a proven case of toxoplasmosis - bmj

J. cliti. Path. (1953), 6, 253.

A PROVEN CASE OF CONGENITAL TOXOPLASMOSISBY

J. C. VALENTINE, W. F. LANE, C. P. BEATTIE, AND J. K. A. BEVERLEYFrom the Departnment of Pathology, Bedford General Hospital, the Public Health Laboratory, Bedford,

and the Department of Bacteriology, University of Sheffield

(RECEIVED FOR PUBLICATION MAY 22, 1953)

Congenital toxoplasmosis has been recognizedwith increasing frequency since it was first des-cribed by Wolf, Cowen, and Paige in 1939, andhas now been reported from many parts of theworld. The first description of a case in thiscountry was given by Jacoby and Sagorin in 1948.Since then a number of others have been reported(Farquhar and Turner, 1949; Wilson and Smith,1949; Ridley, 1949; Nutt, 1949; Hutchison,1949; Cathie and Dudgeon, 1949; Wyllie, Fisher,and Cathie, 1950; Farquhar, 1950; Riley andArneil, 1950; Campbell and Clifton, 1950; Sutton,1951 ; Hart, Paulley, Rivers, and Westlake, 1951 ;Valentine, 1952). Surveys of the incidence of sub-clinical infection by serological methods have alsobeen published (Macdonald, 1950; Fisher, 1951).The cases so far described in Britain have been

diagnosed on clinical and serological grounds, andin 1950 Garnham wrote:

It is therefore important to try to clinchthe diagnosis in suitable patients by recovering thecausative organism either during life (by repeatedexaminations of body fluids or biopsy material) orpost mortem. Serological tests or clinical findingsin the present state of knowledge cannot be acceptedas final proof."While few would now regard isolation of the

organism as essential for the diagnosis of clinicalcases there must still remain an element of doubtunless this can be done. We believe that the casereported here is the first in this country in whichthe diagnosis has been confirmed by isolation ofthe organism.

Case HistoryMrs. A. W. F., aged 24, was first seen at the Bed-

ford General Hospital in April, 1946, when she wasadmitted for a miscarriage at about four months.After delivery a fibroid tumour was felt, but no treat-ment was advised. In 1947 she was delivered of afull-term female infant (birth weight 6 lb. 6 oz.). Shewas seen again in November, 1949, complaining of avaginal discharge which had been present since thebir:h of the baby. In June, 1950, dilatation of the

s

cervix and curettage of the uterus were carried out.A soft, anteverted and bulky uterus was found. Theendometrium was hyperplastic, but no microscopicalexamination was made. In February, 1951, she wasdelivered of a healthy, full-term, female infant (birthweight 7 lb. 8 oz.). She attended the orthopaedicdepartment in January, 1952, for spinal curvature. Asa child she had worn a spinal brace. An old disclesion was suspected and manipulation tried withoutmuch benefit. She attended the antenatal clinic onSeptember 1, 1952, her expected date of delivery be-ing February 25, 1953. The vaginal discharge hadcontinued despite the dilatation and curettage, and wasstill present at that time. From the beginning of herpregnancy she had had severe vomiting and diarrhoeawith abdominal pain. The pain started in the rectumand radiated to the epigastrium. The only other un-usual incident which she could recall was an insectbite on the leg which she received about the secondmonth of pregnancy. This caused a small swellingwith a central puncture wound and caused severeirritation. A clear, watery discharge issued from thepuncture for about three days. In February, 1953,there was still a reddish-brown mark on the skin. Theidentity of the insect which caused the bite is notknown.On December 8, 1952, she was admitted to hospital

with vaginal bleeding for one day and backache. Atthis time she also had a cold. It was thought thatthe abdomen was larger than it should be accordingto her expected date of delivery. The membraneswere intact and there was a brownish vaginal dis-charge. Her baby was born spontaneously on Decem-ber 22. The infant was said to have taken a fewgasping breaths and died in 15 minutes.The vaginal discharge present since 1947 cleared up

spontaneously shortly after delivery, and two monthslater she remained quite healthy.There were a large number of mice in and around

the house in which she was living during her preg-nancy, and there were also rats in the neighbourhood.A cat had been obtained to keep away the mice, butshe denied having nursed or handled it. This cat wassubsequently destroyed as too prolific. A male catwas then obtained and is still in good health. Duringher pregnancy she prepared rabbits for her family,but did not clean or sk'n themn.

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J. C. VALENTINE AND OTHERS

Necropsy Report on the Premature InfantThe examination was made 11 hours after

delivery. The placenta had been discarded. Thebody was of a female infant weighing 1,140 g. and25 cm. from crown to rump. There was gener-alized cyanosis and very obvious tenseness andprominence of the abdomen, in the skin of whichwere a few petechial haemorrhages. The peri-toneal cavity contained deep yellow, almostgelatinous fluid, but there was none in the pleuralcavities, and the pericardium contained only a smallamount. Apart from a few petechiae on itsexternal surface the heart was entirely normal.The aorta and great vessels were also healthy andshowed no congenital deformities. The tongueand mouth were normal. There was some stickymucus in the trachea and main bronchi. Bothlungs were small and collapsed and selectedportions of all lobes sank in water. A rimof possibly aerated lung tissue was presentalong the anterior margin of both lungs, but evenportions of this did not float. The spleen wasconsiderably enlarged, weighing 45 g. It wasextremely dark, but showed no external abnor-mality, and on section was a uniform dark plumcolour, with no obvious structure. In the sternumthe bone marrow was dark red and appearednormal for a newly born infant; the vertebralmarrow was similar. There was no lymph nodeenlargement. The liver weighed 130 g. andappeared larger than normal. It was very darkin colour and showed a slight unevenness of thecapsular surface. When sectioned the structurecould not be made out on account of the verydark, brownish-red colour which obscured thenormal markings. The gall-bladder and pancreasappeared normal. The stomach showed a fewsmall mucosal haemorrhages, but apart fromthis the alimentary tract appeared healthy. Thekidneys were of normal size and weighed 5 g. each.They were extremely congested apart from a thinrim just beneath the capsule. The renal veins werenot thrombosed. The ureters, bladder, and geni-talia showed no abnormality. Apart from con-gestion of the medulla the suprarenals werehealthy. The thyroid and thymus were likewisenormal. No centre of ossification was found atthe lower end of the femur.The scalp showed little abnormality, but there

was some bruising and oedema of the underlyingtissues. There was no noticeable hydrocephalus andthe skull itself showed no external abnormality.On reflecting the skull bones, however, a streamof deep yellow fluid escaped. It was found thatthe cerebral hemispheres were virtually non-

existent, being almost completely replaced byyellow fluid contained within a paper-thin mem-brane over the surface of which ran small bloodvessels. It was this fluid which had escaped froman accidental puncture wound made while openingthe skull. Scattered irregularly over the surface ofthe cystic spaces which represented the cerebralhemispheres were numerous yellow flecks of vary-ing size and irregular shape. They measured fromless than a millimetre to a centimetre or so across.The brain-stem and cerebellum were relativelywell preserved though clearly grossly abnormal.Throughout they showed areas of ochre yellowsoftening and necrosis with localized areas ofhaemorrhage and congestion, both externally andon section. The cervical portion of the spinal cordshowed similar changes diminishing in intensityfrom above downwards, and the thoracic andlumbar segments appeared normal. The duramater of the spinal theca was likewise healthy.Both eyes showed some yellowness of the sclera

and opacity of the lens. On section there wasmassive haemorrhage into the vitreous chamber onboth sides.

Microscopical ExaminationLiver.-There was very marked congestion with

separation of the liver cords and extensive extra-medullary haemopoiesis throughout. There werea few small areas of haemorrhage and in someplaces the cellular infiltration contained a con-siderable number of polymorphs, but neither herenor elsewhere were any toxoplasma found.

Kidney.-There was a well-marked neogeniczone and a considerable amount of haemopoietictissue between the nephrons. There was gross con-gestion amounting to haemorrhage in places,particularly in the pyramids. The tubules andglomeruli appeared normal. No toxoplasma werefound.

Heart (Left Ventricle).-The muscle washealthy. There was slight infiltration of the epi-cardial tissues by lymphocytes and plasma cellswhich were mainly congregated around bloodvessels. No toxoplasma were found.Bone Marrow.-The bone marrow was highly

cellular and normoblastic. No toxoplasma wereseen.Eye.-The sclera showed little abnormality

and the conjunctiva was healthy. There waspatchy basophilic staining of the lens and theciliary body showed a moderate infiltration bylymphocytes and plasma cells. The retina hadbeen completely destroyed. Between the choroidand the sclera were a moderate number of plasma

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255CONGENITAL TOXOPLASMOSIS

FIG. 2

FIG. 4.

FiG. 1I-Optic CUSP of infant showing inflammatory infiltration.Optic nerve cut obliquely top right. Haematoxylin and eosin,x 70.

FIG. 2.-Microglial nodule in brain of infant. Haematoxylin andeosin, x 270.

FIG. 3.-Choroid plexus of infant showing chronic inflammation andhyalinization of capillaries. Nodule of calcium top left.Haematoxyiin and eosin, x 95.

FIG. 4.-Proliferative form of toxoplasma in infant brain. Azure-eosin, x 1,300.

FIG. I.

Fiw. 3.

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cells and lymphocytes. Almost the whole of thevitreous chamber was filled with blood andprotein-laden fluid. Just behind the lens the bloodclot was undergoing organization by fibroblastsand young capillaries. A few granules of calciumwere found in this region. Disorganized cells ofthe choroid were seen streaming out behind thelens into the partially organized blood clot. Theoptic disc and nerve contained very large numbersof chronic inflammatory cells (Fig. 1). These were

mainly lymphocytes and plasma cells and were

limited to these two structures. There was prac-tically no infiltration of the surrounding connectivetissue. Apart from the inflammatory infiltrationthe optic nerve appeared normal. Nowhere in theeye or optic nerve could any toxoplasma be found.

Brain-stem and Fourth Ventricle-Through-out the section there was considerable chronicinflammatory exudate consisting of lymphocytes,plasma cells, and microglial cells with occasionalpolymorphs. There were small foci (microglialnodules of Frenkel) in which the cellular exudatewas more dense (Fig. 2). These foci were oftenrelated to blood vessels and sometimes perivascularcollections of inflammatory cells could be seen.

Over the external surface of the brain the cellularexudate was extremely intense and was related toa zone of necrosis of varying depth involving thesuperficial portion of the brain. In this necroticzone the brain tissue had bezn largely destroyed,and there was much fibrinoid material between thenecrotic cells. Only the blood vessels remainedrelatively normal. Also found in the necrotic zone

was a fine dusting of calcium particles. Beneaththe floor of the fourth ventricle a much deeperzone of necrotic brain tissue was found. Theappearance of this zone suggested that it was dueto infarction and in this instance the blood vesse!swere also seriously affected, showing fibrinoidnecrosis of their walls. Within the fourth ventricleitself, in addition to the choroid plexus, which wasin places normal, there was much chronic inflam-mation and granulation tissue formation. Therewas an abundant fibrin exudate and large numbersof red cells. The choroid plexus was in mostplaces heavily involved in the chronic inflam-mation, and a striking feature was the occasionalvery marked hyalinization of the capillary walls(Fig. 3). The lumen of the small vessels wasgreatly reduced thereby and in places almostobliterated. The cellular exudate in the choroidplexus consisted predominantly of plasma cellsand lymphocytes. Portions of the cerebellarpeduncles also included in the section showedgross necrosis, cellular infiltration, and fine

calcification similar to that within the brain-stem.There were also a few much larger patches ofcalcification.Numerous collections of toxoplasma were

found in this section. They were readily visiblein the ordinary haematoxylin and eosin section(Helly fixation) and appeared for the most part asround or oval collections of parasites approxi-mately 15 x 9 [x across. Between 10 and 20 para-sites could be counted in these aggregations (Fig.4). The individual parasites were round or oval,occasionally semilunar with a central haematoxy-lin-staining nucleus surrounded by eosinophiliccytoplasm. The distinction between nucleus andcytoplasm was more readily appreciated by theuse of one of the Romanowsky staining methods.but could be s-en quite clearly in the routinehaematoxylin and eosin preparation. In none ofthese collections could anything in the nature of acapsule be found either by the periodic-acid-Schiff or Wilder's silver techniques. In addition tothese localized collections numerous intracellularforms could be found, the parasites being presentsingly or up to six in a cell (Fig. 5). In these

_.r ~~~~.1_~

FIG. 5.-Free and intracellular forms of toxoplasma in infant's brain.A collection of free forms to left of mid-line and three cellscontaining parasites to right of mid-line. Azure-eosin, x 1,300.

instances the characteristic crescentic or semilunarshape was more obvious. In places where theparasites were numerous one could feel fairlycertain that free forms were present in the sur-rounding tissue. These individual parasitesme-sured 4-5 ,u in length and 2-3 IL in breadth.

Animal InoculationsA provisional diagnosis of congenital toxoplas-

mosis was made and portions of the brain wereground in a Griffiths tube to make an approxi-mately 10% w/v emulsion with broth. Two mice

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CONGENITAL TOXOPLASMOSIS

were inoculated with this suspension on December23, 1952. After an interval of about 10 days theanimals became sluggish in movement and showedroughening of their coats. On January 5, 1953,they were killed and portions of brain emulsifiedand injected intracerebrally into two further miceand intraperitoneally into three mice. Sections ofthe brains were also made and showed encephal-itis; toxoplasma were found. On January 16 thetwo mice inoculated intracerebrally were showingsymptoms similar to those noticed in the first-passage mice, and in order to increase the chancesof establishing the strain one of these mice was

changes. These took the form of perivascular in-filtration by lymphocytes and plasma cells. Therewere also small localized areas of microglial pro-

liferation. Scattered throughout the sectionicould be found numerous collections of toxo-plasma. They were much more numerous in thebrains of the second-passage mice than in thoseof the first, in which they were found with diffi-culty. With repeated passage the organisms be-came more and more numerous and the inflam-matory reaction more acute. The animals diedmore rapidly with the repeated passages. Afterthe eighth passage death occurred regularly in six

DIAGRAM OF ANIMAL PASSAGE

3A. PASSAGE 4'

YOUNG G - PIG (I.C.& IP)2W1/53 TEMP >104 F2911153 DIED

TOXOPLASMA IN PERITONEALFLUID

PASS3AGE MICE P

TOXOPLASMA INPERITONEALSTH. PASSAGE FLUID5/2153 1

4 M;CE (IP.)TOXOPLASMA IN PERITONEAL

FLUID6 TH PASSAGE9/2/53

3 MICE (I. P.)

BEDFORD DATEINFANT BRAIN 23/12/52

1ST

2 M ICE (I.C) PASSAGE

ENCEPHALITIS, TOXOPLASMAIN BRAIN 25/1/53

PASSAGE

ENCPHAITS, OXPLASMAIN BRAIN 2S/3

a 3RD.

2 G -PIGS(I.C.) PASSAGE

BRAIN OF ONE G-PIG

TOXOPLASMA

4THPASSAGE512153

2 MICE (I.P.)

KILLED 912/53IN PERITONEAL FLUID

sent with the permission of the Home Secretary toSheffield for further passage. From this stageanimal passage was continued independently inboth Sheffield and Bedford. A diagram showingthe direct line of passage omitting numerous sidelines is seen above. At a later date infected mouse

brain was inoculated into fertile hens' eggs pre-viously incubated for 10 days. After a furtherfive days' incubation the chorio-allantoic mem-

brane showed small white nodules which containednumerous toxoplasma in the free form.The brains of the affected mice when examined

microscopically showed very marked inflammatory

to seven days. In th2 second-passage mice some

difficulty was experienced in deciding on the pre-

cise nature of the toxoplasmic aggregations, forthey did not exactly correspond with the descrip-tions given by Frenkel of either the proliferativeor pseudocyst forms. They contained many more

organisms than were present in the proliferativeforms as found in the brain of the infant. Manycontained 50 or more parasites but measured only20 to 30 ,u across. Furthermore they were oftenseen in close association with areas of inflam-mation as well as in apparently normal braintissue. Several showed quite definite argyrophil

DATE

2111153

SHEFFIELD(C.P. BEATTIE)

I MOUSE

(I.C.) - INTRA-CEREBRAL INOCULATION(I.P.) INTRA-PERITONEAL INOCULATION

I

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"capsules" by Wilder's method (Fig. 6). Anenclosing membrane could also be demonstratedby the periodic-acid-Schiff technique. Parasitescould not be seen in the livers or spleens of several

.7't

4f1

. . r., ,, I

~ZFIG. 6.-Pseudocyst in mouse brain. Wilder's silver method, x 950.

mice which had abundant toxoplasma in their peri-toneal fluid, although there was well-marked roundcell infiltration of the portal tracts of the liver.Two mice which were inoculated intracerebrallywith spleen and liver of the infant remainedhealthy and were killed on February 18, 1953.The brains of both these animals were macro-scopically and microscopically normal and didnot show any toxoplasma.

Serological InvestigationsSerum from the mother and father and from

their two surviving children were examined bySabin and Feldman's "dye" test as modified byBeverley and Beattie (1952) and by the complementfixation test using infected egg antigen. The resultsof these investigations are set out in Tab'e I.

TABLE IRESULTS OF SEROLOGICAL INVESTIGATIONS

Dye Test Complement Fixation Test

Mrs. F.:611/53 .. .. Positive 1/7 000 Positive 1/32

1 12.l53 .. .. 1/2,000 , 1 I/80(partial 11160)

Mr. F.: 1112/53 .. ,, 1/14 NegativeJ. F., aged5: 11/2/53 NegativeP. F.,aged2: 11/2/53 ,,

DiscussionThe naked eye and microscopical changes in

congenital toxoplasmosis have been described inconsiderable detail by Frenkel and Friedlander(1951) and the findings in our case were substan-tially similar. In common with many previouslyreported cases the changes were largely confined

to the central nervous system and the eye. Minorand non-specific abnormalities were found in theother organs.The main interest in this case lies in the demon-

stration of the infecting parasite in sections of thebrain and in its transmission to laboratory animals.Thus there has been established for the first timea strain of toxoplasma derived from a naturallyoccurring infection in Great Britain.The parasites were readily visible in routine

haematoxylin-and-eosin sections and no greatdiffizulty was experienced in finding them. Theywere most easily seen in the proliferative form inclusters of 10 to 20. Frankel and Friedlander havedrawn attention to the distinction between the pro-liferative form and the pseudocyst. The main dis-tinctions are that the pseudocyst is considerablylarger than the proliferative form, contains manymore organisms, and has a limiting membranewhich is argyrophilic and positive to the periodic-acid-Schiff test. Frenkel and Friedlander insistthat care should be taken not to use the termpseudocyst except in the strict sense which theydefine. The pseudocyst is usually found in appar-ently normal brain tissue and is characteristic ofthe chronic stage of the disease. We have foundstructures resembling the pseudocyst in mousebrain of the second passage with quite considerableinflammatory reaction around them.Two of us had no previous experience with these

organisms and we found it easier to recognize theparasites in sections of the brain than in smearsof brain tissue. Free forms do not appear in thep-ritoneal fluid in the early passages. Despite ourinexperience we had no great difficulty in isolatingthe parasite, but in this it is probable that we wereextremely fortunate. It is likely that our successwas due to the fact that the infection in the infantwas in an acute phase with large numbers of stillviable parasites present. In many cases the diseaseprocess is arrested in utero by the transfer ofmaternal antibodies to the foetus, and this accountsfor the failure to isolate the parasite in such in-stances. Had the infant not been born prematurelya similar state of affairs might have resulted in ourcase.Owing to the small numbers of mice available it

was not possible to follow the technique suggestedby Frenkel (1949), who recommends the use of twogroups of four to six mice each. One of thesegroups should be inoculated intracerebrally andthe other intraperitoneally. Successive passagesare then made from these groups. In the case ofthe cerebral route control is maintained by histo-logical examination. The intraperitoneal route

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CONGENITAL TOXOPLASMOSIS

remains " blind " until the infection is established,when the organisms are readily visible in the peri-toneal fluid. The presence of the infection can,however, be demonstrated by the injection of theperitoneal fluid into the brain of other animals.When the pzritoneal route is used subinoculationsare made every four to six days, at about whichtime antibodies begin to appear. One advantageof the intraperitoneal route is that larger quantitiesof material can be used and contaminatingbacteria can be destroyed by mixing the materialwith antibiotics. The peritoneal route is also themost convenient method of keeping a strain oftoxoplasma in the laboratory, and forms the sourceof the suspension used in the dye test. If initialisolation has been by the intracerebral route itshould be possible to adapt the parasite to the peri-toneal cavity. This may take time, and Gard(personal communication) mentioned one case inwhich it took six months.

In order to exclude the possibility that the mani-pulations are exciting a latent infection in stockanimals Frenkel suggests the " blind passage " ofbrain or other organs of the stock animals. Themice in the Bedford laboratory are all obtainedfrom the same breeder, and three blind passages ofthis type using the intracerebral route failed toproduce any infection in the mice used, three micebeing used for each passage.We noticed that in sections of the infant's brain

the organisms were more plentiful in the braintissue at the edges of the necrotic zones and thatno organisms could be found within areas ofnecrosis. We therefore suggest that when selectingbrain tissue for animal inoculation completelynecrotic areas should be avoided.

In common with other published cases there islittle in the mother's history to suggest at whatstage of the pregnancy or by what route infectionwas acquired. There are, however, two featuresof possible importance in the history. The first isthe insect bite received in early pregnancy. Thework of Piekarski (1949), van Thiel (1949), Lavenand Westphal (1950), and Blanc, Bruneau, andChabaud (1950) suggests that the parasites may betransmitted by blood-sucking insects such as fleas,lice, ticks, bed bugs, and blood-sucking flies. Suchinsects are known to become infected when theyfeed on infected mice. Furthermore, mice may beinfected by inoculating them with the ground-upbodies of such insects or by feeding infectedanimals to mice. The parasites have been found inthe body of a tick on a dog belonging to an in-fected patient (Giroud, Jadin, and Reizes, 1951),but transmission by the bite of such insects has so

far not been proved.

It is not uncommon for a history of an insectbite to be obtained in cases of toxoplasmosis, butthe danger of extracting such information by theuse of leading questions must not be forgotten.There can be no doubt that the mother of thisstillborn infant did in fact suffer such a bite, asthe mark still remained many months later. Inspite of the unusual severity of the bite, she had,however, failed to mention it in her unaided state-ment. It is therefore more than probable that lesssevere bites may have passed unnoticed in the pub-lished reports of cases in which no mention ofthem is made. It would seem important, there-fore, while recognizing the danger of leading ques-tions, to inquire in subsequent cases about insectbites and when positive answers are obtained togive some idea as to how the information wasacquired.We would also urge the recording in the fullest

detail of all incidents which the mother canremember, however trivial they may appear. Inthis way some common factor may be found whichwould provide a clue to the method of infectionin this mysterious disease. It is for this reasonthat we draw attention to the second incident inthe pregnancy-namely, the cramp-like pains in theabdomen. We did not at first pay much attentionto them, although it is clear that the mother herself,who had had two previous pregnancies, regardedthem as abnormal. Moreover, a number of casesin the literature have given similar histories (Gard,Magnusson, Wahlgren, and Gille, 1949; Lelong,Le Tan Vinh, Desmonts, and Dupre-Bouteloup,1951 ; Mellgren, Alm, and Kjessler, 1952). Sinceit has been shown (van Thiel) that mice can beinfected orally, although with difficulty, it seemspossible that these pains and diarrhoea may be ofimportance. On the other hand an investigation ofmothers of normal infants might show a similarincidence of abdominal disturbances. The oppor-tunity for oral infection certainly exists by the con-tamination of food by the faeces or urine ofanimals. Toxoplasma have been found in theexcretions of dogs and cats and also in the tissuesof rats (Perrin, Brigham, and Pickens, 1943;Eyles, 1952). Laboratory mice have also beenfound to harbour the parasite in Switzerland(Mooser, 1950). Pigeons are commonly infected,and Beattie and Beverley (1953) have recently sug-gested that rabbits may be a source of infection.A low titre of antibodies is found in 28% of theadult population, 35% of slaughterhouse workers,but 65% of rabbit handlers. This may be a falsecorrelation in that rabbit handlers may come intogreater contact with other animals such as rats ormice or be more frequently subject to insect bites.

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Hares, too, have been shown to have a high inci-dence of toxoplasmna antibodies in Denmark(Christiansen and Siim, 1951). The mother of ourcase had ample opportunity for contact withanimals two cats, many mice, and possibly rats.Although she bought rabbit for her family on anumber of occasions during her pregnancy it hadalways been cleaned and skinned before purchase.

SummaryThe pathological findings in a newly born pre-

mature infant with congenital toxoplasmosis aredescribed.The infecting parasite has been demonstrated in

sections of the infant's brain.Toxoplasna have been transmitted from the

brain of this case to laboratory animals. A briefoutline of the methods used is given.

Attention is drawn to an insect bite and cramp-like abdominal pains during the pregnancy. It issuggested that full details of even apparently trivialincidents should be recorded in future cases in thehope that they may provide a clue as to the sourceof infection in this disease.Some possible sources of infection are briefly

discussed.

We wish to thank Mr. F. W. G. Nash for permis-sion to publish this case, and Dr. A. F. Sladden forkindly arranging to collect serum from the motherand two children. We are also indebted to Dr. G. S.Wilson for helpful criticism.The work was aided bv an expenses grant to one

of us (C. P. B.) from the Medical Research Council.

REFERENCESBeattie, C. P., and Beverley, J. (1953). Proc. Path. Soc. Gt. Britai.i

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Pathology, 5, 350.Blanc, G., Bruneau, J., and Chabaud, A. (1950). Ann. Inst. Pastelr.

78, 277.Campbell, A. M. G., and Clifton, F. (1950). Brain, 73, 281.Cathie, I. A. B., and Dudgeon, J. A. (1949). Journal of Clinical

Pathology, 2, 259.Christiansen, M., and Siim, J. C. (1951). Lancet, 1, 1201.Eyles, D. E. (1952). J. Parasitol., 38. 226.Farquhar, H. G. (1950). Lancet, 2, 562.--and Turner, W. M. L. (1949). Arch. Dis. Childh., 24, 137.Fisher, 0. D. (1951). Lancet, 2, 904.Frenkel, J. K. (1949). J. Amer. med. Ass., 140, 369.--and Friedlander, S. (1951). Toxoplasmosis. U.S. Public

Health Service Pub'ication, No. 141.Gard, S., Magnusson, J. H., Wah gren, F., and Gille, G. (1949).

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Bouteloup, L. (1951). Bull. Soc. mid. H6p. Paris, 67, 541.Macdonald, A. (1950). Lancet, 2, 560.Mellgren, J., Alm, L., and Kjess!er, A. (1952). Acta path. microbiol.

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Dis., 72, 91.Piekarski, G. (1949). Z. Parasitenk., 14, 388.Ridley, H. (1949). Brit. J. Ophthal., 33, 397.Riley, I. D., and Arneil, G. C. (1950). Lancet, 2, 564.Sutton, D. (1951). Brit. J. Radiol., 24, 31.Thiel,P. H. van(1949). Docum. neerl. indones. Morb. trop., 1,264Valentine, G. H. (1952). Proc. roy. Soc. Med., 45, 857.Wilson, B. D. R., and Smith, J. F. (1949). St. Thom. Hosp. Rep.,

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