Sp. duttoni. GENERAL CHARACTERS OF SPIROCH^TES. 37 The occurrence of conjugation in some form or other appears to be universal among protozoa, and if spiro- chaetes are to be assigned to this class it will presumably be proved to take place among them also. At present the accounts given of such an occurrence are not con- clusive (Figs. 35, 36). An instance which I observed of what appeared to be conjugation in Sp. anodontcz (Fig. 37) was probably only a stage in the process of longitudinal division. Krzystalowicz and Siedlecki have explained certain forked forms of Sp. pallida FIG. 38. FIG. 39. FIG. 38. Spirochaeta pallida; formation of gametes. (Krzys- talowicz and Siedlecki.) FIG. 30. Spirochaeta pallida; conjungation. (Krzystalowicz and Siedlecki.) which they observed as resulting from the conjugation of a small individual with a larger one (Figs. 38, 39) ; and Leuriaux and v. Geets describe microgametes and macrogametes. The four writers last mentioned agree in considering Sp. pallida to be in reality a species of trypanosome (Trypanosoma luis, Krz. and S.), the macrogamete being definitely trypanosomatoid and the microgamete spirochaetal. Male, female and indifferent forms of Sp. balbianii are described by Perrin, but he failed to find any certain instance of conjugation (see Fig- 35)- Carter gives figures of what appears to be conjuga- tion of a spirochaete which he found in human blood in SPIROCILETES. S. Arabia. Large globular swellings were formed in the bodies of the organisms and fusion seemed to take place between two individuals at these points (Fig. 40) . FIG. 41. FIG. 40. FIG. 40. Arabian spirochaste; conjugation. FIG. 41. Spirochaeta balbianii; encystment. (Carter.) (Perrin.) The forms depicted are, however, so unlike those seen in any other spirochaetes that it seems possible that Carter was dealing with a spirochsetoid form of some other organism. FIG. 42. FIG. 43. FIG. 44. FIG. 45. FIG. 42. Spirochaeta anpdontae, rolled up forms. X 500. FIG. 43. Spirochaeta spiculifera, rolled up. (Schellack.) FIG. 44. Spirochaeta pallida. Depression stage. X2250. (Prowazek.) FIG. 45. Resting stage of Spirochaeta buccalis. X2250. (Prowazek.) Encystment was believed by Perrin to take place in Sp. balbianii, and he gives illustrations of the movements of the organism in assuming this phase (Fig. 41). The GENERAL CHARACTERS OF SPIROCELETES. 39 figures which he gives of the encysted stage are not very convincing. In the case of Sp. anodonta I have found rolled up specimens after keeping the organisms for a day or two in the fluid which escapes from the mantle- cavity of the mussel (Fig. 42). These forms in some FIG. 46. Spirochaeta anodontae; stages in formation of resting spore (?). instances lay in or in close apposition to large epithe- lioid cells ; but whether the spirochaetes entered the cells at this stage, or the cell engulfed the spirochaete, or the apposition was merely due to some physical attraction, I cannot say (compare Figs. 69, 86, 87). The cells were V FIG. 460. Portion of Cladothrix putridogenes (Veszpremi) for comparison with Fig. 46. necessarily somewhat degenerated after being kept so long in the fluid, and it seems unlikely that they would have been able to engulf the spirochaetes. Rolled up specimens of Sp. duttoni were seen by Mayer, and of Sp. pallida by Levaditi and others. 40 SPIROCILETES. Oval forms were found by Leuriaux and v. Geets in Sp. pallida; they suggest that these develop subse- quently into filaments. Ovoid bodies are also depicted by Krzystalowicz and Siedlecki as apparently constitut- ing a stage in Sp. pallida (see Fig. 50), and somewhat similar bodies were found by Castellani along with Sp. pertenuis. Sporulation. In the case of Sp. anodontce I have found some specimens showing about the middle of the body a rounded swelling or a darkly staining oval body FIG. 47. FIG. 48. FIG. 47. Spirochaeta balbianii, with central swelling (so-called " male" form). (Perrin.) FIG. 48. Arabian spirochaete. (Carter.) (Fig. 46) suggestive of a "resting spore." In figure 460 is depicted for comparison a portion of a filament of cladothrix showing a very similar swelling. These appearances may be compared with the illustrations given by Perrin of peculiar forms of Sp. balbianii (Fig. 47), and also Carter's figures of his Arabian spirochaete (Fig. 48). Cox states that within the blood-corpuscles Sp. obermeieri breaks up into minute granules; and Leish- man finds that Sp. duttoni gives rise to coccoid forms within the tick, no spirochaetes being discoverable within ticks which are yet capable of conveying the infection. The so-called "moniliform" specimens of spirochaetes (Fig. 27), are usually looked upon as degenerative forms but it is possible that the granules thus formed are cap- able of subsequent development, and are the equivalent GENERAL CHARACTERS OF SPIROCTLETES. 41 of bacterial spores. The terminal nodules of the smaller spirochaetes are very suggestive of such a formation. Associated with Sp. anodonta are found chains of coccoid bodies, similar in length to the spirochaetes. The arrangement of the staining material in the bodies of the latter, which may break up into regular portions FIG. 49. Development (?) of Spirochaeta anodontae: a, Spi- rochaete apparently undergoing segmentation; b, chain of cocci, possibly resulting from this process of fission. of about equal size, suggests that they may give rise to the cocci by a process of multiple fission (Fig. 49) . * In this connexion it is interesting to note the occur- rence of rod-shaped bodies, containing dots resembling nuclei, in association with different kinds of spirochaetes. Thus they were found by Krzystalowic and Siedlecki along with Sp. pallida (Fig. 50) by Prowazek in connex- 1 1 hope to publish shortly further observations supporting the probability of this mode of development in Sp. anodontce. 42 SPIROCH^ETES. ion with Sp. gallinarum (Fig. 51) and with Sp. lutra (see Fig. 71), by Mayer in the blood of a mouse infected with Sp. duttoni (Fig. 52), and by other observers else- where. Loewenthal found rod-shaped and sausage- FIG. 50. FIG. 51. FIG. 50. Abnormal forms associated with Spirochseta pallida. (Krzystalowicz and Siedlecki.) FIG. 51. Spirochaeta gallinarum and rod forms. (Prowazek.) shaped bodies along with spirochaetes in ulcerated cancers. Qury believes that Sp. pallida is a stage in the development of a bacillus which he cultivated; from it he prepared a serum which Hallopeau found to have FIG. 52. Rod forms (a, c) and Spirochaeta duttoni (6) in blood of mouse. (Mayer.) some curative value in syphilis. Von Niessen also holds that the Sp. pallida is a developmental form of a special cocco-bacillus which he obtained in pure culture. ASSOCIATION WITH OTHER ORGANISMS. The association of spirochaetes with other organisms is of considerable interest as either constituting an example of symbiosis or suggesting the possibility that GENERAL CHARACTERS OF SPIROCH^TES. 43 these organisms are a stage in the development of some other form. The best-known example of such constant associa- tion is that of the spirochaste met with in Vincent's an- gina with the fusiform bacilli which are often regarded as the cause of this condition. The idea that the two forms may be stages in the life-history of one and the same organism is attractive and is supported by the experiments of Ruth Tunnicliffe who found that in cultures of B. fusiformis spirochsetes made their FIG. 53. Spirochaeta vincenti (a) with fusiform bacilli (6) and (?) filament of cladothrix (c). appearance. This observation has not, however, been confirmed. Schmiedlechner found bacilli which di- vided longitudinally along with Vincent's spirochaetes. Organisms resembling B. fusiformis were found by Mayer along with Sp. duttoni and by Krzystalowicz and Siedlecki with Sp. pallida; and Leishman, Harvey and Bousfield, and Launois and Loederich noted the coexistence of Sp. pallida with fusiform bacilli in syphi- litic lesions. Wellmann found Sp. pertenuis along with fusiform bacilli and with Sp. refringens. Other bacterial forms are also found associated with spirochaetes, as by Button, Todd and Tobey in onychia, by Schereschewsky in syphilis (B. pyocyaneus), by 44 SPIROCILETES. Cleland in castration-tumours in pigs, and by Cleland and by Bosanquet in ulcerative granuloma. Levaditi found it impossible to cultivate Sp. pallida and Sp. rejringens in collodion sacs in the peritoneal cavities of animals without the simultaneous development of bacterial forms. In gangrenous stomatitis the spirochaetes are found most deeply situated in the tissues, the bacilli in the more superficial parts; while in ulcerative granuloma bacilli and spirochaetes are found together deeply situ- ated in the tissues, where it would seem unlikely that merely saprophytic germs would be able to establish themselves. The bacteria do not here resemble any known pathogenic variety. The coexistence of trypanosomes with spirochaetes was noted by Theiler in cattle, by Wenyon in mice, and by Petrie in birds (martins). Balfour found spiro- chaetes in intestinal ulcers, in dogs and monkeys, pro- duced by inoculation with trypanosomes (7". dimorphon); but as spirochaetes or spirilla are common in the ali- mentary canals of animals, they may have been only accidentally present in these cases. 1 Gauducheau noted the appearance of spirillar bodies in a culture of amoebae. 2 The question as to the relationship between spiro- chaetes and other organisms must at present be left undecided. In view of observations recorded in this and in the preceding section the possibility that spiro- chaetes are only one stage in the development of a poly- morphic organism must not be lost sight of as a probable explanation of this association, though it is at present far from proof. Balfour, Jour. Trap. Med., 1906. 2 Gauducheau, C. R. Soc. de BioL, 1908, LXIV, 493; Leishman, Jour. R. Army Med. Corps 1905, IV, 321; Petrie, Jour, of Hygiene, 1905, V, 195. GENERAL CHARACTERS OF SPIROCILETES. 45 PATHOGENICITY. Since it has been found impossible to produce pure cultures of any spirochsetes, rigorous proof of their causal connection with disease, such as is demanded by the well-known "postulates" of Koch, cannot be furnished. Nevertheless, the pathogenicity of certain forms appears to be fairly established. RELAPSING FEVER. In the case of relapsing fever the spirochaete dis- covered by Obermeier and generally known by his name is universally admitted to be the exciting cause of the disease. It is present in all cases of the malady; it disappears during the remissions and reappears during the relapses. The blood of a patient reproduces a similar affection when injected into animals, and no other germ has been found present which might be looked upon as pathogenic. The disease is characterised by a sudden onset, after an incubation-period of varying length (from a few hours up to fourteen days). The first access of fever lasts about a week and ends by crisis. A period of apyrexia ensues, to be followed by a second access of fever, and this sequence may be repeated a third and even more times. The spleen and liver are much en- larged, and the spirochaete may be found in the spleen during the remissions. Monkeys are the only lower animals directly susceptible to the disease. In mankind infection may be conveyed by direct inoculation, as by a scratch at a necropsy; it may also occur by aerial conveyance in some instances, like the infection in scarlet fever, typhus, etc. 1 It has been supposed that the infection may be conveyed 1 Ker, "Infectious Diseases" London, 1908, p 229. 46 SPIROCILETES. from person to person by the bites of bugs, and it is probable that at least accidental infection may thus he produced, as Tictin found the spirochaete present in these insects and infected monkeys by injection of their macerated bodies; but it is not proved that an intermediate host is necessary or that any develop- ment of the spirochaete takes place in the bug. Man- teufel and also Sergent and Foley believe that infection is conveyed by lice (Pediculi capitis et corporis). The blood of a convalescent from relapsing fever contains substances capable of destroying the spiro- chaetes (spirillicidins) , and passive immunity is con- ferred by injection of such blood into another indi- vidual. Agglutinating substances are also formed. Metchnikoff holds that the spirochaetes are mainly de- stroyed by phagocytosis; Rabinowitsch states that a hyperleucocytosis is produced in the blood of animals, and also a change in the bone marrow "like leukaemia." Relapsing fever has been chiefly studied and described as it occurs in Europe especially in Russia. Closely al- lied forms of disease occur in other parts of the world, caused apparently by spirochaetes which are mor- phologically almost indistinguishable from that of ordinary relapsing fever, but are probably different species. AFRICAN TICK FEVER. African tick fever is an affection met with in East Africa, and is conveyed by the bite of a species of tick, Ornithodorus moubata. The general features of the disease are similar to those of relapsing fever, but the relapses are often more numerous. The spirochaete present in this disease is said by Uhlenhuth and Haendel to be rather thicker than Sp. obermeieri, and by Schel- lack to move more vigorously. An attack confers GENERAL CHARACTERS OF SPIROCH^TES. 47 immunity against this parasite, but not against Sp. obermeieri; and agglutination tests also point to a specific difference between the two spirochaetes. Mice and guinea-pigs can be inoculated with this organism, as can also rabbits, horses and monkeys. The patho- logical changes seen after death are the same as in infection with Sp. obermeieri. The spirochaetes are taken up by the ticks from the blood of an infected person and are passed on in the egg to the young ticks of a second generation. Koch describes filamentary forms of the spirochaete in these animals. Levaditi and Manou^lian believe that destruction of the spirochaete and cure of the disease are brought about by phagocy- tosis; some of the symptoms of the malady are attrib- uted by them to thrombosis of blood-vessels caused by impaction of masses of spirochaetes. OTHER FORMS OF RECURRENT FEVERS. Relapsing fever as seen in America is said to be caused by yet another spirochaete. Schellack gives the follow- ing description of the three allied organisms: Length Breadth African form (Sp. duttoni) American form 24-3 OfJL (long forms) o-45j (Sp. novyi) Russian form (Sp. obermeieri) (long forms) 19-20/1 (long forms) -39^ It is not impossible that other species may be found to exist in different parts of the world where forms of relapsing fever are encountered. Thus the 48 SPIROCaETES. spirochaete of relapsing fever as seen in Bombay was found by Novy to differ from the American variety. Spirochaetes were also found by Carter in cases of fever occurring of S. Arabia. The illness consisted in head- ache, backache, prostration and enlargement of the spleen. Infection appeared to be conveyed by ticks (Ornithodorus Sp. ?). The relation of the disease to those described above is uncertain. Darling believes that the spirochaete of relapsing fever in Panama is again a special variety, the immun- ity produced by an attack not being protective against the spirochaetes of the 'other forms. The blood is infec- tive in the intervals between the paroxysms. Apes and mice are susceptible to this parasite. SYPHILIS. The spirochaete discovered by Schaudinn in the lesions of syphilis and first named by him Spirochcsta pallida is now generally accepted as the cause of this disease. Since it is not possible to obtain the organism in pure culture and to use such cultures for the inocula- tion of animals, rigorous proof of causal connection can- not be furnished. It is held, however, that as the spirochaete is constantly present in syphilis (100 per cent, of cases, Hoffmann and Prowazek) and is not found in any other conditions, it has as much claim to be regarded as the infective agent as has the Bacillus leproz in leprosy. In view of its presence in the initial chancre, its subsequent passage to the neighbouring lymphatic glands, its presence in the blood in the secondary stage of the disease, and the occurrence only of degenera- tive forms in tertiary lesions (gummas) which are not supposed to be infective, the features of the disease may be satisfactorily explained as due to this organism. The discovery of immense quantities of spirochastes GENERAL CHARACTERS OF SPIROCILETES. 49 in still-born foetuses, the offspring of syphilitic mothers, is also urged as a strong argument in favour of the infective character of the organism. The serum of syphilitic subjects is said to agglutinate these spirochaetes. While we may admit that a strong prima-facie case can be made out for this view, it must be admitted that there are still some objections to be overcome before the Spiroch&ta pallida can be accepted as the proved cause of syphilis. 1. In the absence of cultures of the organism it can only be identified by its morphological characters. It is practically admitted that only those observers who have made a prolonged study of this spirochaete and of similar organisms can be sure of distinguishing it from other forms. This condition of affairs some- what vitiates the statistical method of proof, dependent on the frequency of the finding of Sp. pallida in syphil- itic lesions. On the other hand, this difficulty of identification may be used as an argument by the up-holders of the spirochaetal hypothesis against those who, like Kiolo- menoglou and Cube, Krienitz and Scholtz, have found spirochaetes which they identified as pallid in non- syphilitic conditions. 2. The question of the possible variability of form of Sp. pallida has already been discussed (page 30) ; if such variation be admitted, it becomes practically impossible to be sure that it is only in syphilitic lesions that this spirochaete is found, and its presence elsewhere would of course be fatal to its causal connection with syphilis. 3 . Most observers have failed to find the spirochaete in all the cases of syphilis which they examined. The following figures may be quoted : SPIROCH^ETES. Primary lesion Secondary stage Cases Posi- tive Nega- tive Cases Posi- tive Nega- tive Arning and Klein 112 108 4 179 169 10 Bandi and Simonelli 5 3 2 Bodin 16 10 6 1 7 10 7 Ferre" 14 1 1 3 J 7 17 o Kraus and Prantschoff . . . 37 32 5 25 18 7 Metchnikoff 6 2 Miihlens 22 22 o 7 6 i Shennan 10 5 5 Siebert 18 13 5 47 39 8 Bertarelli and Bovero examined forty-two cases and found the spirochaste present in twenty-six, absent in sixteen. They noted the scanty numbers of the organisms which could be found in the primary sore. Jaquet and Sevin were also struck by the difficulty of finding it in this position. Risso and Cipollina, and also Siebert, record the inconstancy of the organism in syphilitic lesions. There appears to be agreement that the spirochsete is not found in cases of "malig- nant syphilis" (see below). This is curious, since the more severe the disease, the greater the numbers of the pathogenic organisms which should theoretically be present. Even if these cases depend rather on a weak- ness of resistance on the part of the patient than on in- creased virulence of the spirochaete, there should still be plenty of the latter present. 1 The possibility that the condition is due to a mixed infection must, however, be borne in mind. The relationship of the spirochaetes to the actual lesions of the disease presents some points of peculiar- ^he title of a paper by Herxheimer (Deut. med. Wochenschr., 1905, XXX, 1687) suggests that he found Sp. pallida in malig- nant syphilis, but the paper is not given in full. GENERAL CHARACTERS OF SPIROCH^TES. 51 ity. It would be natural to expect that in so well- marked a condition as the primary chancre, which appears to be produced by some intense irritant, there would be found large numbers of the causal organisms. As a matter of fact, spirochaetes are al- most invariably scanty in the tissues forming the chancre, and in many instances observers have failed altogether to find them. (Their presence on the sur- face of the ulcer is of comparatively little impor- tance, in view of the ubiquity of similar organisms.) Others have failed to find the spirochaete in blood from a syphilitic case, which was definitely proved to be infective. The possibility of the existence of other stages of the parasite, e. g., granules or coccoid bodies (p. 40), must, however, be borne in mind. Again, spirochaetes may be present in the organs of a syphilitic patient without apparently giving rise to any anatomical changes ; as, for example, in an eye which appeared quite healthy (Bab). In considering the striking abundance of spirochaetes in still-born syphilitic foetuses it must be remembered that such bodies may be found full of other (bacterial) organisms, scattered throughout all the tissues; and also that Karlinski found spirochaetes distributed throughout the tissues of a foetal pig, having there presumably spread out from the intestine (see Fig. 57). The presence of the spirochaetes in gummas, which are not supposed to be infectious, is somewhat curious, for while this non-infectivity might be explained on the ground that the spirochaetes here found are usually few and degenerate, yet if they are the cause of the dis- ease at this stage, they must be of very notable virulence, since a gumma consists of a considerable mass of inflam- matory tissue and may undergo rapid degeneration and softening, both presumably due to active micro bial 52 SPIROCILETES. action. So much irritation could hardly be attributed to the presence of only a few degenerate spirochaetes. 4. The fact that the Sp. pallida is found in the lesions artificially produced by inoculation of lower animals with syphilitic material constitutes a two-edged argu- ment, since the only animals which are definitely sus- ceptible to syphilitic infection are the apes, while the spirochaete has been found living in dogs, cats, rabbits and guinea-pigs. It is necessary to assume that the pathogenic agent of syphilis can exist as a saprophyte in lower animals which are insusceptible to the disease a condition which is at least unusual in the case of infective organisms. Otherwise it must be held to be saprophytic in both cases. In this connection the observations of Gaylord on the transmission of spiro- chastes in mice may be brought into comparison. This observer found spirochaetes in certain cases of cancer in mice, and on inoculating other mice with emulsions of the tumours, he found that the spirochaetes were also discoverable in the growths which resulted. The natural inference that the spirochaetes were the cause of the cancer was, however, proved to be erroneous; and it appeared that the organisms were frequently present in mice and could be transmitted from one to another, but were harmless parasites of these animals. Of course, the parallel is not very close, since the Sp. pallida is not found in normal men or animals, but the possible transmission of spirochaetes which are in no sense pathogenic must be noted. 5. The discovery of spirochaetes, very like Sp. pallida in the closely allied diseases, yaws and ulcerative gran- uloma of the pudenda, would seem to constitute an ad- ditional argument in favour of the Sp. pallida being the true cause of syphilis. Herein also lies, however, a certain source of difficulty. It is generally said that the GENERAL CHARACTERS OF SPIROCILETES. 53 spirochsete of yaws (Sp. pertenuis) is indistinguishable from Sp. pallida. So far as the silver- stained prepara- tions made by Levaditi, for example, are concerned, this is true. (On the other hand, Sp. pertenuis as de- picted by Castellani is different in appearance from Sp. pallida, not showing the same regular curls.) If then we have in yaws an organism exactly resembling Sp. pallida, the argument that this organism is only found in syphilis would seem to break down, since Sp. pallida is only recognised by its morphological characters. The identity of form is noted by Beurman and Gougerot, by Levaditi and Nattan-Larrier, by Schiiffner and by Wellmann, and was admitted by Schaudinn himself. 6. Levaditi succeeded in cultivating Sp. pallida (i.e., in causing some multiplication of the organisms and keeping them alive) in collodion sacs placed within the peritoneal cavities of monkeys. These cultures failed to produce infection when inoculated in other monkeys susceptible to syphilitic infection. The negative result is not perhaps in itself a very strong argument against the causality of the spirochaete, as the organism may easily have become attenuated by this procedure. Nevertheless it may be pointed out that Levaditi allows that a similar failure in the case of the spirochaete of balanitis is evidence against the causal connection of this organism with this disease, and the argument is as strong in one case as in the other. A positive result from inoculation of a culture has since been recorded by Bruckner and Galacesco. 7. The argument derived from the destructive and agglutinating action of the serum of syphilitic pa- tients on the Spiroch&ta pallida is somewhat weakened by the fact that De Lisle and Jullien 1 found a coccus in 1 La Semaine Medicate, 1900, page 279. 54 SPIROCILETES. syphilitic patients which was agglutinated by their serum, but this organism is not now supposed to have any causal connection with the malady. 8. It is usually said that the result of antisyphilitic treatment is to cause the disappearance of the spiro- chsetes; but Rille and Vocquerodt, and also Benda, found that no apparent effect was produced by treat- ment on the number of spirochaetes present. 9. It is stated that whereas the syphilitic virus is active when infective material is mixed with gly- cerine, spirochaetes are destroyed by contact with this reagent. After a review of all the evidence at present available we can therefore only conclude that while there is a considerable probability that the Spiroch&ta pallida is the infective agent in syphilis, its position is not yet established with absolute scientific certainty. The clinical phenomena of syphilis consist in (i) a primary lesion at the site of inoculation, consisting in an ulcer with a deeply indurated base; here the spiro- chaete is found on the surface of the ulcer and in the fluid that can be squeezed from its deeper layers, and it can also be found by the silver-staining method lying in the lymphatic spaces between the bundles of fibrous tissue. Enlargement of lymphatic glands takes place in the re- gion towards which the lymph from the ulcer drains, and by puncture of these glands with a hypodermic syringe the organism can usually be obtained in the fluid with- drawn. (2 ) . The secondary stage is marked by constitu- tional symptoms, such as fever and feeling of illness, along with eruptions on the skin and often with super- ficial ulceration of the throat (tonsils, fauces). In this stage the spirochaetes may be found in the blood and in any vesicular lesions which may develop, or in the fluid obtained by blistering. (3). In a certain num- GENERAL CHARACTERS OF SPIROCILETES. 55 ber of cases a tertiary stage is met with, consisting in the formation of localised inflammatory swellings, which may occur in any part of the body (the so-called gummas, from the "gummy" nature of the material formed by breaking down of the inflammatory cells). In these either no spirochsetes are found, or only a few degenerate specimens. This stage is not infective. Malignant syphilis is the name applied to certain forms of the disease in which ulcerative lesions appear at an early stage. Anaemia and cachexia develop to a severe degree, and the condition is not amenable to treatment with mercury. It "must be distinguished from severe syphilis which is characterised by dangerous localisa- tion of the disease, or by association with other morbid conditions. The cause of malignant syphilis is doubt- ful; it has been attributed both to excessive virulence of the microbe and to secondary infection with other organisms. It would appear more probable that it is due to the implantation of the microbe on virgin soil i.e., on persons whose ancestors have been free from syphilis" (C. F. Marshall 1 ). Infection is usually contracted in coitu and is con- veyed by the discharge from the primary sore. It can also be conveyed by means of drinking vessels or of a tobacco pipe recently used by an infected person in the secondary stage, in which there are infective lesions in the mouth and throat. Thus, either direct contact is necessary or very direct conveyance by an intermediary object. Some abrasion of the skin is probably required for the entrance of the infective organism, and surgeons are often infected through slight wounds in the fingers in the course of examining syphilitic patients. Infection does not seem to arise from contamination with the fluids of the dead body, 1 " Syphilology and Venereal Disease," 1906, London, pp. 18-19. 56 SPIROCH^TES. as in making post-mortem examinations; hence it would seem that the organism quickly loses its viru- lence on the death of the host. Congenital Syphilis. Infection may be conveyed to the foetus in utero from either parent. Whether the actual spermatozoon is infected cannot be demonstrated ; certainly the causal organism can pass from the mater- nal blood, by way of the placenta, into the vessels of the foetus. In this way congenital syphilis is produced. The syphilitic foetus often dies before birth, and in such still-born foetuses the Spiroch&ta pallida is found in practically all the organs of the body most abundantly in the liver (see Fig. 88), and suprarenal capsules. 1 It is generally supposed that resistance to the Sp. pallida is mainly effected by phagocytosis; but Zabo- lotny and Maskalowetz find that the serum of syphilitic subjects has an agglutinating and also a "lytic" power, so that the processes at work in producing recovery and immunity may be complex in character. 2 Most attempts to pass the virus of syphilis through a porcelain filter have failed; but Jancke records one 1 Some of the actual findings are : In congenital syphilis in the eye and nasal mucus (Bab), in the blood and in the lungs (De Sousa and Pereira), in the bronchial epithelium and in miliary gummas (Benda), in the bullae of pemphigus (Hoffmann, Leixer, Levaditi), in the testicles (Fouquet), in osteitis (Bertarelli), in the urine (Huebschmann), in the meconium (Simmonds), and in the placenta of the mother (Wallich and Levaditi). In the acquired disease, besides its localisation in the connective tissue of the pri- mary sore, and in the lymphatic glands and in the blood in the secondary stage, it was found by Ehrmann in the nerve-sheaths, by Follet in the saliva. Veillon and Girard attribute the roseolar rash to the formation of embolic masses of the spirochaetes in the blood-vessels. The organism may in rare instances be found in the cerebro-spinal fluid (Gaucher and Merle). It is also found in aortitis (Reuter, Schmorl) . The spirochaetes lie as a rule between the cells of the host; but they may be seen in polymorphonuclear leucocytes (Gierke) where they may be undergoing phagocy- tosis, and also inside the cells of the liver in congenital syphilis (Levaditi). 2 The formation of a copula or amboceptor has already been noted. An account of the so-called Wassermann Reaction, based on this occurrence, does not fall within the scope of this little work. GENERAL CHARACTERS OF SPIROCILETES. 57 positive result obtained with the material from a syphilitic foetus. YAWS. The disease called yaws or pian (Frambcesia tropica) is in many ways like syphilis, going through a primary stage characterised by a local lesion at the point of inoculation, and a secondary stage of generalised phenomena, which take the form of multiple nodular inflammatory lesions or granulomas. It is generally supposed to be a distinct malady, but some writers still maintain that it is only a variety of syphilis. The Sp. pertenuis, first described by Castellani, is supposed to be the causal agent of the disease. It so closely re- sembles Sp. pallida (page 112) that some writers are constrained to argue from the diversity of the two affec- tions to prove the distinct characters of the two para- sites (e.g., Wellmann). Schiiffner (who believes in the identity of yaws and syphilis) found the spirochaste present in 98 per cent, of all the cases he examined. Von dem Borne found it in seventy-three of seventy-six non-ulcerated cases: in ulcers it is found along with other kinds of spirochastes. Levaditi and Nattan-Larrier found the organisms on the surface of the primary lesion, in the glands, and in the spleen, but not in the blood. Mclntosh states that the position in which this spirochaete is found in the skin is not the same as that in which Sp. pallida occurs ; Sp. pertenuis being found in the superficial layers of the ulcer, in the fibrinous crust containing leucocytes and degenerated epithelium, whereas Sp. pallida occurs especially in the corium around the blood-vessels. LYMPHADENOMA. Proescher and White discovered spirochaetes (Sp. lymphatica) present in a case of " lymphosarcoma. " 58 SPIROCILETES. With material containing it they inoculated a monkey (Macacus rhesus) and thus produced a local lesion at the point of inoculation, followed by the appearance of other nodules at a distance. They further inoculated a second monkey from the first, also with positive re- sults. The spirochaetes were found in all the lesions. These spirochaetes so closely resembled Sp. pallida that they were at first mistaken (?) for this organism. It seems possible that in this case either a syphilitic adenitis was mistaken for lymphadenoma, or that a secondary infection with Sp. pallida occurred in a patient suffering from this disease. ULCERATIVE GRANULOMA. Spirochaetes were first found in the disease called ulcerative granuloma of the pudenda by Wise, who stated that some forms resembled Sp. pallida and others Sp. pertenuis. They have since been found in this disease by MacLennan and by Cleland. They exist in the deep layers at the base of the ulcer, at some distance from the surface, and may be found in the blood-vessels. Bacteria are present along with the spirochaetes. The pathogenicity of these organisms cannot be held to be proved as yet, but their position deep in the tissues is against a purely saprophytic character. * VINCENT'S ANGINA. Spirochaetes are found along with fusiform bacilli in the disease called Vincent's angina, and also in some other conditions in which there is necrosis of tissue (e.g., 1 M. Carter states that he has found in a case of this disease, pro- tozoon parasites in the form of minute rounded bodies within the cells. He believes that they are related to Leishmania donovani (Lancet, 1910, II, 1128). GENERAL CHARACTERS OF SPIROCH^ETES. 59 in noma or gangrene of the cheek, in hospital gangrene, etc.). Uffenheimer thinks the spirochaetes are the pathogenic agents in Vincent's angina, as, if the tonsils are removed in cases in which these organisms are present, further ulceration occurs. Ellermann also points out that the spirochaetes are found more deeply situated in the tissues in cases of noma than are the bacteria, and that they seem to prepare the way for the latter. The relationship between the spirochaetes and the fusiform bacilli has already been discussed (page 43). Veszpr&ni thinks that the spirochaete of Vincent's angina is identical with the common spiro- chaete of the mouth, Sp. buccalis. OTHER DISEASES IN MAN. Moritz found spirochaetes in the bone-narrow and in the muscular coat of the intestine in a man who died with symptoms of intense anaemia, fever and diarrhoea, and in whom there were found after death an ulcer of the stomach and miliary nodules of new growth (en- dothelioma?) in the lungs. The primary seat of the tumour was not discovered. The spleen was enlarged. He thinks the spirochaetes in this case were different from any previously described species, but their nature and relation to the disease must remain problematical. Castellani found spirochaetes present in certain cases of haemorrhagic bronchitis (Sp. bronchialis) . He believes that they may be the cause of the disease. Waters also noted spirochaetes in a series of cases of bronchitis, without haemoptysis. Branch found or- ganisms of this nature in a case of pulmonary tuber- culosis, in which they were present in the expectora- tion along with tubercle bacilli; they may have been derived from the mouth. 60 SPIROCHjETES. Spirochaetes are also supposed to be responsible for the diseases known as balanitis and ulcus tropicum (see pp. 107, 103). DISEASES OF ANIMALS. A number of diseases in the lower animals are associ- ated with the presence of Spirochaetes. The best known is the so-called spirillosis of fowls, caused by the Sp. gallinarum. The disease is characterised by weakness, drowsiness and diarrhoea. It may prove fatal or recovery may ensue. The anatomical lesions met with consist in a fatty degeneration of the liver, with accu- mulation of uninucleated cells round the vessels, and hyaline necrosis in the spleen. The spirochastes are found in and around the vessels, in their walls, and between the cells of the liver. They do not usually become intracellular, but may be found in the mature ovules. Hereditary infection does not occur, the offspring of infected fowls being immune. The fertilised egg can, however, be artificially inoculated and then the chick is born infected. In such chicks the liver is first invaded and undergoes the change above described. Haemorrhages also occur, and the blood is described as "myeloid" or "embryonic" or both to- gether (containing granular myelocytes, vacuolated uninucleated cells, and nucleated red corpuscles with basophile granules) . The Spirochaetes are agglutinated by the serum of the infected birds. Levaditi considers that they are de- stroyed by phagocytosis, carried out especially by the macrophages of the liver and spleen. Neufeld and Prowazek deny this, and attribute recovery to the action of the serum, which is parasiticidal in vitro and also capable of protecting other birds. Gabritchewsky states that "lytic" bodies (bacteriolysins) appear in GENERAL CHARACTERS OF SPIROCILETES. 6 1 the blood before phagocytosis occurs (in the goose), while Levaditi and Lange find exactly the reverse, the spirochastes disappearing before the formation of anti- bodies ("immobilisines") in the rabbit. Infection is conveyed by the bites of ticks (Argas miniatus, A. reflexus. A. persicus, Ornithodorus moubata, not by Dermanyssus avium). Atoxyl, a drug containing ar- senic which is found useful in the treatment of trypano- somiasis, is also valuable in fowl spirochaetosis, being both preventive and curative. Salvarsan ("606") is also very efficacious. A disease of cattle characterised by fever and diarrhoea with enlargement of the spleen was described by Thei- ler. Crises and subsequent relapses may occur. Infec- tion is conveyed by the bite of the tick Rhipicephalus decoloratus, and it would seem that some develop- mental stage may occur in this host, as direct injec- tion of the blood of an infected animal into a healthy one does not result in infection. Spirochaetes were also found by Theiler in sheep and horses suffering from fever; he believes that these may have been the same organism as was found in the cattle. Baruchello and Pricolo found Spirochaetes in cases of infective pleuropneumonia in horses, the organisms being present in the spleen, in the pulmonary alveoli, in the pleural effusion, and in the blood. Martin also found Spirochaetes in a sick horse, which, however, re- covered, and Stordy in a horse which died with symp- toms of wasting and oedema; with these organisms the latter failed to infect a dog. A disease due to a spirochaete (Sp. vesperuginis) was described in the bat, Vesperugo kuhlii, by Nicolle and Compte. Enlargement of the spleen was found in a 62 SPIROCH^ETES. fatal case. Recovery by crisis and subsequent relapse were noted. Dodd found spirochaetes in certain lesions of the skin in a pig, infection being conveyed by contact. The or- ganisms disappeared and reappeared during the course of the disease ; they did not get into the blood of the animal, and inoculation was only possible in the skin. The lesions in some cases healed, yet the pig died. Anaemia and pneumonia were found post mortem. Breinl and Kinghorn noted enlargement of the spleen in mice infected with Sp. laverani. This organism may be the same as Sp. muris, described by Wenyon, but the dimensions given by these writers are not identical, and Wenyon states that Sp. muris is a harmless parasite. He thinks it may be identical with Spirillum minor (minus) found by Carter in the rat. SUMMARY OF THE PHENOMENA OF THE PATHOGENICITY OF SPIROCH^ETES. Summarising the facts just recorded, we find that there is a group of spirochaetes associated with affections in which the symptoms are fever, a tendency to relapses, and enlargement oj ike spleen. In this group we may place the spirochaetes of the various forms of relapsing fever, the spirochaetes of fowl-spirillosis, and perhaps those found in the bat. In these diseases the spiro- chaetes give rise to a septicaemia a generalised infection in which the organisms multiply in the blood-stream without the formation of any local lesion. The causal connection of the spirochaetes with these affections is clearly established. On the other hand, we have in syphilis and yaws diseases in which there is a well-marked primary local GENERAL CHARACTERS OF SPIROCILETES. 63 lesion, followed by a generalised infection. Relapses do not occur as a notable feature, and enlargement of the spleen is also inconstant. The causality of the spirochsetes present is not yet absolutely proved. In a third group, in which we may place Vincent's angina, ulcerative granuloma of the pudenda, and per- haps the disease recorded by Dodd in the pig, there is merely a local affection of the skin or of mucous mem- brane, conveyed in the last two cases by direct contact. The three classes may be considered to constitute a descending scale of virulence on the part of the para- sites, a local lesion being caused when the degree of virulence is slight, a local lesion with subsequent gen- eralisation when it is rather greater, and an immediate septicaemia when it is most intense. Cases of congenital syphilis in which death occurs, but no anatomical lesions are discovered, have been attributed to a septi- csemic action of the Sp. pallida. METHODS OF STAINING. The larger spirochaetes may be stained by the ordi- nary methods used for protozoa haematoxylin (Dela- field's or Heidenhain's), Giemsa's stain, etc. They are not stained by carmine thus resembling bacteria rather than protozoa. For the smaller spirochaetes, especially for Sp. pal- lida, a large number of methods have been recom- mended. Giemsa's Stain. This is made as follows: Azur II eosin 3 grm., azur II 0.8 grm., pure glycerine 250 grm., methyl alcohol 250 grm. One drop of this solution is added to i c.c. of distilled water. Stain for ten to fifteen minutes (see Plate, Fig. A) . Schereshewsky recommends diluting 13 to 15 drops of this solution with 10 c.c. of 0.5 per cent, solution of 64 SPIROCIOETES. glycerine. The mixture is wanned and, if no precipi- tate occurs, is poured on to the specimen and left for two or three minutes. Schmorl uses Giemsa's stain for sections of tissue, following it by a watery solution of alum. He admits that this method is inferior to Levaditi's silver method. Forest stains first with Ziehl's carbol-fuchsine in the cold, which dyes all spirochaetes except Sp. pallida, and then stains with Giemsa's stain for twelve to sixteen hours in the cold and for one-half hour at 70 C. Foix and Mallein note that the staining by Giemsa's solution may be hastened by the use of an electric current. Other Methods. Davidsohn recommends the use of cresyl violet for staining Sp. pallida; Oppenheimer and Sachs use carbolic gentian violet (concentrated alcoholic gentian- violet solution, 10 c.c., 5 per cent, solution of phenol, 100 c.c.). Proca and Vasilescu use Gino de Rossi's cilia-stain (dissolve 50 grm. pure phenol and 40 gr. tannin in 100 c.c. water and add to this 2.5 grm. basic fuchsine dissolved in 100 c.c. absolute alcohol. Stain in this for ten minutes, wash and dry. Then stain with a mixture containing concentrated alco- holic gentian violet 10 c.c., phenol 5 grm., distilled water 100 c.c.). Reitmann advises that films should be first treated with 5 per cent, solution of phosphoric acid in water for five minutes and then stained with carbol-fuchsine, warmed. Goldhorn uses a complicated preparation of poly- chrome methylene blue (methylene blue, lithium car- bonate and eosin), and McNeal also uses methylene blue and eosin (crude methylene blue 20 parts, pure medicinal methylene blue 10 parts, eosin (yellowish) 20 parts, and pure methyl alcohol 100 parts. Stain on GENERAL CHARACTERS OF SPIROCILETES. 65 cover-slip for forty-five to sixty seconds ; wash in dilute solution of sodium carbonate i drop of i per cent, solution in 10 c.c. water). Herxheimer and Hubner advise the use of bleu de Nil or bleu de Capri. Modifications of Jenner's or Romanowsky's stain are used by Simonelli and Bandi and by Von dem Borne. The former writers advise the method of May Grunwald, viz., dissolve i grm. of eosin (Grubler) in i litre distilled water, and i gr. of methyl- ene blue (Meister, Lucius and Briining) in a similar quantity of water; mix these solutions, allow to stand for two to seven days, and filter. Dissolve the sedi- ment in pure methyl alcohol, and stain preparations with this solution for four to ten minutes. Impregnation with Silver. Bertarelli and Volpino first introduced this mode of staining spirochaetes in tissue, but the modification of their method devised by Levaditi is usually preferred. His original method is as follows: Fix fragments of tissue, about i mm. thick, in 10 per cent, formol solution; wash in water, and harden in 96 per cent, alcohol ; then place in distilled water till they sink. Next place in the silver solution (silver nitrate 1.5 to 3 per cent.) at a temperature of 33 C. for three to five days. Wash in distilled water, and place in the reducing fluid (pyrogallic acid 2 to 4 per cent., formol 5 c.c., distilled water 100 c.c.) for twenty- four to forty-eight hours. Wash in distilled water, dehydrate, embed and cut (see Plate, Fig. B). A subsequent staining of the sections with Giemsa's stain or with toluydene blue may be carried out. A subsequent modification of this method was de- vised by Levaditi and Manouelian, by which the first solution is made of i per cent, silver-nitrate solution with the addition of 10 per cent, pyridine; the tissues 5 66 SPIROCILETES. are then washed in pyridine (10 per cent.) ; and reduc- tion is effected by a fluid containing pyrogallic acid, 4 per cent., 10 per cent, acetone, and 15 per cent, pyridine in distilled water. Ravaut and Ponselle use an albuminate of silver ("largine") in 2 per cent, solution, followed by 5 per cent, pyrogallic acid ; the largine bath may be repeated a second time after the pyrogallic solution, the tissue being washed with distilled water between the two baths. Yamamoto uses a 5 per cent, solution of silver ni- trate, followed by a solution of 2 per cent, pyrogallic and i per cent, tannic acid. He prefers embedding in celloidin, and uses LoefBer's methylene blue as a counter- stain. INDIAN INK METHOD. A special method of identifying these and other organisms on a field rendered opaque by means of indian ink has been devised by Burri. For this purpose ordinary indian ink is diluted with water (i part in 6 or i in 10). The solution is sterilised and allowed to stand for two weeks, the supernatant fluid being then ready for use. A loopful of suspension of the organ- isms is mixed with a drop of the ink-solution, spread on a slide and allowed to dry. The spirochaetes are then easily seen as colourless spirals on a dark background. Some writers prefer a stronger solution of the ink than that given above, e.g., i in 2 of water. EXAMINATION OF LIVING SPIROCHAETES. Dark Field Examination. The identification of living spirochaetes of the small varieties is most easily effected by examination on a "dark field" under the microscope, by means of one of the forms of par- GENERAL CHARACTERS OF SPIROCILETES. 67 aboloidal reflector. The scrapings of tissue can be examined in physiological saline solution or in the fluid exuding from the sore, or a drop of blood can be mounted and sealed so as to exclude the air. The movements of the spirochaetes render them easily visible. It is preferable, however, to add a drop of dis- tilled water to "the fluid containing the organisms, as this causes them to swell somewhat without losing their motility: they are thus more easily recognisable. Intra-vitam Staining. Mandelbaum stained living Sp. pallidaz in a hanging drop by adding a loopful of Lceffler's methylene-blue solution along with a loopful of decinormal soda-solution. Meirowsky makes a paste of methyl- violet and salt- solution, and rubs it into the (previously cleaned) sur- face of a syphilitic chancre. In the serum which exudes there are found stained specimens of Sp. pallida and Sp. refringens. (Certain more deeply staining dots in. the substance of the organisms he regards as nuclei.) Crystal violet is as efficacious as methyl violet. Sp. dentium may be stained by spreading a drop of fluid containing the organisms on a cover- slip, and placing this face downwards on a drop of concentrated watery solution of neutral red on a warm slide. PSEUDO-SPIROCH^TES. A vigorous controversy was at one time waged as to the reality of the spirochaetes seen in sections of tissue stained by the silver method, but there is now little doubt as to the genuine nature of these organisms. It may be conceded that the novice might be deceived by appearances presented by nerve fibres, by spirals of fibrin or elastic tissue, or by the edges of cells which take up the silver and present a crinkled appearance (Fig. 54) ; but those who have seen actual spirochaetes 68 SPIROCILETES. stained by this method could hardly confuse them with such objects or mistake the latter for them. It is not often that a doubt arises as to the reality of FIG. 56. FIG. 54. FIG. 55. FIG. 54. Pseudospirochaetes; edges of cells. (Baling.) tes in a smear fro (From a specimen by Professor E. A. ng. FIG. 55. Pseudospirochastes in a smear from the alimentary canal of Glossina palpalis. Minchin.) FIG. 56. Free flagellum of Trypanosoma lewisi. spirochaetes when other stains are used, but Professor E. A. Minchin has in his possession a film made from a "smear" of the contents of the alimentary canal of FIG. 57. Pseudospirochaetes or spirochaetes in a pig foetus. (Saling.) Glossina palpalis (the tse-tse fly) in which are spiral objects which appear to be artifacts, but which have GENERAL CHARACTERS OF SPIROCELETES. 69 almost exactly the appearance of true spirochaetes (Fig. 55) . The reason for regarding them as artifacts is that none were seen in other specimens of the same material and that their arrangement often in crosses or radiat- ing lines is peculiar ; but their resemblance is so exact that, if this view be correct, doubt may be thrown on many descriptions of spirochaetes given by other writers. Objects somewhat resembling spirochaetes are the male gametes of some protozoa (coccidium, plasmodium) , the flagella of trypanosomes which may occasionally be found free (Fig. 56), and attenuated forms of these last organisms and of Herpetomonas or Leishmania. The appearances found by Karlinski in a macerated pig- fcetus and figured by Baling (Fig. 57) may be either real or simulated spirochaetes. CLASSIFICATION. It has already been pointed out that the position of the spirochaetes in nature whether they are to be re- garded as protozoa or bacteria is doubtful. Their relations as a group are almost equally undecided. The resemblance of the smaller to the larger spirochaetes is not very close. Indeed, while each of these groups is fairly well marked, the relationship between the two is almost less striking than that of the smaller organisms to a group of bacterial organisms the large spirilla. The Sp. obermeieri was originally classed with these, and it seems not impossible that this view is more correct than the recent classification of these little organisms with the spirochaetes. Certain peculiarities observed in the Sp. pallida led Vuillemin and afterward Schaudinn to separate it from the other small spirochaetes and to put it in a dis- tinct genus, called by the former Spironema and by the 70 SPIROCH,ETES. latter (as this name was already occupied) Treponema. The characteristics of this genus were: The round shape of the body in section, as opposed to the flattened shape of the spirochaetes ; the fixity of the curls exhib- ited by the organism; the absence of an undulating membrane; and the presence of terminal filaments. Sp. pertenuis, from its close resemblance to Sp. pallida, was afterward placed in the same genus. Examination of the qualities on which this distinc- tion is founded does not tend to strengthen a belief in its validity. The round shape of the organism in section may be admitted, but the ribbon-like shape of the other small spirochaetes is not very clearly established. The existence of an undulating membrane is doubtful even in the larger spirochaetes, and still more problematical in the smaller group. Terminal filaments may be found in other species besides Sp. pallida; and finally the even curls presented by this spirochaete may at times be ab- sent, as is admitted even by Schaudinn himself. Nor- ris, Pappenheimer and Flournoy point out that the Sp. obermeieri exhibits all the characteristics assigned to a treponema. Blanchard gives the following classification : A. SPIRO BACTERIA. Cohn, 1875 (Spirillaceae, Mi- gula, 1890). Curved bacteria; rigid; exhibiting trans- verse division. 1. Spirosoma, Migula, 1900. Curved rigid rod; no flagella. (Sp. nasale, Wibel, 1887. Sp. linguale, id., 1888.) 2. Vibrio, Ehrenberg, 1878. (Microspira, Schrotter, 1886.) Rigid, flagellated rods, joined end to end, no spores. (V. cholera, etc.) 3. Spirobacillus, Metchnikoff, 1889. Large spiral bacteria; lateral flagella; spores. GENERAL CHARACTERS OF SPIROCH.ETES. 71 4. Spirillum, Ehr., 1833. Spiral, cylindrical or- ganisms ; blunt ends ; no undulating membrane ; spores ; terminal flagella (many species) . B. TRYPANOSOMID^:. Doflein, 1901. Flagel- lated; flexible; undulating membrane; longitudinal division; not cultivable. 1. Spirochata, Ehrenberg, 1833. (Spirochaete, Cohn, 1 83 5 .) Thin, spiral ; flattened ; undulating mem- brane; no flagella; filiform nucleus and chro- matin granules (type, Sp. plicatilis). 2. Treponema, Schaudinn, 1905. (Spironema, Vuillemin, 1905). Characters as stated above. (Trep. pallidum.) 3. Trypanosoma, Gruby, 1844. Liihe divides spirochaetes into : 1. True spirochsetes, including Sp. plicatilis, bal- bianii, buccalis, dentium, vincenti, vaccines, refringens, pseudo-pallida, and the spirochaete of dysentery. 2. Blood-spirochaetes, including Sp. gallinarum, anserina, obermeieri, duttoni, theileri. 3 . Treponema : Tr. pallidum and pertenue. Gross who believes that spirochaetes are closely allied to the bacteria, coins a new name for the whole genus, Cristispira, derived from the crest or ridge which he believes to run along one side of the body or around it (this formation having given rise to the statement that spirochaetes possess an undulating membrane). SECTION II. SYSTEMATIC DESCRIPTION OF SPECIES. The various spirochaetes will be considered here in the following order : LARGE FORMS. Spirochaeta plicatilis. Sp. balbianii. Sp. anodontae and other spirochaetes in shell-fish. Sp. polyspira. SMALL FORMS. (Spirilla?) Sp. obermeieri. Sp. duttoni and other species in relapsing fever. Sp. pitheci. Sp. anserina. Sp. gallinarum. Sp. lagopodis. Sp. lovati. Sp. vesperuginis. Sp. lutrae. Sp. theileri and allied forms. Sp. suis. Sp. laverani, Sp. muris, Sp. minor, Spirochaetes in mouse-cancer. Sp. gondii. Sp. culicis, Sp. minei. Sp. gadi, Sp. pelamydis, Sp. jonesii. Sp. hartmanni. Sp. bufonis. 72 SYSTEMATIC DESCRIPTION OF SPECIES. 73 Sp. buccalis, Sp. dentium, Sp. vincenti, Sp. gracilis. Sp. schaudinni. Spirochaetes in gangrenous processes, haemoptysis, etc. Sp. microgyrata. Sp. in small-pox and vaccine lymph. Sp. refringens, Sp. balanitidis. Sp. pseudo-pallida. Sp. pallida. Sp. pertenuis. Sp. lymphatica and forms found in anaemia. Sp. aboriginalis. Sp. interrogans. Various doubtful spirochaetes and spirilla. LARGE SPIROCHAETES. SPIROCH^ETA PLICATILIS. (Ehrenberg, 1833.) This, the first discovered species of spirochsete, is found in stagnant fresh water, especially along with algae of putrefaction. It attains a length of 200^, but its average length is 80/1 and its breadth 0.5;* (Doflein). 1 In shape it shows a double series of spiral curves, a larger series producing a generally undulating appear- ance, and a smaller series imposed upon these (Figs, i, 58) . Its extremities are rounded, according to Biitschli : but Laptschinsky thinks that they are normally sharp and that blunt ends indicate that the organism has broken into pieces. It is flattened in form, like a ribbon. It possesses a periplastic sheath and contained ento- plasm. Along the central axis is a refringent central rod, which stains darkly; granules of staining sub- stance (nuclei) are arranged along this rod. This spiro- chaete, according to Butschli, has no undulating mem- 1 Illustrations of the organism make it appear much broader. 74 SPIROCILETES. brane, Schaudinn who attributed to it such a membrane probably having mistaken for it the loose periplastic sheath. It exhibits screw-like movements, but also creeping and feeling (kriechend, tastend) movements, while the contraction of its sheath may lead to a thicken- ing and thinning of the body at different places. Its mode of multiplication is not known, but it has been seen to break up transversely. IG. 58. Spirochaeta plicatilis. (Schaudinn.) The most recent description of this organism is due to Zuelzer, according to whom it is round in section, with a central axial thread of elastic substance and a simple spiral twist. A round refringent body is placed at the central point of each wave, and fine granules of volutin are also present. Sometimes a terminal gran- ule is seen at one extremity, from which the axial filament starts. The length may reach 500/1 and the breadth /*. The ends may be rounded or sharp. Transverse division occurs, either two or more frag- SYSTEMATIC DESCRIPTION OF SPECIES. 75 ments being thus produced. A streaming of protoplasm may be seen. There is no undulating membrane or distinct periplast. The axial thread is important for classification. Sp. plicatilis may be found in the sea (Naples) as well as in fresh water. The organism is dissolved by trypsin. As Sp. plicatilis is the "type species " and other spiro- chaetes must justify their inclusion in the genus by their FIG. 59. Diagrammatic representations of Spirochaeta plicatilis; a, according to Zuelzer, straight central rod and dots in the curls; b, after Schaudinn, central rod follows the curves, dots superposed on it at random; c, after Doflein, double series of curls with cor- responding dots and indications of central rod; d, imaginary figure showing central rod corresponding with dots in the diagram resemblance to this, it is unfortunate that so great a diversity obtains between the descriptions given by various writers. Thus the organism is flat (Schaudinn, Doflein) , round (Zuelzer) ; it has a double series of curls, smaller and larger (Doflein) , a single series (Zuelzer) ; its axial filament follows the curves of the organism (Schaudinn) ; it runs in a straight line (Zuelzer) . These differences are illustrated in the accompanying dia- 76 SPIROCILETES. gram (Fig. 59). It is noteworthy that the nuclei (?) are distinct from the axial filament, whereas in Sp. balbianii the central staining rod is regarded as nuclear. Very remarkable is the conflict of opinion between such observers as Butschli and Schaudinn as to the possession of an undulating membrane by so large an organism as this. Its creeping and feeling movements are also noteworthy, as being unlike those seen in other spirochaetes. The movements of swelling and thinning may be compared with the "euglenoid" movement seen by Plaut in Sp. vincenti. It has been pointed out to me by Mr. T. P. Collings, to whom I am indebted for the preparation of the illustrations in this little work, and whose experience in drawing from the microscope is very extensive, that the series of dots seen in the illustrations of Sp. plicatilis is very suggestive of the existence of a spiral rod or filament seen in optical section in the tissues of the ' ' cork- screw". Fig. 59, d, shows such a rod corresponding with the position of the dots in the diagram above it. The vast experience, however, of the authors who have described Sp. plicatilis makes it unlikely that they would have failed to recognise such a structure if it had been present. SPIROCELETA DAXENSIS. (Cantacuzfene, 1910.) Cantacuzene found in the water of the hot springs of Dax (52 to 56 C.) a spirochaete closely resembling Sp. plicatilis. It was from 30 to loo/* in length by ^ to 2%n in breadth, flattened in form, and exhibited a double series of curls, smaller waves being superposed on the larger undulations. It possessed a longitudinal chromatin filament and was narrower toward the ex- tremities, but these were not actually pointed. The SYSTEMATIC DESCRIPTION OF SPECIES. 77 organism creeps about on the surface of the algae present in the water. Cantacuzfene distinguishes three kinds of individuals : i , slender forms (/* in breadth) , the axial filament of which did not extend quite to the extrem- ities; 2, shorter, thicker forms (i to i%p in breadth), exhibiting no axial filament and sometimes occurring in small masses; and 3. a few specimens showing a central swelling, some 2^ in thickness, in which all the chro- matin was collected, though the rest of the organism stained darker than did the other forms. Sometimes two swellings were seen, one to the right and the other to the left of the central point. SPIROCH^ETA BALBIANII. (Trypanosoma balbianii, Certes, 1882.) This large spirochsete was first described by Certes in 1882, though it had been previously seen by Moebius. It is found in the crystalline style of the oyster (Ostrea angulata, 0. edulis). It attains a length of 100 to i2o/x and a breadth of 5/x (extremes 26 to zoo/* in length; 3 to 5/1 in breadth, Perrin). Perrin describes an in- different form, a female form, and male and female gametes. Taking the so-called indifferent form as typical, the general proportions being those described above, the organism consists of a periplastic sheath with fluid protoplasmic contents. The former is of some- what firm consistency, retaining its form when the contents have escaped. It is furnished with an un- dulating membrane, running spirally round the body (Fig. 2). This has a dark peripheral fibre (border fibre, randfibrille) or thickening of the edge of the membrane. There is a dark nodule at each end of the periplast. The nucleus consists of a spiral band (karyosome) formed of achromatic substance with bars of chromatin 78 SPIROCTLETES. at regular intervals; sometimes the bars may exist separately without the connecting band (Figs. 7, 60). Multiplication takes place by longitudinal division, and may be very rapid in suitable conditions, giving rise to the appearance of very attenuated individuals, scarcely visible under the microscope. Divi- sion of the undulating membrane precedes that of the body of the organism. When fission is nearly complete, the daughter individuals remain attached by a strand of periplast for some time, appearing as a single individual of abnormal length with a thin portion in the middle. In the process of division the nucleus first condenses to form a straight rod, lying in the central axis of the animal. This rod breaks up into short segments, shaped first like bacilli and then as dumb-bells; these are next broken up into little spherical masses, which take up posi- tions in two rows and finally in groups of four. Perrin believes that the total number of these is sixty-four. When fission has oc- Spirochseta curr ed and the new individuals are formed, balbianii. the nucleus of each reforms a spiral band. (Schellack.) ^ ^ 1 , e Encystment takes place by a senes of movements by which the two ends of the spirochaete first travel alternately up and down its length, and then the whole organism rolls up into a coil (Fig. 41). The periplast then bursts, and the entoplasm escapes, tak- ing a spherical form, but not secreting any covering membrane. The female forms are described as larger and stouter, with a thicker periplast. They have a smaller undulat- ing membrane, and encyst less readily. The nucleus goes through a somewhat different course of changes in SYSTEMATIC DESCRIPTION OF SPECIES. 79 encysting. Masses of chromatin are formed, connected by thin threads. These divide into fragments, of which the greater number degenerate, but two remain and conjugate (autogamy) , subsequently giving rise to the female gametes. The male gamete is distinguished by the appearance of a rounded swelling of the entoplasm in the middle of the body, followed by longitudinal division of the organism, starting simultaneously at both ends. A reduction of chromosomes takes place in the central swelling, thirty-two remaining. Presumably the result- ing individuals conjugate with female forms, but Perrin notes that he was able to observe only a few doubtful examples of cojugation (Fig. 35). Fantham confirms Perrin's account of the general form of the nucleus. Further confirmation is needed of the different forms distinguished by Perrin, and of their true meaning, but we may compare Gonder's account of Sp. pinnce. It is noteworthy that Perrin found that not all these spirochaetes had undulating membranes, and also that he observed little difference in the movements of the forms with it and those with- out it. He does not accept the view of Laveran and Mesnil that the organism is furnished with a sheath, rather than with an undulating membrane, but agrees with them that it is a spirochsete, though he describes it as a trypanosome. SPIROCH^ETA ANODONT^E. (Keysselitz, 1906.) This large spirochsete was discovered by Keysselitz in the fresh- water mussel (Anodonta cygnea) ; it also occurs in Anodonta mutabitis. It exists in the crys- talline style, and may also be found in the liver and in 80 SPIROCELETES. the gastric epithelium. It attains a length of 130^ and a breath of 3 to 4^. It is said by Keysselitz, to have a flattened form and either sharp or blunt extremities (Figs. 61, 62, 620). Those with sharp ends show peri- plastic appendages (periplastfortstaze). The periplast is fibrillary in appearance, and there is a granule (basal- korn) at each end and an undulating membrane. The nuclear chromatin takes the form of balls, irregular masses and elongated bands; it may collect in a single strand toward the centre of the organism. Keysselitz FIG. 61. Spi'-ochseta spiculifera. (Schellack.) did not observe a spiral arrangement like that described by Perrin in Sp. balbianii, but admits that such may exist. Division is by longitudinal fission. Schellack notes that the border fibre of the undulat- ing membrane is of variable thickness, tapering toward the end, unlike that of trypanosomes, and believes that it is not a true membrane, but an artifact due to sepa- ration of periplast. I am inclined to agree with this view, as I find that the better the preparation is fixed the fewer organisms appear with this formation (see page 20). The nucleus, according to Schellack, consists of a series of bands, not of a spiral, and the whole SYSTEMATIC DESCRIPTION OF SPECIES. 81 organism is built up of a series of chambers arranged longitudinally. Rolled up forms occur which may possibly represent cysts. He also believes that multi- plication is by transverse, not by longitudinal division (Fig. 28), but I have seen a spirochaete apparently in process of longitudinal fission. The blunt and pointed forms described by Keys- selitz are held by Schel- lack to constitute different FIG. 62. FIG. 62 a. FIG. 62. Spirochasta anodontae; specimen with blunt extremi- ties; different sizes. FIG. 620. Spirochaeta anodontse (Sp. spiculifera) forms with pointed ends; different sizes. species ; to the latter he gives the name Sp. spiculifera (Fig. 61). He describes a long form, from 39 to 50. 5// long and o . 9 to i . 2ju broad (average, 46/1 by i/x), and a sharp-pointed form, 28 to 36^ long and 0.7 to i . i/t broad (av. 32^ by 0.9^). In my own experience four- teen specimens with blunt ends gave an average length of exactly IOQ/J. (extremes, 130 and 76jw), while of fifteen sharp-pointed specimens the average length was 55.6^ 82 SPIROCILETES. (extremes, 96 and 34^). The short variety tends to be rather thicker than the long. I find, however, spirochaetes differing greatly in length and even more remarkably in thickness, which it would be difficult to sort out into two distinct species. I am inclined to regard the specimens with pointed ends as having re- cently divided. Schellack admits that it is curious that two forms should be found to coexist in each of three FIG. 63 . Small spirochaetes from the alimentary canal of Anodonta. different molluscs (Anodonta, Tapes, and Ostrea), and there does not seem any good reason for making separate species of these slightly divergent forms at present. On the other hand, without stronger grounds we are not justified in describing them even as sexual forms of the same organism. I have found in the alimentary canal of Anodonta minute spirochaetes, 10 to i2// in length (Fig. 63) which may be identical with Sp. hartmanni of Gonder or with Sp. pusilla of Schellack (see below) . SPIROCH^TES OF OTHER MOLLUSCS. Schellack has examined a large number of different shell-fish and found spirochaetes in many of them, as shown in the following list. He believes that the average measurement of individuals taken just after division is a good criterion of species. He depicts many spirochsetes with a line of separation in the middle of their length, pointing to transverse division. I have not myself been able to observe such specimens in the case of Sp. anodontoz, and even in the longest in- SYSTEMATIC DESCRIPTION OF SPECIES. a* E S a"a"3"3 S S S S "3 E S E E g '. I 1 ! i. 111 * * 1 ..3 a J a "S -a 'g. a| Ullliil 3|-S-3a 3 g SlggggS^ -Sag.SS rrr rrfr^rf rr rr ? M M M O O O O M* M* H H 6 M M O I ? I I iiiilliiiii 6o6d tfS iiii M fi ^ s HjDa^^O Oi Cj*2 O. 3 i 1 1 1 ^ I ,- - -g g eo O < J ii )! - ! ___ ddddddd cncoco c/jcococncowco H d d en co 84 SPIROCILETES. dividuals which I have seen no sign of division was dis- coverable. I have, on the other hand, noted the exis- tence of thin forms, which look as if they were formed by longitudinal fission, as was noted by Perrin in Sp. balbianii. Hence the above criterion does not seem adequate for the differentiation of species. Fantham describes Sp. balbianii as occurring in Tapes which points to the probable identity of Sp. tapetos and Sp. balbianii, and throws further doubt on Schellack's classification. The following table embodies the lat- ter's observations (see also Fig. 64) : SPIROCH^ETA PINN.E. (Gonder, 1908.) This organism occurs in Pinna squamosa and P. nobilis. It varies from 10 to 60/1 in length and in breadth from | to 3/x. 1 One end is blunter than the other, and here is situated a blepharoplast. An undu- lating membrane is present. The nucleus may take the form of a single rod or of irregular masses, which are sometimes arranged in groups of four. The rod- form is uncommon and is seen in very motile forms, which Gonder regards as possibly male elements, the irregular masses then characterising female or indiffer- ent forms. A concentration of all the chromatin into one rounded mass was sometimes observed. Such individuals may constitute involution forms. En- cysted forms also occur. SPIROCH^ETA MACTR^E. (Prowazek, 1910.) Found in the crystalline style of the mollusc, Mactra sulcataria (Deshayes), in Japan, this organism is from 45 to 70^ in length by 0.8 to i/i in breadth. It has an undulating membrane. 1 The dimensions of this organism given by Schellack are some- what different (see table above). SYSTEMATIC DESCRIPTION OF SPECIES. 85 FIG. 64. Spirochaetes from mussels. (Schellack.) a, Sp. spiculifera; b, Sp. cardii papillosi; c, Sp. saxicavae; d, Sp. tapetos (X 2250); e, Sp. spiculifera; /, Sp. pusilla; g, Sp. pusilla; h, Sp. anodontae; i, Sp. limae; k, Sp. ostreae; /, Sp. modiolas. X 1000 (ex- cept d) . 86 SPIROCH^TES. SPIROCH^TA PECTINIS. (Cristispira pectinis, Gross, 1910.) Gross found spirochaetes free in the alimentary canal of the mollusc, Pecten jacob&us. They were 72/1 long, and 1.5/1 thick, round in section, with blunt ends. They had a ridge or comb (kamm, crista) running along one side, but no terminal filaments. They seemed to consist of a series of chambers placed one behind the other, like a filament of some alga. SPIROCH^ITA INTERROGATIONS. (Cristispira interrogationis, Gross, 1910.) This organism was also found by Gross in Pecten jaco- b&us. It is 25/4 in length by 0.5/1 in breadth, and has pointed ends, bearing apparently to Sp. pectinis a rela- tion similar to that of Sp. spiculifera to Sp. anodontcs. SPIROCH^ETA POLYSPIRA. (Wolff, 1907.) This organism was found by Wolff in putrid potato and grows on ordinary media. He describes two forms : one with sixty to seventy curls, 70 to 8o/z long by 1.5 to i. 6/1 broad, which multiplies by longitudinal division, and a second 140/1 long by 0.25 to 0.3/1, with sixty to eighty curls. Wolff is inclined to class this organism as a treponema. It is placed here on account of its length, but should perhaps rather be included with the small spirochaetes. SMALL SPIROCHJETES OR SPIRILLA. SPIROCH-ffiTA OBERMEIERI. (Cohn, 1877.) (Sp. recurrentis, Lebert, 1874.) According to the recent descriptions of Novy and Knapp and other observers this spirochsete or spiril- SYSTEMATIC DESCRIPTION OF SPECIES. 87 him is from 7 to 19 p in length, and perhaps /* in breadth (Fig. 65) . Long forms may be met with, up to 100 fj. (i20fi, Popovitch). It multiplies by transverse division (see Fig. 29), usually binary, but it is possible that multiple fission may at times occur. It usually stains homogeneously throughout, with the exception that the ends take the dye rather more faintly. Termi- nal appendages or flagella may be present. It has no undulating membrane or lateral flagella. Tangled masses of spirochsetes may at times be seen, or two or more individuals twisted together. Granules are occasionally visible in the length of the organism, and monili- form degeneration occurs (see Fig. 27). Cox found spirochsetes inside the blood-corpuscles, where they broke up into sections and finally into granules. Norris, Pappenheimer and Flournoy state spirochaeta that they cultivated these spirochsetes in ( r |p U1T ober? citrated blood. The spirochaetes can be kept meieri). i- f e i *. -j A i (Schellack.) alive for as many as forty days outside the body (Novy and Knapp) , but multiplication under such conditions is doubtful. Destructive (spirillicidal) and agglutinating bodies are formed in the blood of im- munised animals, and passive immunity is conferred by injection of their serum. Apes, rats and mice can be infected with these organisms, but not rabbits, sheep, goats, fowls or pigeons (Fraenkel) . Fuchsine, gentian violet, Giemsa's stain and Levaditi's silver method may be used for staining Sp. obermeieri. It is said that infection with relapsing fever may be carried by the air. The bites of insects have also been assigned as a means of conveyance of the disease. Klodnitsky describes a development of the spirochaetes into long filaments within the bodies of bugs; but 88 SPIROCH^ETES. Nuttall suggests that he mistook the spermatozoa of the animal for spirochaetes (see Fig. 34). Sp. obermeieri is destroyed by glycerine (Gabrit- chewsky) . The action of a variety of different reagents upon these organisms was studied and tabulated by MacKinnon. Sp. obermeieri in some form or other is capable of passing through a Berkfeld filter. The spirochaetes met with in cases of relapsing fever in America, in Bombay and in African tick fever are slightly different from the species met with in Russian relapsing fever, the typical form of the disease. Sp. duttoni of tick fever is described be- low. The spirochaete of American relapsing fever (Sp. novyi) is more delicate than that of the Russian disease and shows more regular and closely-set curls (Fig. 66) . The spiril- lum f Bomba 7 fever (SP- carter $ is thinner, less regularly curled, and forms loops and "figures of 8" (Novy and Knapp). Animals inoculated with one species become immune to subsequent infection with this form, but not to infection with the other species. SPIROCH^ETA DUTTONI. (Novy and Knapp, 1906; Breinl, 1906.) This organism was first discovered by Ross and Milne and found independently by Button and Todd. It occurs in the disease known as tick fever on the east coast of Africa. Infection is conveyed by the bite of the tick, Ornithodorus moubata, which exists in great numbers in the huts of the natives. The spirochaete is from 14 to 16/1 long, with six to seven spiral turns; SYSTEMATIC DESCRIPTION OF SPECIES. 89 long forms may be found up to 45/1 in length. It has a dark central rod of staining material, and a faint sur- rounding periplast. It often exhibits dark or refrin- gent granules in its body. Multiplication is probably by transverse division (Fig. 67), but forked forms are found. Rolled up specimens are seen within leucocytes, but these are considered by Levaditi and Mancunian to be degenerative, and not resting forms. The cilia described as present on these spirochaetes by some writers are probably artifacts (Mayer). Koch states that Sp. duttoni shows no chromatin granules, but Mayer describes a differentiation of nuclear matter and protoplasm (see Fig. 24). The latter writer found in an infected mouse, forms resembling B. fusiformis, which may be stages in the development of the organ- FlG 6 _ Sp i ro . ism. These may be compared with chaeta duttoni. ^1 1 T^ j. 1 j o- j (Schellack.) those seen by Krzystalowicz and Sied- lecki in cases of syphilis (possibly stages of Sp. pallidd) . L. A. and R. S. Williams state that they cultivated Sp. duttoni in defibrinated blood at room temperature, but it is doubtful whether true cultivation was effected. Duval and Todd devised a special medium for this pur- pose (see page 31) and succeeded in keeping the organ- isms alive for forty days. Levaditi "cultivated" these spirochaetes in collodion sacs in the peritoneal cavities of rabbits along with the serum of monkeys (Macacus cynomolgus) and found that vibrio-forms developed. A form of spirillum fever was observed by Hodges and Ross in Uganda, which is believed by Moffat to be different from the tick fever of the Zambesi region. The spirochastes found by Hodges and Ross were 90 SPIROCHJETES. apparently very large from 36 to 40^ in length by 4fi in breadth. Allusion has already been made (page 37) to the spirochaetes found by Carter in S. Arabia. No detailed description of the organism is given, but the writer describes longitudinal fission as taking place and also a process of conjugation. Figures 40 and 48 are copied from his original paper and show some of the forms ob- served ; but the nature of their appearance is so peculiar that it would be premature to draw definite conclusions from the observations thus far made. SPIROCH^ETA PITHECI. (Thiroux and DufougerS, 1910.) Thiroux and Dufouger found spirochaetes in mon- keys (Cercopiihecus patas) suffering from an affection characterised by irregular attacks of fever a condition resembling relapsing fever in man. The organisms were 15 to 20/x in length by o. 25/1 in thickness, and pre- sented five or six curls. Rolled up forms were also seen. The blood of the monkey was infective between the attacks of fever, and the disease was readily trans- missible to mice, less easily to rats. In mice the incu- bation period was two to six days, and death usually occurred on the twenty-fifth or twenty-sixth day after- ward. The spirochaetes were present in one case in the cerebro-spinal fluid, and the monkey in this instance suffered from epileptiform attacks. The authors point out a resemblance to the position and action of the trypanosomes of sleeping sickness. SPIROCH^ETA ANSERINA. (Sacharoff, 1890.) Sacharoff found these organisms in geese suffering from a fatal malady, characterised by fever, wasting SYSTEMATIC DESCRIPTION OF SPECIES. QI and diarrhoea. The bird sits apathetic and will not eat. The joints of the feet are so tender that the slight- est handling of them causes cries of pain. The disease is a septicaemia, masses of spirochaetes being found in the blood. According to Sacharoff geese and ducks are the only birds susceptible, the incubation period of the malady being two days. The blood of the infected bird is spirochaeticidal, and immunity is produced in this way, not by phagocytosis (Gabritchewsky) . Sacharoff, however, saw spirochaetes inside leucocytes. Gabritchewsky injected a horse with the infected blood and obtained a preventive and Curative serum. for comparison. Cantacuzene holds that bacterioly- ( Sacharo -) sis and agglutination, in the case of these spirochaetes, are phenomena which only occur in vitro, and states that destruction of the organisms takes place by phagocytosis in the spleen. The spirochaete (Fig. 68) is from 10 to 30 /* long and thinner than Sp. obermeieri. It multiplies by transverse division. A somewhat curious formation is depicted by Cantacuzene in organisms which are dividing, viz., the appearance of a faint rounded nodule in the centre at the point of division. Borrel believes that Sp. anserina is the same as Sp. gallinarum, but this is not consistent with SacharofFs statement that only ducks and geese are susceptible to the former. SPIROCH-fETA GALLINARUM. (Marchoux and Salimbeni, 1903.) According to Prowazek these spirochaetes have flattened bodies, terminal processes, and an undulating Q2 SPIROCILETES. membrane (?). He believes that they possess a central rod (axenstrang) which is elastic, and a contractile sheath. In length they vary from 4 to 20;*, and may show as few as two curls or a large number. Terminal granules are often seen, and the chromatin may gather to the centre of the organism, leaving the ends colour- less. Division is longitudinal. Resting forms occur some with terminal loops, others closely curled up, others again in the form of a "figure of eight" (see Figs. 26, 33, 51). They cling together in masses, but no true agglutination occurs, as the organ- isms free themselves again from the clumps. They may get inside the red blood-corpuscles (Fig. 69). Prowazek notes that the undulating membrane is FIG. 69. Spiro- chaeta gailinarum best seen in macerated specimens. It de. bl (Prowazeko is > therefore, probably an artifact. The cilia described by Zettnow as present on these organisms are also probably artifacts and due to plasmolysis. These spirochaetes are killed by glycerine. The spirochaetes can be directly inoculated from fowl to fowl, and are also conveyed by the bites of ticks (Argas miniatus, A. persicus, A. reflexus, Ornithodorus moubatd) . Rabbits can be infected with this organism (Levaditi and Lange) . Marchoux noted a loss of viru- lence in these spirochaetes when they were passed through a series of fowls and thinks that the original virulence is regained by sojourn in the body of a tick. The crisis of the disease is not due to the formation of antibodies, but may be due to phagocytosis. Atoxyl is both protective against the affection and curative when it already exists. Salvarsan (Ehrlich-Hata) is also very efficacious. SYSTEMATIC DESCRIPTION OF SPECIES. 93 SPIROCH^TA LAGOPODIS. (Fantham, 1910.) Fantham found this spirochaete in the blood of the grouse. It is from 10 to 18/1 in length, and relatively broad (see Fig. 25). It is variable in form. Its ends taper to points, and it has an undulating membrane, spirally wound round its body. Within its substance may be seen a series of chromatin bars, and sometimes a helicoid core. It multiplies by both longitudinal and transverse division. It may be transmitted from one bird to another by the parasite, Ixodes ricinus. SPIROCH^TA LOVATI. (Fantham, 1910.) This organism is found in the caecum of the grouse. It is from 16 to 3 2 . 5/1 in length, and its ends are usually pointed, rarely rounded. It possesses an undulating membrane, and multiplies by both transverse and longitudinal fission. SPIROCH^ETA VESPERUGINIS. (Gonder, 1908.) Nicolle and Compte found spirilla in a Tunisian bat (Vesperugo kuhlii). The organisms are from 12 to i8/* long, and /* or less in breadth ; they have pointed ends and no undulating membrane, and multiply by trans- verse division. Crisis and relapse occur, and there is enlargement of the spleen; some immunity is conferred by an attack. Nicolle and Compte regard the or- ganism as a bacterium, but Gonder claims it as a protozoon. The latter found individuals up to 30^ in length; and small forms, 3 to 5^ long, were x 2250. (Gonder.) p IG . 7 o. Spiro- 94 SPIROCELETES. found in ticks (Fig. 70) . He believes that this spiro- chaete divides longitudinally and has terminal appen- dages of periplast and an undulating membrane ; but as he notes that this last only becomes visible on addition of glycerine, it is likely that the apparent membrane was an artifact. Gonder also describes dots of chro- matin in the substance of the organism, which at other times are replaced by a chromidial network. SPIROCH^ETA LUTR^E. (Prowazek, 1907.) This organism was found by Prowazek in the blood of the otter. The only description which he gives of it is that it is a broad, band-shaped spirochsete, with blunt ends, and that large chromatin bodies (Chro- FIG. 71. Spirochaeta lutrae and rod-shaped bodies. (Prowazek.) matinbrocken) were visible in its protoplasm (Fig. 71). Whether it had any relation to certain oval bodies ("like pbrine corpuscles") present in the blood along with it, he leaves undetermined. SPIROCH.ETA THEILERI. (Laveran, 1902.) This organism was found by Theiler in cattle suf- fering from a disease characterised by fever, diarrhoea, and enlargement of the spleen. Disappearance and re- appearance of the spirochaetes may take place, as in the relapses of recurrent fever. The parasite is from SYSTEMATIC DESCRIPTION OF SPECIES. 95 20 to 30/1 long and \ to |/* in breadth; it appears in regular "cork-screws" and in irregular forms. It shows undulating movements, and may be free or attached to the blood-corpuscles. Infection may take place by the bite of the tick, Rhipicephalus decoloratus, and possibly a developmental stage may occur in this host, as direct inoculation did not succeed. Theiler also found spirochaetes in horses and sheep suffering from fever, and suggests that these may be the same organisms. He succeeded in inoculating a sheep with the bovine organism. Martin found spirochaetes in a sick horse in French Guiana; this form measured 12 to i$/y. in length by \fj. in breadth. Baruchello and Pricolo found spirochastes in in- fective pleuropneumonia of horses; these organisms were apparently very small, measuring 3.2^ by 0.5^. They occurred in the spleen, pulmonary alveoli, pleural effusion and blood. They sometimes exhibited terminal granules. Heanley found spirochaetes in buffaloes in China, and Martoglio and Carpano found organisms of this nature in sheep. The relationship between all these spirochaetes is doubtful. Dodd believes that the spiro- chaetes met with in the horse, ox, and sheep (called by Nov^y and Knapp Sp. equi, Sp. bovis, and Sp. ovis, respectively) are identical. SPIROCH^TES IN THE PIG. (Spirochaeta suis?) Dodd found spirochaetes in a disease affecting the skin of the pig, communicated by contact and inocu- lable in the skin of a healthy animal. The organisms (Fig. 72) were not found in the blood; they disappeared 96 SPIROCH^TES. and reappeared in the cutaneous lesions from time to time. Cleland observed spirochaetes in tumours occurring at the site of castration in pigs. The organisms were from 6 to i2/x in length and exhibited three or four irregular curls. Along with these organisms were large FIG. 72. Spirochaeta suis. (After Dodd.) bacillary forms, some of which were slightly undulat- ing and suggestive of being modified forms of the spirochaetes. SPIROCELETA LAVERANI. (Breinl and Kinghorn, 1906.) These organisms, found in mice by Breinl and King- horn, measured from 1.8 to 3.75^ in length, and o.i to 0.2/4 in breadth. They had pointed ends (one more so than the other) and one to four curls. They were transmissible by inoculation, with an incubation period of five days. Transmission by fleas and lice was not effected. The mice showed enlargement of the spleen. SPIROCHAETA MURIS. (Wenyon, 1906.) Found by Wenyon in mice, this organism (Fig. 73), is from 3 to jn long and 2/1 broad. It has no undulat- SYSTEMATIC DESCRIPTION OF SPECIES. 97 ing membrane, and multiplies by transverse division. The blood of the mouse is not infective, nor was trans- mission by fleas effected. It is apparently a harmless parasite. Wenyon thinks it may be identical with the form found by Borrel in mouse-cancer and perhaps with the spirilla discovered in the rat by Carter. FIG. 73. Spirochaeta muris. (After Wenyon.) SPIROCH^TA MINOR. (Spirillum minor, Carter, 1887.) Carter found in the rat, Mus decumanus, spirilla (spirochaetes ?) measuring 5 to gft in length, and pos- sessing four to eight curls. He describes them as shorter and slenderer than Sp. obermeieri. They have pointed ends, and exhibit movements of rotation, pro- pulsion, and lashing. They disappear and reappear in the blood of the rat, being replaced during their absence by granular particles and filaments. SPIROCH^TES IN MOUSE-CANCER. Gaylord found spirochaetes constantly present in mouse-cancers, both primary and secondary. They were studied by Calkins, who describes them as 2.5 to 7.8/1 in length, o.6// broad, and possessing four to thirteen curls. The ends are blunt and rounded, and they have no undulating membrane or flagella. Borrel had previously observed these organisms in 1905. They are not causally connected with the 7 98 SPIROCELETES. tumours, but are passed from mouse to mouse in inocu- lating the growths. Calkins identified them with Sp. microgyrata (see below). SPIROCH^ETA GONDII. (Nicolle, 1907.) Nicolle found spirochaetes in the blood of the rodent, Ctenodactylus gondi. They measured 16 to igji in length by 0.3^ in breadth. SPIROCH^ETA CULICIS. (Jaffd, 1907.) Jaffe found in the alimentary canal of the gnat spiro- chaetes visible with a comparatively low magnification (X 220). They were flattened, band-shaped organisms, showing deeply stained granules in their protoplasm when treated with Giemsa's stain. Their movements were lashing, undulating, and "cork-screw-like." They were not furnished with an undulating membrane, and no examples of division were seen. SPIROCH^TA MINEI. (Prowazek, 1910.) These organisms are found in the stomachs of "worker" and "soldier" ants (Termes lucifugus, Rossi) in Japan. They are from 15 to 5o/x in length, by 0.3 to i/j. in breadth. The extremities are pointed and chro- matin granules are seen in the protoplasm. Division is longitudinal and rolled up forms and rosettes are found. SPIROCH^TA GADI. (Neumann, 1909.) This organism, found in the fish, Gadus minutus, resembles Sp. gallinarum, measuring 10 to i6/* in length, SYSTEMATIC DESCRIPTION OF SPECIES. 99 with a wave-length of 3 . 5 to 4/z. It occurred both in the peripheral blood and in the internal organs, and was actively motile. SPIROCH^ETA PELAMYDIS. (Neumann, 1909.) These spirochaetes were found in the blood and organs of Pelamys sarda. They are shorter and thicker than Sp. gadi, measuring 9 to ioft in length, occasionally as much as 18 to 20/1. The wave-length of the curls is i to 1.9/1. Movement is active. SPIROCH^TA JONESII. (Button, Todd, and Tobey, 1906). These spirochaetes from the fish, Clavias angoknsis, measured i8/ in length by 0.6/1 in breadth. They ap- peared round at one end and pointed at the other, a fea- ure which suggests transverse division. They occurred both isolated and in clumps. SPIROCH^ETA HARTMANNI. (Gonder, 1908.) This small spirochaete was found by Gonder in the intestine of Pinna squamosa and P. nobilis. It meas- ures 6 to I4/* in length by i/i in breadth. It is said by Gonder to multiply by longitudinal division, on the strength of certain forked forms observed. It has pointed ends and periplastic appendages. SPIROCH.ETA BUFONIS. (Dobell, 1908.) This organism was found by Dobell in the rectum of the toad (Bufo vulgaris) . It resembled Sp. buccalis, and measured 8 to io// by i.5/x. It -had an undulating membrane. The same writer describes another form 100 SPIROCILETES. in the large intestine of the toad, which he compares with Sp. pallida and regards as a treponema, but the illustrations which he gives do not show the same regu- larity of curls. SPIROCH^TA BUCCALIS. (Cohn, 1877.) Several spiral organisms are found in the human mouth. The largest of these, Sp. buccalis, is from 12 FIG. 74. Mouth spirochaetes. (Spirochaeta buccalis.) FIG. 75. FIG. 76. FIG. 75. Spirochaeta buccalis: a, c, Showing sheath; b, with terminal filament; a 1 , Spirillum sputigenum. (Hoffmann and Prowazek.) FIG. 76. Spirochaeta buccalis (below). Spirochaeta dentium (above). X 2200. (Schaudinn.) to 20fi in length and to i/i broad (Figs. 74, 75, 76). It exhibits long undulations (wave-length 2 p., Miihlens and Hartmann) rather than short curls, and is active in SYSTEMATIC DESCRIPTION OF SPECIES. IOI its movements. Goadby, however, describes spiro- chsetes in the mouth, apparently Sp. buccalis, as having a sluggish oscillating movement. It has terminal peri- plastic appendages, and Hoffmann states that it has an undulating membrane ; this is doubtful. Division is said to be longitudinal. SPIROCH^ETA DENTIUM. (Koch, 1877.) This small spiral organism is from 4 to lo/t long, and exhibits well-marked regular curls (Figs. 76, 77, 78). Its breadth is about /i. It very closely resembles Sp. pallida in general appearance, but is said to be rather thicker, usually shorter, and to have rather less sharply- wound curls (Muhlens and Hartmann) . It is uncertain FIG. 77. FIG. 78. FIG. 77. Spirochaeta dentium. X 1500. (Hoffmann and Prowazek.) FIG. 78. Spirochaeta dentium. Culture. (Muhlens.) whether these organisms have any pathogenic influence ; they are found chiefly in dirty mouths, in the tartar on teeth, and in the discharges of pyorrhoea ; and Miller found tangles of them in a dental abscess, of which he thought that they were the cause. These organisms may perhaps be the same as Loewen- thal's Sp. microgyrata (see below). An intermediate form, between Sp. buccalis and Sp. dentium is also described (Sp. media (Prowazek); (?) Sp. denticola, Arndt). Spirillar forms with lateral flagella (Spirillum sputigenum) also occur (Fig. 75). 102 SPIROCILETES. SPIROCH^JTA VINCENTI. (Blanchard, 1906.) This spirochaete is met with in the affection known as Vincent's angina (a form of oral and pharyngeal ulcer- ation described by Vincent) along with fusiform bacilli. The spirochastes are usually about lo// long (extreme, 40 fi, Mackie) ; they show rather sluggish movements (see Fig. 53). Plaut describes an euglenoid movement, or gradual swelling of the organism, passing like a wave along its length. These spirochaetes are constantly associated with fusiform bacilli, of which some writers believe them to be a developmental form (see page 43). These or very similar associated organisms are found not only in the throat, but also in gangrenous processes in other parts of the body. The spirochaetes have not been satisfactorily cultivated, but the bacilli may be grown on artificial media. The resemblance of this organism to Sp. buccalis is very close, and some writers believe that they are identical (compare also Sp. gracilis) . SPIROCH^ETA GRACILIS. (Veszpr6mi, 1907.) This organism, found by Veszprdmi in a case of ab- scess in connexion with the jaw, in a man, appears to be identical with Sp. vincenti. It occurred along with fusiform bacilli and cladothrix. Levaditi and Stanesco, however, obtained this organism (?) from a chancre and cultivated it by Schereschewsky's method. They state that it is a distinct species, almost indistinguishable from Sp. pallida : it exhibits, however, rather less regu- lar spirals, is rather thicker, moves more actively, and is stained blue by Giemsa's method. The description is suggestive of Sp. microgyrata or Sp. pseudo- pallida. SYSTEMATIC DESCRIPTION OF SPECIES. 103 SPIROCH^ETA SCHAUDINNI. (Prowazek, 1907.) Spirochaetes and fusiform bacilli are found in the affection known as tropical ulcer of the leg (Fig. 79). Prowazek states that they are band-shaped organisms, possessing an undulating membrane, and that they multiply by longitudinal fission. In a specimen (from case of this disease?) sent to me by Capt. A. Whitmore, from Rangoon, the spirochaetes were accompanied by a FIG. 79. FIG. 80. FIG. 79. Spirochaete of ulcus tropicum. Sexual forms. X 2250. (Prowazek.) FIG. 80. Spirochaetes and cladothrix (?) in ulcus tropicum. (From a specimen by Capt. A. Whitmore.) large number of threads resembling filaments of cladothrix (Fig. 80). The spirochaetes were of about the same thickness as the threads, and stained almost exactly the same tint with fuchsine. It was difficult to resist the conclusion that they were forms of the same organism. (Vide sub Sp. gracilis) . Spirochaetes and elongated rod-shaped bodies were found by Assmy in phagedaenic ulcers. SPIROCHAETES IN GANGRENOUS PROCESSES. Polland found spirochaetes in cases of hospital gan- grene; the organisms were usually from 15 to 20/4 in length, but forms were met with up to 140;*. They 104 SPIROCILETES. usually showed five or six blunt curves, and occurred along with fusiform bacilli. R6na found spirochaetes in noma, hospital gangrene, ulcus gangrenosum genitalium and pulmonary gan- grene. They occurred along with fusiform bacilli. Those in noma and gangrene were of the same kind, but those seen in ulcus gangrenosum were smaller. Possibly the latter were Sp. microgyrata, the former Sp. vincenti. SPIROCH^TA PSEUDOPALLIDA. (Mulzer, 1905.) This name was given by Mulzer to spirochaetes closely resembling Sp. pallida, but not identical with it, found in sores on the genital organs. He thinks this is the same organism as was seen by Kiolomenoglou and Cube and by them described as Sp. pallida. SPIROCH^ETA BRONCHIALIS. (Castellani, 1907.) Castellani found spirochaetes in cases of Haemorrhagic Bronchitis occurring in Ceylon. He noted the presence of four different lands: (i) a thick form, with irregular curls, measuring 1 5 to 30^ ; (2) a form like Sp. refringens; (3) a thin delicate form with tapering ends and small curls ; and (4) another thin form with fewer curls. He speaks of an acute and a chronic bronchial spirochaetosis. Waters also found spirochaetes associated with febrile bronchitis, and Branch noted two kinds in the sputum of a tuberculous patient (along with tubercle bacilli) one resembling Sp. pallida and the other like Sp. refringens. Bertarelli and Volpius found spirochaetes resembling Sp. buccalis and others resembling Sp. pallida, but stain- SYSTEMATIC DESCRIPTION OF SPECIES. 105 ing more readily, in the expectoration of a patient suffer- ing from heart-disease. SPIROCH^TA MICROGYRATA. (Loewenthal, 1906.) Loewenthal found spirochaetes in the discharges from the surfaces of ulcerated cancers. They stained more readily than Sp. pallida. Long individuals meas- ured 5 to iifj. by i^ to 2//; and smaller specimens 2^ to 6/j. by & to //. The small forms showed from four to twelve curls, with a wave-length of //, or half that of Sp. pallida. Along with the spirochaetes were rod-shaped and bent sausage-shaped F . IG - 8l - bodies. Figure 81 shows one of these f P ukerated organisms as depicted by Schaudinn. Krienitz found Sp. microgyrata in cases of cancer of the stomach, and noted that the form of the organism changed with changing conditions, the altera- tions involving both length, thickness, and arrangement of curls. He therefore doubts the possibility of distin- guishing spirochaetes by their morphological characters alone. Calkins identified the spirochaetes found by Gaylord in mouse-cancer as a variety of Sp. microgyrata (see page 98). Hoffmann found spirochaetes in ulcerated cancers along with fusiform bacilli. SPIROCHAETES IN SMALL-POX. Sakurane found spirochaetes in the lesions of a patient suffering from small-pox, both in the contents of the pustules and in the tissues below these. They were long and slender, and showed numerous regular curls; forms with irregular curves were also seen. 106 SPIROCH^TES. SPIROCH^ETES IN VACCINE LYMPH. Bonhoff reported the presence of spirochaetes in vaccine lymph, but other writers believe them to have been artifacts. SPIROCHAETA REFRINGENS. (Schaudinn, 1905.) This spirochaete was found by Schaudinn in syphi- litic lesions along with Sp. pallida (Fig. 82), but it may occur apart from the latter in simple lesions of the genital regions. It is broader than Sp. pallida, less FIG. 82. FIG. 83. FIG. 82. Spirochaeta pallida and Sp. refringens. Smear from a syphilitic chancre; a, Sp. pallida; b, doubtful forms; c, Sp. refringens. FIG. 83. Spirochaeta refringens. (Schaudinn.) sharply curled (Fig. 83), and stains more readily and deeply. Its length is from 8 to 12 p and its breadth about /*. It has terminal periplastic appendages, but no undulating membrane (Levaditi) . Its body is said to be flattened (?), and not round like that of Sp. pallida. Some writers believe that Sp. refringens is the same as S^. balanitidis (Rille, Kraus) . It may be the same organism as was described by Donn6 in 1837 as Vibrio lineola in syphilitic lesions. Eitner believes that more SYSTEMATIC DESCRIPTION OF SPECIES. 107 than one species of spirochaete is included under the name of Sp. refringens. Richards and Hunt distin- guished three forms of Sp. refringens, somewhat differing in appearance, and also believed that this organism might be a stage in the development of Sp. pallida (see page 30). Sp. refringens was cultivated by Levaditi in human blood in collodion sacs placed in the peritoneal cavities of rabbits. The spirochaetes developed, showing short vibrio-like forms along with long spirochaetes ; different species of bacteria also developed in symbiosis. Inocu- lation of these cultures failed to induce balanoposthitis, and Levaditi does not think the spiro- chaetes are the cause of this disease. Sp. refringens was found by Baer- mann in enlarged glands in a monkey infected with syphilis, along with Sp. pallida; it may therefore become a blood parasite, and not be confined to superficial lesions. SPIROCH^TA BALANITIDIS. (Hoffmann and Prowazek, 1906.) The causal (?) organism of balanitis is believed by Hoffmann and Prowazek to be distinct from Sp. refringens; they describe it as a band-shaped spirochaete (Fig. 84) with six to ten curls, \ to f// broad, and furnished with periplastic appendages and an undulating membrane (the illustration showing the later formation is not convincing) . It exhibits wave-like and rotatory movements. It is stained red by Giemsa's reagent. Scherber states that these spirochaetes can be grown anaerobically on media containing serum; FIG. 84. Spiro- chaeta balanitidis. a, Terminal fila- ments and close curls; b, dividing; c, supposed undu- lating membrane. (Hoffmann and Prowazek.) io8 SPIROCH^TES. he also finds that they make their way into the blood- vessels and are not confined to the surface of the ulcera- tive lesions, as is usually supposed. SPIROCH^TA PALLIDA. (Schaudinn, 1905.) (Spironema pallida, Vuillemin, 1905; Treponema pallidum, Schaudinn, 1905; Spiroschaudinnia pallida, Sambon, 1907.) This organism was discovered by Schaudinn in March, 1905, and announced in a communication by Schaudinn and Hoffmann. It is usually from 4 to 14^ long, and exhibits six to fourteen curls; but longer forms are encountered, up to 40 /* or more. Its breadth is almost immeasurable, and may be /* or less. 1 It has pointed \ FIG. 85. Spirochseta pallida: a, After Schaudinn; b, c, after Krzystatowicz and Siedlecki. ends and terminal appendages of periplast, but no undulating membrane (Fig. 85). Its body is round in section, and the curls are very constant and regular. It differs from most other spirochsetes in staining a red- dish colour with Giemsa's stain, instead of blue. Its movements are rotatory and undulating, occasionally lashing, the curls remaining constant during these motions. In certain conditions, however, the curves 1 They appear considerably thicker when stained by Levaditi's silver method than with ordinary stains. SYSTEMATIC DESCRIPTION OF SPECIES. IOQ are obliterated, and straight and other atypical forms are seen (Schaudinn). Such irregular forms are com- mon in "cultures" (Levaditi and Macintosh, Schere- schewsky) . They may closely resemble Sp. refringens. In movement the long slender organ- isms may become short and plump (Krzystalowicz and Siedlecki). Forked forms of Sp. pallida are found and also specimens showing apparently . ... f, , , , , ' T , y FIG. 86. Spiro- two individuals twisted together ; from chseta pallida in these appearances a longitudinal mode of division has been inferred, but Leva- diti states that division is transverse. Refringent granules may be seen in the length of the organism, and also terminally placed. The spirochaete is easily found by mixing a loopful of secretion from a syphilitic sore with a drop of distilled water on a slide, dropping on a cover-slip, and observing FIG. 87. Spirochseta pallida in leucocytes. (Gierke.) in the "dark field" (see p. 66). Smears from such a sore may be fixed in osmic vapour and stained with Giemsa's reagent, or fixed and stained simultaneously with this fluid (see plate, Fig. A) . In the body the spirochastes lie chiefly between the cells in the lymphatic spaces, in lymphatic vessels and glands, and in the blood. Occasionally they become intracellular (Figs. 86, 87). The appearance of the organisms in the liver of a syphilitic foetus, when stained 110 SPIROCH^TES. by Levaditi's method, is shown in figure 88 (see also plate, Fig. B). A sexual cycle has been described by Krzystalowicz and Siedlecki. According to these writers, certain spirochaetes become thicker and less sharply curved, and constitute the female gametes. Other individuals are found with many nuclei, and these by fragmentation produce a large number of minute spirillar forms, which are the male gametes (Fig. 38). One of these conjugates with a female gamete, and the individual FIG. 88. Spirochaeta pallida in liver of syphilitic foetus stained by Levaditi's silver method. thus formed probably enters on a resting stage, which has not been definitely identified. These writers con- sider the Spirochazta pallida to be a trypanosome, and call it Trypanosoma luis. The same view is taken by Leuriaux and v. Geets, who describe oval bodies which elongate and give rise to fine filaments ; these latter are the microgametes (the spirochsetal form), while the female gametes are represented by a tryponosome-like stage. They suggest that the oval forms found by them are identical with Siegel's Cytoryctes luis. The observations of Krzystalowicz and Siedlecki SYSTEMATIC DESCRIPTION OF SPECIES. Ill have not been confirmed. Apart from the sexual cycle which they describe, it is clear that if the variations in the form of Sp. pallida described by them really occur, the foundations of the whole theory of its causal connection with syphilis are shaken, resting as they do upon the morphological constancy of this organism, with consequent facility of identification, and its occurrence only in syphilitic lesions. The observations of these writers would point to the existence of forms indistin- guishable from Sp. rejringens and possibly from other organisms. Peculiar bodies were found by Krzystalowicz and Siedlecki in the fluid obtained by blistering with the actual cautery over a syphilitic papule; these were much larger than the ordinary spirochaetes and showed irregular undulations and often an enlargement at one end. They were irregular in shape and seemingly amoeboid. Their relationship to Sp. pallida was un- certain. They seem to be the same bodies as were found by Horand, who noted that they were twenty- seven or twenty-eight times the diameter of a red blood- corpuscle and had a head, neck and tail. Babes and Panea also found in a case of congenital syphilis bodies resembling spermatozoa, having an elongated head, i to 2/j. long, and a wavy tail or two tails. They were inclined to doubt whether these were parasites. Forms somewhat resembling B. fusiformis were noted by Krzystalowicz and Siedlecki, but they do not seem to have regarded them as bacterial. Many attempts have been made to cultivate Sp. pal- lida. Recently success has been obtained by Schere- schewsky and by Miihlens ; and Bruchner and Galacesco state that they inoculated rabbits with cultures and produced syphilis (see p. 33). 112 SPIROCELETES. SPIROCH^ETA PERTENUIS. (Castellani, 1905.) (Spirochaeta pallidula, Castellani, 1905.) Castellani found spirochaetes present in eleven out of fourteen cases of the disease called yaws, framboesia, or pian; and the discovery was confirmed by other observers (Borne, Schiiffner, etc.). The organisms are very slender, and vary in length from a few microns up to 1 8 or 20 p.. Their extremities are pointed as a rule, though some individuals appear to have blunt ends. Their curls are numerous and symmetrical, but some- times part of the organism may appear straight (Fig. 89). Nodules may be visible at their extremities, and FIG. 89. Spirochaeta pertenuis. (Castellani.) also in their length (Fig. 21). Ovoid bodies were also found by Castellani (5 to 8/t by 4 to 6/*) and were thought by him to be possibly a stage in the develop- ment of the spirochaetes; they were very rare. Monkeys were inoculated with the spirochaetes, and the organisms were found in the resulting lesions. Monkeys thus inoculated showed no immunity to syphilis; this is held to prove the two diseases to be different. These spirochaetes are almost exactly like Sp. pallida, especially when stained with silver by Levaditi's method; but Mclntosh states that the positions they respectively occupy in the lesions are different (see page SYSTEMATIC DESCRIPTION OF SPECIES. 113 57). In the illustrations given by Castellani Sp. per- tenuis does not appear so regularly curled as is Sp. pallida. SPIROCH/ETA OBTUSA. SPIROCH^ETA ACUMINATA. (Castellani, 1905.) Along with Sp. pertenuis Castellani found other forms of spirochaetes which he called respectively Sp. obtusa a thin delicate organism with blunt extremities and Sp. acuminata, also very slender, but with tapering ends. Wellman could not identify these varieties in the lesions of yaws. Their nature and their relation- ships to Sp. pertenuis are doubtful. SPIROCH^ETA LYMPHATICA. (Proescher, 1909.) Proescher and White found spirochaetes in two cases of lymphadenoma ; the organisms were present in enormous numbers in the .glands, being demonstrated by Levaditi's silver method. A rhesus monkey was inoculated with material from the glands, and developed first a local nodule at the site of inoculation, and sub- sequently further secondary nodules in distant parts of the body. Spirochaetes were found in all the lesions. A second monkey was successfully inoculated from the first. The spirochaetes resembled Sp. pallida so closely that Proescher at first believed the case to be syphilitic. 1 We may here mention a spirochaete found by Moritz in a case of severe anaemia and cancerous lymphangitis, the organisms being present in the bone-marrow and in the wall of the gut. With the spirochaetes in the latter position were bacterial forms. The spirochaetes were 1 It is possible that there was actually a syphilitic infection in this case. 114 SPIROCTLETES. from 2 to 6/1 in length, and had from three to ten curls. They differed from S^. obermeieri in their appearance, being plumper and more compact (gedrungen) ; they had also thicker ends. SPIROCH^TA ABORIGINALIS. (Cleland, 1909.) Spirochaetes were found by Wise in cases of the de- structive local lesion called ulcerative granuloma of the pudenda and have been described by Cleland and FIG. 90. Sp. aboriginalis and bacteria. (Bosanquet.) by Bosanquet (Fig. 90). The organisms are about 12/1 in length, ranging from forms a few microns only in length to long forms attaining 18 or 20^. They are irregular in their curls, thus being clearly distinguished from Sp. pallida, and from Sp. pertenuis, as seen in the tissues. They closely resemble, however, the pictures given by Castellani of Sp. pertenuis as found in the secretion of yaws. The spirochaetes exist in the tissues along with bac- terial forms, their relationship to which has already been discussed (see page 58). SPIROCH^TA INTERROGANS. (Stimson, 1909.) Schaudinn and also Novy suggested that yellow fever might be due to the action of a spirochaete, but failed to find such organisms in cases of the disease. Stimson has recently, by Levaditi's method, found in the kid- neys of one such patient spirochaetes (?) which often SYSTEMATIC DESCRIPTION OF SPECIES. 115 took the form of a note of interrogation and which he has consequently named Sp. interrogans. They are 14/1 and upward in length by about /* in thickness, and the wave-length of the curls is i^ to 2fi. They were situa- ted in the renal cells and in the tubules, but not in the blood-vessels. The disco verv has not been confirmed. VARIOUS DOUBTFUL SPIROCH^ETES AND SPIRILLA. Adele Oppenheimer found spirochsetes in the mucus of the alimentary canal of the dog; some exhibited snake-like movements (lashing or wriggling), while others had only cork-screw movements, the curls in the body remaining fixed. These may correspond with the spirilla discovered by Bizzozero in the dog ; these organisms had three to seven curls, and were 3 to Sft long; they lay within vacuoles in the epithelial cells. Salomon also found spirilla in the intestines of dogs, cats and rats; these were longer, and he distinguished three forms a thick form with seven to nine curls, thicker at the middle than at the ends; a long form with fifteen to twenty- four curls, the axis being often bent ; and a form about as long as the first, but with only two to five wavy curls. They had terminal flagella and lay in the mucus of the alimentary canal and also in vacuoles in the cells. Rigaud found spirilla like Spirochata pallida in the stomachs of dogs and cats, lying at the bottom of the peptic glands. 1 Spirilla were found by Kowalski in the dejecta of cholera patients, resembling Sp. dentium. They had two to three curls and pointed ends, and did not grow in culture media (Abel) . Rechtsamer found that they l Cf. Balfour's discovery of spirochaetes in ulcers of the intestines of dogs and monkeys, recorded on page 44. Il6 SPIROCH^ETES. lived a little while in broth : he also noted that the more cholera-vibrios there were present, the fewer were the spirilla, and vice versa. Le Dantec found spirilla in the stools of certain pa- tients suffering from dysentery. Werner found in the human alimentary canal two forms of spirochaetes one with long undulations, 4 . 6 to 7 . 3/1 in length, which may occur in masses (this form is not identical with any of the mouth-spirochsetes) ; and a second, with finer curls, 3.5 to 6 . i/i in length, resem- bling Sp. dentium. The former he calls Sp. eurogyrata and the latter, Sp. stenogyrata. Smith (Theobald) found spirilla along with comma bacilli (vibrios) in the intestines of pigs ; they had two to three curls, with a wave-length of 2//. He could not cultivate them. Novy and Knapp found spirilla (Spirillum glossince) in the stomach of the tse-tse fly; short forms measured 8/z in length and long ones 1 5^. The spirilla were shorter, narrower, and more closely curled than Sp. obermeieri. They multiplied by transverse division, the long forms probably being about to divide (see also page 68). Mezinescu found spirilla in the pus from a case of calculous pyelitis ; they were from 3.6 to 8// long, rarely attaining a length of 10 or i2/x. Doerr found spirilla in the pleural and pericardial fluid of a syphilitic sub- ject and thinks they may have been the same as those described by Mezinescu. BIBLIOGRAPHY. (*)Papers thus marked I have not been able to consult in the original. GENERAL, CLASSIFICATION, ETC. Beurmann and Gougerot. Bull. Soc. Mid. des Hdpitaux, 1907, p. 943. Blanchard. Semaine medicate, 1906, I, i. Gonder. Centralbl.f. Bakt., 1909, XLIX, 190. Gross, Mitih. a. d. Zool. Station zu Napel, 1910, XX, 41. Leishman. Journ. Prevent. Medicine, 1906, XIV, 513. Levaditi and Rosenbaum. Ibid., 1908. Miihlens. Zeitschr.f. Hygiene, 1907, LVII, 405. Novy.* Proc. Pathol. Soc. of Philadelphia, 1907. Prowazek. Centralbl.f. Bakt., 1908, XL VI, 229. Reichert.* Hygien. Rundschau, 1907, XVII, 1121. Schwellengrebel. Compt. rend. Socitte de Biologie, 1907, LXII, 213. Schwellengrebel. Annales de I'Inst. Pasteur, 1907, XXI, 448, 562. Schwellengrebel, Centralbl.f. Bakt., 1909, XLIX, 529. Schilling. Centralbl. f. Bakt., 1908, Suppl. to XLII, 80. STAINING METHODS. Bertarelli and Volpino. Centralbl. f. Bakt., 1906, XLI, 74. Davidsohn. Berlin, klin. Wochenschr., 1905, XLII, 985. Foix and Mallein. C. R. Soc. de Biol., 1907, LXII, 1201. Forest. Centralbl.f. Bakt., 1906, XLII, 608. Giemsa. Deutsch. med. Wochenschr., 1905, XXXI, 1026. Goldhorn.* Postgraduate, 1906, No. 2 (abstr. Zentralbl. f. inn. Med., 1906, 707). Herxhiemer and Hubner. Deutsch. med. Wochenschr., 1905, XXXI, 1023. Hoffmann and Beer. Ibid., 1906, XXXII, 869. Levaditi. Ann. de I'Inst. Pasteur, 1906, XX, 41. Levaditi. C. R. Soc. de Biol., 1906, LX, 67. MacNeal. Journ. Amer. Med. Assoc., 1907, XL VIII, 609. 117 Mandelbaum. Muenchener med. Wochenschr., 1907, LIV, 2268. Meirowsky. Ibid., 1910, LVII, 777. Oppenheimer and Sachs. Deutsch. med. Wochenschr., 1905, XXXI, 1156. Petresco. Ibid., 1905, LIX, 680. Proca and Vasilescu. C. R. Soc. de Biol., 1905, June 29. Proca and Vasilescu.* Rivista Stiintelor. Med., 1905, 2 (abstr. Zentralbl.f. -inn. Med., 1906, 131). Proescher and White. Journ. Amer. Med. Assoc., 1908, XLIX, 1908. Ravaut and Ponselle. C. R. Soc. de. BioL, 1908, LXV, 438. Reitmann. Deutsch. med. Wochenschr., 1905, XXXI, 997. Sabraz^s and Duperrie\ C. R. Soc.de Biol., 1909, LXVI, 690. Schereschewsky. Centralbl. f. Bakt., 1907, XLV, 91. Schmorl. Deutsch. med. Wochenschr., 1907, 270. Simonelli and Bandi. Centralbl. f. Bakt., 1906, XL, 159. Von dem Borne. Joiirn. Tropical Med., 1907, X, 345. Yamamoto.* Centralbl. f. allg. Path. u. path. Anat., 1909, Feb. 27. Yamamoto. Centralbl. f. Bakt., 1908, XLVII, 571. DARK FIELD EXAMINATION. Bayly. Practitioner, Feb., 1910. Gastou and Commandon. Bull. Soc. med. des Hdpitaux, Mar., 1909. Harrison. Journ. R. Army Med. Corps, 1910, XIV, 506. Ogilvy. Lancet, Oct. 2, 1909. INDIAN-INK METHOD. Burri, Das Tiischeverfahren, Jena, 1909. Fruhwald. Berlin, klin. Wochenschr., 1909, 2121. Gins. Centralbl. f. Bakt., 1919, LII, 620. Hecht and Wilenko. Wiener klin. Wochenschr., 1909, XXII, 932. Plaut. Berlin, klin. Wochenschr., 1909, 2276. Rosenhauer. Muench. med. Wochenschr., 1909, 2394. PSEUDO-SPIROCH^TES. Beitzke. Centralbl. f. Bakt., 1907, XLIII, 369. Friedenthal. Berlin, klin. Wochenschr., 1907, 99. BIBLIOGRAPHY. 1 1 9 Gierke. Ibid., Jan. 21. Meyer. Centralbl.f. Bakt., 1908, XLVL 319, 339. Omeltschenko.* Rousski Vratch., July 23, 1905 (abstr. New York Med. Journ., Sept. 30, 1905). Baling. Centralbl. f. Bakt., 1907, 70, 162, 229, 362. Saling. Centralbl.f. Bakt., 1906, XLII, 38, 120. Schulze. Berlin, klin. Wochenschr., 1906, No. 37, XLIII, 1213. Schulze.* Klin. Monatshefte f. Augenheilk., 1907, XLV. Wolff. Ibid., 1907, XLIII, 156, 222. SP. PLICATILIS. Biitschli.* Ueber dem Bau der Bakt. u. verwandten or- ganismen, Leipsig, 1892. Biitschli. Deutsch, med. Wochenschr., 1906, No. 2. Doflein. Lehrb. der Protozoenkunde, 1909. Ehrenberg.* "Die Infusionsthierchen," Leipsig, 1833. Laptschinsky.* Centralbl. f. d. med. Wissensch., 1880 XVIII, 319. Schaudinn. Arb. a. d. kaiserl. Gesundheitsamte, 1907, XXVI, u. Schaudinn. Deut. med. Wochenschr., 1905, No. 42. Zuelzer. Zoologishe Anzeiger, 1910, XXXV, 795. SP. BALBIANII. Borrel and Cernovodeanu. C R. Soc. de Biol., 1907, XLII, 1102. Certes.* Bull Soc. Zool. de France, 1882, VII, 347. Fantham. Ann. and Mag. of Natural History, 1907, XIX, 439- Fantham. Quart. Journ. of Micr. Sci., 1908, LII, pt. 1. Fantham. Parasitology, 1910, II, 392. Rolling. Centralbl. /. Bakt., 1907, XLIV, 665. Laveran and Mesnil. C. R. Soc. de Biol. 1901,881. Lustrac.* Act. Soc. Linn, de Bordeaux, 1896, X. 265. Perrin. Arch. f. Protistenkunde., 1906, VII, 131. Schwellengrebel. C. R. Soc. de Biol., 1907, LXII, 214. Schwellengrebel. Centralbl. f. Bakt., 1908, XLVI, i. Vtes. C. R. Soc. de Biol., 1906, LXI, 408. 120 SPIROCILETES. SP. ANODONT.E. Keysselitz. Arb. a. d. kaiserl. Gesunheitsamte, 1906, XXIII, 566. Schellack. Ibid., 1909, XXX, 379. SP. PINNAE. Gonder. Centralbl. f. Bakt., 1908, XLVII, 491; 1909, XLIX, 191. SP. MACTR.E. Prowazek. Arch. /. Schiffs. u .Tropenhygiene, 1910, XIV, 297. SP. PECTINIS. SP. INTERROGATIONIS. Gross. Mitth. a. d. Zool. Station zu Napel, 1910, XX, 41. SP. POLYSPIRA. Wolff. Centralbl. f. Bakt., 1907, XVIII, Ref., 448. SP.OBERMEIERI. 1 Bardach. Ann. de I'lnst. Pasteur, 1899, XIII, 365. Bertarelli. Centralbl. f. Bakt., 1906, XLI, 492. Bohne. Arch. f. Schiffs. u. Tropenhygiene, 1908, XII, 343. Browse. British Med. Journ., 1905, I, 532. Carlisle. Journ. Infect. Diseases, 1906, III, 233. Cohn.* " Beitr. z. Biol. der Pflanzen," 1877. Cox. Brit. Med. Journ., 1906, I, 1400. Fischer. Centralbl. f. Bakt., 1907, XL VI, 715. Fraenkel. Berlin, klin. Wochenschr., 1907, V, 68 1. Fraenkel. Centralbl. f. Bakt., 1908, XLVII, 349, 471. Fiilleborn and Mayer. Mediz. klinik., 1907, III, 487. Gabritchewsky. Ann. de I'lnst. Pasteur, 1896, X, 630. Gabritchewsky. Centralbl. f. Bakt., 1906, XXXVII, Ref., 397. Karwacki and Szokalski. C. R. Soc. de Biol., 1910, CXVIII, 228, 286, 449. Klodnitzky. Ibid., 1907, XLV, 126. Kretz. Wien. klin. Wochenschr., 1906, XIX, 1462. Lafforgue. Semaine medic ale, 1905, 152. 1 Only recent papers are quoted. BIBLIOGRAPHY. 121 Mackinnon. Parasitology, 1907, II, 267, 281. Manteuffel. Arbeiten a. d. kaiserlichem Gesundheitsamte , 1908, XXVII, 327. Mathis. C. R. Soc. de Biol., 1908, LXIV, 753. Norris, Pappenheimer and Flournoy. Journ. Infectious Diseases, 1906, III, 266. Norris, Pappenheimer and Flournoy. Centralbl. f. Bakt., 1906, XXXVIII, Ref., 324. Novy and Knapp. Journ. Infect. Diseases, 1906, III, 291. Novy and Knapp. Journ. Amer. Med. Assoc., 1906, I, 116. Novy and Knapp. Centralbl. f. Bakt., 1906, XXXVIII, Ref., 325. Nuttall, Fantham and Porter. Parasitology, 1908, 1, No. 4. Nuttall. Ibid., 1908, I, 218. Oppenheimer.* Collected Studies from the Research Lab., Dep. of Health, N.Y., 1906, Vol. II. Popovitch. Th^se de Paris, 1906, No. 158. Rabinowitch. Centralbl. f. Bakt., 1908, XL VI, 581. Rabinowitch. Ibid., 1909, XLIX, 183. Schellack. Arb. a. d. kaiserl. Gesundheitsamte, 1908, XXVII, 364. Schellack. Ibid., 1909, XXX, 359. SergentandFoley.* Bull. Soc. Path. Exotique, 1908, I, 174. Soudakewitch. Ann. de I'lnst. Pasteur, 1891, V, 515. Uhlenhuth and Haendel. Arb. a. d. kaiserl. Ges., 1907 XXVI, Heft I. Yersin. C. R. Soc. de Biol., 1906, LX, 1037. SP. DUTTONI. Blanchard. Bull, de I'Acad. Med., Paris, 1907, 511. Breinl. Liverpool School of Trop. Med., 1906, XX, 69, 72 Breinl and Kinghorn. Ibid., Mem. XX, 1906, 61. Breinl and Kinghorn. Ibid., 1906, XXI, i. Breinl, Kinghorn and Todd. Centralbl. f. Bakt., XLII, 537 Carter. Ann. Trop. Med. and Parasitol., Liverpool, 1907, I.I57 Carter. Indian Med. Gaz., 1908, XLIV, 370. Button and Todd. Brit. Med. Journ., 1905, II, 1259. Duval and Todd. Lancet, 1909, I, 834. Fraenkel. Muenchener med. Wochenschr., 1907, No. 5. Fraenkel. Centralbl. f. Bakt., 1908, XL VII, 471. 122 SPIROCBLETES. Hodges and Ross. Brit. Med.Journ., 1905, I, 713. Koch. Deutscher med. Wochenschr., 1905, No. 47. Koch. Muenchener. med. Wochenschr., 1906, LIII, 390. Koch. Berlin, klin. Woch., 1906, XLIII, 185, Leishman. Trans. Soc. Trop. Med. and Hygiene, Jan., 1910, 77. Levaditi. C. R. Acad. des Sciences, 1906, CLXII, 1099. Levaditi, and Manou&ian, C. R. Soc. de Biol., 1906, LXI, 566. Levaditi and Manou&ian. Ann. de I'lnst. Pasteur, 1907, XXI, 295. Levaditi and Roch. C. R. Soc. de Biol., 1907, LXII, 619, 815. Manteuffel. Arb a. d. kaiserl Gesundheitsamte, 1908, XXVII, 327. Mayer.* Arch. f. Schiffs- u. Tropen-hygiene, 1908, XII, 7. Moffat. Lancet, 1907, Jan. 26. Newstead. Liverpool Sch. of Trop. Med., Mem. XVII. Ross and Milne. Brit, Med. Journ., 1904, II, 1453. Stephens. Lancet. 1906, II, 438. Strong.* Philippine Journal of Science, 1908, III, 231. Tedeschi. Centralbl. f. Bakt., 1910, LIV, 12. Vassal. C. R. Soc. de Biol., 1907, LXII, 414. Williams, L. and S. Liverpool Sch. of Trop, Med., Mem. XXI, 101. SPIROCH^TA PITHECI. Thiroux and Dufougere". Compt. rend. Acad. des Sciences, 1910, CL, 132. SP. ANSERINA. Borrel. C. R. Soc. de Biol., 1906, LX, 138. Cantacuz&ie. Ann. de I'lnst. Pasteur, 1899, XIII, 529. Gabritchewsky. Centralbl. f. Bakt., 1898, XXIII, 365, 439. 6 35. 721, 778. Sacharoff. Ann. de I'lnst. Pasteur, 1891, V, 564. SP. GALLINARUM. Balfour. Brit. Med. Journ., 1907, I, 744. Balfour. Journ. Trop. Med., 1909, X, I. Bevan.* Journ. Comp. Path, and Therap., 1908, XXI, i, 43- BIBLIOGRAPHY. 123 Blaizot. C. R. Soc. de BioL 1910, LXVIII, 29. Dodd.* Journ. Comp. Path, and Therap., 1910, XXIII, i. Borrel. C. R. Soc. de B-iol., 1906, LX, 138. Borrel and Burnet. Ibid., 1906, LX, 540. Picker and Rosenblatt.* Hygienische Rundschau, 1907, XVII, 1114 (abstr. Journ. de Phys. et Path. Gin., 1907, 1121). Galli-Valerio. Centralbl.f. Bakt., 1908, XL VII ,494. Gilruth. Proc. R. Soc. Victoria, 1910, XXIII, 102. Levaditi. Ann. de VInst. Pasteur, 1906, XX, 924. Levaditi and Lange. C. R. Soc. de BioL, 1905, LVIII, 843- Levaditi and Manouelian. Ann. de VInst. Pasteur, 1906, XX 593. Marchoux. C. R. Soc. dc BioL, 1907, LXIII, 298. Marchoux and Salimbeni. Ann. de VInst. Pasteur, 1903, XVII, 569. Neufeld and Prowazek. Arb. a. d. kaiserl. Gesundheit- samte, 1907, XXV, 494. Okhubo. C. R. Soc. de BioL, 1910, LXVIII, 655. Prowazek. Ibid., 1906, XXIII, 554. Reaney. Indian Medical Gazette, 1907, XLII. Schellack. Centralbl.f. Bakt., 1908, XL VI, 486. Schellack. Arb. a. d. kaiserl. Gesundheitsamte, 1909, XXX, 351- Simond, Albert and Noc. C. R. Soc. de BioL, 1909, LXVI, 714. Uhlenhuth and Gross. Arb. a. d. kaiserl. Gesundheit- samte, 1908, XXVII, 231. Uhlenhuth Gross and Brickel. Deutsch. med. Wochen- schr., 1907, 129. Zettnow. Ibid., 1906, XXXII, 376. SP. LAGOPODIS. SP. LOVATI. Fantham. Proc. Zool. Soc. Lond., Oct., 1910, pp. 697, 701. SP. VESPERUGINIS. Gonder. Arb. a. d. kaiserl. Gesundheitsamte, 1908, XXVII, 406. Nicolle and Compte. Ann. de VInst Pasteur, 1906, XX, 311. 124 SPIROCILETES. SP. LUTR.E. Prowazek. Arb. a. d. kaiserl. Gesundheitsamte, 1907, XXVI, 31. SP. THEILERI. Dodd.* Journ. Comp. Path, and Therap., 1906, XIX, 318 Laveran and Valle. C. R. Acad. des Sciences, 1905, CXL, 1575. Theiler.* Journ. Compar. Path, and Therap., 1904, XVII, 47- Baruchello and Pricolo.* La Clin. Veter., 1906. XIX (abstr. Bull. Inst. Pasteur, 1906, 999). Heanley.* Journ. Comp. Path, and Therap., 1906, XIX. 322. Martin. C. R. Soc. de Biol., 1906, LX, 124. Martoglio and Carpano.* Ann. d'Igien. Sperim., 1904, XIV. Stordy.* Journ. Comp. Bact. and Therap., 1906, XIX, 226. SP. SUIS. Dodd.* Journ. Comp. Path, and Therap., 1906, XIX, 216. Cleland. Parasitology, 1908, 218. Gilruth. Proc. R. Soc. Victoria, 1910, XXIII, 105. SP. LAVERANI. SP. MURIS. SP. MINOR. Breinl and Kinghorn. Lancet, 1906, II, Sept. 8. Carter. Sci. Mem. by Officers of the Indian Army, 1887, HI, 45- Wenyon. Journ. of Hygiene, 1906, VI, 580. SP. IN MOUSE CANCER. Calkins. Journ. Infect. Dis., 1907, IV, 171. Borrel. C. R. Soc. de Biol., 1905, LVIII, 780. Deetjen. Muench. med. Wochenschr., 1908, No. 22. Gaylord. Journ. Infect. Dis., 1907, IV, 155. Gaylord. Berlin, klin. Wochenschr., 1908, 2296. SPIROCH^ETA GONDII. Nicolle. Compt. rend. Soc. de Biologie, 1907, LXIII, 213. BIBLIOGRAPHY. 125 SP. CULICIS. Jaffe. Arch.f. Protistenk., 1907, IX, 100. SP. MINEI. Prowazek. Arch. f. Schiffs. u. Tropen-Hygiene , 1910, XIV, 297. SPIROCH^TA GADI. SP. PELAMYDIS. Neumann. Zeitschr.f. Hygiene, 1909, LXIV, i. SPIROCH^TA JONESII. Button, Todd and Tobey. Journ. of Med. Research, 1906, XV, 491. SP. HARTMANNI. Gonder. Centralbl. f. Bakt., 1908, XL VII, 491; 1909, XLIX, 19 1. SP. BUFONIS. Dobell. Quart. Journ. Micr. Sci., 1908, LII, 121. SP. BUCCALIS. SP. DENTIUM. Arthaud. C. R. Acad. des Sciences, 1909, CXLIX, 1409. Bertarelli and Volpino. Centralbl. f. Bakt., 1906, XXXVII, i. Feldmann. Wiener klin. Wochenschr., 1906, XIX, 695. Goadby. Lancet, 1906, II, 1281. Hoffmann. Centralbl. f. Bakt., 1906, XXXVIII, Ref., Beiheft, 112. Hoffmann and Prowazek. Ibid,, 1906, XLI, 818. Miller. Deutsch. med. Wochenschr., 1906, XXXII, 348. Schaudinn. Arb. a. d. kaiserl. Gesundheitsamte, 1907. XXVI, ii. Zettnow. Zeitsch.f. Hygiene, 1906, LII, 485, 539. SP. VINCENTI. 1 Eichmeyer. Jahrb. f. Kinderheilk., 1905, XIII, 65. Ellermann. Zeitschr.f. Hygiene, 1907, LVI, 453. 'For list of other articles see Beitzke: Centralbl. f. Bakt., 1904, XXXV, orig. 126 SPIROCH^ETES. Launois and Loederich. Bull. Soc. m6d. des Hdspitaux, 1905, XXII, 601. Lewkowitz. Centralbl,f. Bakt., 1906, XLI, 153. Mackie. Lancet, 1905, II, no. Miihlens and Hartmann. Zeitschr. f. Hygiene, 1906, LV, 81. Plaut. Centralbl.f. Bakt., 1907, XLIV, 310. Popovitch. Thlse de Paris, 1906, No. 158. Reiche. Muench. med. Wochenschr., 1905, No. 32. Scherber. Dermatol. Zeitschr., 1907, XIV, 88. Schmiedlechner. Zeitschr. f. Gebiirtshilfe u. Gyn., 1905, LVI, 291. Tunnicliffe. Journ. Infect. Dis., 1906, 148. Vincent. Lancet, 1905, I, 1260. Vincent. Muench. med. Wochenschr., 1905, LII, 1287. Weaver and Tunnicliffe. Journ. Infect. Dis., 1905, II, 446. Weaver and Tunnicliffe. Journ. Amer. Med. Assoc., 1906, XL VI, 481. Wright. Lancet, 1904, II, 73. SP. GRACILIS. Levaditi and Stanesco. C. R. Soc. de BioL, 1909, LXVII, 188. Veszprdmi. Centralbl. f. Bakt., 1907, XLIV, 408, 515, S3 2 - 6 48. SP. SCHAUDINNI. Assmy. Arch. f. Schiffs. u. Tropenhyg., 1909, XIII, p. 657. Keysselitz and Mayer. Ibid., 1909, XIII, 137. Prowazek. Arb. a. d. kaiserl. Gesundheitsamte, 1907, XXVI, 23. SP. IN GANGRENOUS PROCESSES. Polland. Wien. klin. Wochenschr., 1905, XVIII, 1236. Prowazek. Arb. a. d. kaiserl. Gesundheitsamte, 1907, XXVI, 23. R6na. Verhandl. d. deutsch. dermatol. Ges. (1906), 1907, IX, 471- SP. PSEUDO-PALLIDA. Mulzer. Berlin, klin. Wochenschr., 1905, XLII, 1144. BIBLIOGRAPHY. 127 SP. IN BRONCHIAL SECRETION. Bertarelli and Volpino. Centralbl.f. Bakt., 1906, XXXVII, Ref., 230. Branch. Brit. Med. Journ., 1906, II, 1537. Castellani. Lancet, 1906, May 19. Castellani. Journ. Trop. Med., 1909, 399. Waters. Lancet, 1909, I, 689. SP. MICROGYRATA. Hoffmann. Berlin, klin. Wochenschr., 1905, 880. Krienitz. Deutsch. med. Wochenschr., 1906, XXXII, 872. Krienitz. Centralbl.f. Bakt., 1906, XLII, 43. Loewenthal. Berlin, klin. Wochenschr., 1906, XLIII, 283. Simmonds. Verhandl. d. deutsch. pathol. Ges., 1908, 116. SP. IN SMALL-POX. Sakurane.* Vortrag in d. med. Gesellsch. z. Osaka, May 20, 1907 (abstr. Centralbl.f. inn. Med., 1907, 835). SP. IN VACCINE-LYMPH. Bonhoff. Berlin, klin. Wochenschr., 1905, XLII, 1142. Carini. Centralbl.f. Bakt., 1905, XXXIX, 685. Miihlens and Hartmann. Ibid., 1906, XLI, 49. Supfle. Ibid., 1906, XL, 495. SP. REFRINGENS. Dreyer. Deutsch. med. Wochenschr., 1907, No. 18. Eitner. Muench. med. Wochenchr., 1907, April 16. Levaditi. C. R. Soc. de Biol., 1906, LXI, 182, 185. Richards and Hunt. Lancet, 1906, I, 667. Rille. Muench. med. Wochenschr., 1905, 1377. Schaudinn. Arb. a. d. kaiserl. Gesundheitsamte, 1907, XXVI, ii. Schaudinn and Hoffmann. Ibid., 1905. SP. BALANITIDIS, Hoffmann and Prowazek. Centralbl. f. Bakt., 1906, XLI. 741. Kraus. Arch. f. Dermatol. u. Syph., 1906, LXXX, 255. 128 SPIROCILETES. SP. PALLIDA. Alvarez. Journ. Amer. Med. Assoc., 1906, XL VI, 1687. Arning and Klein. Deutsch. med. Wochenschr., 1907, XXXIII, 1482. Bab. Ibid., 1906, XXXII, 1945. Babs and Mironescu. Berlin, klin. Wochenschr., 1906, XLIII, 1119. Babs and Pan6a. Ibid., 1905, XLII, 1506. Bandi and Simonelli. Riforma Medica, 1905, No. 29. Bandi and Simonelli. Muenchener, med. Wochenschr., 1905, LII, 1668. Bandler. Prager med. Wochenschr., 1905, XXX, 475. Beer. Deutsch. med. Wochenschr., 1906, XXXII, 1192. Benda. Riforma Medica, 1906, XXII, 1115. Benda. Berlin, klin. Wochenschr., 1907, Apr. 15 and 22. Berger. Muench. med. Wochenschr., 1906, LIII, 862. Bertarelli. Centralbl. f. Bakt., 1906, XLI, 639. Bertarelli Ibid., 1907, XLIII, 167, 238. Bertarelli and Volpino.* Boll. R. Acad. Med. di Torino, 1905, June 16 (ref. Centralbl. f. Bakt., 1906, XXXVII, 230). Bertarelli, Volpino and Bovero. Centralbl. f. Bakt., 1906, XL, 56. Blaschko. Berlin, klin. Wochenschr., 1907, XXXIV, 336. Bodin. Ann. de Dermatol., 1905, 984. Boing. Aerztlichen Rundschau, 1907, No. 43. Bosc. C. R. Soc. de Biol., 1906, LX, 338, 340. Bourgsdorf.* Rousski Vratch, 1908, 446 (abstr. Journ. de Phys. et Pathol. Gin., 1908, 769). Brandweiner. Wiener klin. Wochenschr., 1906, XIX, 339. Bronnum and Ellermann. Deutsch. med. Wochenschr., 1905, XXXI, 1757. Bruckner and Galacesco. C. R. Soc. de Biol., 1910, LXVIII, 684. Burnet and Vincent. C. R. Soc. de Biol., 1905, LIX, 474. Buschke.* Verein f. inn. Med., Berlin, Dec. 19, 1905 (abstr. Zentralbl.f. inn. Med., 1906, 58. Buschke and Fischer. Deutsch. med. Wochenschr., 1905, XXXI, 791. Buschke and Fischer. Berlin, klin. Wochenschr., 1906, XLIII, 6, 383. Campbell. Journ. Amer. Med. Assoc., 1910. LIV, 924. BIBLIOGRAPHY. I2Q De Beurmann and Gougerot. Bull. Soc. medic, des Hdpitaux, 1907, XXIV, 943. De Souza and Pereira. Berlin, klin. Wochenschr., 1905. XLII, 1385. Dohi. Centralbl.f. Bakt., 1907, XLIV, 246. Doutrelepont and Grouven. Deutsch. med. Wochenschr., 1906, XXXII, 908. Dudgeon. Lancet, 1906, I, 669. Ehrmann. Deutsch. med. Wochenschr., 1906, No. 28. Erhmann. Wiener klin. Wochenschr., 1906, XIX, 828. Ehrmann. Centralbl.f. Bakt., 1907, XLIV, 243. Ferre. C. R. Soc. de Biol., 1906, LX, 97. Fliigel. Deutsch. med. Wochenschr., 1905, XXXI, 1755. Follet. C. R. Soc. de Biol., 1907, LXII, 667. Fouquet. C. R. Acad. des Sciences, 1906, CXLIII, 792. Fouquet. C. R. Soc. de Biol., 1907, LXII, 225. Friedenthal. Berlin, klin. Wochenschr.. 1906, XLIII, 1217. Galli-Valerio and Lesseur. Revue medicale de la Suisse romande, 1905, No. 7. Galli-Valerio and Salomon. Centralbl. f. Bakt.. 1907, XLV, 37. Gauche and Merle. C. R. Acad. des Sciences, 1909, CXLVIII, 862. Giemsa. Deutsch. med. Wochenschr., 1907, 676. Gierke. Muench. med. Wochenschr., 1906, LI.II. 393. Gierke. Centralbl.f. Bakt., 1907, XLIV, 348. Gordon.* American Medicine, 1905, July 23. Gradle.* Trans. Pathol. Soc. of Chicago, 1907, VII, 54. Greeff and Clausen. Deutsch. med. Wochenschr., 1906, XXXII, 1454. Grouven. Medizinische Klinik, 1908, No. 8. Grouven and Fabry. Deutsch. med. Wochenschr., 1905, XXXI, 1469. Hansteen.* Norsk. Mag.f. Leagevid., 1906, No. 7 (abstr. Centralbl.f. inn. Med., 1906, 1193). Harris and Corbus. Journ. Amer. Med. Assoc., 1908, LI, 1928. Harvey and Bousfield. Journ. Royal Army Med. Corps, 1905, V, 263. Hedrn. Centralbl.f. Bakt., 1908, XLVI, 232. 130 SPIROCH^ETES. Herxheimer. Deutsch. med. Wochenschr., 1905. XXX, i7- Herxheimer. Muench. med. Wochenschr., 1905, No. 39. Herxheimer and Loser. Ibid., 1905, LII, 2212. Herxheimer and Opificius. Ibid., 1906, LIII, 301. Hoffmann. Berlin, klin. Wochenschr., 1905, XLII, 729, i4Si. Hoffmann. Verein. f. inn. Med., Berlin, 1905, Dec. 19. Hoffmann. Centralbl. f. Bakt., 1906, XXXVIII, Ref. (Beiheft), 108. Hoffmann and B riming. Deutsch. med. Wochenschr., 1907, XXXIII, 553. Hoffmann and Halle. Muench. med. Wochenschr., 1906, LIII, 1516. Hoffmann, Lohe and Mulzer. Deut. med. Wochenschr., 1908, XXXIV, 1185. Horand. Lyon midicale, 1905, CIV, 1223. Huebschmann. Berlin, klin. Wochenschr., 1906, XLIII, 796. Jacquet and Sevin. Bull. Soc. mid. des Hdpitauoc, 1905, XXII, 420. Jacquet and Szary. Ibid., XXIV, 114. Jancke. Med. Klinik, 1907, No. 17. Kiolomenoglou and Cube. Muench. med. Wochenschr., 1905, No. 27. Kowalewsky. Deutsch. med. Wochenschr., 1905, No. 52. Kraus. Prager med. Wochenschr., 1906, XXXI, 354. Kraus and Prantschoff. Wiener klin. Wochenschr.. 1905, XVIII, 941. Kreibich. Ibid., 1906, XIX, 199. Krzystalowicz and Siedlecki. Bull, de I'Acad. de Sciences de Cracovie, Nov., 1905. Landsteiner and Mucha. Wiener klin. Wochenschr., 1906, No. 45. Lebailly. C. R. Acad. des Sciences, 1908, CXLVI, 312. Leixer. Zentralbl.f. inn. Med., 1905, 701. Leuriaux and v. Geets. Centralbl. f. Bakt., 1906, XLI 684. Levaditi. C. R. Soc. de BioL, 1905, LVIII, 845. Levaditi. Ibid., 1905, LIX, 326, 342. Levaditi. Ann. de VInst. Pasteur, 1906, XX, 41. BIBLIOGRAPHY. 131 Levaditi and Macintosh. Ibid., 1907, XXI, 784. Levaditi and Mancunian. C. R. Soc. de BioL, 1905, LIX, 527, 529. Lavaditi and Manouelian. Ibid., LX, 134, 304. Levaditi and Marie. Ibid., 1907, LXII, 872. Lavaditi and Salmon. Ibid., 1905, LIX, 465. Levaditi and Sauvage. Ibid., 1905, LIX, 344. Levaditi and Yamamouchi. Ibid., 1908, LXIV, 313, 408. Levaditi and Yamamouchi. C. R. Acad. des Sciences, 1908, CXLVI, 1 120. Lipschutz. Deutsch. med. Wochenschr., 1905, XXXI. 1832. Mclntosh. Journ. of Path, and Bacterial., 1909, XIII, 2 39- MacLennan. Brit. Med. Journal, 1906, I, 258. MacWeeney. Ibid., 1905, I, 1262. Marinesco and Mina.* Revue Neurologigue, 1906, XIV 388. Menetrier and Rubens-Duval. Butt. Soc. mid. des Hdfr- taux, 1905, XXII, 1059. Metchnikoff. Semaine medicale, 1905. 234. Methnikoff and Roux. Ann. de I'lnst., Pasteur., 1905, XIX, 673. Milman.* Rousski Vratch, 1906, 205 (abstr. Journ. de Phys. et de Pathol. Gin., 1906, 556). Mucha and Scherber. Wiener klin. Wochenschr., 1906, XIX, 145- Miihlens. Deutsch. med. Wochenschr., 1907, 1207. Miihlens. Centralbl.f. Bakt., 1907, XLIII, 694. 586. Muhlens. Ibid., 1909, XXXV, 1261. Miihlens and Lohe. Centralbl. f. Bakt., 1908, XLVII, 487. Miihlmann. Ibid., 1906, XXXVII, Ref., 650. Mulzer. Berlin, klin. Wochenschr., 1905, No. 36. Nattan-Larrier and Brindeau. C. R. Soc. de BioL, 1906, LX, 181. Nicolas, Favre and Andr. Ibid., 1905, LIX, 497. Nicolas, Favre and Andr. Lyon mtdicale, 1905, LIV, 1367. Niessen (Von). Wiener, med. Wochenschr., 1908, LVIII, 2524, 2578. 132 SPIROCILETES. Nigris. Deutsch. med. Wochenschr., 1905, 'XXXI, 1431. Nobdcourt, Levaditi and Darr. C. R. Soc. de Biol., 1905, LVIII, 1021. Noeggerath and Staehelin. Muench. med. Wochenschr., 1905, 1481. Oppenheimer and Sachs. Wien. klin. Wochenschr., 1905. XVIII, 1177. Pasini. Riforma Medica, 1907, XXIII, 52. Pauli. Johns Hopkins Hosp. Bulletin, Nov., 1908. Ploeger. Muench. med. Wochenschr., 1905, LII 1381. Popovitch. Thtse de Paris, 1906, No. 158. Preisz.* Pester med.-chir. Presse, 1908, Nov. 8 and 15. Proca and Vasilescu. C. R. Soc. de Biol., 1905, LVIII, 1044 Qu6y. C. R. Soc. de Biol., 1907, LII, 379. Queyrat and Jol train. Bull. Soc. m6d. des. Hdpitaux, i95. 559- Queyrat, Levaditi and Feuillid. Ann de. Dermatol., 1905, 982. Rach and Wiesner. Wiener klin. Wochenschr, 1907, XX, 5 21 - RadaelL Lo Sperimentale, 1906, LX, 397. Raubitschek. Wiener klin. Wochenschr., 1905, XVIII, 752. Ravaut and Ponselle. Gaz. des Hdpitaux, 1906, LXXIX, 1023. Reischauer. Deutsch. med. Wochenschr., 1905, XXXI, Renter. Zeitschrift f. Hygiene, 1906, LIV, 49. Ribadeau-Dumas and Poisot. C. R. Soc. de Biol., 1907, LXII, 247. Richards. Medical Chronicle, 1906, X, 273. Richards, and Hunt. Lancet, 1905, II, 963. Rille. Muench. med. Wochenschr., 1905, LII, 1377. Rille and Vockerodt. Ibid*, 1905, 1620. Risso and Cipollina. Riforma medica, 1905, XXI, 848, 938. R6na.* Wiener, wed. Presse, 1907, No. 34. Roscher. Berlin, klin. Wochenschr., 1905, XLII, 1382, 1418, 1447. Rosenberger. Amer.Journ. Med. Sciences, 1906. CXXXI, 143- BIBLIOGRAPHY. 133 Rosenberger.* Proc. Pathol. Soc. Philadelphia, 1906, IX, 49; 1908, XI, 68. Saling. Centralbl.f. Bakt., 1906, XLI, 737. Saling. Ibid., 1907, XLIV. Saling. Fortschritte der Medizin, 1907, Hft. 19. Salmon. C. R. Soc. de Biol., 1905, LVIII, 883. Sambon. Brit. Med. Journ., 1907, II, 1321. Schaudinn. Deutsch. med. Wochenschr., 1905, XXXI, 711, 1665. Schaudinn and Hoffmann. Berlin, klin. Wochenschr., 1905, XLII, No. 22, 673. Schaudinn and Hoffmann. Deutsch. med. Wochenschr., 1905, XXXI, 771. Schereschewsky. Centralbl.f. Bakt., 1908, XL VII, 41. Schereschewsky. Deut. med. Wochenschr., 1909, XXXV, 835, 1260. Schlimpert. Berlin, klin. Wochenschr., 1906, XXXI, 1037. Schmorl. Muench. med. Wochenschr., 1907, 188, 239. Scholtz. Deutsch. med. Wochenschr., 1905, XXXI, 1487, Schor.* Rousski Vratch, 1905, 1123 (abstr. Journ. de Phys. et Path. Gen., 1906, 353). Schuller. Centralbl. f. Bakt., 1907, XLIII, 794. Schiitz. Muench. med. Wochenschr., 1906, LIII, 543. Shennan. Lancet, 1906, I, 663, 746, 1323. Selenew. Centralbl. f. Bakt., 1910, LIV, 7. Sezary and Paillard. C. R. Soc. de Biol, 1910, LXVIII, 295. Siebert. Deutsch. med. Wochenschr., 1905, XXXI, 1426. Siegel. Centralbl.f. Bakt., 1907, XLV, 218. Siegel. Ibid., 1906, XL VI, 315. Siegel. Ibid., 1909, XL VIII, 599. Simmonds. Muench. med. Wochenschr., 1906, LIII, 1302. Sobernheim and Tomasczewsky. Muenchener med. Woch- enschr., 1905, 1857. Spitzer. Wien. klin. Wochenschr., 1905, XVIII, 822. Stanziale. Centralbl.f. Bakt., 1909, XLIX, 551. Thesing. Centralbl.f. Bakt., 1906, XL, 350. Thesing. Muenchener med. Wochenschr., 1905, No. 28. Thibierge. Gaz. des Hdpitauoc, LXXIX, 123. Thibierge, Ravaut. and Burnet. C. R. Soc. de Biol., 1906, LX, 298. 134 SPIROCELETES. Thibierge, Ravaut, and Le Sourd. Bull. Soc. med. des Hbpitaux, 1906, 383. Tomasczewski. Muench. med. Wochenschr., 1906, LIII, 1301. Truffi. Centralbl.f. Bakt., 1909, XL VIII, 597. Uhle and Mackinney.* Proc. Pathol. Soc. Philadelphia, 1906, IX, 195. Uhlenhuth, Hoffmann, and Weidanz. Deutsch. med. Wochenschr., 1907, XXXIII, 1592. Uhlenhuth and Mulzer. Arb. a. d. kaiserl, Gesundheit- samte, 1909, XXXIII, 183. Veillon and Girard. C. R. Soc. de BioL, 1905, LIX, 652. Vincent. Bull. Soc. mid. des Hdpitaux, 1905, XXII, 603. Volpino and Fontana. Centralbl. f. Bakt., 1906, XLII, 666. Vuillemin. C. R. Acad. des Sciences, 1905, CXL, 1567. Wallich and Levaditi. C. R. Soc. de Biol., 1906, LX, 191. Wersilowa. Centralbl.f. Bakt., 1906, XLII, 513. Wolff. Ibid., 1907, XLIII, 803. Wolters. Mediz. klinik, 1905, I, 963. Zabolotny.* Rousski Vratch, 1906, 212 (abstr. Journ. de Phys. et Pathol. Gin., 1906, 556). Zabolotny and Maslakowetz. Centralbl. f. Bakt., 1907. XLIV, 534. SP. PERTENUIS. Asburn and Craig.* Philippine Journal of Science, 1907, II, 441- Castellani.* Arch. f. Schiffs- u. Tropen-hygiene, 1907, XI, 19. Castellani. British Med. Journal, 1905, II, 1280. Castellani. Deutsch. med. Wochenschr., 1906, XXXII, 132. Castellani. Journ. Trop. Med., 1906, IX, i. Levaditi and Nattan-Larrier. Ann. de VInst. Pasteur, 1908, XXII, 260. Mayer. Deutsch. med. Wochenschr., 1907, No. 12. Neisser, Baermann and Halstadter. Muenchener med. Wochenschr., No. 28. Schiiffner. Muenchener med. Wochenschr., 1907, LIV, BIBLIOGRAPHY. 135 Von dem Borne. Journ. of Tropical Med., 1907, X, 345. Wellmann. Journ. Trop. Med., 1905, VIII, 345. Wellmann.* Arch. f. Schiffs- u. Tropen-hygiene , 1908, XI, Hft. 17. SP. LYMPHATICA. Proescher. New York Med. Journ., 1909, LXXXIX, 848. White and Proescher. Journ. Amer. Med. Assoc., 1907, XLIX, 1115, 774. White and Proescher. Muench. med. Wochenschr.. 1907, 1868. SP. IN ANEMIA. Moritz. Deutsch. Arch. f. klin. Med., LXXXIV, Hft. 5-6. Thomas and Rolleston. Brit. Med. Journ., 1910, I, 16. SP. ABORIGINALIS. Bosanquet. Parasitology, 1910, II, 345. Cleland. Journ. Trop. Med. and Hygiene, 1909, May 15. MacLennan. Medico-Chirurg. Transactions, 1907, XC, 700. Wise. Brit. Med. Journ., 1906, I, 1274. SPIROCH^TA INTERROGANS. Stimson. Trans. Soc. Tropical Med., London, 1909, HI, 56- VARIOUS SPIROCH^TES AND SPIRILLA. ONYCHIA. Button, Todd and Tobey. Liverp. Sch. Trop. Med., 1906, Mem. XX, 87. SPIROCH^TES IN ALIMENTARY CANAL. Oppenheimer.* Collected Studies Res. Lab. Dept. of Health, New York, 1906, II, 145. Rigaud. C. R. Soc. de Biol., 1909, LXVI, 229. Salomon. Centralbl.f. Bakt., 1896, XIX, 433. Smith. Ibid., 1894, XVI, 324. Werner. Centralbl.f. Bakt., 1909, LII, 241. 136 SPIROCH^TES. SPIRILLA IN CHOLERA DEJECTA. Abel. Centralbl.f. Bakt., 1894, XV, 213. Aufrecht. Ibid., 1894, XVI, 405. Escherich. Ibid., 1894, XV, 408. Kowalski. Ibid., 1894, XVI, 321. Lustig and Giaxa. Ibid., 1894, XV, 721. Recbtsamer. Ibid., 1894, XV, 795. SP. GLOSSING. Novy and Knapp. Journ. of Infect. Dis., 1906, III, 291. SPIRILLA IN PYELITIS (SP. PYOGENES). Mezinescu. Centralbl.f. Bakt., 1904, XXXV, 201. SP. IN DYSENTERY. Le Dantec. C. R. Soc. de Biol., 1903, LV, 617. SPIROCH^TA DAXENSIS. Cantacuzfene. Compt. rend. Soc. de Biologie, 1910, LXVIII, 75- BIBLIOGRAPHIC INDEX. ABEL, 115 Arndt, 101 Arning and Klein, 50 Ascoli, 26, 27 Ass my, 103 BAB, 51, 56 Babes and Pane"a, 1 1 1 Baermann, 107 Balfour, 44, 115 Bandi and Simonelli, 29, 50, 65 Baruchello and Pricolo, 26, 61, 95 Beer, 32, 34 Benda, 54, 56 Bertarelli, 56 Bertarelli and Bovero, 50 Bertarelli and Volpino, 30, 65 Bertarelli and Volpius, 104 Beurman and Gougerot, 53 Bizzozero, 115 Blanchard, 70, 102 Bodin, 50 Bonhoff, 1 06 Borne, 112 Borrel, 34, 91, 97 Borrel and Burnet, 32 Borrel and Cernovodeanu, 21 Bosanquet, 28, 44, 114 Bosc, 30 Bousfield and Harvey, 43 Bovero and Bertarelli, 50 Branch, 30, 59, 104 Breinl and Kinghorn, 62, 96 Bruckner and Galacesco, 33, 53, in Briining, 65 Burnet and Borrel, 32 Burn, 66 Butschli, 73 Butschli and Schaudinn, 76 CALKINS, 97, 98, 105 Cantacuzene, 76, 77, 91 Carpano and Martoglio, 95 Carter, 37, 38, 40, 48, 58, 62, 9. 97 Castellani, 18, 28, 29, 30, 40, 53. 57. 59. 83, 104, 112, 113, 114 Cernovodeanu and Borrel, 21 Certes, 77 Cipollina and Risso, 50 Cleland, 44, 58, 96, 114 Cohn, 70, 71, 86, 100 Collings, 76 Compte and Nicolle, 34, 61, 93 Cox, 40, 87 Cube and Kiolomenoglou, 49, 104 DARLING, 48 Davidsohn, 64 De Lisle and Jullien, 53 De Sousa and Pereira, 56 Delafield, 63 Dobell, 99 Dodd, 62, 63, 95, 96 Doerr, 116 Doflein, 17, 23, 71, 73, 75 Donne', 106 Dudgeon, 28 Dufouger and Thiroux, 90 Dutton, 28, 43 137 138 BIBLIOGRAPHIC INDEX. Button and Todd, 88 Grubler, 65 Button, Todd, and Tobey, 99 Gruby, 71 Buval and Todd, 31, 34, 36, 89 Grunwald, 65 EHRENBERG, u, 70, 71, 73 Ehrlich and Hata, 92 Ehrmann, 56 Eitner, 30, 106 Ellermann, 59 FANTHAM, 21, 23, 28, 34, 79, 84, 93 Fantham and Gross, 18 Ferr6, 50 Flournoy, 70, 87 Flournoy, Norris, and Pappen- heimer, 32 Foix and Mallein, 64 Foley and Sergent, 46 Follet, 56 ' Fontana and Volpino, 32 Forest, 64 Fouquet, 30, 56 Fraenkel, 27, 87 GABRITCHEWSKY, 60, 88, 91 Galacesco and Bruckner, 33, 53. I" Gaucher and Merle, 56 Gauducheau, 44 Gaylord, 52, 97, 105 Geets and Leuriaux, 26, 32, 37, 40, no. Giemsa, 26, 63, 64, 65, 87, 98, 102, 107, 108, 109 Gierke, 56, 109 Gino de Rossi, 64 Girard and Veillon, 56 Goadby, 101 Goldhorn, 64 Gonder, 20, 26, 34, 35, 36, 79, 82, 84, 93, 94, 99, 109 Gougerot and Beurman, 53 Gross, 18, 36, 71, 86 Gross and Fanthan, 18 HAENDEL and Uhlenhuth, 46 Hallopeau, 42 Hartmann and Miihlens, 100, 101 Harvey and Bousfield, 43 Hata and Ehrlich, 92 Heanley, 95 Heidenhain, 63 Herxheimer, 28, 50 Herxheimer and Hubner, 65 Hodges and Ross, 89 Hoffmann, 26, 48, 56, 101, 105 Hoffmann and Prowazek, 100, 101, 107 Hoffmann and Schaudinn, 108 Horand, in Hubner and Herxheimer, 65 Huebschmann, 56 Hunt and Richards, 107 JAFFE\ 98 Jancke, 56 Jaquet and Sevin, 50 Jenner, 65 Jullien and Be Lisle, 53 KARLINSKI, 51, 69 Kenrick, 26 Ker, 45 Keysselitz,i7, 21, 22, 33, 79, 80, 81 Kinghorn and Breinl, 62, 96 Kiolomenoglou and Cube, 49, 104 Klein and Arning, 50 Klodnitsky, 35, 36, 87 Knapp and Novy, 86, 87, 88, 95. n6 Koch, 29, 34, 36, 45, 47, 89, 101 Kowalski, 115 Kraus, 106 BIBLIOGRAPHIC INDEX. 139 Kraus and Prantschoff, 50 Krienitz, 30, 105 Krienitz and Scholtz, 49 Krzystalowicz and Siedlecki, 25. 27, 30, 34, 35, 37, 40, 41, 42, 43, 89, 108, 109, no, in LANGE and Levaditi, 61, 92 Laptschinsky, 73 Launois and Loederich, 43 Laveran, 94 Laveran and Mesnil, 20, 79 Le Dantec, 116 Lebailly, 32 Lebert, 86 Leishman, 16, 40, 43, 44 Leixer, 56 Leuriaux and von Geets, 26, 32, 37, 40, no Levaditi, 26, 32, 39, 53, 56, 60, 64, 65, 87, 89, 106, 107, 108, 109, no, 112, 113, 114 Levaditi and Lange, 61, 92 Levaditi and Macintosh, 109 Levaditi and Mancunian, 47, 65, 89 Levaditi and Nattan-Larrier, S3. 57 Levaditi and Stanesco, 33, 102 Levadir.i and Wallich, 56 Levaditi and Yamamouchi, 34 Loederich and Launois, 43 Loeffler, 66, 67 Loewenthal, 30, 42, 101, 105 Lucius, 65 Liihe, 71 MACKIE, 102 Mallein and Foix, 64 Mandelbaum, 67 Mancunian and Levaditi, 47, 65, 89 Manteufel, 46 Marchoux, 92 Marchoux and Salimbeni, 91 Marshall, 55 Martin, 35, 60, 95 Martoglio and Carpano, 95 Maskalowetz and Zabolotony, 56 Mayer, 28, 39, 42, 43, 89 Mayer and Newstead, 34 Mclntosh, 57, 112 Mclntosh and Levaditi, 109 McKinnon, 34, 88 McLennan, 58 McNeal, 64 McNeal and Novy, 16 Meirowsky, 67 Meister, 65 Merle and Gaucher, 56 Mesnil and Laveran, 20, 79 Metchnikoff, 46, 50, 70 Mezinescu, 116 Migula, 70 Miller, 29, 101 Milne and Ross, 88 Minchin, 68 Moebius, 77 Moffat, 89 Moritz, 30, 59, 113 Mtihlens, 50, 101, in Miihlens and Hartmann, 100, IOI Miihlens and Schereschewsky,32 Mulzer, 104 NAPLES, 75 Nattan-Larrier and Levaditi, S3, 57 Neufeld and Prowazek, 60 Neumann, 98, 99 Newstead and Mayer, 34 Nicolle, 98 Nicolle and Compte, 34, 61, 93 Niessen, 42 Norris, 70, 87 Norris, Pappenheimer, and Flournoy, 32 Novy, 48, 114 140 BIBLIOGRAPHIC INDEX. Novy and Knapp, 86, 87, 88, 95, 116 Novy and MacNeal, 16 Nuttall, 34, 88 OBERMEIER, 45 Oppenheimer, 115 Oppenheimer and Sachs, 64 PANE A and Babes, in Pappenheimer, 70, 87 Pappenheimer, Norris, and Flournoy, 32 Pereira and De Sousa, 56 Perrin, 17, 18, 19, 20, 21, 22, 23, 33, 36, 37, 38, 40, 77, 78, 79, 80, 84 Petrie, 44 Plaut, 25, 76, 1 02 Polland, 103 Ponselle and Ravaut, 66 Popovitch, 87 Porter, 34 Prantschoff and Kraus, 50 Pricolo and Baruchello, 26, 61, 95 Proca and Vasilescu, 64 Proescher, 113 Proescher and White, 57, 113 Prowazek, 26, 27, 29, 34, 35, 38, 41, 42, 84, 91, 92, 94, 98, 101, 103 Prowazek and Hoffmann, 48, 100, 101, 107 Prowazek and Neufeld, 60 QUE"RY, 42 RABINOWITSCH, 46 Ravaut and Ponselle, 66 Rechtsamer, 115 Reichert, 27 Reitmann, 64 Reuter, 29, 56 Richards and Hunt, 107 Rigaud, 115 Rille, 1 06 Rille and Vocquerodt, 54 Risso and Cipollina, 50 Romanowsky, 65 R6na, 104 Ross and Hodges, 89 Ross and Milne, 88 Rossi, 98 SACHAROFF, 90, 91 Sachs and Oppenheimer, 64 Sakurane, 105 Salimbeni and Marchoux, 91 Saling, 68, 69 Salomon, 115 Sambon, 108 Schaudinn, n, 16, 26, 27, 28, 48, 53, 69, 70, 71, 74, 75, 100, 105, 106, 108, 109, 114 Schaudinn and Biitschli, 76 Schaudinn and Hoffmann, 108 Schaudinn and Vuillemin, 25 Schellack, 18, 20, 21, 27, 28, 30, 33. 34, 35, 38, 46, 47, 78, 80, 81, 82, 83, 84, 85, 87, 89 Scherber, 107 Schereschewsky, 30, 33, 43, 63, 102, IO9, III Schereschewsky and Muhlens 32 Schmeidlechner, 14, 43 Schmorl, 56, 64 Scholtz and Krienitz, 49 Schrdtter, 70 Schiiffner, 53, 57, 112 Schwellengrebel, 12, 13, 33 Sergent, 16 Sergent and Foley, 46 Sevin and Jaquet, 50 Shennan, 50 Siebert, 50 Siedlecki and Krzystalowicz, 25, 27, 30, 34, 35, 37, 40, 41, 42, 43, 89, 108, 109, no, in BIBLIOGRAPHIC INDEX. 141 Siegel, no Simmonds, 56 Simonelli and Bandi, 29, 50, 65 Smith (T.) 116 Sobernheim and Tomasoli, 30 Stanesco and Levaditi, 33, 102 Stephens, 26, 27 Stimson, 114 Stordy, 61 THEILER, 44, 61, 94, 95 Thiroux and Dufougere, 90 Tictin, 46 Tobey and Todd, 28, 43 Tobey, Dutton, and Todd, 99 Todd and Dutton, 88 Todd and Duval, 31, 34, 36, 89 Todd and Tobey, 28, 43 Todd, Dutton, and Tobey, 99 Tomasoli and Sobernheim, 30 Tunnicliffe, 43 UFFENHEIMER, 59 Uhlenhuth and Haendel, 46 VASILESCU and Proca, 64 Veillon and Girard, 56 Veszpremi, 39, 59, 102 Vincent, 102 Vocquerodt and Rille, 54 Volpino and Bertarelli, 30, 65 Volpino and Fontana, 32 Volpius and Bertarelli, 104 von dem Borne, 57, 65 von Geets and Leuriaux, 26, 32, 37, 40, no von Niessen, 42 Vuillemin, 69, 71, 108 Vuillemin and Schaudinn, 2 5 WALLICH and Levaditi, 56 Wassermann, 56 Waters, 59, 104 Wellmann, 43, 53, 57, 113 Wenyon, 35, 44, 62, 96, 97 Werner, 116 White and Proescher, 57, 113 Whitmore, 103 Wibel, 70 Williams, 32 Williams (L. A. and R. S.) 89 Wise, 58, 114 Wolff, 86 YAMAMOTO, 66 Yamamouchi and Levaditi, 34 ZABOLOTNY and Maskalowetz, 56 Zettnow, 29, 92 Ziehl, 64 Zuelzer, 74 INDEX. AFRICAN tick fever, 46 Alimentary canal of dog, spi- rilla in, 115 spirochaetes in, 115 spirochaetes in, 116 American relapsing fever, 47 Angina, Vincent's, 58 Animals, diseases of, 60 Antisyphilitic treatment, effect of, on spirochaeta pallida, 54 Arabian spirochsete, conjuga- tion in, 38 sporulation in, 40 Association of spirochaetes with other organisms, 42 Atoxyl in fowl spirochaetosis, 61 Autogamy, 79 Axenstrang, 92 BACILLUS fusiformis, associa- tion of spirochaetes with, 43 spirochaeta duttoni asso- ciated with, 43 pallida associated with, 43 pertenuis associated with, 43 refringens associated with, 43 Balanitis, 60 Basalkorn, 80 Bat, disease due to spirochaete in, 6 1 Bertarelli and Volpino's stain, 65 Bibliography, 117-136 Biological position, 1 1 Blanchard 's classification, 70 Blepharoplasts, 20 Blood-spirochaetes, 71 Bodies, coccoid, associated with spirochaeta anodontae, 41 ovoid, 40 rod-shaped, associated with spirochaeta duttoni, 42 gallinarum, 42 lutrae, 42 pallida, 41 with spirochaetes, 41 Bombay, relapsing fever in, 48 Bronchitis, 59 haemorrhagic, 59 Burn's india ink method of identifying spirochastes, 66 CALCULOUS pyelitis, pus from, spirilla in, 1 1 6 Canal, alimentary, of dog, spi- rilla in, 115 spirochaetes in, 115 spirochaetes in, 116 Cancer in mice, spirochastes in, 52, 97 Cattle, fever of, spirochaetes in, 61 Chancre, spirochaeta pallida in, 5i Chemical reagents, action of, on small spirochastes, 15 Cholera, feces of, spirilla in, 115 Chromatin in spirochaeta ano- dontae, 21 in spirochaeta balbianii, 21 143 144 INDEX. Chromatinbrocken, 94 Classification, 69 Coccoid bodies associated with spirochaeta anodontae, 41 forms from spirochaeta dut- toni, 40 Congenital syphilis, 56 Conjugation, 14, 37 in spirochaeta anodontae, 3 7 Arabia, 38 balbianii, 37 pallida, 37 Corpuscles, pebrine, 94 Cristispira, 71 interrogationis, 86 pectinis, 86 Cultivation, 31 failure of, 13 of spirochaeta balanitidis, 33 duttoni, 31 gallinarum, 32 gracilis, 33 obermeieri, 32 pallida, 32, 33, 53, in refringens, 32 DARK field examination, 66 Davidsohn's stain, 64 Degeneration, moniliform, 29, 40 Description of species, 72 of spirilla, 86 Development, 33 into filaments, 36 Division by incurvation, 36 in spirochaeta anodontae, 33 balbianii, 33 duttoni, 34 gallinarum, 34 hartmanni, 35 obermeieri, 34 pallida, 34 vesperuginis, 34 Division, longitudinal, in large spirochaetes, 14 in small spirochaetes, 14 mode of, 33 Dog, alimentary canal of, spi- rilla in, 115 spirochsetes in, 115 Dysentery, feces of, spirilla in, 116 ENCYSTMENT in spirochaeta ano- dontae, 39 balbianii, 38 duttoni, 39 pallida, 39 Ends of large spirochaetes, shape of, 1 8 Enlargement of spleen in mice infected with spirochaeta laverani, 62 Entoplasm, 19 structure of, 21 Euglenoid movement in spiro- chaeta vincenti, 25 Examination of living spiro- chaetes, 66 dark field method, 66 FECES of cholera, spirilla in, 115 of dysentery, spirilla in, 116 Fetus, spirochaeta pallida in, 56 Fever, African tick, 46 of cattle, spirochaetes in, 61 of horses, spirochaetes in, 6 1 of sheep, spirochaetes in, 61 relapsing, 45 American, 47 in Bombay, 48 in Panama, 48 Filaments, development of spirochaetes into, 36 in spirochaeta duttoni, 36 obermeieri, 36 Fish, shell-, spirochaetes in, 82, 83 INDEX. 145 Flagella in spirochaeta duttoni, 27 obermeieri, 27 of large spirochaetes, 14 Fly, tse-tse, stomach of, spirilla in, 1 1 6 Forest's stain, 64 Form, change of, in spirochseta pallida, 30 variability of, 29 of spirochaeta pallida, 49 Fowls, spirillosis of, 60 Framboesia tropica, 57 Fusiform bacillus. See Bacillus fusiformis. GANGRENE, spirochaetes in, 103 Gangrenous stomatitis, spiro- chsetes in, 44 Gedrungen, 114 Giemsa's stain, 63 Gino de Rossi's stain, 64 Goldhorn's stain, 64 Granules in spirochaetes, 27 Granuloma, ulcerative, of pu- denda, 58 spirochaetes in, 44 spirochaetes resembling spirochaeta pallida in, 52 Grunwald's stain, 65 Gumma, spirochaeta pallida in, HABITAT, 31 Haemorrhagic bronchitis, 59 Horses, fever of, spirochaetes in, 61 Hospital gangrene, spirochaetes in, 103 IMMOBILISINES, 61 Incurvation, division by, 36 India ink method of identi- fying spirochaetes, 66 Intestines of pig, spirilla in, 1 16 Intra-vitam staining, 67 Involution forms, 24 KARYOSOME in spirochaeta bal- bianii, 21 Kriechend, 74 LARGE spirochaetes, 73. See also Spiroch&tes, large. Leg, tropical ulcer of, 103 Length of large spirochaetes, 18 Levaditi and Mancunian's stain, 65 Levaditi's stain, 65 Lice in conveying relapsing fever, 46 Living spirochaeta dentium, staining, 67 pallida, staining, 67 spirochaetes, examination of, 66 dark field method, 66 staining, 67 Longitudinal division in large spirochaetes, 14 in small spirochaetes, 14 Loop in spirochaeta pallida, 29 pertenuis, 29 in spirochaetes, 29 Luhe's division of spirochaetes, 7i Lymph, vaccine, spirochaetes in, 1 06 Lymphadenoma, 57 Lymphosarcoma, 57 MALIGNANT syphilis, 50, 55 Mandelbaum's stain, 67 Mancunian and Levaditi's stain, 65 Masses, tangled, 29 McNeal's stain, 64 Meirowsky's stain, 67 146 INDEX. Membrane, undulating, in spiro- chaeta buccalis, 26 gallinarum, 26 refringens, 26 vesperuginis, 26 of large spirochaetes, 14, 20 of small spirochastes, 14, 26 Mice, cancer in, spirochaetes in, 52, 97 infected with spirochaeta laverani, enlargement of spleen in, 62 Molluscs, spirochaetes of, 82 Moniliform degeneration, 29, 40 Morphology, 16 Movements, euglenoid, in spiro- chaeta vincenti, 25 in spirochaeta pallida, 25 in treponema pallidum, 25 of large spirochastes, 19 of small spirochaetes, 25 Mouse-cancer, spirochaetes in, 52. 97 Multiplication, 33 Mussels, spirochaetes from, 85 NODULES in spirochaeta aborig- inalis, 28 duttoni, 28 pallida, 28 pertenuis, 28 in spirochastes, 27 Noma, spirochaetes in, 104 Nucleus in spirochaeta bal- bianii, 21 ONYCHIA, spirochastes in, 43 Oppenheimer and Sachs' stain, 64 Ornithodorus moubata, 46 Ovoid bodies, 40 in spirochaeta pallida, 40 pertenuis, 40 PANAMA, relapsing fever in, 48 Pathogenicity, 45 summary of, 62 P6brine corpuscles, 94 Pediculi capitis et corporis in conveying relapsing fever, 46 Periplast, 19 Periplastfortstaze, 80 Phagedaenic ulcers, 103 Phagocytosis, effect of, on spiro- chaeta pallida, 56 Pian, 57 Pig, intestines of, spirilla in, 1 1 6 skin of, lesions, spirochaetes in, 62 spirochaetes in, 95 Ponselle and Ravaut's stain, 66 Pseudo-spirochaetes, 67 Pudenda, ulcerative granuloma of, 58 spirochaetes in, 44 spirochaetes resembling spirochasta pallida in, 52 Pulmonary tuberculosis, spiro- chaetes in, 59 Pus from calculous pyelitis, spi- rilla in, 116 Pyelitis, calculous, pus from, spirilla in, 1 1 6 RANDFIBRILLE, 20 Ravaut arid Ponselle's stain, 66 Reaction, Wassermann, in syphilis, 56 Recurrent fever, spirochaetes of, 12 Reitmann's stain, 64 Relapsing fever, 45 'American, 47 in Bombay, 48 in Panama, 48 Relation between large and small spirochaetes, u INDEX. 147 Reproduction in large spiro- chaetes, 14 in small spirochaetes, 14 Rod-shaped bodies associated with spirochaeta dut- toni, 42 gallinarum, 42 lutrae, 42 pallida, 41 with spirochaetes, 41 SACK and Oppenheimer's stain, 64 Salvarsan (606) in fowl spiro- chaetosis, 61 Schellack's list of spirochaetes found in shell-fish, 83 Schereshewsky's stain, 63 Schmorl's stain, 64 Serum, syphilitic, action of, on spirochaeta pallida, 53 Sexual cycle of spirochaeta pallida, no Shape of large spirochaetes, 18 of small spirochaetes, 25 of spirochasta anodontae, 18 balbianii, 18 plicatilis, 18 Sheath in spirochaeta buccalis, 26 duttoni, 26 pallida, 26 Sheep, fever of, spirochaetes in, 61 Shell-fish, spirochaetes in, 82, 83 Silver stain, 65 Skin of pig, lesions of, spiro- chaetes in, 62 Small spirochaetes, 86. See also Spirochates, small. Small-pox, spirochaetes in, 105 Species, description of, 72 Spirilla, description of, 86 doubtful, 115 Spirilla in alimentary canal of dog, 115 in feces of cholera, 115 of dysentery, 116 in intestines of pig, 1 1 6 in pus from calculous pye- litis, 116 in stomach of tse-tse fly, 116 Spirillicidins, 46 Spirillosis of fowls, 60 Spirillum, 71 giganteum, 12, 13 glossinae, 116 minor, 97 obermeieri, 12 sputigenum, 101 volutans, 12 Spirobacillus, 70 Spirobacteria, 70 Spirochaeta, n, 71 aboriginalis, 114 nodules in, 28 acuminata, 113 anodontae, 12, 14, 79 chromatin in, 21 coccoid bodies associ- ated with, 41 conjugation in, 37 description, 79 division in, 33 encystment in, 39 shape of, 18 sporulation in, 40 staining material in, 24 structure of, 17, 21 anserina, 90 description, 90 Arabia, conjugation in, 38 sporulation in, 40 balanitidis, 107 cultivation, 33 description, 107 balbianii, 12, 13, 14, 77 chromatin, in 21 conjugation in, 37 148 INDEX. Spirochaeta balbianii, descrip- tion, 77 division in, 33 encystment in, 38 female forms, 78 karyosome in, 2 1 male forms, 79 nucleus in, 21 shape of, 18 sporulation in, 40 structure, 16, 21 bo vis, 95 bronchi alis, 59, 104 buccalis, 100 description, 100 sheath in, 26 undulating membrane in, 26 bufonis, 99 carteri, 88 culicis, 98 daxensis, 76 description, 76 in water, 31 denticola, 101 dentium, 101 description, 101 living, staining of, 67 duttoni, 88 associated with bacillus fusiformis, 43 coccoid forms from, 40 cultivation, 31 description, 88 division in, 34 encystment in, 39 filaments in, 36 flagella in, 27 nodules in, 28 rod-shaped bodies asso- ciated with, 42 sheath in, 26 equi, 95 eurogyrata, 116 gadi, 98 Spirochaeta gallinarum, 60, 91 cultivation, 32 description, 91 division in, 34 rod-shaped bodies asso- ciated with, 42 undulating membrane in, 2 6 gondii, 98 gracilis, 102 cultivation, 33 description, 102 hartmanni, 99 description, 99 division in, 35 interrogans, 114 interrogationis, 86 jonesii, 99 lagopodis, 93 laverani, 96 enlargement of spleen in mice infected with, 62 lovati, 93 lutrae, 94 rod-shaped bodies asso- ciated with, 42 lymphatica, 57, 113 mactrae, 84 media, 101 microgyrata, 105 minei, 98 minor, 97 muris, 62, 96 novyi, 47, 88 obermeieri, 12, 45, 86 cultivation, 32 description, 86 division in, 34 filaments in, 36 flagella in, 2 7 staining, 87 obtusa, 113 ovis, 95 pallida, 48, 108 action of syphilitic serum on, 53 INDEX. I 49 Spirochaeta pallida associated with bacillus fusiformis, 43 change of form in, 30 conjugation in, 37 cultivation, 32, 33, 53, in description, 108 developmental form of a bacillus, 42 division in, 34 effect of anisyphilitic treat- ment on, 54 of phagocytosis on, 56 of syphilitic virus on, 54 encystment in, 39 in chancre, 51 in congenital syphilis, 56 in fetus, 56 in gumma, 51 in lesions artificially pro- duced by inoculation of lower animals with spyhilis, 52 in non-syphilitic condi- tions, 49 living, staining of, 67 loop in, 29 movement in, 25 nodules in, 28 objections to, as cause of syphilis, 49 ovoid bodies in, 40 relationship of, to actual lesions of syphilis, 50 rod-shaped bodies asso- ciated with, 41 sexual cycle, no sheath in, 2 6 spirochaetes resembling, in ulcerative granu- loma of pudenda, 52 in yaws, 52 staining, 63, 64 variability of form, 49 pallidula, 112 Spirochaeta pectinis, 86 pelamydis, 99 pertenuis, 53, 57, 112 associated with bacillus fusiformis, 43 description, 112 loop in, 29 nodule in, 28 ovoid bodies in, 40 pinnae, 79, 84 description, 84 pitheci, 90 plicatilis, n, 73 description, 73 in water, 31 shape of, 18 structure, 17, 23 polyspira, 31, 86 pseudopallida, 104 recurrentis, 12, 86 refringens, 106 associated with bacillus fusiformis, 43 cultivation, 32 description, 106 undulating membrane in, 26 schaudinni, 103 spiculifera, 19, 8 1 stenogyrata, 116 suis, 95 tapetos, 84 theileri, 94 description, 94 vesperuginis, 61, 93 description, 93 division in, 34 undulating membrane in, 26 vincenti, 102 description, 102 euglenoid movement in, 25 Spirochaetes, associated forms, 3 INDEX. Spirochaetes, association of, with bacillus fusiformis, 43 with other organisms, 42 biological position, 1 1 blood-, 71 change in form, 29 classification of, 69 conjugation in, 14, 37 cultivation of, 31 failure, 13 development of, 33 into filaments, 36 division in, 33 by incurvation, 36 doubtful, 115 entoplasm of, 19 structure, 21 form of, variability in, 29 general characters, n granules in, 27 habitat of, 31 in alimentary canal, 1 1 6 of dog, 115 in cancer in mice, 52, 97 in congenital syphilis, 56 in fever of cattle, 61 of horses, 61 of sheep, 61 in gangrenous processes, 103 stomatitis, 44 in lesions of skin in pig, 62 in mouse-cancer, 52, 97 in noma, 104 in onychia, 43 in phagedaenic ulcer, 103 in Pig, 95 in shell-fish, 82, 83 in small-pox, 105 in stomach, change in form, 30 in tropical ulcer of leg, 1 03 in ulcerative granuloma, 44 in vaccine lymph, 106 india ink method of iden- tifying, 66 Spirochaetes, large, 73 and small, relation be- tween, ii ends of, shape, 18 flagella of, 14 length of, 1 8 longitudinal division, 14 movements of, 19 reproduction in, 14 shape of, 18 staining material in, ar- rangement of, 13 structure of, 16, 19 undulating membrane of, 13, 14, 20 Irving, examination of, 66 dark field method, 66 staining of, 67 loop in, 29 masses of, tangled to- gether, 29 moniliform degeneration, 29, 40 morphology of, 16 multiplication of, 33 nodules in, 27 objects resembling, 69 of African tick fever, 46 of balanitis, 60 of bronchitis, 59 of haemorrhagic bronchitis, 59 of lymphadenoma, 57 of molluscs, 82 of mussels, 85 of pulmonary tuberculosis, 59 of relapsing fever, 45 American form, 47 in Bombay, 48 in Panama, 48 of spirillosis of fowls, 60 of syphilis, 48 of ulcer of stomach, 59 of ulcerative granuloma, 58 of Vincent's angina, 58 of yaws, 57 INDEX. Spirochaetes, ovoid bodies in, 40 pathogenicity of, 45 summary, 62 periplast of, 19 pseudo-, 67 resembling spirochaeta pal- lida in ulcerative granuloma of pu- denda, 52 in yaws, 52 rod-shaped bodies associ- ated with, 41 small, action of chemical reagents on, 15 and large, relation be- tween, ii description of, 86 movements of, 25 nature of, 14 reproduction in, 14 shape of, 25 structure of, 25, 26 undulating membrane of, 14, 26 staining of, methods, 63 trypanosomes associated with, 44 variability in form, 29 Spironema, 69 pallida, 108 Spiroschaudinna pallida, 108 Spirosoma, 70 Spleen, enlargement of, in mice infected with spirochaeta laverani, 62 Sporulation, 40 in spirochaeta anodontae, 40 Arabia, 40 balbianii, 40 Stain, Bertarelli and Volpino 's, 65 Burri's, 66 Davidsohn's, 64 Forest's, 64 Giemsa's, 63 Stain, Gino de Rossi's, 64 Goldhorn's, 64 Grunwald's, 65 Levaditi and Mancunian's, 65 Levaditi's, 65 Mandelbaum 's, 67 McNeal's, 64 Meirowsky's, 67 Ravaut and Ponselle's, 66 Reitmann's, 64 Schereshewsky's, 63 Schmorl's, 64 silver, 65 Yamamoto's, 66 Staining, intra-vitam, 67 living spirochaeta dentium, 67 pallida, 67 Spirochaetes, 67 material in large Spirochaetes, arrangement of, 13 in spirochaeta anodontae, 24 methods of, 63 spirochaeta obermeieri, 87 pallida, 63, 64 Stomach of tse-tse fly, spirilla in, 116 Spirochaetes in, change in form, 30 ulcer of, 59 Stomatitis, gangrenous, spiro- chaetes in, 44 Structure of large Spirochaetes, 1 6, 19 of small Spirochaetes, 25, 26 of spirochaeta anodontae, 17, 21 balbianii, 16, 21 plicatilis, 17, 23 Syphilis, 48 clinical phenomena, 54 congenital, 56 malignant, 50, 55 relationship of spirochaeta pallida to actual lesions of, 50 152 INDEX. Syphilis, treatment of, effect on spirochasta pallida, 54 Wassermann reaction in, 56 Syphilitic serum, action of, on spirochaeta pallida, 53 virus, effect of, on spiro- chaeta pallida, 54 TANGLED masses of spirochaetes, 29 Tastend, 74 Tick fever, African, 46 Treponema, 70, 71 pallidum, 108 movements in, 25 Tropical ulcer of leg, 103 Trypanosoma, 71 balbianii, 77 dimorphon, 44 luis, 37, no Trypanosomes associated with spirochaetes, 44 Trypanosomidae, 71 Tse-tse fly, spirilla in stomach of, 116 Tuberculosis, pulmonary, spiro- chaetes in, 59 ULCER, gangrenous, spirochaetes in, 104 of stomach, 59 phagedaenic, 103 tropical, of leg, 103 Ulcerative granuloma of pu- denda, 58 Ulcerative granuloma of pu- denda, spirochagtes in, 44 spirochaates resembling spirochaeta pallida in, 52 Undulating membrane in spiro- chaeta buccalis, 26 gallinarum, 26 refringens, 26 vesperuginis, 26 of large spirochaetes, 14, 20 of small spirochaetes, 14, 26 VACCINE lymph, spirochaetes in, 106 Variability of form of spiro- chaeta pallida, 49 Variola, spirochaetes in, 105 Vesperugo kuhlii, 61 Vibrio, 70 lineola, 106 Vincent's angina, 58 Volpino and Bertarelli's stain, 65 WASSERMANN reaction in syphi- lis, 56 Water, spirochaeta daxensis in, 31 plicatilis in, 31 YAMAMOTO'S stain, 66 Yaws, 57 spirochaetes resembling spi- rochaeta pallida in, 52 Date Due .S.A. CAT. NO. 24 161 A 000 499 571 8 QW155 1911 Bosancuet, William Cecil. Spirochaetes ; a review of recent work... MEDICAL SCIENCES LIBRARY UNIVERSITY OF CALIFORNIA, IRVINE IRVINE, CALIFORNIA 92664