Section of Comparative Medicine

Sectional Proceedings of the Royal Socidy of Medicine Vol. XLIIpage 25 9 707

Section of Comparative MedicinePresident-Professor WILSON SMrrIH, M.D., F.R.S.

[April 13, 1949]DISCUSSION ON LEPTOSPIROSIS

Dr. J. M. Alston:General Survey

In November 1914, at the Imperial UJniversity in Kyushu, Japan, R. Inada and hiscolleagues demonstrated that a spirochiete-which they named the Spirochata ictero-hwmorrhagice-is the cause of Weil's disease. They cultured the organism and producedwith it in guinea-pigs a disease closely resembling the human illness. They also demon-strated antibodies to it in the blood of patients and of animals experimentally infected.

In 1917 and 1918 Noguchi compared the Spirochweta icterohlumorrhagie of Inada withsimilar organisms from British cases of Weil's disease in Flanders and with strains whichhe isolated from wild rats in the U.S.A. He found that from these three sources the or-ganisms were the same in form and by immunological tests, and that they resembled noother organism already described except Spirocheta biflexa, which Wolbach and Binger(1914) had isolated in July 1913 from a fresh-water pond in Massachusetts. Noguchigave to all these strains the generic name of Leptospira. The original strain of L. biflexafound by Wolbach and Binger did not survive its first subculture and the name is now usedfor some non-pathogenic Leptospiras which have been found in fresh water.

Since 1917 the genus Leptospira has been expanded by the addition of many more species.The differential criteria for these have been chiefly serological and much less pathogenicityin experimental animals and the protection of them by active and passive immunization;morphology and cultural characters have shown very few distinctions. Broadly speaking,this serological separation of species has been done most thoroughly in Japan, Malaya, theNetherlands East Indies, Holland and Denmark. The work has been based on agglutina-tion, or agglutination and lysis, of strains by serum of immunized rabbits with or withoutabsorption of antibodies. The results, therefore, lack the precision obtained in theSalmonellas by the chemical and physical separation of antigens.To give an outline of the progress of the work 1 have made a table from several sources

of the species in their approximate serological relationships. Such information was firstpublished extensively by Walch-Sorgdrager in 1939 and has been continued by Borg-Petersen among others.

TABLE I.-FIRST IDENTIFICATION OF LEPTOSPIRAL SPEcIEsSpecies Date Country Species Date Country

Icterohiem. 1914 Japan Akiyami A 1925 JapanSalinem 1925 N.E.I. =AutumnalisCanicola 1931 Holland =Rachmat 1923 N.E.I.Australis B 1934 Queensland Andaman B 1928 Andaman Is.=Zanoni =Grippotyphosa 1928 RussiaPoi 1941 Italy Australis A 1934 QueenslandBallum 1943 Denmark =Ballico 1934 Queensland

Hebdomadis 1918 Japan Andaman A 1928 Andaman Is.=Akiyami B. JapanH.C. N.E.I. Pomona 1937 QueenslandSejroe 1937 Denmark =Mezzano 1940 ItalySaxkoebing 1942 Denmark

Suis 1944 ArgentineBatavik 1926 N.E.I.=Swart v. Tienen N.E.I. Bovis 1947 Palestine=Mitis 1938 Italy==Oryzeti 1939 Italy

To this grouping it may be added that Borg-Petersen found L. icterohwmorrhagia to exist intwo forms which, because of their serological rplationships, he named AB and A. LikewiseL. rachmat is a partial form of L. akiyami A.

1 shall now confine this brief outline of leptospirosis throughout the world mainly tothe sources and methods of human infection and the forms which human infection takes.SEPT.-COMP. MED. 1

Proceedings of the Royal Society of Medicine

The spread of L. icterohwemorrhagiw to man is almost entirely due to the fact that somesmall rodents and a few other anirnals harbour the organism for a longer or shorter. timeand excrete it in the urine. By far the most important are rats, of which many- speciesharbour the organism in most countries of the world, with the chief exception of most partsof Africa. Much less often field-mice and ferrets have been found infected. Next torodents, dogs and wild and silver foxes suffer infection. Pigs, horses, cattle and perhapscats are rarely infected.Of some of the other Leptospiras, also, an important source of infection is the rat, includ-

ing L. salinem, L. akiyami A, L. bataviaw in the Netherlands East Indies, and L. australis Aand B in Queensland. Otherwise, Leptospiras have as their principal known carriers,various mice for L. hebdomadis, L. sejroe, L. saxkoebing, L. ballum and for L. bataviain Europe, dogs for L. canicola, pigs for L. suis and for L. pomona in Europe, cattle forL. bovis. L. batavik has also been found in dogs and cats in the Netherlands East Indies.

There are several species for which an animal host has not yet been found in some of thelocalities where they are frequent. Such are L. poi and the two species from the AndamanIslands. These Leptospiras are particularly associated with human infections after long-lasting contact with water in rice fields and swampy land. The absence of a known animalhost has led some writers such as Van Riel (1948) to claim that, in general, the survival ofpathogenic Leptospiras in water is more important to man than their presence in animalswhich may contaminate the water. This is probably too extreme, but it emphasizes thatin almost all circumstances infection from animal carrier to man is not through directcontact but is by Leptospiras which have been excreted by animals on to damp ground orinto water which allows the organism to survive.The rodents which are the commonest carriers suffer very little from their leptospiral

infection and may excrete the organisms for a large part of their lifetime. To some of theother animals-dogs, pigs and cattle-Leptospiras are more pathogenic.The route of infection of human beings can be generally exemplified' by L. icterohwemo-

rrhagiw. The skin, especially through cuts, abrasions, bites or sodden surfaces, is theusual site of entry. Accidental infections of workers in laboratories have shown that theconjunctive and the mouth may give entrance, and infection in bathing may sometimes beby these routes. Entry by the lungs is suspeoted. Infection by contact between humanbeings is almost unknown.One purpose of this outline is to emphasize that in Great Britain only two species-

L. icterohwemorrhagiw and L. canicola-have yet been identified in contrast with at leastten on the Continent of Europe. I have, therefore, made a list of British Muridw and againstthe appropriate names placed the species of Leptospiras found in various continental coun-tries. Table fI shows that four species of Leptospiras unknown in nature in this countryoccur abroad in muride which are to be found in various parts of the British Isles and thattwo more Leptospiras have been found on. the Continent in rodents nearly related toBritish species.

TABLE IILeptospiras in

British Muridw Continental EuropeMICROTINN (voles and lemmings)Evotomys glareolus L. grippotyphosaMicrotus hirtusMicrotus agrestisArvicola amphibius amphibiusArvicola amphibius reta

MURINAE (rats and mice)CL. grippotyphosa

Apodemus sylvaticus { L. sejroeLL. batavia?

Apodemusflavicollis wintoniMicromys minutus L. bataviaRattus rattusRattus norvegicusMus musculus

ALSO, Muride, nearly related to those above, are on theContinent infected with Leptospiras, thus:

Apodemus flavicollis L. saxkoebingrL. ballum

Mus musculus spicilegus X, L. saxkoebingLL. sejroe

.268708

27 Section of Comparative Medicine 709

The most virulent species towards man is L. icterohwmorrhagiw and next to it are akiyamiA, rachmat, salinem and, in the East, batavile. Their greater virulence compared with theremainder is shown by higher case mortality, and by more jaundice and more acute nephritis.At the same time, milder infections without jaundice and with very little nephritis constituteat least half the cases of such infections, with mild meningitis as the chief feature of some ofthem. In contrast to the species named, the others, including infections in Europe by L.batavice, cause little or no jaundice, slight nephritis and very few deaths. The chief featuresin these diseases are fever, malaise and muscular pains, or mild meningitis. It is the caseswith meningitis which are most likely to be found when infections by a particular speciesof mildly virulent Leptospiras are first recognized; this is the case in Great Britain at presentwith L. canicola.The history ofhuman leptospirosis in Great Britain consists of the knowledge of infections

of L. icterohwmorrhagire since 1922 and of infections by L. canicola since 1945.In 1922 a man was infected with L. icterohamorrhagia, by immersion in the Thames and

the organism was found in his blood by H. C. Brown. In 1924 equally well proved infectionsof coal-miners and others in E. Lothian were reported by Gulland and Buchanan. Aftera gap of ten years, Fairley (1934) reported that a sewerman in London died of the disease,as established by the isolation of the infecting Leptospira and by serological tests; also,serological tests indicated previous infection in 8 other sewermen. In 1935, H. C. Brownreported on the value of the adhesion test and Schuiffner's agglutination test for serologicaldiagnosis. As a result he was able in seven months to diagnose the infection in 40 patientsliving in all parts of England and Wales. Since then diagnosis has been practised chieflyin about six laboratories. From the published and unpublished records I have collectednearly 1,000 proved cases of leptospirosis icterohlemorrhagica from July 1933 to July 1948.Three-quarters of these have been analysed as to the patient's occupation at the time ofinfection and a relation to rat infestation in wet areas is evident in most (Table III).

TABLE III.-OCCUPATION RELATED TO 716 CASES OF WEIL'S DISEASE IN THE BarMSH ISLESJULY 1933-JULY 1948

Occupation or cause Per cent of totalFish-worker .. .. .. .. .. .. .. .. .. .. 30Butcher, tripe-scraper, &c. .. .. .. .. .. .. .. .. 3Coal-miner .. .. .. .. .. .. .. .. .. .. 20Sewer worker .. .. .. .. .. .. .. .. .. .. 11Army .. . . . . . . . . . . 9Royal Navy .. .. .. .. .. .. .. .. .. .. 2Royal Air Force .. .. .. .. .. .. .. .. .. .. 2Bathing, paddling, &c., in fresh water.. .. .. .. .. .. 6Farm-worker . .. .. 6Worker in water including canal, &c :. .. .. 2Bite, &c., of rat, dog or ferret .. .. .. .. .. .. .. ..2Builder, &c. ....... . . . . . . . .1Gardener, &c. I.. .. .. .. .. .. .. .. .. 1Laboratory worker .. .. .. .. .. .. .. .. 1

Miscellaneous, e.g. bottle-washer .. .. .. .. .. .. .. 4

100

The infection has been found widely in the British Isles. In Aberdeen, Davidson and Smith(1939) have detected over 200 instances among men and women handling white fish in un-hygienic sheds. Infections in coal-miners in wet and rat-infested pits have been foundchiefly in the West of Scotland by R. D. Stuart and in Northumberland and Durham andin South Wales by H. C. Brown and J. C. Broom. In London, sewer workers provide mostof the patients and my own experience has been largely with them. In the Services, camps,bivouacs, rat-infested ships and aerodromes have caused infections. Bathing and paddlingin fresh water cause infections in the summer. In the other occupations, also, contact ispossible with Leptospiras excreted by rats.

Males are much oftener infected than females, due to the greater exposure of men toinfection in some occupations. For instance, Broom and I found that of 189 cases duringthe years 1940-46 only 4-4% were women.

Patients of all ages from 4 years to 78 years have been recorded in this country.There is a seasonal variation of incidence. Bathing in fresh water in the summer and

autumn obviously contributes to this, but I found in sewer workers during 1934-45 a clearpreponderance in the months of the second half of the year. Similar variation has been foundin the fish-workers in Aberdeen and in cases generally in Holland and Denmark.The accuracy of the fatality rates depends on the number of mild infections which are

included. Death does not occur without jaundice even when meningitis is present. In two

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series of 256 cases in this country between 1933 and 1946 the death-rate was, 18%; over90% of all the patients were jaundiced. Age increases the case mortality rate. Broom and Ifound a rate of 16% below the age of 46 and 42% later.Buzzard and Wylie reported 5 instances of meningitis, without jaundice, that occurred

in this country in 1946. This form was previously known elsewhere. Broom and I haveinvestigated four other instances. A big proportion of such clinical forms are due to bathingin fresh water. Confusion with acute anterior poliomyelitis has occurred before serologicaldiagnosis was made.The history in Great Britain of undoubted human infections by L. canicola is much

shorter. This species of Leptospira was first isolated in 1931 by Klarenbeek and Schuffnerfrom the urine of a dog, and in 1934 the same Dutch workers and two colleagues recordedthe first infections knowif in human beings. Since then 150 cases have come to light. Thesehave been about 50 each in Holland and Denmark and the remainder in other Europeancountries, the U.S.A.. Argentine and China. It is presumed that dogs are the source of allhuman infections. Entry of the Leptospira is by the skin or sometimes by the eye or mouth.Most cases occur in the second half of the year. Infection is usually domestic and equal inthe sexes. Mild meningitis is the most prominent feature in two-thirds of the cases found;conjunctivitis, iritis and skin rashes are frequent. Only one death has been recorded.As regards Great Britain, in 1945 a boy fell ill of this infection twelve days after swimming

in the Thames, as recorded by Baber and Stuart (1946) and in 1947 and early 1948 4 more suchcases occurred in England. I had some part in examining 3 of these with J. C. Broom andthey were all 4 published in 1948. Since then I have found 3 more cases and Broom severalothers. In 5 out of 7 patients there was contact with a dog, which was shown to be infectedby L. canicola in 2 instances and had been ill in 2 more. So far as I know, meningitis hasbeen the most obvious evidence of disease, and recovery has occurred in the published casesand in others which I observed.

REFERENCESBABER, M. D., and STUART, R. D. (1946) Lancet (ii), 594.BORG-PETERSEN, C. (1944a) Ugeskr. Leg., 106, 617.

(1944b) Acta path. microbiol. scand., 21, 165, 504.and CHRISTENSEN, H. I. (1939) Ugeskr. Leg., 101, 697.

BROOM, J. C., and ALSTON, J. M. (1948) Lancet (ii), 96.BROWN, H. C. (1935) Brit. med. J. (i), 411.BUZZARD, E. M., and WYLIE, J. A. H. (1947) Lancet (ii), 417.DAVIDSON, L. S. P., and SMITH, J. (1939) Brit. med. J. (ii), 753.DHONT, C. M., et al. (1934) Ned. Tifdschr. Geneesk., 78, 5197.FAIRLEY, N. H. (1934) Brit. med. J. (ii), 10.GULLAND, G. L., and BUCHANAN, G. (1924) Brit. med. J. (i), 313.INADA, R., et al. (1916) J. exp. Med., 23, 377.KLARENBEEK, A., and SCHUFFNER, W. (1933) Ned. Tijdschr. Geneesk., 77, 4271.LAURENT, L. J. M., et al. (1948) Lancet (ii), 48.NOGUCHI, H. (1917) J. exp. Med., 25, 755.

(1918) J. exp. Med., 27, 609.VAN RIEL, J. (1948) Brux. mid., 28, 2054.WALCH-SORGDRAGER, B. (1939) Bull. Hlth. Org. League of Nations, 8, 143.WOLBACH, S. B., and BINGER, C. A. L. (1914) J. med. Res., 30, 23.

Miss J. 0. Joshua:Introduction

Leptospiral infection in dogs in this country has received very little attention, either in theliterature or from clinicians.

In 1925 Okell, Dalling and Pugh described L. icterohemorrhagice infection in dogs, towhich they gave the name of "Yellows". They described the condition as being sporadicin adults and enzootic in young dogs. In the acute form they found initial high temperature,severe depression, muscular pain, vomiting and thirst. Death often occurred before icterusdeveloped. The subacute form was similar but icterus developed in two to six days.

Typical post-mortem findings were a hemorrhagic inflammation of the alimentary tract,jaundice and albuminuria; lung hemorrhages were a regular finding; intussusceptionwas common in puppies. This has remained the classical picture of leptospiral jaundice indogs until this day, and apart from occasional clinical reports of isolated cases from time totime canine leptcspirosis remained a neglected subject until Stuart in 1946 stimulated interestby his report of the examination of serum from street dogs in Glasgow, 52% of which showedagglutinins to one or other type of Leptospira.

In 1947 Freak and I described a series of cases ofL. canicola infection, with special referenceto their treatment by penicillin, and later, in 1948, drew attention to the existence of a formof infection with L. icterohwmorrhagice which gave a purely renal syndrome and was clinically

Section of Comparative Medicine

indistinguishable from canicola fever. In 1948 Mills described the clinical aspects of bothL. icterohwemorrhagie and L. canicola infection in dogs.

I must at this stage acknowledge the debt which I, personally, owe to Dr. MaTgrit Scheitlin,of Zurich, whose visit to my practice in 1946 resulted in my recognition of leptospirosis as aby no means uncommon disease of dogs in this country. Since then clinicians in manyparts of the country have recognized leptospirosis due to both types of organism, as beingof relatively high incidence in the canine population.

I should like to deal briefly with the incidence of leptospiral infection as judged on theresults of the agglutination test carried out on 100 random blood samples; my own viewsas to the method and spread of infection; a brief indication of the clinical features of thedisease in dogs, and finally, a few words on the public health angle.

IncidenceThe following figures are based on 100 blood samples taken from dogs of all types and

ages, some healthy, but most destroyed for a wide range of conditions; the 100 samplesinclude bloods from cases of active leptospiral infection. In view of the accepted specificityof the agglutination test I have taken the somewhat arbitrary line of assuming that thepresence of agglutinins, no matter in how low a titre, is an indication that the dog has atsome time in its life come into contact with the organism, but not necessarily that clinicaldisease has occurred. In this way it is possible to get some idea of the prevalence of theorganism.

43 dogs showed agglutinins to one or other species of Leptospira. Of these 31 showed ahigher titre to L. canicola, 8 to L. icterohamorrhagke and 4 showed agglutinins, in low titreonly, equally to both organisms.The sex incidence does not at present appear to show any very significant difference,

although the percentage of reactors in males is slightly higher. Of the 100 bloods 61 werefrom dogs and 39 from bitches; of the 43 positives 29 were dogs and 14 bitches; i.e. approx.48% dogs and 36% bitches were positive.The age incidence is probably of some significance quite apart from the fact that older

animals have had a longer period of potential exposure to infection. Only three dogs under1 year old showed agglutinins, all were males and all showed clinical evidence of the disease.None was under 6 months.There were 13 positives under 5 years of age, 1 1 dogs and 2 bitches. In view of later com-

ments on possible methods of infection it is of some interest to note that these two positivebitches were a Pekingese and a Scottish Terrier, both low-to-ground breeds. Of these 13 inthis age-group only two were dogs not suspected of clinical leptospirosis.Of the 30 positives of over 5 years of age only 5 were considered to be showing symptoms

attributable to recent leptospiral infection. Very many of the remaining 25 had never shownevidence of an illness which could have been attributed to leptospirosis. Naturally, a fullclinical history was not obtained in all these cases. These figures do suggest, however,that a subclinical infection can occur in dogs, a matter of considerable importance in con-sidering the spread of infection.The over-all figure of 43% reactors agrees very closely with Stuart's findings in Glasgow,

the slightly lower total figure in my case probably being due to the inclusion of a larger numberof dogs 1 year old or less, 21 in my series as compared with 8 in that of Stuart. The ratio ofcanicola to icterohemorrhagie infection is also strikingly similar. Similar figures fromother parts of the country would be of great interest.

Methods of Infection and SpreadL. icterohaeniorrhagie.-It has always been considered that infection by this organism in

dogs is acquired from rats, the natural reservoir of this species, usually from food or groundcontaminated by rat urine. This is probably true in the case of acute outbreaks of leptospiraljaundice, when direct or indirect contact with rats can usually be traced. In my series ofcases, however, of the subacute renal type which have subsequently proved to be due toL. icterohamorrhagike infection, there have been several instances where it has been quiteimpossible to trace any connexion with rats at all, no matter how remote, and I have feltthat in some, at least, of these, indirect dog to dog transmission via wet ground, &c. hasbeen responsible.

L. canicola.-The dog is the only known natural host of this species, yet it is said that thecarrier state persists only for a relatively brief period, viz. about three months; Wirthrecords a leptospiruria persisting for six and a half months, in one case; Walch-Sorgdragerrecords persistence up to four months.Judged by the peculiar area incidence of canicola fever in dogs which has been observed

by a number of clinicians these facts do not appear to me to represent the whole story. From

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712 Proceed1ings of the Royal Society of Medicine 30

clinical observation in my own and other practice areas I cannot help feeling that L. canicolais capable of survival outside the animal body for very long periods, in suitable environment,viz. damp ground and stagnant water.The incidence of the disease in dogs coming from areas where they have access to ponds,

&c., is too marked to be mere coincidence. My findings agree with those of Winsser, thatit is possible in a very high proportion of clinical cases to trace a history of immersion,partial or complete, in stagnant or static water some four to six weeks before the onset ofclinical symptoms. Curiously enough, drinking such water does not appear to cause infection,since it is common to know of dogs which habitually drink from ponds from which otheranimals appear to have contracted infection following immersion, yet remain healthy.

This suggests that the route of infection is more frequently via the mucosa of the genito-urinary tract than via the alimentary canal, a suggestion which is borne out by the figuresfor age incidence and certain rather general observations on breed incidence.

After sexual maturity in the dog (at about 8-10 months) the act of urination may well bethe cause of actual contact between the preputial hairs and the wall or lamp posts againstwhich other dogs have previously urinated, in my view a very probable source of infection.This theory is borne out by the incidence of a number of cases of leptospirosis occurringwithin a short period in dogs living within a few hundred yards of one another, and yetbetween which there has been no actual contact, nor is there any source of water-borneinfection as suggested previously. Wirth suggests that the habit of dogs to sniff at urineor the external genitalia of other dogs may be responsible for the acquisition of infection.

Further support for this suggested route of infection lies in breed incidence. It hasalready been noted that the only cases of leptospirosis occurring in young bitches were inlow-to-ground breeds; in addition veterinary clinicians have for many years recognizeda very high breed incidence of acute and subacute nephritis in the Scottish Terrier; sincerecognizing leptospiral infection I have been able to incriminate the organism in all suchcases in this breed. It therefore seems probable that low-to-ground breeds, particularly theScottie, which carries a very heavy "whisker" around the external genitalia in both sexes, arevery prone to infection via the genito-urinary tract.My views on the persistence of infection in water or other suitable ground outside the

animal body are borne out by instances such as the following: unfortunately I have noaccurate data as to the period between the cases cited, but on one particular premises threedogs had been lost in succession, certainly with a lapse of some weeks between the cases,from the disease known to clinicians as Stuttgart disease (which I now believe to be theacute form of canicola fever); the last case only was tested and was positive for L. canicolainfection; in the grounds in question there is a pond to which the dogs had access, andthere seems little doubt that this was the source of infection, the organism having remainedviable in it for a matter of weeks, at least.

In my practice area there has been some seasonal variation in the incidence of the disease,the great majority of cases occurring between late October and April (inclusive), i.e. thewetter periods of the year. I do not think that this finding is borne out by all clinicians,but from personal observation it does suggest greater viability of the organism in wetterperiods of the year. It is noteworthy that during this unusually dry autumn and winter(1948-49) my cases of leptospirosis have been few. Many damp areas and small ponds inmy locality are dried up.

Clinical Features of Leptospirosis in DogsAcute L. icterohamorrhagice infection has already been adequately described by Okell,

Dalling and Pugh. Acute canicola fever in my view is the syndrome known to cliniciansin this country as Stuttgart disease, comprising acute vomiting, rapid dehydration andcollapse, occasionally the passage of blood-stained freces, with finally, if the dog surviveslong enough, rapid necrosis and sloughing of the buccal mucosa and tongue. The mor-tality rate, prior to the introduction of penicillin therapy, was high, death occurring inthirty-six hours to four days.

Subacute disease, caused by either organism, is more common and it does not appear tobe possible to diagnose the causal organism on clinical grounds alone. The syndrome ispredominantly a renal one, although widespread tissue damage in many organs does occa-sionally occur, and icterus may even be found in cases of canicola fever, due to liver damage.Meningeal symptoms have not been observed. Temperature rise may be noted early inthe disease, but seems not to be invariable.Symptoms commonly observed include profound depression, vomiting, muscular pain

in the early stages, and a tucked-up appearance usually associated with pain in the renal area;thirst may be in abeyance or excessive, with corresponding oliguria or polyuria.

1 have not noted the episcleral injection described by Winsser as being a regular feature


in cases of leptospirosis, although it does occasionally occur and is very characteristic.Discoloration of the tongue, either the tip or the entire dorsum, is a very common feature,the tongue becoming brick-red or brownish and dry in appearance. Ulceration of thebuccal mucosa is common.Marked enlargement of the kidneys may occur and it is often possible to palpate the left

kidney very easily. Abdominal palpation in dogs not grossly fat often reveals markedaortic pulsation, but what is the diagnostic significance of this feature I am as yet undecided;I do not recall having noted it in other diseases. It seems probable that some cases ofapparently simple vomiting and depression, diagnosed variously as gastritis, liver attacks,&c., may be instances of very mild leptospiral infection.

Urine analysis is of little value in diagnosis, specific gravity varying with the fluid intake;albuminuria may be present in slight degree or may be absent; traces of bile pigment arecommon.

In the majority of such cases death, when it occurs, is due to urxmia. The atiologicalsignificance of a leptospiral infection in cases of nephritis in old dogs is at yet uncertain.Of a total of 10 nephritis cases in my series of blood examinations (not including currentleptospiral infection) 5 were positive and 5 negative for antileptospiral agglutinins.

Treatment.-In canicola fever penicillin is almost a specific, and in my view is useful as adiagnostic aid for differentiation between the two organisms, since the response of L. ictero-hwmorrhagia infection is absent or slight; response in primary canicola cases is spectacular.Serum in L. icterohwmorrhagie cases gives very variable results, possibly due to rather

late administration in some cases. Otherwise treatment is carried out on symptomaticlines.

1 do not propose to discuss diagnosis other than to say that up to the present I haverelied upon the clinical picture, confirmed by blood examination at a suitable stage in thediseae. f am not yet clear as to the effect penicillin therapy has in cutting short antibodyformation and thus masking the result of subsequent serological examination. I feel thatdetection of the organism in blood or urine is a matter for an experienced bacteriologist,and is not a method likely to be of value to the average clinician.

Public Health ConsiderationsThe veterinary clinician is faced with a somewhat awkward problem in advising clients

as to the possibility of transmission of infection from dog to man.That a very definite human hazard does exist is undeniable, yet looking back over several

years of practice I can think of no case where I could feel certain an owner had contractedleptospiral infection from a dog. Possibly the tardy recognition of canicola fever in manin this country may have masked the true position. In these circumstances I do not feelone should adopt anything of an alarmist attitude, yet we should be remiss in our duty if wedid not point out to the owner of an infected dog that human infection is possible.The course I adopt is to warn owners fairly strongly in cases where I suspect L. ictero-

heemorrhagiue as the causal organism, in view of the relative seriousness of Weil's disease inman. In the case of canicola infection I point out that while human infection is a possi-bility it is not a probability.

In view of the fact that infection is likely to be acquired from urine I advise accordingly,and recommend the wearing of rubber gloves in cases where the dog is very ill and nursingentails frequent contact with urine, soiled bedding, &c. I cannot feel that we should panicowners into having leptospirosis cases destroyed needlessly, yet we must recognize that wehave a definite public health duty in connexion with this disease. I should like to hear theviews of medical members on this point.May I conclude by expressing my thanks to Dr. Broom for carrying out the serological

examinations I have quoted and for his help and advice during the few years 1 have beeninterested in this disease.

REFERENCESFREAK, M. J., and JOSHUA, J. 0. (1948) Vet. Rec., 60, 252.JOSHUA, J. O., and FREAK, M. J. (1947) Vet. Rec., 59, 595.MILLS, S. (1948) Vet. Rec., 60, 267.OKELL, C. C., DALLING, T., and PUGH, L. P. (1925) Vet. J., 81, 3.STUART, R. D. (1946) Vet. Rec., 58, 132.WALCH-SORGDRAGER, B. (1939) Bull. Hlth. Org. League of Nations, 8, 143.WINSSER, J. (1943) Z. InfektKr. Haustiere, 60, 103.WIRTH, D. (1939) Wien. tierdrztl. Mschr., 24, 97.


Dr. C. Borg-Petersen (State Serum Institute, Copenhagen):Experience of Leptospirosis in Denmark

Danish experience of leptospirosis practically speaking dates from 1934. Before that timeonly a few cases of Weil's disease had been diagnosed in our country, and consequently itwas the general belief that the occurrence of this disease was extremely rare. In the summerof 1934, the German microbiologist, Zuelzer, visiting the Danish State Serum Institute,proved that Danish rats were infected with Leptospira icterohaemorrhagie to about the sameextent as rats in other countries. The attention of medical men in Denmark was immediatelydrawn to this fact, and they were called upon to send in to the Institute samples of bloodfrom suspect cases. These samples were examined by Professor Schuiffner at the Instituteof Tropical Hygiene at Amsterdam, and during the last half of 1934 no less than 14 cases ofWeil's disease were diagnosed. Thus it was obvious that the disease was in no way uncommonin Denmark, and in 1935 a diagnostic Leptospira laboratory was established at the StateSerum Institute.

In 1936 it was found that leptospirosis was prevalent among dogs in Denmark, so from1937 the Danish State Veterinary Serum Laboratory took over the bacteriological Leptospiradiagnosis in dogs and other animals.

Since 1934, leptospirosis has been bacteriologically verified in a total number of 808human patients, and this figure probably represents the majority of diagnosed cases inDenmark, but of course actually far more cases of the disease have occurred. The yearlynumber of diagnosed cases is shown in the first column of Table I.

I have to state that, naturally, we have not isolated Leptospiras from all the 808 patients,only from 81 among them; in the majority of cases the diagnosis is founded on the demon-stration of antibodies in sera from the patients. For the seroreaction we used the agglutination-lysis-test with living cultures and with microscopical reading with dark-field illumination.

In the beginning these seroreactions were made with L. irterohamorrhagia? and L. canicolaonly. In 1935 and 1936 only infections by L. icterohamorrhagiwe were found, and practicallyall of these were jaundiced cases. Now, as it was known from other countries that themajority of cases of leptospirosis icterohiemorrhagica did not show any jaundice, it wasobvious that only severe infections had been diagnosed in Denmark. Consequently, in orderto detect the cases without jaundice as well, we examined in 1937 about 8,000 sera sent tothe Institute for the Widal reaction. In this way we succeeded in finding, first: 10 infectionsby L. icterohwmorrhagie, 8 of which were without jaundice, and secondly: 6 of L. canicola,all without jaundice. The examination of Widal sera was continued in the following yearsand revealed many cases which would not otherwise have been diagnosed.

In the course of the period 1936-37, we had met with several cases which clinically weretypical of leptospirosis, but which showed equal, rather weak, seroreactions to both L. ictero-hamorrhagia and L. canicola and which could not therefore be classified. This fact wasexplained towards the end of 1937, when, from the blood of a patient, we cultivated aLeptospira strain serologically different from icterohlmorrhagiae and canicola. With thisstrain the sera just mentioned gave strong positive reactions. On comparison with the otherserological types hitherto described, the new strain was found to differ from all of themand, therefore, had to be regarded as a new serological type, which we named L. sejroeafter the locality in Denmark where it was first discovered.

Naturally, a strain of L. sejroe was at once included among the strains used in our routineserum test; and in the following years a considerable number of infections caused by thistype were diagnosed, as will be seen in Table I. In 1939 L. grippotyphosa, in 1941 L. bataviaand L. pomona, and in 1945 L. poi were added, since infections caused by these types hadbeen found in other parts of Europe. From Table f it will be seen that only a few infectionsby L. grippotyphosa, L. bataviw, and L. poi have been found in Denmark, while we have notseen any case of leptospirosis pomona. Nor have we seen any human infections caused bytype ballum, which was found in 1943 in Denmark in a mouse, and which has since 1944been included among the serum-test strains. The last column in Table I shows some caseswhich for various reasons could not be classified.The classification in serological types was made under the impression of the pluralistic

conception current in the latter part of the 'thirties, according to which the prognosis andthe epidemiology of the leptospiroses are related to the serological type of the infecting Lepto-spiras, and we shall now see whether it is possible to find such relations in our material.As for the clinical features, we have at the State Serum Institute only very incomplete

data about the patients, but for all the cases examined we know: (1) Whether the patientsurvived or died from the infection, and (2) whether the patient was jaundiced or not. Thisinformation is presented in Table fI.

Section of Comparative Medicine

Ictero-Total hoem.

TABLE ISejroe Grippo-

Canicola (&c.) typhosa Batavie Poi Pomona Ballum Type ?

14142231162021121116241816118

254

625442

24112511

9

95

25101998

341985928101121

414

1 1

l9

115

2553

16 2 0 0 12

% Men 86 57 66 100 100% Women 14 43 34 0 0

Icterohxm. .0/0.

Canicola0/0.

Sejroe . . ..0/o.

GrippotyphosaBatavix ..

Type ? ..

1934-38Total Icterus Fatal

97 79 2381 24

8 1 013 0

17 2 012 0

2 .2 0

TABLE II1939-43

Total Icterus Fatal

80 48 960 11

39 5 013 0

268 35 213 1

11 1 03 0 07 3 3

1944-48Total Icterus Fatal

77 39 551 6

48 6 013 0

129 19 115 1

4 0 013 3 03 1 0

As regards leptospirosis icterohimorrhagica, the figures for the fatality rate show a definitefalling tendency for the three periods in question. Whether this corresponds to a real changein virulence or whether it is caused wholly or partially by other factors, I do not propose todiscuss now. As regards the canicola type, we have not had any fatal cases yet, and for thesejroe type the fatality rate seems to be about 1 %. The number of cases of the other typesis too small to allow of any estimate of the fatality rate.

It will be seen that in the life and death prognosis there is a definite distinction between theicterohimorrhagiae type on the one side and the canicola and sejroe types on the other side.As forjaundice, this syndrome was seen in the three five-year periods in 81 Y., 60% and 51 %

of the icterohxmorrhagie cases, whereas in the canicola and sejroe infections it was onlyobserved in 12 to 15% of the cases. Here I must add that in most of the cases of canicola andsejroe infections the observed jaundice, was very slight, in many instances the patients onlyshowed jaundiced sclerae. In the icterohf*orrhagixe infections, jaundice was generally muchmore pronounced. Also for the grippotyphosa and batavie infections the icterus percentageis low, but the absolute figures are small.With regard to the other clinical symptoms, I have no exact figures to offer, and I can

only state that just as icterus may appear among patients infected with any of the serologicalLeptospira types, so also do the other symptoms characteristic of the classical Weil's diseaseappear in patients infected with the other types, though generally in a smaller degree. Onprinciple, therefore, the clinical observations are inadequate to the determination in eachindividual case of the cause of the infection.

Before entering on the epidemiological facts, I shall mention some results obtained fromexaminations made on animals. These examinations mainly concerned rats, dogs, and mice.

In 1934, Zuelzer, examining 93 rats, found 23 Leptospira carriers. In 4 of these carriersthe Leptospiras excreted were avirulent to guinea-pigs. It does not appear that these avirulentLeptospiras were submitted to serological examinalion, but the virulent ones were sero-

33 715

1934 141935 141936 241937 421938 301939 461940 371941 241942 481943 2531944 1021945 781946 431947 221948 31

Total 808

221

42

1

- -I

716 Proceedings f the Royal Society of Medicine 34

logically L. icterohemorrhagie. About 1940, Ottosen, at the State Veterinary SerumLaboratory, examined 685 rats, and from 33 % of these he cultivated Leptospiras from thekidneys. 112 of the isolated strains were inoculated in guinea-pigs and 18 of these, i.e. 16%,proved to be avirulent, although serologically 14 of these strains were icterohiemorrhagime(the.remaining 4 were not submitted to serological examination). Among 16 strains isolatedby me from 67 rats I did not come across any such avirulent strains. All were L. ictero-hemorrhagia and all virulent to guinea-pigs.From dogs in Denmark L. icterohemorrhagia and L. canicola have been cultivated.

Leptospirosis canicolaris is most prevalent among the dogs in Copenhagen and in the largeprovincial towns, mainly occurring in the autumn months. During the period of 1943-45it actually became epizootic. Since then the prevalence has decreased considerably. In therural districts infection with L. icterohamorrhagie appears to be the more prevalent. In1937, in one village, 53 dogs were examined and 19 of them found to have positive sero-reactions. Only one of these showed a strong reaction for L. canicola and the remaining 18for L. icterohwemorrhagiae; Leptospiras were discovered in only two of the dogs. In dogs,excretion of Leptospiras has been seen to continue for several months. Usually, however,it is of shorter duration; in a considerable number of seropositive dogs Leptospiras werenot discovered in the urine.

Investigations on mice were commenced in 1939, as in many instances epidemiologicalinformation from L. sejroe patients seemed to preclude rats as the source of infection,whereas the evidence pointed to mice as the most probable source. The first mouse to beexamined was a harvest mouse (Mus musculus spicilegus) from a farm where one case ofL. sejroe had occurred. This mouse had L. sejroe in the kidneys. A total number of 164harvest mice from various parts of the country have been examined. From the kidneys of 18of these mice Leptospiras were isolated. Of the 18 strains 16 were L. sejroe. The 17th straincould not be identified with any of the known Leptospira types, wherefore, in 1944, it wasdescribed as a special type: L. ballum. The 18th strain, isolated from the harvest mice, wasserologically identical with two strains previously isolated from 2 out of 8 big wood mice(Apodemus flavicollis). These strains represent another serological type, L. saxkoebing,which is, however, closely related to the sejroe type. Of 123 voles (Microtus arvalis) 29 carriedL. grippotyphosa, while 32 of another vole species (Microtus agrestis) proved negative.To recapitulate: From mice we have isolated 4 different serological types of Leptospiras,

viz.: L. sejroe and L. ballum from harvest mice, L. saxkoebing from harvest mice and woodmice, and L. grippotyphosa from voles.Animal species other than the ones already mentioned have been investigated only in-

adequately, and no conclusive results were obtained.L. batavie and L. poi have not been isolated in Denmark either from man or animal, but

regarding the other types there is good agreement between the findings already made inanimals and the information available from many of the patients with reference to theprobable source of infection. These findings, moreover, afford a natural explanation of thedistribution of the various infections in man with regard to seasons, sex, and occupations.

Fig. 1 shows the monthly distribution of cases of the various Leptospira infections, coveringthe fourteen years 1935-48. It is a matter of 780 cases, viz. 240 icterohemorrhagime, 95canicola, 414 sejroe, 15 grippotyphosa, and 16 batavik. In the graphs all the five curvesshow a level part and a peak.The L. sejroe infections show a rise in the curve in August, reaching a maximum in October,

and again returning to level in January. It is interesting to note that practically all the casesofL. sejroe infection were among the rural population, and that the harvest time in Denmarkis in August and the first part of September. The harvest mice, which keep to the fields inthe spring and summer seasons, follow the grain crop to the farms, and since the harvestmice are carriers of the sejroe type, it is easily understood why the incidence of humaninfections accumulates during the months of August-December.

If curves are made for men and women separately it is seen that while the curve for menbegins to rise in August, the curve for women does not begin to rise until September. Thisshows clearly that in the case of women the infection takes place mainly in the farmhouses.To this I may add that in 1943 an unusually great number of mice appeared in Denmark

resulting, as might be expected, in a very great number of sejroe cases in the same year, asyou see in Table I.The peak of the curve for the grippotyphosa infections is much flatter than that of the

sejroe infections, and the maximum is in August, i.e. in the beginning of the harvest season.This may be explained by the fact that the voles, the carriers of the grippotyphosa type,unlike the harvest mice, remain on the fields and do not go to the farms. Correspondingly


all the instances of grippotyphosa infection in Denmark have occurred among rural peoplein males, who in Denmark do the main field work. All the cases occurred in Jutland andmostly in South Jutland. This incidence corresponds to the dispersion of the grippotyphosa-harbouring species of the voles (arvalis). This species is most prolific in South Jutland,with a decrease in density towards the northern part of Jutland; it does not exist in theDanish islands. Also the incidence of grippotyphosa infections was at its highest peak inthe "mouse-year" 1943.The curve for the batavie infections is almost coincident with the grippotyphosa curve,

the maximum of the peak being reached in September; still, instances of bataviie infectionmay appear also at other seasons. As in the case of the grippotyphosa infections, all thebatavie infections occurred among rural males in Jutland. As previously said, the bataviktype has not been found in animals in Denmark. We have yet to investigate the pigmymouse (Mus minutus) proved by Mino to be a carrier of the L. batavie in Italy. However,the fact that the prevalence of batavie infections during the "mouse-year" of 1943 was notexcessive might indicate that in Denmark mice are not carriers of the batavix type.The incidence of canicola infection piles up during the months of October-December,

corresponding to the prevalence in the autumn of canicola-infected dogs. Almost half ofthe number of canicola patients are women; which is in agreement with the fact that it isusually women who take care of ailing dogs and mop up their excreta.For the greater prevalence of icterohemorrhagia infections during the last half of the

year I can offer no explanation. In Denmark, as in most other countries, the victims oficterohiemorrhagie attacks are pre-eminently men. More than one-half of the cases are

CASES90 A

80*-- ICTEROHAEMORRHAGIAE\

70 _ ...0 CANICOLA*-.-.-- SEJROE;

60 A.. - GRIPPOTYPHOSA I+ + BATAVIAE . \

50

40i

30t i" '-@ '

20 o.1,.,.0+~ '10~~ ~ ~ ~ ~~

30~~~~~~~

0 + w~I_ IT Iz m a: > z j C a. > c)< < G.i < D D D ul 0Lo7, L . < Z n < <: 0 z C

FIG. 1.

rural. In the towns, butchers appear to be the most exposed, those employed in this occupa-tion alone accounting for about one-fifth of the icterohiemorrhagih infections among menin the urban districts.

I now propose to make some remarks on the bacteriological diagnosis of leptospirosis.The ideal diagnosis consists of course in the isolation and determination of the Leptospiras

in each single case. For a classification of the cultivated Leptospiras we have relied upontheir antigenic properties. Morphologically all Leptospiras are alike, and cultural methodsto distinguish pathogenic Leptospiras have not yet been found. The virulence is not a stablequality, as it usually decreases quickly when the Leptospiras grow in vitro. Moreover, forthe determination of virulence we introduce another changeable factor, namely the powerof resistance of the experimental animal. The antigenic properties of the Leptospiras, onthe other hand, show a very high degree of stability. Therefore, we have identified new strainsby serological comparison with those previously known, using cross-absorption tests instrains showing similarity to one another. This is how in 1938 we were forced to concludethat L. sejroe was a new serological type. And later in the same way we have had to describe


L. saxkoebing and L. ballum as new serological types. In this way also we distinguished thetwo types of L. icterohemorrhagice, named A and AB. The great majority of ictero-hmmorrhagive strains isolated in Denmark could be classified as one of these two types,but two strains, one from a man and one from a rat, were not serologically identical with eitherof these two types, neither were they identical one with the other.

Similar results have been obtained in other countries, and there is no doubt that by appli-cation of the cross-absorption test to the numerous strains which are now being isolatedall over the world we shall finish up with a very considerable number of serological typesin the strict sense of this word.

In practical diagnostic work we can isolate the Leptospiras from only a minority of cases.For the rest we must be content with the microscopical demonstration of Leptospiras in theurine or we must rely on the demonstration of specific antibodies.

In routine work we cannot, of course, use strains of all serological types for our serum test.We must confine ourselves to the use of strains of such types as are known from t1b cultiva-tion experiments to occur in the area in question, and perhaps a few others, the occurrenceof which we want especially to investigate.On the basis of seroreactions alone it is not always easy to decide the serological type of

the infection of the patient, as the sera mostly react with strains of several types. Generallywe may reckon that the strain which gives the strongest reaction corresponds to the onewhich has caused the infection of the patient, but in the first few weeks of the disease it isnot uncommon that heterologous reactions are stronger than homologous reactions. How-ever, if the antibody content in the serum of the patient can be followed during a sufficientlylong time, the homologous reaction will finally be the dominating one.But it is also possible that all the observed reactions are actually co-reactions, namely in

such cases where the infection is caused by Leptospiras of a serological type which is relatedto, but not serologically identical with, any of the strains used for the seroreaction.'

Therefore, in connexion with material from patients like that dealt with in the first partof this paper, it is really not correct to speak of infection of different types, it would be morecorrect to say that we have here been dealing with infections of different serological groups.

REFERENCESBORG-PETERSEN, C. (1938) Acta convent. III de trop. morb. Amsterdam, 1, 396.

(1944) Acta path. microbiol. scand., 21, 165, 504.. and JACOBSEN, E. (1937) C. R. Soc. Biol. Paris, 126, 799.

OrrOSEN, H. E. (1939) Maanedsskr. Dyrlag., 51, 15.(1941) Maanedsskr. Dyrlkg., 53, 173.

ZUELZER, M. (1935) Acta path. microbiol. scand., 12, 511.

Dr. J. C. Broom: The first human case in England of infection with L. canicola wasreported by Baber and Stuart in 1946. In 1947 Dr. Alston and I confirmed the diagnosis in3 cases, and during 1948 we had no less than 14. There is no reason to suppose that theinfection rate in dogs has been increasing, so it is likely that human cases occurred in earlieryears but were not diagnosed; many cases may still be going unrecognized.

Although the disease presents no pathognomonic symptom, the clinical picture is fairlytypical when viewed as a whole, and closely resembles other benign forms of leptospirosis.The disease generally runs a mild course, but severe nephritis sometimes develops. InBukh's case (1940) the blood urea rose to 280 mg. %, and the urinary output fell to 25 ml. aday. The patient was critically ill but he finally recovered.One fatal case occurred in England last year, in a woman who suffered from chronic

nephritis. Albuminuria and oliguria persisted during the 2nd apyrexial stage. The bloodurea reached 500 mg. %, anuria supervened, and the patient died of uraemia. Details of thiscase have been published in the Lancet by Weetch, Colquhoun and Broom. We knowof one other fatal case in Holland. No report has yet been published but Professor Ruysand Professor Wolff told me that polycystic disease of the kidneys was found at autopsy.The presence of pre-existing kidney damage may thus gravely prejudice the patient's chanceof recovery in a severe attack.

In this country only L. icteroheemorrhagia and L. canicola have been found to causehuman infections. We have tested serum from a number of patients presenting signs ofaseptic meningitis against L. grippotyphosa, L. pomona, L. batavic and L. sejroe, but invariablywith negative results.The rodent carriers of these species are present in England, but no adequate surveys have


been, undertaken so far to determine whether they are infected. The only evidence I know iscontained in a paper by Elton et al. (1931) who were investigating the ecology of a colonyof wood mice (Apodemus sylvaticus). Leptospiras were seen in the kidneys of 29 mice, butinjection of the material into guiniea-pigs prodiuced only one infection, and that strain wasnot cultivated. With present knowledge and facilities, however, such a survey might lead tomore definite results.

REFERENCESBABER, M. D., and SUART, R. D. (1946) Lancet (ii), 594.BuKH, N. (1940) Ugeskr. Lieg., 102, 1142.ELTON, C., FoRD, E. B., BAKER, J. R., and GARDNER, A. D. (1931) Proc. zool. Soc. Lond., p. 657.WEETCH, R. S., COLQUHOUN, J., and BROOM, J. C. (1949) Lancet (i), 906.

Dr. R. D. Stuart (Glasgow) described briefly the observations made by Mr. I. McIntyre(Royal Dick Veterinary College, Edinburgh) and himself on canine leptospirosis. Thehigh incidence of L. canicola infections and their specific relationship to canine renal diseasehad been adequately determined in the examination of 270 dogs. Serological evidence ofthis type of leptospirosis was found in 90% of 130 dogs with detectable renal disease, butonly in 23% of 140 other dogs. A raised blood urea was accepted as unequivocal evidenceof renal disease, and the specificity of the L. canicola agglutinins was confirmed by the isola-tion of the organism from blood culture in a number of cases. An attempt had then beenmade to outline the course of L. canicola disease in dogs in relation to pathogenesis andclinical findings. It was suggested that the disease process could be divided into the followingstages:

(1) Invasive.-The stage of leptospiral infection of the blood stream, identifiable by bloodculture.

(2) Primary renal when signs of renal damage first appeared. It followed about one or twoweeks after the primary invasive stage and was identified by a high serum titre to leptospire,a raised blood urea and usually leptospiruria.

(3) Secondary renal.-This followed at a variable interval, sometimes weeks, sometimesyears, after the primary renal stage, and was generally associated with a recurrence ofrenal symptoms. It was due to the persistence and progression of renal damage after animalshad recovered from leptospiral infections. Thus it was often associated with a low serumtitre for leptospirn and a high blood urea but leptospire were never found in the urine.

Leptospira canicola infections also occurred in humans. The illness was often mild andfeatureless and consequently was extremely difficult to diagnose clinically. On one occasionMr. McIntyre was able to suggest that the owner of one of his canicola-infected dogs hadherself been suffering from the same disease. This was confirmed serologically. It seemedpossible, therefore, that veterinary workers who had the opportunity of observing what wasa fairly characteristic disease in dogs nught be in a very good position to assist their medicalcolleagues by drawing attention to the possible etiology of some obscure febrile process inthe owners of infected animals.

Mr. H. I. Field (Institute of Animal Pathology, Cambridge): Members may be interestedto know that we have recently diagnosed Leptospira infection in a 14-day-old AberdeenAngus calf. The animal died after a five-day illness characterized by an initial temperatureof 1050 F., dullness, inappetence, salivation and a brownish discoloration under the tongue.An intense icterus developed during the twenty-four hours preceding death. The history onthe farm suggested that calves had died previously of the same type of infection. Somesupporting evidence that the affected calf was not an isolated case of Leptospira infectionwas obtained later. Subsequent to the diagnosis being established another calf on the samefarm showing similar symptoms made a dramatic recovery following the injection of L.icterohawmorrhagi, hyperimmune serum.There is no record to show that Leptospira infection has been diagnosed in cattle previously

in this country, yet it may be regarded as surprising, if the calf is naturally susceptible, thatthe disease does not occur frequently in view of the high incidence of rats in and aroundfarm buildings. We have isolated Leptospira from trapped rats on the farm on which theclinical case occurred, and while this in itself does not prove that rats acted as the sourceof infection to the calves, it does at least show that a potential source of infection waspresent on the farm.

Leptospira infection of cattle has been reported from Russia, Palestine and the U.S.A.,but the strains isolated appear to be distinct antigenically from L. icterohamorrhagie.

Proceedings of the Royal Society of Medicine

The examination of the strain isolated by us is not completed but there is every reason tobelieve from the preliminary observations that it is a virulent strain of L. icterohaemorrhagie.

Dr. J. T. Edwards (London) said he had been much struck by the statements made byDrs. Borg-Petersen and Stuart. He recalled his own early experiences at the PathologicalDepartment of the Royal Veterinary College, London, where the lesions of "small whitekidney" (chronic interstitial nephritis) and "enlarged white kidney" (chronic fatty infiltration)were observed to be exceedingly common in the adults of the dog and cat species, respectively;he had always been under the impression that these conditions arose through some as yetundisclosed metabolic disorder. That both types of lesion could arise through a commondisorder of that kind was now evident from the address given recently before that Sectionby Professor Himsworth (Proc. Roy. Soc. Med., 1949, 42, 201) dealing with liver damageof metabolic origin. Now, however, Dr. Stuart had supplied data that would lead one tosuspect that the canine disorder, at any rate, could be attributed, in its proximate origin, toa specific infective process, namely leptospirosis, in view of the disclosures made of theunsuspected widespread prevalence of that infection among dogs. Dr. Borg-Petersen, in hisinvestigations upon the prevalence of the same infection among animals, had also relatedits discovery in cats. He would like to know from him whether he could give some moreprecise information regarding its prevalence in that species. That a specific infection of thiskind could precipitate the onset of pathological states which had all the appearances of meta-bolic disturbances was, of course, quite possible. The information now forthcoming wasteaching them to be wary of ascribing the proximate cause of such states to idiopathic faultymetabolism until every precaution had been taken to exclude the possibility of a specific in-fection. Many alleged disorders in the human subject which had been attributed in the past to agreat variety of idiopathic disturbances had been traced through the surveys of Dalrymple-Champneys (Public Health, 1948, 61, 239) to be essentially sequels of chronic brucellosis.These afforded yet another lesson of the kind in the realm of comparative medicine.

Dr. C. Borg-Petersen (Copenhagen), in reply: Information regarding feline leptospirosisin Denmark is very scanty. In a cat with jaundice and pulmonal haemorrhages Ottosenfound a positive seroreaction with L. icterohamorrhagia 1 : 1,000, but cultivation experimentsand guinea-pig inoculation were negative: In 7 other cats the results were entirely negative.

In relation to the findings of Dr. Stuart and Mr. McIntyre in dogs in Edinburgh it mightbe of interest to mention some very similar results from Copenhagen: By histologicalexamination of the kidneys from 197 stray dogs Mr. Ottosen found chronic interstitialnephritis in 45 dogs; of these 45 dogs 36, or 80%°, were seropositive. Of the 152 dogswithout nephritis only 19, or 13%, were seropositive.

720 38

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Section of Comparative Medicine