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Saturday 5 January I980
ACUTE HEPATITIS B ASSOCIATED WITHGYNÆCOLOGICAL SURGERY
REPORT OF A COLLABORATIVE STUDY BY THECOMMUNICABLE DISEASE SURVEILLANCE CENTRE ANDTHE EPIDEMIOLOGICAL RESEARCH LABORATORY OF THEPUBLIC HEALTH LABORATORY SERVICE TOGETHER WITH A
DISTRICT CONTROL-OF-INFECTION SERVICE*
Summary In a district in England, seven patientsin whom acute hepatitis B (AHB) devel-
oped between January and July, 1978, had had majorsurgery by the same gynæcological team within sixmonths of onset. Hepatitis B surface antigen (HBsAg) athigh titre, hepatitis B e antigen, and Dane particles werefound in the serum of the team registrar. The HBsAgsubtype of the registrar and patients was ad. A postalinquiry of family doctors revealed an additional patientwho had been jaundiced and had probably contractedAHB within six months of major surgery performed bythe same registrar. Among this registrar’s patients AHBarose in 8 (5%) of 153 who had had major operations,but in none of 300 who had had minor operations andin none of 136 obstetric patients. No cases were foundin 188 major-surgery, 425 minor-surgery, and 130 ob-stetric control patients. Infection was probably transmit-ted by sharp instruments after accidental puncture ofthe surgeon’s glove and skin.
Introduction
IN the United Kingdom, hepatitis is recognised as anoccupational hazard of health-service staff. Hepatitis Binfections of staff probably acquired from patients arereported from time to time.! Transmission of the infec-tion in the opposite direction-that is, from staff topatients-seems rare. Indeed, in two recent reports aW.H.O. Expert Committee on Viral Hepatitis concludedthat there was no evidence of any special hazard frommembers of the medical or other professions who arecarriers of hepatitis B surface antigen (HBsAg) in closecontact with the general population.2,3 The only reportof transmission from a symptomless carrier surgeon topatients concerned an outbreak in the U.S.A. among pa-tients of a dental surgeon who at no time had any clini-cal evidence of hepatitis.4
This paper reports a cluster of cases of acute viral
hepatitis B (AHB) among patients who, within six
*Prepared by the Epidemiological Research Laboratory (Hepatitis),Central Public Health Laboratory, Colindale Avenue,
London NW9 5HT.
months of onset, had undergone gynaecological surgeryin either of two hospitals in a district in England.
Recognition of Clustering and Initial InvestigationsBetween January and July, 1978, 7 cases of AHB
were recognised by the control-of-infection officer (CIO)and nursing officer at hospital A as patients who had un-dergone gynaecological surgery within six months ofonset (table i). At first, in the light of the accepted viewthat staff rarely transmit hepatitis B to patients, the CIOinvestigated the possibilities of transmission via blood orcontaminated intravenous fluids, and of cross-infectionbetween patients. However, when the sixth and seventhpatients were discovered in July it became clear that theonly apparent connecting link was surgery performed bya single gynaecological team, of which only one member,a registrar, took part in all seven operations.The CIO then obtained serum samples from the team
members, and on July 31, 1978, HBsAg was reportedpresent in the registrar’s serum but not in any other.Tests showed HBsAg at high titre, Dane particles, andhepatitis B e antigen (HBeAg)-all indicators of poten-tial infectivity. The aspartate aminotransferase level waswithin normal limits. The registrar, who is British inboth nationality and ethnic origin, had no history ofhepatitis. The sera of the other team members showedno evidence of past hepatitis B infections.The area medical officer was informed and the regis-
trar voluntarily agreed with his consultant colleaguesand the hospital authorities -that, pending further inves-tigations, the wisest course was to discontinue operativework.
After discussion with the area medical officer, themedical officer for environmental health asked for theassistance of the Public Health Laboratory Service
(PHLS) Communicable Disease Surveillance Centre
(CDSC) in making further investigations.A collaborative study was designed at the Epidemio-
logical Research Laboratory to find out if there were anymore AHB cases among patients in whose operations ordeliveries the registrar took part during the period heworked in the district-May, 1977, to August, 1978. Itwas also designed to estimate the AHB attack-ratesamong these patients and to compare them with ratesamong similar patients of another gynaecological team inthe same hospitals.
Methods
Identification and Follow-up of Patients and ControlsDetails of surgical and obstetric patients of the team that in-
cluded the HBSAg carrier, from May, 1977, to August, 1978,
2
inclusive, were extracted from theatre records at hospitals Aand B. All patients of another gynaecological team at the samehospitals were selected for comparison. At hospital B, patientsof other teams were also selected as controls because the orig-inal control team had rarely performed major surgery there.Each patient delivered by the registrar was matched to anotherobstetric patient by the time and type of delivery.
.
Relevant details and family doctors’ names and addresseswere taken from the patients’ hospital records.A postal inquiry was made of the family doctors. The chief
question asked was "Since operation/delivery has the patientconsulted with an illness (with or without jaundice) that youconsider was hepatitis?"A second inquiry was sent to any doctor who did not reply
within two weeks. A medical officer arranged to visit the fewfamily doctors who did not reply to inquiries.A family doctor who reported a case was asked to complete
a sickness record. He was also asked if he would arrange tohave a serum sample taken from the patient.
Serum Samples and Laboratory Test MethodsRadioimmunoassay (RIA) for HBAg.-Solid-phase sand-
wich technique employing polystyrene tubes and affinity col-umn purified 1251 anti-HBs-5 Detection sensitivity 0.2 ng/mlHBsAg. -
RIA HBsAg subtyping.-Solid-phase sandwich techniqueemploying tubes coated with anti-d anti-y antibody. 5
RIA for anti-HBs.—Solid-phase sandwich technique. Poly-styrene tubes were coated with an equal mixture of purifiedHBsAg subtypes ad and ay. A sample of the same purifiedHBsAg was used for preparing the 1251 reagent. Limit ofanti-HBs detection set at 0-005 lU/ml.RIA for anti-HBc.—Solid-phase competition radioim-
munoassay employing polystyrene tubes coated with purifiedcores from the post-mortem liver of an immunosuppressed pa-tient. Detection sensitivity for anti-HB, set at .12 x thatobtained with the complement fixation test (CFT).RIA for HBeAg/anti-HBe.—Solid-phase sandwich tech-
nique.6
CFT for anti-HBc.—Done with semipurified suspension ofa liver containing intranuclear cores and a suitable normalliver control antigen.
Immunodiffusion (ID) test for HBcAg/anti-HBc.—Seemethod of Tedder. 7
Anti-HBs subtyping.-A dilution of the patient’s serum wasmixed with an equal quantity of an ad HBsAg positive serumdiluted to contain 10 ng/ml HBsAg and also with a similardilution of an ay HBsAg positive serum. Both mixtures wereassayed for HBsAg by RIA and the percentage reduction incounts was compared.
Immuno-electronmicroscopy.—0.2 ml of the serum to be ex-amined was mixed with a suitable dilution of horse anti-HB.,left at +4°C overnight, and centrifuged at 38 000 g for 1z h.The resuspended pellet was negatively stained_ with phospho-tungstic acid. The criteria for recognition of HBV particleswere (a) size approximately 42 nm; (b) stain penetration suffi-cient to demonstrate the core; and (c) clumping with small andlong HBsAg forms.RIA for anti-HA V.-’Havab’ (Abbott Laboratories Ltd).Aspartate aminotransferase.-Measured on a Vickers M300
’AutoAnalyzer’. -
Reverse passive hæmagglutination (RPH).-‘Hepatest’(Wellcome Reagents Ltd).
’ ’
Statistical MethodProbabilities by Fisher’s exact test.
Definitions ’
Carrier.-A symptomless HBsAg carrier.Major gyncecological surgery.-All operations involving
laparotomy; all hysterectomies; major repairs; radical vulvec-tomies.Minor gynæcological surgery.-All gynæcological surgery
other than the above.Team C.—Gynæcological team that included the carrier
registrar.Results
Details of 1920 patients of 298 family doctors weretaken from hospital records. Of these, 1103 were teamC patients and 817 were controls. The registrar had
TABLE I-PATIENTS WITH ACUTE HEPATITIS B WITHIN SIX MONTHS OF GYNECOLOGICAL OPERATIONS AT HOSPITALS A AND B
* Age at operation (yr); t H = hysterectomy; BSO == bilateral salpingo-oophorectomy; § specimens not stored and not available for subtypinglater; 11 patient discovered by postal inquiry.
3
TABLE II—PATIENTS WHO HAD SURGERY DELIVERY IN WHICH
THE CARRIER REGISTRAR TOOK PART AND SIMILAR PATIENTS
TREATED BY OTHER MEMBERS OF TEAM C OR BY OTHER TEAMS
DURING PERIOD MAY, 1977, TO AUGUST, 1978
* Team C included the carrier registrar; t = Matched control pa-tients.
taken part in surgical procedures on 646 patients. Table11 shows the number in each patient category.
}
Team C patients and controls were similar in age dis-tribution and in the number of blood-transfusionsreceived.
Family doctors completed forms for all but 12 of the1920 patients. Of 1908 patients 13 had died and 152had moved from the practice areas within six months ofoperation. The outcome was known for 1743 (91%) ofthe 1920 patients.
Only 1 patient with a history of jaundice was reportedby a family doctor (patient 8, table n). This patient’sserum had not been examined for HBsAg but, as in theother 7 patients, an icteric illness developed within sixmonths of major surgery in which the registrar hadtaken part. Tests of serum, taken eight months after theonset of hepatitis, revealed anti-HBs and anti-HB, andalso antibodies to hepatitis A virus. These results wereconsistent with a recent hepatitis B infection (table III).Test results were consistent with subtype ad infectionfor this patient, for 6 patients in whom it was possibleto ascertain the subtype, and for the registrar (table III).One family doctor reported 2 patients with anicteric
gastrointestinal illness-possibly atypical attacks of
viral hepatitis. Tests of serum, taken four and sixmonths after the onset of these illnesses, showed no evi-dence of past or present hepatitis B or hepatitis A infec-tion. None of the control patients was reported to havehad hepatitis.The outcome was known for 589 of the 646 patients
who had had surgical procedures in which the registrartook part. The AHB attack-rate in these patients was1-4% (table IV). All 8 patients with AHB were amongthe 153 who had had major surgical procedures-a rateof 5.2%. The differences between the incidence of AHBin the 153 major-surgery patients and in both the 300minor-surgery and the 136 obstetric patients (of whom81 were delivered by caaarean section) were highly sig-nificant. The difference between the incidence of AHBin the 153 major-surgery patients and in the 188 controlpatients was also highly significant.
Of the 153 major surgical operations, 95 had beenperformed by the registrar and 58 by another teammember with his assistance: AHB developed in 7 of the95 and 1 of the 58 but this difference was not significant(p=0.12). The presence or absence of junior surgicalstaff at major surgery with the registrar did not affectattack-rates.
The 8 patients with hepatitis were among 79 who hadundergone surgery from August, 1977, to February, ,1978 (see figure). The registrar had taken part in 30major procedures before and 44 after this period (tablev): none of these patients had hepatitis. The differencebetween the AHB incidence in August, 1977, to Feb-ruary, 1978, and in the later period reached signifi-cance. However, 6 infected patients had operations inthe same theatre and the difference in the AHB inci-dence after surgery performed in this theatre and allothers was also significant. A comparison of incidenceafter surgery in this theatre and others during August,1977, to February, 1978, showed that the trendremained but the difference did not reach significance.This theatre is normally used for ear, nose, and throatsurgery but it was used by team C from August, 1977,
TABLE III-RESULTS OF LABORATORY TESTS OF SERUM SAMPLES FROM PATIENTS AFTER ATTACKS OF ACUTE HEPATITIS B AND FROM
THE CARRIER REGISTRAR
*HB,Ag RIA neg=<0.2 ng/ml; † Anti-HBsRIA neg=0.005 IU/ml.
4
TABLE IV-ACUTE HEPATITIS B IN PATIENTS WITHIN SIX MONTHS OF GYNÆCOLOGICAL SURGERY OR DELIVERY
* AHB = acute hepatitis B. † d compared with e. ‡ d compared with f. § a compared with b. a compared with c.
to June, 1978, when other theatres in turn were under-going maintenance and repair work. It is similar in sizeto other theatres in hospital A. Its lighting and otherfacilities are adequate, staff are drawn from a commonpool, and instrument trays are delivered wrapped andsterilised from central supplies. Operating lists in thistheatre always included a smaller number of patientsthan lists in other theatres because it is geographicallyrelatively remote from the gynaecological wards andtransport of patients is therefore more difficult.A serum sample taken from the registrar in February,
1979, was tested in parallel with the first specimen takenseven months before. There was no change in any of thehepatitis B markers.
Discussion
The U.K. has a relatively low incidence of all types ofviral hepatitis.8 The annual incidence of AHB in onearea was recently estimated at 5 per 100 000 populationand the disease is more common in men than in women.9
Against this background, the appearance of AHB in 8patients, within seven months, after surgery performed
Month of operation for 153 major-surgery patients: registraroperating/assisting.Hatched area represents patients with AHB.
by one gynaecological team, seemed unlikely to be due tochance. The probability of an association was increasedwhen the team registrar proved to be a symptomlessHBsAg carrier with serological markers of high infecti-vity and with an HBsAg subtype the same as that of thepatients. When a high local incidence of this infectionwas excluded by finding no evidence of hepatitis in alarge control group there could be little doubt that theregistrar was the source of the patients’ infections.Though tests for HBsAg have been available in the
U.K. for about ten years there are no previous accountsof transmission from staff to patients. There are a fewpublished reports from other countries of transmissionfrom staff incubating or convalescent from AHB, orwith chronic hepatitis, 10-12 but only two of transmissionfrom symptomless carriers, a physician13 and a dentalsurgeon.4 The physician was not fully established as theorigin of the infection and the route was unexplained;the dental surgeon apparently transmitted infectionfrom cuts and abrasions on his ungloved hands.The absence of reports of transmission from surgeons,
other than dental surgeons, raises the question of howthe infection was transmitted in this instance. A sero-
logical survey to discover symptomless infections wasnot feasible and so, if there were any inapparent infec-tions, their distribution in the various patient categoriesis unknown. Nevertheless, the fact that AHB occurredonly after major deep pelvic surgery suggests thattransmission resulted from events that were much more
TABLE V-ACUTE HEPATITIS B IN PATIENTS WITHIN SIX MONTHSOF MAJOR SURGERY WITH THE CARRIER REGISTRAR OPERATING ORASSISTING IN THEATRE D OR OTHER THEATRES BEFORE, DURING
AND AFTER AUGUST, 1977, TO FEBRUARY, 1978
* AHB = acute hepatitis B; t Total (d) compared with total (e)p = 0.037; :j: Total (b) compared with total (c)p = 0025.
All other comparisons not statistically significant.
5
common in, or perhaps limited to, these procedures.Probably the infections resulted from accidents that in-volved puncture through the surgeon’s glove and skin.After such an accident it would be diffcult to discard theneedle or other sharp instrument contaminated with thesurgeon’s serum without coming into contact with somepart of the operation site. In general surgery, such acci-dents are probably uncommon but the registrar andseveral of his hospital colleagues believe they are morecommon in gynaecological surgery, when the surgeon,operating deep within the pelvic cavity, often guides aneedle with the fingers of his free hand. This explana-tion of the way in which the infection was transmittedis consistent with the distribution of the cases and withtransmission of hepatitis B by the usual route, that is,blood to blood.
Though it is highly probable that the registrar’sHBsAg carriage was initiated by inoculation of infectiveblood during surgery, the source of his infection and thetotal period of his carrier state could not be determined.The first of his patients with AHB in the two hospitalswas infected three months after he started work there.The registrar’s blood may not have been infective beforethen but he may have been a carrier throughout hisemployment in the two hospitals and the absence ofhepatitis from his earlier patients may have been fortuit-ous. The absence of hepatitis in patients who had theiroperations after February, 1978, was surprising andseemed less likely to be due to chance. The distributionof AHB cases in time, however, could not be completelydisassociated from the higher infection rate found in pa-tients who had major surgery in one theatre. Adverseconditions in a theatre-e.g., crowding, bad lighting-might tend t6 increase the incidence of accidental fingerpricks. However, conditions in this theatre were ade-quate in all respects and no reason for the increased inci-dence of infection could be identified. The absence ofhepatitis in patients who had operations after February,1978, might be explained by a change in, or modifica-tion of, techniques, but the registrar was certain that hehad made no alterations at any time.Whatever the cause of the non-appearance of hepa-
titis in patients after July, 1978, the fact remained thatAHB had developed in 8 patients. Though none wasseverely ill the registrar clearly had to cease work in thetheatre temporarily. When further investigations con-firmed the association it was considered unwise for himto resume his full duties until laboratory tests suggestedthat his blood was no longer infective. In the short term,with the support of the health authority and the good-will of colleagues, a carrier surgeon who has inadver-tently transmitted infection to patients might be able totolerate limitations on his professional activities. Thesituation becomes more difficult if the carrier state per-sists for more than a year or so, as it well may.14The findings of this study do not contradict the belief
that carrier staff rarely present a hazard to patients. Thedistribution of the cases suggests that patients are at riskonly if they have direct blood-to-blood contact with thestaff carrier and this is in keeping with the results of pro-spective studies which showed no risk to patients froma nurse and two physicians who were HBsAg positive.’sIt seems that the areas in which transmission from staff
may occur are operating theatres and dental surgeries
and, even there, the patient is not exposed without arelevant accident.The number of carriers among surgeons in the U.K.
must be small and the number with sufficient virus par-ticles in a minute quantity of blood to infect a patienteven smaller. A carrier rate of 0.6% was found in astudy of 500 dental surgeons.16 If this rate is assumedfor all surgeons in England and Wales17,18 the approxi-mate number of carriers should be 14 gynaecologists, 80dental surgeons, and 42 surgeons in other specialties.However, virological tests for markers of infectivity,HBeAg in particular, suggest that among HBAg-posi-tive blood-donors only about 10% are highly infective(personal communication, D. S. Dane). On this basisthere are probably at any time 1 or 2 gynaecologists, 8dental surgeons, and 4 surgeons in other specialtieswhose blood, in a minute inoculum, would present ahazard. However, though HBeAg and other tests use-fully indicate relative infectivity, there is no test yetavailable to designate with certainty any HBsAg positiveblood as non-infective.
It might be argued that the small risk posed by thefew infective carriers ought to be eliminated by screen-ing of staff for HBsAg carriage, just as blood-donors arenow screened. The circumstances of blood-donors andhealth-service staff are not, however, analogous. Accept-ance of carrier blood-donors would certainly exposesome patients to large amounts of infective. blood,whereas staff carriers might never endanger a patient.Rejection as a blood-donor is a matter of small import-ance to the individual, but suspension of a staff carriermust affect his employment and may even end his car-eer. The registrar described here has had to give upoperative surgery and midwifery until such time as viro-logical tests indicate that his blood is no longer infective.It would, however, be difficult to justify requiring simi-lar action after identification, by routine screening tests,of a staff carrier who had never been shown to transmitinfection to patients.Anyway, it is not practicable to ensure that staff are
free of hepatitis B virus at all times; there must be someinterval between screening tests during which the carrierstate could begin and, furthermore, staff incubatingAHB are usually viraemic for several weeks before theonset of symptoms.
Another, perhaps less obvious, disadvantage of rou-tine HBsAg screening of staff is the possibility of itsadverse effect on staff-patient relationships. Historically,staff have always accepted an increased risk of illness asa result of acquiring infection from patients. If, how-ever, there is also the possibility of being unable to workas a result of the detection on routine examination of a
symptomless carrier state (probably acquired from apatient) the risk of treating HBsAg positive patientsmight not be accepted so readily. There are probablyabout 50 000 carriers in the U.K., and health services tothis group must not be compromised.
Routine HBsAg screening of staff as a means of pre-venting an apparently rare type of transmission couldtherefore offer only minute advantage but would almostcertainly create enormous problems.
At present there is no method of eliminating the car-rier state by treatment, though various substances arebeing investigated. In the long term, active immunisa-
6
tion of staff at the beginning of training may provide thebest means of protection against transmission of hepa-titis B infection between patients and staff in eitherdirection. Vaccines have been developed and are beingassessed for safety and efficacy.19 Meanwhile, anti-HBsimmunoglobulin is available for prophylaxis after acci-dental inoculation or contamination of abrasions andmucous membranes with HBsAg positive material.
We are greatly indebted to the family doctors for their generous re-sponse to the request for assistance; by completing and returning thestudy records they ensured an almost complete follow-up of the pa-tients who remained in their care. We thank the staff of the recordsdepartment and the theatre and obstetric staff at hospitals A and B,clerical and secretarial staff of the area health authority, and the Epi-demiological Research Laboratory for the large contributions theymade to the study.
All the collaborators have chosen to remain anonymous to facilitatethe reorganisation of their colleague’s professional life.
The epidemiological studies were made by the following: the hospi-tal control of infection officer and nursing officer; the district medicalofficer for environmental health and a senior registrar in communitymedicine, area health authority; a statistician, PHLS CommunicableDisease Surveillance Centre; a senior registrar, Virus ReferenceLaboratory and a consultant epidemiologist, Epidemiological ResearchLaboratory, Central Public Health Laboratory. The virological studieswere done at the Department of Virology, Middlesex Hospital. Somespecimens were also examined at the Virus Reference Laboratory,Central Public Health Laboratory.
Requests for reprints should be addressed to the EpidemiologicalResearch Laboratory (Hepatitis), Central Public Health Laboratory,Colindale Avenue, London NW9 5HT.
REFERENCES
1. Public Health Laboratory Service. Communicable disease weekly reports,1973-79. Unpublished.
2. World Health Organisation. Viral hepatitis. World Health Org Tech Rep Serno. 570, 1975.
3. World Health Organisation. Advances in viral hepatitis. World Health OrgTech Rep Ser no. 602, 1977.
4. Rimland D, Parkin WE, Miller GB, Schrack WD. Hepatitis B outbreaktraced to an oral surgeon. N Engl J Med 1977; 296: 953-58.
5. Heathcote J, Cameron CH, Dane DS. Hepatitis B antigen in saliva andsemen. Lancet 1974; i: 71-73.
6. Barbara JAJ, Mijovic V, Cleghorn TE, Tedder RS, Briggs M. Liver enzymeconcentrations as measure of possible infectivity in chronic asymptomaticcarriers of hepatitis B. Br Med J 1978; ii: 1600-02.
7. Tedder RS. Testing for e antigen and e antibody by immunodiffusion. J MedVirol 1978; 3: 51-57.
8. Department of Health and Social Security. Annual Report of the Chief Med-ical Officer. London: H.M. Stationery Office, 1974.
9. Stewart JS, Farrow LJ, Clifford RE, et al. A three-year survey of viral hepa-titis in West London. Quart J Med 1978; 47: 365-84.
10. Garibaldi RA, Rasmussen CM, Holmes AW, Gregg MB. Hospital-acquiredserum hepatitis. JAMA 1972; 219: 1577-80.
11. Levin ML, Maddrey WC, Wands JR, Mendeloff AI. Hepatitis B transmissionby dentists. JAMA 1974; 228: 1139-40.
12. Snydman Dr, Hindman SH, Wineland MD, Bryan JA, Maynard JE. Nosoco-mial viral hepatitis B: a cluster among staff with subsequent transmissionto patients. Ann Intern Med 1976; 85: 573-77.
13. Grob PJ, Moeschlin P. Risk to contacts of a medical practitioner carryingHBsAg. N Engl J Med 1975; 293: 197.
14. Sampliner RE. The duration of hepatitis B surface antigenemia. Arch InternMed 1978; 138: 145-46.
15. Alter HJ, Chalmers TC, Freeman BM, et al. Health-care workers positivefor hepatitis B surface antigen. N Engl J Med 1975; 292: 454-57.
16. Glenwright HD, Edmondson HD, Whitehead FIH, Flewett TH. Serumhepatitis in dental surgeons. Br Dent J 1974; 136: 409-13.
17. Medical Manpower Division, Department of Health and Social Security.Medical staffing and prospects in the NHS in England and Wales 1977.Health Trends 1978; 10: 61-64.
18. Health and Personal Social Services Statistics for England 1977. H.M. Sta-tionery Office, 1977.
19. Gunby P. Clinical trial of vaccine for type B hepatitis to begin next month.JAMA 1979; 241: 979-80.
THE INCIDENCE OF HEPATITIS B INFECTIONAFTER ACCIDENTAL EXPOSURE AND
ANTI-HBs IMMUNOGLOBULIN PROPHYLAXIS
A COMBINED MEDICAL RESEARCH COUNCIL* AND PUBLICHEALTH LABORATORY SERVICE† REPORT
Summary In a two-year period 322 persons whoreported accidental exposure to material
containing hepatitis B surface antigen (HBsAg) and whowere HBsAg negative, were given 500 mg anti-hepati-tis-B immunoglobulin (anti-HB Ig) within 14 days of theaccident. Afterwards serum samples were taken eachmonth for six months, with others after nine months anda year. Of the 240 who completed the follow-up 21 (9%)had pre-existing anti-HBs detectable by radioimmunoas-say. Acute hepatitis B developed in 7 individuals (3%)and 4 (2%) acquired anti-HBs without symptoms.
Introduction
IMMUNOGLOBULIN (anti-HB Ig) with high titres of anti-body (anti-HB,) to hepatitis B surface antigen (HBsAg)became available in England and Wales in 1973. Its useamong a small number (unpublished observations, Y. E.Cossart) and experience with a similar preparation inFrance’ suggested that it was protective.A follow-up study was made from September, 1973,
to September, 1976, of persons given anti-HB Ig withintwo weeks of accidental exposure to HBsAg positivematerial. It was not considered justifiable to include acontrol group.
Materials
Plasma was separated from blood donations collected by theNational Blood Transfusion Service. Donations found HBsAgnegative by counterimmunoelectrophoresis (CIE) and havingan anti-HBs titre of at least 2 were used by the Blood ProductsLaboratory to prepare anti-HB Ig. The preparation has beendescribed.2 The solution was issued in vials of 5 ml containing10 g percent total protein.The anti-HB titres of the five batches were similar (table I).
Methods
The following accidents were included: inoculation, con-tamination of the conjunctiva or of skin cuts or abrasions, in-gestion of (or massive contamination of apparently unbrokenskin with) HBAg-positive blood, laboratory reagents, or bodyfluids from HBsAg positive patients. 5 patients given HBsAgpositive transfusions or renal transplants were included.
After an accident was reported the inoculum was tested forHBsAg, and serum from the inoculated or contaminated per-
* MRC Hepatitis Working Party: Dr C. J. BURRELL, Dr Y. E. COS-SART, Mr I. D. HILL (secretary), Prof. D. N. S. KERR (chairman), SirWILLIAM MAYCOCK, Dr C. S. OGG, Dr S. POLAKOFF, Dr M. SMITH, DrR. S. WILLIAMS.
t PHLS Hepatitis Committee: Dr C. M. P. BRADSTREET, Dr S. K. R.CLARKE, Dr Y. E. COSSART (chairman), Dr J. CpASKE, Dr A. D.EVANS, Dr T. H. FLEWETT, Dr J. V. T. GOSTLING, Dr J. H. HALE, DrM. H. HAMBLING, Dr R. J. C. HART, Dr D. M. JoNES, Dr J. B. KURTZDr F. 0. MACCALLUM, Dr J. NAGINGTON, Dr S. POLAKOFF (secretary),Dr G. C. TURNER, Dr M. A. WILSON.
The study was co-ordinated and the report was prepared by DrSheila Polakoff, Epidemiological Research Laboratory, Central PublicHealth Laboratory, London NW9 5HT.
