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337 Clinical and Laboratory Notes. A CASE OF SPIROCHÆTOSIS ICTEROHÆMORRHAGICA. BY A. COWAN GUTHRIE, M.B., C.M. EDIN. Spirochaetosis icterohaernorrhagica is a rare disease in England, although several cases have been described recently from Norfolk.l Owing to its rarity I venture to give a somewhat detailed account of the history, various phases, and progress of this affection as it occurred in a patient whom I attended. History.—On April 23rd, 1925, I was first called to see the invalid, a single lady in early middle age. She informed me that she had just returned from a visit to Egypt and that towards the end of her stay there she had begun to suffer from general malaise. Her health did not improve during the homeward journey and in addition a tendency to sick- ness began to supervene. On her arrival in England she still felt rather weak and out of sorts although not seriously ill. Examination.—The patient was lying in bed looking apathetic and somnolent, the pulse 76, temperature 98’60 F., the tongue coated with a yellowish-white fur. On abdominal examination no splenic enlargement could be detected, or tenderness in the region of the gall-bladder ; hepatic dullness was only slightly increased. Iii the somewhat poor light of the room the skin generally showed a yellowish tinge, which took on a deeper hue in the conjunctiva. The usual remedies for such a condition were prescribed-a mild saline in the morning, a mixture of bismuth and bicarbonate of, soda before food, a euonymin pill at night, and a milk diet. As, however, the patient’s condition did not improve I was called to see her again on April 27th. The jaundice was now apparent, and she complained of sickness. On re-examination no tenderness over the gall-bladder or over any part of the abdomen could be detected. The urine on examination showed a few leucocytes and numerous epithelial cells of vesical and renal origin (pelvis and calyces), all bile-stained. No tube casts were present. Chemical examination showed a trace of albumin, no blood, a positive reaction for bile 1 per cent., and also the presence of indican. Examination of the blood showed haemoglobin deficiency. There was variability of the red cells in size and shape, many cells appearing frayed, and there was variability also in their staining qualities, although there was no basophilic degeneration. No spirochsetes were found, or evidence of protozoal infection in either the red or white cells. The differential count of the white cells presented fairly normal features, the leucocytes showing variable staining qualities as well as evidence of degenerative changes by the presence of fatty granules. The Widal test was negative. Up to this time the case was considered one of simple catarrhal jaundice, which had resisted the usual methods of treatment. In order to determine whether or not there was obstruction van den Bergh’s test was utilised, the result being indirect reaction positive with negative direct reaction, indicating toxic jaundice, including catarrhal. On April 28th the patient seemed somewhat better and the slight improvement was maintained throughout the next day till late in the evening, when there was a recurrence of the sickness, the vomit being dark in colour. This condition slightly improved during the next 24 hours. When I called on the morning of May 1st the patient looked very ill, the pulse was feeble, the temperature subnormal, and there was occasional retching and vomiting of dark coffee-ground material. The next day the patient’s con- dition appeared critical and she tended to lapse into a semi-comatose condition. Colon irrigations of a mixture containing sodium bicarbonate and citrate were administered and this mixture also was given orally with no beneficial effect. It became apparent that the patient was suffering from profound toxaemic jaundice and symptoms of bronchial catarrh now appeared. On examination of the blood collected on May lst spiro- chaetes were discovered for the first time, and in enormous numbers ; they were present also, though to a lesser extent, in the urine collected on the same date. Immune horse serum was given intramuscularly with no beneficial result. Lumbar puncture was performed to obtain cerebro-spinal lluid and on examination this showed no excess of either albumin, globulin, or chlorides. It contained 4’1 lympho- cytes per c.mm. and no spirochaetes were seen in the deposit. The Wassermann reaction gave a clear negative result. , 1 Brit. Med. Jour. 1926, ii., 108. On May 3rd the patient was in a very collapsed state and only semi-conscious ; intravenous saline injections containing sodium bicarbonate were given, adrenalin was also administered, but the patient gradually sank and died the following day. A blood film taken two days before death showed haemoglobin deficiency; the red cells showed alteration in shape and size ; polychromasia was exhibited, although no basophilic degeneration was noticed ; platelets were few. The white cells showed vacuolation and fraying i of the nuclear material. Discussio)z. It is to be remarked that the symptoms shown in this case were not quite classical. At no time was there any great rise of temperature, 99’ being the highest, and in point of fact the temperature was subnormal. The patient had the usual slow pulse Spirochætes seen in liliii of blood. and the symptoms gradually deepened from a catarrhal to a grave toxæmic type of jaundice. There was no glandular swelling, but haematemesis with semicoma were the salient features of the last phase. It is somewhat important to observe that even at an early stage there was variability in the size, shape, and staining qualities of the red cells, that many cells appeared frayed, and haemoglobin was deficient. The leucocytes also showed variable staining qualities as well as evidence of degenerative changes. It is well known that rats are carriers of this disease, their urine, teeming with spirochaetes, can contaminate food and drink, and that this is the usual source of infection for human beings. It was noted that there were rats in the ships in which the patient made the journey to England. Authorities state that the spirochaetes may be observed in the peripheral blood till the fifth or even the seventh day by dark-ground illumination. By inoculation of the patient’s blood (till the seventh day) into a guinea-pig the animal develops albuminuria and jaundice, and the spirochaetes will be found in its liver and blood. After the seventh day the spirochaetes are entirely absent from the blood, passing into the internal organs ; between the ninth and fifteenth day they may be seen in the urine. Before death, however, in this case they appeared in the blood and also in the urine. A reproduction of a drawing is given to show the disposition of the spirochaetes as they appeared in the film of the patient’s blood. I have not entered into details of all the therapeutic measures adopted during the illness. which varied from time to time as the patient’s condition demanded and included a strict diet of milk, citrated and otherwise, fruit juice, and bland fluids; irrigations

A CASE OF SPIROCHÆTOSIS ICTEROHÆMORRHAGICA

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Page 1: A CASE OF SPIROCHÆTOSIS ICTEROHÆMORRHAGICA

337

Clinical and Laboratory Notes.A CASE OF

SPIROCHÆTOSIS ICTEROHÆMORRHAGICA.

BY A. COWAN GUTHRIE, M.B., C.M. EDIN.

Spirochaetosis icterohaernorrhagica is a rare diseasein England, although several cases have been describedrecently from Norfolk.l Owing to its rarity I ventureto give a somewhat detailed account of the history,various phases, and progress of this affection as itoccurred in a patient whom I attended.

History.—On April 23rd, 1925, I was first called to see theinvalid, a single lady in early middle age. She informed methat she had just returned from a visit to Egypt and thattowards the end of her stay there she had begun to sufferfrom general malaise. Her health did not improve duringthe homeward journey and in addition a tendency to sick-ness began to supervene. On her arrival in England shestill felt rather weak and out of sorts although not seriouslyill.

Examination.—The patient was lying in bed lookingapathetic and somnolent, the pulse 76, temperature 98’60 F.,the tongue coated with a yellowish-white fur. On abdominalexamination no splenic enlargement could be detected,or tenderness in the region of the gall-bladder ; hepaticdullness was only slightly increased. Iii the somewhat poorlight of the room the skin generally showed a yellowish tinge,which took on a deeper hue in the conjunctiva. The usualremedies for such a condition were prescribed-a mild salinein the morning, a mixture of bismuth and bicarbonate of,soda before food, a euonymin pill at night, and a milk diet.

As, however, the patient’s condition did not improve Iwas called to see her again on April 27th. The jaundicewas now apparent, and she complained of sickness. Onre-examination no tenderness over the gall-bladder or overany part of the abdomen could be detected.The urine on examination showed a few leucocytes and

numerous epithelial cells of vesical and renal origin (pelvisand calyces), all bile-stained. No tube casts were present.Chemical examination showed a trace of albumin, no blood,a positive reaction for bile 1 per cent., and also the presenceof indican. Examination of the blood showed haemoglobindeficiency. There was variability of the red cells in sizeand shape, many cells appearing frayed, and there wasvariability also in their staining qualities, although therewas no basophilic degeneration. No spirochsetes were found,or evidence of protozoal infection in either the red or whitecells. The differential count of the white cells presentedfairly normal features, the leucocytes showing variablestaining qualities as well as evidence of degenerative changesby the presence of fatty granules. The Widal test wasnegative.Up to this time the case was considered one of simple

catarrhal jaundice, which had resisted the usual methods oftreatment. In order to determine whether or not there wasobstruction van den Bergh’s test was utilised, the resultbeing indirect reaction positive with negative direct reaction,indicating toxic jaundice, including catarrhal.On April 28th the patient seemed somewhat better and

the slight improvement was maintained throughout thenext day till late in the evening, when there was a recurrenceof the sickness, the vomit being dark in colour. Thiscondition slightly improved during the next 24 hours.When I called on the morning of May 1st the patient looked

very ill, the pulse was feeble, the temperature subnormal,and there was occasional retching and vomiting of darkcoffee-ground material. The next day the patient’s con-dition appeared critical and she tended to lapse into asemi-comatose condition. Colon irrigations of a mixturecontaining sodium bicarbonate and citrate were administeredand this mixture also was given orally with no beneficialeffect. It became apparent that the patient was sufferingfrom profound toxaemic jaundice and symptoms of bronchialcatarrh now appeared.On examination of the blood collected on May lst spiro-

chaetes were discovered for the first time, and in enormousnumbers ; they were present also, though to a lesser extent,in the urine collected on the same date. Immune horseserum was given intramuscularly with no beneficial result.Lumbar puncture was performed to obtain cerebro-spinallluid and on examination this showed no excess of eitheralbumin, globulin, or chlorides. It contained 4’1 lympho-cytes per c.mm. and no spirochaetes were seen in the deposit.The Wassermann reaction gave a clear negative result. ,

1 Brit. Med. Jour. 1926, ii., 108.

On May 3rd the patient was in a very collapsed stateand only semi-conscious ; intravenous saline injectionscontaining sodium bicarbonate were given, adrenalin wasalso administered, but the patient gradually sank and diedthe following day. A blood film taken two days beforedeath showed haemoglobin deficiency; the red cells showedalteration in shape and size ; polychromasia was exhibited,although no basophilic degeneration was noticed ; plateletswere few. The white cells showed vacuolation and frayingi of the nuclear material.

Discussio)z.It is to be remarked that the symptoms shown in

this case were not quite classical. At no time wasthere any great rise of temperature, 99’ being thehighest, and in point of fact the temperature wassubnormal. The patient had the usual slow pulse

Spirochætes seen in liliii of blood.

and the symptoms gradually deepened from a catarrhalto a grave toxæmic type of jaundice. There was noglandular swelling, but haematemesis with semicomawere the salient features of the last phase. It issomewhat important to observe that even at an

early stage there was variability in the size, shape,and staining qualities of the red cells, that many cellsappeared frayed, and haemoglobin was deficient.The leucocytes also showed variable staining qualitiesas well as evidence of degenerative changes.

It is well known that rats are carriers of this disease,their urine, teeming with spirochaetes, can contaminatefood and drink, and that this is the usual sourceof infection for human beings. It was noted that therewere rats in the ships in which the patient made thejourney to England.

Authorities state that the spirochaetes may beobserved in the peripheral blood till the fifth or eventhe seventh day by dark-ground illumination. Byinoculation of the patient’s blood (till the seventhday) into a guinea-pig the animal develops albuminuriaand jaundice, and the spirochaetes will be found inits liver and blood. After the seventh day thespirochaetes are entirely absent from the blood,passing into the internal organs ; between the ninthand fifteenth day they may be seen in the urine.Before death, however, in this case they appeared inthe blood and also in the urine.A reproduction of a drawing is given to show the

disposition of the spirochaetes as they appeared in thefilm of the patient’s blood.

I have not entered into details of all the therapeuticmeasures adopted during the illness. which variedfrom time to time as the patient’s condition demandedand included a strict diet of milk, citrated andotherwise, fruit juice, and bland fluids; irrigations

Page 2: A CASE OF SPIROCHÆTOSIS ICTEROHÆMORRHAGICA

338

containing a mixture of sodium bicarbonate and citrate ;rectal injections of dextrose and starch ; also injectionsof adrenalin and strychnine, inhalation of oxygen, &c.

Corzctusions.It appears to me that in all cases of jaundice, however

mild, examination of the blood for spirochaetes shouldbe a routine measure. Should they not be found theblood cells should be examined for degenerativechanges, and if these be present, then the agglutinationtest with stock spirocht-tes should be performed atonce ; if this is found positive the antiserum for thisdisease should be injected without delay. Thistreatment has been found wonderfully effective inthe early stages of the disease.

A CASE OF MENINGITISDUE TO THE TUBERCLE BACILLUS AND A DIPLOCOCCUS

CLOSELY ALLIED TO MICROCOCCUS TETRAGENES.

BY J. TODESCO, M.D. FLORENCE, M.R.C.S. ENG., D.P.H.,

RESIDENT MEDICAL SUPERINTENDENT, BOROUGH HOSPITAL,CROYDON.

THE following case is of interest on account of thefindings in the cerebro-spinal fluid and the conditionrevealed at autopsy.

S. Af., a boy. aged 2, was admitted to the Croydon BoroughHospital on Oct. 24th, l!J26. lie had previously sufferedfrom measles, and, one month ago, from diarrhœa andvomiting. There was a history of tuberculosis in bothparents, the disease being active in the mother at the timeof his admission. A fortnight before he had become iruitableand sleepy ; on Oct. ltith he was put to bed as he appearedworse and was feverish, and the day before admission hestarted having convulsions and became delirious withhead retraction and rigidity of limbs and neck.On admission the child appeared semi-conscious, was

flushed, and moaned constantly, In addition to rigiditythere were frequent twitchings of limbs. The abdomenwas not tender or wasted ; tache cirebt-ale was marked. Theheart sounds were rapid and weak and there were some ralesover both lungs, with rapid, though not laboured, breathing.The pupils were dilated and fixed and there was sorne bilateral ’,conjunctivitis and photophobia. The right knee-jerk was !,increased, the left absent, and Kernig’s and Babinski’s ’signs were markedly positive on both sides. He had cori-stipation and some difficulty of swallowing. Temperature100.8° 1. on admission. On lumbar puncture the cerebro-spinal fluid was slightly turbid, but not under pressure.On examination it contained a few lymphocytes and brokendown polymorphs and a Gram-positive diplococcus, some intetrad formation. There was excess of fibrin in fluid.Lumbar puncture was repeated on Oct. 2.’)th, 2(ith, 27th,

and 28th, amounts varying between 25 c.cm. and 3U c.em.being withdrawn. On two occasions there was increasedpressure, and on the 28th the fluid withdrawn was clear.The Gram-positive diplococcus was present on each occasionand it was also recovered from the blood on culture. Tuberclebacilli were not at first found in the cerebro-spinal fluid,but were present in the fluid withdrawn on Oct. 26th.

After the first lumbar puncture the child was quieterand there was less rigidity and head retraction. He hadprofuse general sweating at times. He appeared to improveslightly until Oct. 28th when he became less conscious,the rigidity increased, and there were also twitchings oflimbs and teeth-grinding. Cheyne Stokes breathing wasnow observed and greater difficulty of swallowing. Inaddition there was retention of urine and diarrhœa. Hiscondition grew steadily worse and he died on Oct. 2Uthin coma. The temperature kept persistently high through-out. being between 1000 and 105° and reaching above104° on two occasions. The pulse was always rapid andweak and could rot be counted at times, and the respirationrate varied from 44 to 70.

Post-mortem Findings.—Brain : Excess of cerebro-spinalfillid in ventricles. Extensive gelatinous yellow infiltrationof membranes along whole of under surface extending alongtissures of brain. On the vertex the whole of the rightcerebral hemisphere was dotted with small yellow abscesses,but none were present over left hemisphere. Petrous boneswere healthy. Thorax: A few caseating glands alongbronchi ; no free fluid in pleural cavities. Both lungspartially collapsed and studded throughout with miliarytubercles ; no consolidation present ; diaphragm normal.Pericardium contained about 1 oz. of clear yellow fluid ;heart appeared normal. Abdomen : No free fluid or ertlargedglands found anywhere. The intestines were normal,

tlie liver slightly enlarged. and the spleen contained miliarytubereles throughout. Both kidneys showed some cloudyswelling, but no tubercles. ,

(cultures were taken from tlie right hemisphere, spleen,lungs, ami pericardial fluid, and in each case a diplococcus

similar to that present in the cerebro-spinal fluid was

recovered.The following were the cultural characters of the organism

isolated from cerebro-spinal lluid and blood fintra-vitam)and organs : (u) On agar slope after 24 hour’ incnbation:thin hurcelain-likc smooth growth with crenated margin.(b) On gelatine stab after 2 1 hours incubation : fine whitegrowth, no gas, some liquefaction. (:) Sugars : lactose,no change ; glucose, acid; milk, alkaline. (rl) Staining:The organism was Gram-positive and was a. diplococcus.arranged in pairs, also in tetrad formation. It appearedto be closely allied to the Micrococcus tetragenes, but incultural characters resembled the JI. liquefaciens ratherthan tetragenes. (e) The organisrn had no effect on twomice given 0.2.5 c.cm. and 0.5 c.cm. of a broth culture, thusdiffering from the 3/. tetragenes, which is pathogenic to micecausing a septicaemia.

Discussion.The points of interest in this case appear tu be:

(1) The character of the cerebro-spinal flmirl, which inaddition to containing tubercle bacilli, contained a(liplococcus and was turbid inatead of clear as isusual in tuberculous meningitis. (2) The culturalcharacters of the organism, which. though on micro-scopical examination it appeared like 11 true 3jftcro*coccus tetragenes, differel from it on culture and inbeing non-pathogeuic to mice. (3) The post-mortemfindings. The lesions of the right cerebral hemispherewere not suggestive of tubercle and, moreover, thediplococcus was recovered on culture from this organ,the spleen, lungs, and pericardial fluid.

It appears that the child died from a mixedsepticaemia due both to the tubercle bacillus and toa diplococcus recovered from the cerebro-spinal fluid,blood, and various organs. Though M. tetragenes,which the organism closely resembles. is found insuppurative lesi ons and in the respiratory tract in man,it does not usually cause a septicaemia in human beings.

I wish to thank Dr. II. P. Newsholme. medicalofficer of health for Croydon, for permission to publishthis case, and Prof. J. C’. Ledingham, F.R.S., of the1-jister Institute, for his help and confirmation of thebacteriological findings, and for applying inoculationtests.

-

ROYAL MEDICAL BENEVOLENT FUND.—The hon.treasurer of the Fund gratefully acknowledges the sum of £30from Dr. (Phil.) Otto Itank of Vienna, per Dr. Marie Moralt.At the last meeting of the Committee 44 cases were

considered and £769 13s. 6d. voted to 40 applicants. Thefollowing is a summary of some of the cases relieved :-Widow, aged 6.’i, of L..R.C.P. Edin. who practised in London

and died in IV!!). Applicant has worked as a deaconess foryears until August last, when she had to give up on aecount ofleg trouble. Total income £90 per annum. Rent 11s. a week.Voted :626 in 12 monthly instalments.Widow, aged 45, of M.R.C.S. who died in November. Left

with girl of 14 and boy of 12. No private income and only .elOOfrom Insurance. Has had £150 from mother-in-law but it isuncertain whether this will be continued. Now lives in threerooms at a rental of 12s. a week. Voted £20.

Widow, aged 53, of M.D. who died in December last. Leftwith six children ages 11 to 21. Only the eldest one earning.One son studying for the law. Others at school. Voted £30.M.D., aged 83. Married ; one daughter aged 40. Owing to

financial losses had to take up practice again. Receipts donot meet expenses. £200 only received this year. Privataincome £100. Rent £117. Voted £10 in 12 monthly instalments.

Daughter, aged 68, of M.R.C.S. who died in 1881. Owing tobad health is unable to earn much. Only made £6 by fancy-work.£30 per annum from Yorkshire Medical Society. Few smatl gifts from friends. Rent paid by a friend. Voted £26 in 12monthly instalments.

M.R.C.S., aged 73, married, three children. Has had togive up work on account of old age and deafness. Wife has apostin a school. Children are unable to help in any way. Appli-cant has just lost an allowance of 19s. a week through death of*sister. Has the old age pension. Voted .K10 in 13 monthlyinstalments.

L.R.C.P. Edin., aged 47, married, one daughter. Receives£300 a year as an assistant. Was taken ill and had an operatinnfor appendicitis. Now only able to do light duty and hastopay locum to do night work. Asks the Fund to help withextra, expenses connected with his illness. Voted £35.

Subscriptions may be sent to the Honorary Treasurer,Sir Charters Symonds, at 11, t’hamlos-street, Cavendish-square, London, W. 1.