225

- TABLE IH—SUMMARY OF EXPERIMENTS ON COMBINED ACTION

OF ANTITOXIN AND LOCAL CHEMOTHERAPY ON Cll. welchiiINFECTION IN MICE

ture is effective against Cl. welchii, Cl. aedematiens andOZ. septicum, the three main causal organisms of gasgangrene, and has the advantage of diminishing the localtoxic effects of proflavine which are considerable when ,

proflavine crystals are applied to healthy tissue in largeamounts (Russell and Falconer 1943, Hawking 1943).

Our results also emphasise the importance of earlytreatment. Whether the therapeutic measures are

chemotherapy or serum therapy or both, they should beinitiated before serious deterioration of the tissues sets in,and the sooner the better. In our experimental diseasein mice the limiting period appears to be 4 or 5 hoursafter the inception of infection. Thus the time factor isof the utmost importance in the treatment of anaerobicinfections.

SUMMARY

Antitoxin treatment combined with local chemo-therapy is more effective than antitoxin or chemotherapyalone in the treatment of Cl. welchii infection in mic!(.The results indicate that all cases of gas gangrene

should receive as soon as possible adequate doses ofantitoxin combined with full local treatment.

REFERENCES

Hawking, F. (1943) Lancet, i, 710.Henderson, D. W. and Gorer, P. A. (1940) J. Hyg., Camb. 40, 345.McIntosh, J. and Selbie, F. R. (1941) Lancet, i, 240.

— (1942) Ibid, ii, 750.— — (1943) Ibid i, 793.

Russell, D. S. and Falconer, M. A. (1943) Ibid, i, 580.

Medical Societies

SOCIETY OF MEDICAL OFFICERSOF HEALTH

AT a meeting of the fever hospital medical servicesgroup on June 18, with Dr. ANDREW TOPPING (LCC) inthe chair, a discussion onAdministrative and Clinical Control of Diphtheria

was opened by Dr. J. A. SCOTT (Fulham), who said thatbefore immunisation was practised in this country therewere about 60,000 cases of diphtheria in England andWales annually, of which 3000 died. Comparing thiswith an average of 600,000 births annually the risk ofcatching diphtheria before the age of fifteen was about1 in 10. Active immunisation could not be expected toreduce the carrier-rate, which might even increase inpartially immunised communities.. Hence there was afair chance of recovering diphtheria bacilli from swabsfrom immunised children, whether they were sufferingfrom diphtheria or not. In Fulham over 3000 childrenwere immunised during 1934-41, but the number hadnow increased to over 10,000. After a preliminary periodpre-Schick testing was dropped but a post-Schick testwas always performed. Among immunised children22 cases had been notified, but the diagnosis was notconfirmed in 6. Of the remaining 16 confirmed cases, 5contracted diphtheria before full immunity could havedeveloped. In 1 case, on whom there had been no post-Schick test, the attack was fatal. More than half of allchildren under fifteen in Fulham were now immunised,and the average number of cases of diphtheria per yearhad dropped from 350 to 50. A parallel decrease inincidence could also be shown for the County of London,where immunisation had- been actively pursued in mostboroughs since 1934. Dr. Scott encouraged the earlyadmission to hospital of diphtheria cases without waitingfor the results of bacteriological swabs, a policy justifiedby the rising mortality when serum administration wasdelayed. It was unusual for the doctor to be called inbefore the second or third day, which emphasised the needfor prompt admission to hospital. Prompt admissionentailed formal notification, in which the diagnosticerror was high. Correction of notifications is not auto-matic and the information rarely filters through to theRegistrar-General, whose figures are therefore incorrect.Thus the full effect of immunisation might be maskedand a misleading impression given of the incidence ofdiphtheria in the immunised population. De-notificationwas not a simple problem, since parents were sometimesmore inclined to blame the doctor for what they con-sidered a wrong admission to hospital than to expressgratitude for the caution he had displayed. Speaking ofthe possibility of early administration of antitoxin in thehome Dr. Scott regretted that the average amount ofserum issued to practitioners in his area amounted onlyto an 8000 unit dose for each five notified cases. Taking

into account overcrowding, loss of employment amongintimate home contacts and so forth, the proper solutionwas an easy system of hospital admission. Admin-istratively, however, there was a need to correct prelimin-ary notification figures in the light of the final diagnosis.Such a system would probably increase difficulties inhospitals with a shortage of isolation accommodation,but some relief might be expected from a decrease in theincidence of diphtheria. The admission of cases on adiagnosis of suspected diphtheria had much to commendit provided a reliable and prompt system of informingborough MOHs of the corrected diagnosis was evolved.The anti-vaccination societies would doubtless regardthe correction of diagnosis as a further effort to misleadthe public, but in everything connected with diphtheriaand the great immunisation campaign scientific accuracywas all important and would provide the only answer theantivaccinationists needed.

Dr. NORMAN BEGG (LCC) said that the major problemof diphtheria in hospital was the disposal and manage-ment of doubtful cases. The disease always ranked highamong those which tended to be erroneously diagnosed.In 1058 diphtheria admissions to the Eastern Hospital thediagnosis was not confirmed in 35-4%, compared with adiagnostic error of 13-3% in scarlet fever, 11-5% inmeasles and 10-7% in whooping-cough. The commonestmistake was to confuse diphtheria with other throatinfections, particularly those due to the haemolyticstreptococcus. In rather less than half of all certifiedcases it was possible to arrive at a presumptive diagnosisof diphtheria on admission. This meant that for everybed provided for diphtheria in an open ward at least oneother bed must be available for isolation and investiga-tion of doubtful cases. At present isolation accom-modation to this extent could only be provided in barrier-nursing wards. In investigating doubtful cases theclinical findings were easily the most important. Toomuch stress was laid on bacteriological examination,which was often incomplete unless it included full identi-fication of the diphtheria bacillus and specific examina-tion for haemolytic streptococci and Vincent’s organisms.In the large group of admissions where the balance ofclinical evidence was against diphtheria positive bacterio-logical findings might be misleading unless the state of thepatient’s immunity was also revealed by Schick test orestimation of blood antitoxin. Thus in doubtful casesthe three main investigations often had an interrelatedimportance. Among Dr. Begg’s 1058 diphtheria admis-sions the biggest diagnostic error-50-5%-occurred incases referred from the outpatient department of generalhospitals, whereas general practitioners’ cases had a diag-nostic error of 33-1%. An acute aspect of the problemwas the readiness with which diphtheria was diagnosedand formally certified in immunised children. In a seriesof 66 such admissions, diphtheria was confirmed in only13 cases, and 4 of the cases had contracted diphtheriabefore immunisation was complete. In the single fatalcase, a tracheotomised one, details of immunisation, which

226

had been done in an evacuation area, were uncertain.To put no hindrance on admitting suspect diphtheriacases to hospital would encourage early admission and doaway with the need for attaching a definite certificatewhen in doubt about the diagnosis. But it would notresult in more accurate diagnosis in the home, nor solvethe problem of shortage of isolation accommodation.,He favoured the setting up of a clinical consultant servicein infectious diseases closely linked with a good laboratoryservice-all to be available to see patients in the home, orin the hospital outpatient or inpatient department. Con-sultation should be sought, not in isolated cases of doubtbut in all cases who would normally be sent to hospital.

Dr. ROBERT CpuiCESHANK (LCC) said that clinicaldiagnosis was clearly not easy, for 5-6 out of every 10notified cases admitted to the North-Western Hospitalwere not diphtheritic infections. Much unnecessarytrouble, both to parents and to hospital superintendents,would be avoided if doubtful cases were given an injec-tion of antitoxin at home, and a swab sent for examina-tion by a reliable laboratory. Many doctors were stillunaware of the refinement in antitoxin which allowedan adequate dose for an early doubtful case to be given in2-3 c.cm. with the minimum risk of reaction. An accur-ate laboratory diagnosis of diphtheria could only beobtained by the use of a tellurite medium, and culture onblood-agar was required to identify streptococcal infec-tion. The Loeffler slope was still useful for early diagnosis,but it missed up to 30% of clinical infections and gavefalse-positive cultures with swabs from ear, nose or

wound. The tellurite medium, on the other hand, be-sides checking the clinical diagnosis identified the infect-ing type as gravis, intermedius or mitis, eliminated falsepositives and minimised the need for virulence testingsince all gravis and intermedius strains are toxigenic.Identification of type was also of prognostic value, paraly-tic complications being more common z15%) withgravis and intermedius than with mitis (4%). Use of thetellurite medium in the discharge of patients from hospitalhad been criticised on the grounds that it encouragedthe unnecessary detention of the patient in hospital justbecause he had a few diphtheria bacilli in his throat.’ Acomparative analysis of tellurite and Loeffler culturesfrom dismissal swabs showed that only a fifth of thepatients were kept longer in hospital because of positivecultures on the tellurite medium when the Loeffler cul-tures were negative ; of these more than half wereready for discharge within 2 weeks. Persistence of thecarrier condition was due to unhealthy mucous mem-branes, reinfection and secondary streptoccocal infection.The detection of carriers was also facilitated by the tellu-rite medium, which, besides being less laborious, allowed acorrect and quantitative report within 2 days, and byidentifying the infecting type helped to trace the sourceof infection. Swabs for discharge and for detection ofcarriers must always be taken from nose as well asthroat. Knowledge of the relative incidence of theinfecting types was essential for the study of theepidemiology of diphtheria.The CHAIRMAN thought the public could be educated

to appreciate the practitioner’s action in sending a doubt-ful case to hospital even if the diagnosis was not confirmed.The difficulty of adequate isolation accommodation wasnot insurmountable ; we might have to aim at 60% ofsingle-bedded units in the future. He favoured theprovision of a consultant service and a wider use of thesenior staff of fever hospitals in field epidemiology.

Dr. VICTOR FREEMAN (Islington) said that in large-scaleimmunisation labour could be saved by omitting thepre-Schick test in children up to nine years. He had hadonly 6 confirmed cases of diphtheria in his area amongfully immunised children, and only 1 of these had a severeattack. He asked for full and accurate record-keepingin all areas undertaking diphtheria immunisation.Dr. Guy BOUSFIELD (Camberwell) had not encounteredone death from diphtheria in a fully immunised childduring fourteen years. He strongly favoured frequentcontrol of Schick-test toxin on primary cases and thoughtthat some failures in immunisation were attributable tofaulty post-Schick testing or testing with weak material.He was also struck by the low’ incidence of paralysis inimmunised cases who later contracted diphtheria. Dr.BEGG agreed with him that in the immunised cases fromthe Eastern Hospital the course was usually more favour-

able than would have been expected from the initialseverity.

Dr. E. C. BENN (Leeds) described 3 deaths from diph-theria in immunised children, but in 1 the post-Schicktest had been positive. A more common picture was amild sore throat with few or no clinical signs on admissionto hospital. These cases should be classified as truediphtheritic infections in children with a high degree ofimmunity. Other speakers agreed and Dr. CRUICK-SHANK pointed out that these cases, which he preferred tocall diphtheritic tonsillitis, were almost invariably dueeither to a gravis or intermedius infection.

Dr. H. M. LEETE (Hull) thought it right to admit thatdiphtheria can occur in immunes, but as a modifieddisease. He had seen neither death nor paralysis in animmunised case. He described cases with limitedmembrane in which no antitoxin had been given wherethere had been a sharp rise in the blood-antitoxin titrewithin ten days. The post-Schick test might be omittedprovided a reliable antigen was injected in proper dosesand at an adequate interval.

Dr. A. L. K. RANKIN (Twickenham), who also favouredthe early admission of suspect cases, informs the MOHoil the evening of admission whether a certified diphtheriacase is one of (a) clinical diphtheria, (b) no clinical evid-ence of diphtheria, or (c) under observation.

Dr. IAN TAYLOB (LCC) thought that too much hadbeen made of the possibility of immunisation increasingthe carrier-rate. A recent survey of some thousands ofLondon school-children showed that 63% had now beenimmunised and yet the general carrier-rate was well under1%. He supported the idea of a consultant service in infec-tious diseases and thought it unimportant whether it camefrom the hospital or the public-health authority. Betterteaching facilities in fever for students were important.

Dr. R. A. O’BRIEN (Beckenham) thought it clear thatnatural cures from diphtheria in pre-antitoxin days haddepended on the patient producing antitoxin himself,and this was supported by his own observation on a groupof mild cases of diphtheria where the titre of antitoxin inthe blood rose steeply in convalescence.

Reviews of BooksAdvances in Internal Medicine

’

Vol. i. Editor: J. MURRAY STEELE, MD, Welfare Hospital,- New York University Division. (Heinemann. Pp.292. 21s.)

. Tms book comprises ten reviews, each of a subjectwhich has recently attracted interest, and each by a manwho has participated in its investigation. As the titleimplies these reviews are concerned with advanced work,and some knowledge-not always merely elementary-of the subjects is necessary if the articles are to be readwith profit. The first, on the uses of the Miller-Abbotttube in diagnosis and treatment, is a straightforwardaccount by one of the inventors, and should encouragejudicious use of this technique in practice. The articleon the use of insulin and protamine insulin in the treat-ment of diabetes contains little fresh, but shows thattransatlantic thought on diabetes is breaking free fromthe rigid " overproduction

"

theory. The article on thesympathetic nervous control of the peripheral vascularsystem by Wilkins is full, and is followed by two articleson the sulphonamide drugs ; Macleod is lucid on theirmode of action ; Keafer discusses the evidence for theuse of particular sulphonamides in different illnesses.It seems likely that, leaving out of account one or twoillnesses which respond to individual sulphonamides, thepractical problem is to agree which is the most efficientand least toxic of these drugs. A section on infectionsof the urinary tract summarises much useful experience,but the view that chronic pyelonephritis is an importantfactor in the pathogenesis of hypertension is not provenor generally accepted. Other reviews cover epidemicinfluenza, nephrosis, and ariboflavinosis.Air Raid First Aid -

.

(2nded.) W.A.AsHFORD. (Williams & Norgate. Pp.46. ls.6d.)I’ns only nine months since this useful little summary

first appeared. It compresses into , small space themodifications of classic first-aid treatment which havebecome necessary under blitz conditions, and we arehappy to observe that the three errors noted in the firstedition have been corrected.