Feasibility of routine testing for hepatitis B surface antigen in hospital employees and restriction of carriers W-D. LEERS,* MD, PH D, FRCP[C], DIP BACT; G.M. KouRouPis, D SC, M Sc; A. DONG,t MD
In 1972-73, 48 hospital staff members were tested selectively for hepatitis B surface antigen (HB5Ag); 4 (8.3./o) were found to be HB,Ag-positive. In 1974-75, 1415 staff members were tested routinely before employment and at periodic health examination; 25 (1.80/n) were found to be HB8Ag-positive. Of the HBAg-positive staff members SS.20/o were Asians, this proportion being significantly (P K 0.05) greater than that of any other ethnic group, and 31 .O0/o were southern Europeans. Nurses and laboratory technologists were the largest professional groups among the HB5Ag-positive staff, each accounting for 2O.70/o. Our results indicate that it is impractical to carry out routine testing of hospital staff for HB,Ag. Selective testing and restriction from work in their units is proposed for staff of the renal and peritoneal dialysis units, the emergency department and the intravenous team and dietary staff who handle food directly. En 1972-73, 48 employes d'h6pitaux ont subi un test selectif en vue de depister l'antigene de surface de Ihepatite de type B (HB,Ag); 4 (8.3./o) se sont averes positifs. En 1974-75, 1415 membres du personnel ont ete systematiquement testes avant l'emploi et lors dexamens de sante periodiques; 25 (1 .8Gb) se sont montres positifs. Des membres du personnel porteurs de lantigene HBAg 55.20/0 etaient asiatiques, ce rapport etant significativement plus eleve que celui de tout autre groupe ethnique, et 31.00/0 etaient originaires du sud de lEurope. Les infirmieres et techniciens de laboratoire constituaient les deux groupes professionnels les plus grands parmi le personnel porteur de lantigene HB,Ag, chacun representant
From the department of medical microbiology, faculty of medicine, University of Toronto and the department of microbiology, Wellesley Hospital, Toronto Presented at the 43rd annual meeting of the laboratory division of the Canadian Public Health Aesociation, Joint Meeting of Infectious Diseases, Toronto, Nov. 26 to 28, 1975 *Chief, department of microbiology, Wellesley Hospital; assistant professor, department of medical microbiology, University of Toronto tMedical director, employee health service, Wellesley Hospital Reprint requests to: Dr. W-D. Leers, Department of microbiology, Wellesley Hospital, 160 Wellesley St. E, Toronto, Ont. M4Y 1J3
20.70/0. Ces resultats indiquent qu'il nest pas pratique de tester systematiquement le personnel hospitalier pour Ia presence de I'antigene HB5Ag. On propose un depistage selectif et l'interdiction aux sujets positifs de travailler dans les unites de dialyse renale et peritoneale, le service d'urgence, lequipe de soins intraveineux et les services dietetiques charges de manipuler directement Ia nourriture.
Routine testing of health care personnel for hepatitis B surface antigen (HB1Ag) and restriction of HB.Ag carriers from work with patients are still controversial.lA In 1972 the committee on viral hepatitis of the US Department of Health, Education and Welfare recommended routine testing of all blood donors.5 No restrictions were recommended for any occupational group. Then reports of nonparenteral transmission of HB5Ag appeared. HB1Ag was found in saliva, urine and stool,6 in menstrual blood7 and in mosquitoes.8 Transmission of HB1Ag by human bite was reported.9 Close contact in families seems to play a role in transmitting hepatitis)0 The possibility of sexual transmission exists but is controversial.11'12 In 1974 the committee on viral hepatitis released another statement, which still did not recommend any restrictions on members of any occupational group if they were carriers of HB.Ag.13 In the meantime, laboratory tests for the detection of HB5Ag improved in both sensitivity and specificity and therefore were in reach of many laboratories.14"5 The danger of health care personnel acquiring hepatitis B from blood or direct contact with patients is now well established.16-18 However1 there are few reports of possible transmission of hepatitis B by health care staff to patients,4'19-21 and little was known about such transmission when we began in 1972 a prospective study to determine the feasibility of selective or routine testing of hospital staff for HB5Ag and possible restriction of employment of HB.Ag-positive staff within our hospital. Methods Selective testing At the beginning of the study in September 1972 we decided to test hospital
staff on a selective basis only. In cooperation with the hospital's employee health service we established the following guidelines: 1. Selected hospital staff members from the renal dialysis unit were tested for HB5Ag and serum glutamic oxaloacetic transaminase (SGOT) every 3 months. 2. All staff members with clinical or suspected hepatitis B were tested for HB5Ag, SGOT, serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase and followed up in the gastrointestinal clinic. 3. Staff members exposed to blood or secretions from patients or staff with clinical hepatitis B were tested immediately for HB.Ag and SGOT to establish baseline data and again after 2 months. These contacts were followed up in the employee health service if symptoms developed. 4. No restrictions were imposed on any HB5Ag carriers except renal dialysis staff and dietary staff handling food, who were not allowed to work in their departments. 5. Staff members with clinical hepatitis B were allowed to return to work after full clinical recovery. 6. HB.Ag-positive staff members were instructed as to proper personal hygiene and the possibility of infecting others. Routine testing
In January 1974 we decided to test hospital staff on a routine basis. One of our reasons was that radioimmunoassay tests had become available as convenient and very sensitive procedures for the assay of HB.Ag. The guidelines were changed as follows: 1. All staff members were tested for HB5Ag prior to employment and during periodic health examination. No liver function tests were ordered. The periodic health examination was done, depending on age and other possible clinical conditions, at the discretion of the medical director of the employee health service. Renal dialysis staff was tested every 3 months for HB.Ag and SGOT. 2. HB.Ag-positive staff members were followed up in the gastrointestinal clinic with clinical evaluation and liver function tests. 3. All HB.Ag-positive staff members
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
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were interviewed by the employee health service to assess the possible risk of transmission of HB5Ag to patients or other staff and were instructed to use proper personal hygiene. 4. No restrictions were imposed on any HB8Ag carriers except the renal dialysis staff members, who were not allowed to work in their unit, and dietary staff members handling food, who were employed in other areas in the dietary department where they were not handling food directly. 5. Staff members in close contact with patients with clinical hepatitis B were tested for SGOT and HB5Ag immediately and after 2 months only if exposure to a patient's blood or secretions occurred and transmission of HB.Ag was suspected. 6. Staff members with clinical hepatitis B were allowed to return to work after full clinical recovery. Laboratory investigation
We performed the complement fixation test for HB8Ag for the selected staff in 1972.73,14 and after January 1974 we used a modified Ausria radioimmunoassay test (Abbott Laboratories, North Chicago).22 The employee health service was responsible for the clinical examination, arrangement of tests and interviews of staff and contacts.
Results
Of the 48 staff members tested selectively in 1972-73, 4 (8.3%) were HB8Ag-positive, and of the 1415 staff members tested routinely in 1974-75, 25 (1.8%) were HB.Ag-positive. The 29 HB.Ag-positive staff members included 16 men and 13 women. The mean age was 35.8 years and the median, 35 years. Ten had abnormal results of liver function tests. Details for these people are given in Table I. The first four staff members listed were from the selected group. Two were nurses in whom clinical hepatitis developed in 1973. Follow-up was not possible because both left the hospital. The other two were technologists, one in biochemistry and the other in pathology; the latter took blood samples from patients. Both are still carriers. Of the other 25 staff members 24 were found to be HB5Ag-positive as a result of their pre-employment examination. No further details are available on three hecause they were not hired. Patient 14 was HB8Ag-negative at the time of her pre-employment examination in November 1974 and contracted clinical hepatitis B in February 1975. She is now HB8Ag-negative. Patient 23 has had chronic active hepatitis since 1969 and is a chronic carrier. Of the 29 HB8Ag-positive staff mem-
bers 16 (55.2%) came from Asia (fable II); this proportion was significantly higher (P < 0.05) than those of the other ethnic groups. Staff members from Asia or southern Europe accounted for 86.2% of the HB.Agpositive staff. Nine (31%) came from the Philippines (Table III). No significant difference was found between individual countries of origin, probably because of the small numbers. There was no significant difference between any of the occupational groups in numbers of HB5Ag-positive members (Table IV). Nurses and laboratory technologists each represented 20.7% of the total group. After evaluation of these results in October 1975 we established the following guidelines:
Table Il-Ethnic origin of 29 HB3Ag-positive staff No. (and %) of Region of HB8Ag-positive origin staff North America 2 (6.9) Northwestern Europe 1 (3.4) Eastern Europe 0 (0) Southern Europe 9 (31.0) Asia 16 (55.2)* West Indies 1 (3.4) Africa and Australia 0 (0) *Significantly larger (P < 0.05) than the other proportions.
Table I-Details of HB,Ag-positive staff Patient no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Age (yr) 24 29 36 26 22 48
Date hired 1967 1968 1972 1972 1974 1974 1974 1974 1974 1974 1974 1968 1968 1974 1975 1966 1975 1967 1969 1975 1971 1975 1970
Country or region Liver of origin )ccupation function* Remarkst Italy .h. (biochem.) Carrier n Canada Nu rse Hep., 1973 n Carrier Philippines Tei.h. (path.) n Canada Stiid. nurse Hep., 1973 Philippines DIEitary n Carrier Greece Ho usekeeping a Carrier Asia 31 Philippines Nu rse a Carrier Asia Greece 58 a Carrier Greece Ho usekeeping 42 Greece Ho' usekeeping n Carrier Philippines Te .h. (biochem.) 35 n Carrier 29 Hong Kong Nu rse a Hep., 1975 30 Carrier Philippines Nu rse n 49 Carrier Germany CIE.rk n 21 Philippines Ho usekeeping a Carrier 38 Italy Ma intenance n Carrier 36 Greece Ho usekeeping a Carrier 26 Carrier Hong Kong Nu rse a 29 Philippines Te ch. (radiol.) a Carrier 32 Philippines Tei.h. (biochem.) n Carrier 35 Korea Ph armacist a Chr. act. hep. since 1969 24 40 Korea Ma intenance n Carrier 25 China Teich. (radiol.) 35 n Carrier 26 65 Italy DiE.tary a Carrier 27 44 Portugal Ho sp. asst. n Carrier 28 33 Carrier Trinidad DiEitary 29 39 Philippines Ho sp. asst. n Carrier *Results of tests were normal (n) or abnormal (a). tHep. = hepatitis B. - = no information available. Sex F F F M M M M M F M M M M F F F F M F F M F M
996 CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
Table Ill-Country of origin of 29 HB8Ag-positive staff
Country of origin Canada Germany Greece Italy Portugal Philippines Korea China Other Asian West Indies
No. (and %) of HB.Ag-pesitlve staff 2 (6.9) 1 (3.4) 5 (17.2) 3 (10.3) 1 (3.4) 9 (31.0) 2 (6.9) 3 (10.3) 2 (6.9) 1 (3.4)
Table IV-Occupation of 29 HB.Ag-positive staff Occupation Nurse Lab. technologist Housekeeping Dietary Maintenance Hospital assistant Clerk Pharmacist Not known
No. (and %) of HB.Ag-positive staff 6 (20.7) 6 (20.7) 5 (17.2) 3 (10.3) 2 (6.9) 2 (6.9) 1 (3.4) 1 (3.4) 3 (10.3)
1. Routine testing of hospital staff for HB.Ag was discontinued. 2. Selective testing was continued for the following groups: (a) Renal and peritoneal dialysis staff, intravenous (IV) team and emergency nurses before employment and every 3 months. (b) Dietary staff directly handling food before employment and at the periodic health examination. (c) Any staff having close contact with patients with hepatitis B, but only if exposure to a patient's blood or secretions has occurred and transmission of HB5Ag is suspected. 3. Restrictions of employment for HB8Ag-positive individuals were as follows: (a) Renal and peritoneal dialysis staff, IV team and emergency nurses should not be allowed to work in their units. (b) Staff members directly handling food should be transferred to other areas within the department. 4. All HB.Ag carriers should be informed about their carrier state and the danger of infecting others and instructed to use proper personal hygiene. The guidelines were based on the following facts: (a) in no instance of clinical hepatitis B developing in a staff member could transmission be traced back to any of our HB.Ag-positive staff members, either a carrier or an individual with clinical hepatitis B; (b) no staff member became HB5Agpositive because of exposure to a staff member with HB8Ag, either a carrier or an individual with clinical hepatitis B; and (c) no patients known to us contracted hepatitis B that could be traced to HB8Ag-positive staff, either a carrier or an individual with clinical hepatitis B; however, patients who had been in contact with those staff members were not followed up. Discussion
The high proportion (55.2%) of Asians among the HB,Ag-positive staff members is not surprising since Asians are known to have a high prevalence of hepatitis B surface antibodies (antiHBS).'3 However, it is striking when one considers that the ethnic distribution of our entire staff was as follows: North American, 51.5%; northwestern European, 17.7%; eastern European, 2.5%; southern European, 5.7%; Asian, 13.5%; West Indian, 7.4%; and African, 1.1% . Southern Europeans were the second largest HB8Ag-positive ethnic group, after Asians, among patients tested routinely before admission to another Toronto hospital.24 The proportion of southern Europeans in our HB5Ag-
positive staff (31.0%) was also second largest. Nurses and technologists each accounted for the highest proportion of HB8Ag-positive staff members, 20.7%. This supports the finding that nurses and technologists exposed to patients and specimens were at greater risk of contracting hepatitis B than other staff members, although the difference was not significant.16 However, housekeeping and dietary staff, who are not exposed to blood or specimens and only occasionally to patients, accounted for relatively large proportions of HB,Ag-positive staff members - 17.2 and 10.3%, respectively. This could be explained by the fact that these groups come largely from a lower socioeconomic class, which is known to have a high prevalence of anti-HB8.23'. In addition, four of the five HB.Ag-positive housekeeping staff members were from Greece, where the prevalence of HB.Ag is high.26 Therefore ethnic background seems to be an additional factor. There are few reports of staff-topatient transmission of hepatitis B.4 Dentists have been reported to have transmitted HB8Ag to their patients, causing clinical hepatitis B.20'21 Also, clinical hepatitis B developed in 11 patients who had previously been cared for in hospital by a nurse who was in the late incubation period of hepatitis B.19 Alter and colleagues2 recently reviewed the problem of HB.Ag-positive health care workers as a possible hazard to patients. They concluded that no restriction of employment of such persons was warranted because sufficient convincing data were not yet available. However, others disagree.3 Restriction of our dietary staff from direct food handling may seem overcautious since HB5Ag-contaminated food has so far not been implicated in transmission of hepatitis B.27 But there are still many questions unanswered. The selective testing of dietary staff was decided upon because a high percentage of them come from a lower socioeconomic class, which has a high prevalence of HB.Ag.22 We did not have to restrict any nurse from working in any of the high-risk units because none was found to be HB.Ag-positive. However, we do advise that an HB.Ag carrier not work closely with severely ill patients or those receiving immunosuppressive therapy. The selective testing of staff in high-risk areas would allow us to detect early the occurrence of HB.Ag in a staff member. This staff member could immediately be removed from the unit and would therefore not be a risk to staff or other patients. However, there is no
clear evidence that staff HB8Ag carriers are a source of hepatitis B outbreaks in dialysis units.17 Any HB5Ag carrier should be interviewed before a decision regarding restrictions is made. Obviously no staff member with acute hepatitis B should work in a hospital in any area. The question of routine testing for HB8Ag in physicians, especially urologists, nephrologists and surgeons, is difficult. It is desirable that physicians know if they are HB8Ag carriers, especially if there is evidence of previous infection with HB5Ag from clinical disease or accidental exposure. However, routine screening of physicians would be impractical and expensive. Also, the medical staff is not under the jurisdiction of the employee health service in our hospital. A physician or surgeon should be aware of the implications of being an HB5Ag carrier and the possible risk of transmitting this antigen to patients. Although he would be expected to take the necessary precautions, we do not advise restricting a carrier from practising. Routine laboratory testing of any group for any reason is expensive. Any routine or selective testing requires that some tentative guidelines be established beforehand as to the measures to be taken. Any restriction for staff members should be made only after careful consideration. The question of routine testing for anti-HR8 is being studied. If anti-HB, proves protective it may be feasible in the future to employ in high-risk areas mainly staff with anti-HB,, who would be at lesser risk of contracting hepatitis B from patients. We are aware that our guidelines are conservative. However, before more conclusive evidence is presented it is imperative to protect patients and staff from contracting hepatitis B. The guidelines are meant to be flexible and will be changed in the future as necessary. We are indebted to the technical staff of the virus unit of the department of microbiology. We sincerely thank Mr. M.A. Malkani for statistical analysis of the results and Miss Elizabeth Nimmo for preparation of the manuscript. We also thank Mrs. Karen Hume, PHN for her help in obtaining information and coordination of blood samples. References 1. CHALMERS TC, ALTER HJ: Management of the asymptomatic carrier of the hepatitisassociated (Australia) antigen. N Engi .! Med 285: 613, 1971 2. ALTER HJ, CHALMERS TC, FREEMAN BM. et al: Health-care workers positive for hepatitis B surface antigen. Are their contacts at risk? N Engi I Med 292: 454, 1975 3. GOODINO MK: Risk to contacts of HB5Ag carriers. Ibid. p 1079 4. REDEKER AG: Hepatitis B. Risk of infection from antigen-positive medical personnel and patients. JAMA 233: 1061, 1975 5. Committee on viral hepatitis, division of medical services, US Department of Health,
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115 997
6. 7. 8. 9.
Education and Welfare: Public health implications of the presence of hepatitis B antigen in human serum. Morbid Mortal Wkly Rep 21: no 16, 1972 IRwIN GR, ALLEN AM, BANCROFT WH, et al: Hepatitis B antigen in saliva, urine and stool. Inject Immun 11: 142, 1975 MAZZUR S: Menstrual blood as a vehicle of Australia-antigen transmission. Lancet 1: 749, 1973 DIcK SJ, TAMBURRO CH, LEEvY CM: Hepatitis B antigen in urban-caught mosquitoes. JAMA 229: 1627, 1975 MACQUARRIE MB, FOROHANI B, WOLOCHOW DA: Hepatitis B transmitted by a human bite. JAMA 230: 723, 1974
10. SzMUNEss W, PRICE AM, HIRsCH RL, et al:
Familial clustering of hepatitis B infection. N Engi J Med 289: 1162, 1973 II. ADAM E, HOLLINGER FB, MELNICK JL, et al: Type B hepatitis antigen and antibody among prostitutes and nuns: a study of possible venereal transmission. I Inject Dis 129: 317, 1974 12. FAss RJ: Sexual transmission of viral hepatitis? JAMA 230: 861, 1974 13. Committee on viral hepatitis, division of medical sciences, US Department of Health,
14.
15. 16. 17.
Education and Welfare: Public health implications of hepatitis B antigen in human blood. Revised statement. Morbid Mortal Wkly Rep 23: no 14, 1974 KoURoUPIs GM, LEERS W-D: Radioimmunoassay, complement fixation and counterimmunoelectrophoresis in the laboratory diagnosis of hepatitis B. Arch Gesamte Virusjorsch 43: 112, 1973 LEERS W-D, KouRouPIs GM: Comparison of the reversed passive haemagglutination with radioimmunoassay methods for hepatitis B antigen. J Clin Microbiol 2: 8, 1975 Idem: Prevalence of hepatitis B antibodies in hospital personnel. Can Med Assoc 1 113: 844, 1975 POLAKOFF S: Decrease of the incidence of
hepatitis in dialysis units associated with prevention program. Br Med 1 4: 751, 1974 18. WANDS JR, WALKER JA, DAVIS TT, et al: Hepatitis in an oncology unit. N Engi I Med
26: 1371, 1974 et al: Hospital-acquired serum hepatitis. JAMA 219: 1577, 1972 20. RIMLAND D, PARKIN WE: An outbreak of hepatitia B traced to an oral surgeon. Gastroenterology 67: 822, 1974 19. GARIsALDI RA, RASMUS5EN CM, HOLMES AW,
21. LEVIN ML, MADDREY WC, WANDS JR: Hepa-
titis B transmission by dentists. JAMA 228: 1139, 1974 22. KouRoupis GM, LEERS W-D: A rapid radioimmunoassay method for the detection of
hepatitis B antigen. Arch Gesamte Viruslorsch
44: 370, 1974 23. Idem: Prevalence of anti-hepatitis B. antigen
in hospital staff with respect to ethnic origin. Presented at 43rd annual meeting of the laboratory division, Canadian Public Health Association, Joint Meeting of Infectious Diseases, Toronto, Nov. 26-28, 1975
24. FEINMAN SV, KRAS5NITZKY 0, SINCLAIR JC, et al: Prevalence and significance of hepatitis B surface antigen in a general hospital. Can
Med Assoc / 112: 43, 1975 al: Acquisition of antibody to hepatitis B antigen in three socioeconomically different medical populations. Lancet 2: 149, 1972
25. CHERUBIN CE, PURCELL RH, LANDER JJ, et
26. HADZIYANNI5 5, MERIKAS G, PANETSOS 5: Hepatitis associated antigen carriers among
blood donors in Greece. Am J Dis Child 123: 381, 1972 27. PLOTZ PH, ALTER HI, HOLLAND PV: Exposure to a food-handler with hepatitis B (C). Lancet 2: 333, 1972
Detection of core antibody in hepatitis B infection L. SPENCE, FRCP[C]; M. FAUVEL, M Sc
Hepatitis B core antigen (HB.Ag) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HB.Ag prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HB.) by complement fixation. Anti-HB. was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HB,Ag) and from patients with chronic liver or renal disease who were carriers of HB,Ag: It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HB5Ag. La nucleocapside du virus de l'hepatite de type B (HB.Ag) est retrouve sur Ia particule Dane debarrassee de sa game et sur une particule morphologiquement semblable decelee principalement dans le noyau des hepatocytes des patients souffrant d'hepatite de type B. L'HB.Ag prepare a partir du foie d'un chimpanze infect6 avec le virus de l'hepatite de type B a et6 utilis6 afin de d.tecter Ia pr6sence de I'anticorps dirig6 contre I'HB.Ag (anti-HB.) dans le serum humain par fixation du compl6ment. L'anti-HB. a .te retrouve dans les s6rums preleves chez des patients atteints de I'h6patite de type B, From the department of medical microbiology, faculty of medicine, University of Toronto and the department of microbiology, Toronto General Hospital Reprint requests to: Dr. L. Spence, Department of medical microbiology, Banting Institute, 100 College St., Toronto, Ont. M5G 1L5
998
aussi bien durant Ia phase aigue que durant Ia convalescence, chez des porteurs de l'antigene de surface de l'hepatite de type B (HB,Ag) et chez des patients souffrant de maladies hepatiques ou r6nales chroniques et porteurs de l'HBAg. L'anti-HB. n'a pas ete decel6 chez des patients souffrant d'hepatite A ou de mononucleose infectieuse, ou chez des personnes saines qui n'etaient pas porteurs de l'HBAg.
In 1970 Dane, Cameron and Briggs1 described in the blood of hepatitis B patients a particle 42 nm in diameter with a complex structure. By negative staining and examination under the electron microscope it was found to have an outer coat 7 nm in thickness surrounding an inner core 28 nm in diameter. The particle shared an antigen, hepatitis B surface antigen (HB.Ag), with the small spherical and tubular particles previously described in association with Australia antigen.1'2 In 1971 Almeida, Rubenstein and Stott3 reported that treatment of the Dane particle with a detergent, polysorbate (Tween) 80, disrupted the particle and released an internal component (the core), 27 nm in diameter, that resembled a particle Almeida and colleagues4 had found previously in homogenates of liver prepared from two patients who had died from hepatitis. Immune electron microscopy (IEM) showed that the internal component reacted with posthepatitis but not prehepatitis serum and that this represented a new antigen-antibody reaction in hepatitis B infection. Similar results were reported by Deutsch and Spence5 in 1972. In this paper we report the results
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
of further studies with hepatitis B core antigen (HB.Ag) on serum of patients with hepatitis B. Patients and methods Patients The patients in the study, all adults, included the following: (a) healthy women admitted to the maternity ward for delivery and found to be HB5Agnegative by routine screening (not matched for age and sex with the other patients); (b) healthy carriers of HB8Ag, including Red Cross blood donors and healthy maternity patients found to be HB8Ag-positive by routine screening; (c) patients with hepatitis B; (d) HB8Agpositive patients with chronic liver or renal disease; (e) patients with hepatitis A, diagnosed from clinical and epidemiologic history, physical examination and biochemical and virologic tests; and (f) patients with infectious mononucleosis. Serum collection Serum was collected from the patients admitted to or visiting a general hospital for the investigation and treatment of acute hepatitis B and again after* HB.Ag was no longer detectable in the blood. Usually the first HB9Agnegative sample obtained was tested for antibodies to HB8Ag (anti-HB.) and to HB.Ag (anti-HB.). Serum was also collected from all other categories of patients. Preparation of HB.Ag The HB.Ag used in these studies was prepared from the liver of a chimpanzee infected with hepatitis B virus at Connaught Laboratories, Toronto.6
In 1972-73, 48 hospital staff members were tested selectively for hepatitis B surface antigen (HB5Ag); 4 (8.3./o) were found to be HB,Ag-positive. In 1974-75, 1415 staff members were tested routinely before employment and at periodic health examination; 25 (1.80/n) were found to be HB8Ag-positive. Of the HBAg-positive staff members SS.20/o were Asians, this proportion being significantly (P K 0.05) greater than that of any other ethnic group, and 31 .O0/o were southern Europeans. Nurses and laboratory technologists were the largest professional groups among the HB5Ag-positive staff, each accounting for 2O.70/o. Our results indicate that it is impractical to carry out routine testing of hospital staff for HB,Ag. Selective testing and restriction from work in their units is proposed for staff of the renal and peritoneal dialysis units, the emergency department and the intravenous team and dietary staff who handle food directly. En 1972-73, 48 employes d'h6pitaux ont subi un test selectif en vue de depister l'antigene de surface de Ihepatite de type B (HB,Ag); 4 (8.3./o) se sont averes positifs. En 1974-75, 1415 membres du personnel ont ete systematiquement testes avant l'emploi et lors dexamens de sante periodiques; 25 (1 .8Gb) se sont montres positifs. Des membres du personnel porteurs de lantigene HBAg 55.20/0 etaient asiatiques, ce rapport etant significativement plus eleve que celui de tout autre groupe ethnique, et 31.00/0 etaient originaires du sud de lEurope. Les infirmieres et techniciens de laboratoire constituaient les deux groupes professionnels les plus grands parmi le personnel porteur de lantigene HB,Ag, chacun representant
From the department of medical microbiology, faculty of medicine, University of Toronto and the department of microbiology, Wellesley Hospital, Toronto Presented at the 43rd annual meeting of the laboratory division of the Canadian Public Health Aesociation, Joint Meeting of Infectious Diseases, Toronto, Nov. 26 to 28, 1975 *Chief, department of microbiology, Wellesley Hospital; assistant professor, department of medical microbiology, University of Toronto tMedical director, employee health service, Wellesley Hospital Reprint requests to: Dr. W-D. Leers, Department of microbiology, Wellesley Hospital, 160 Wellesley St. E, Toronto, Ont. M4Y 1J3
20.70/0. Ces resultats indiquent qu'il nest pas pratique de tester systematiquement le personnel hospitalier pour Ia presence de I'antigene HB5Ag. On propose un depistage selectif et l'interdiction aux sujets positifs de travailler dans les unites de dialyse renale et peritoneale, le service d'urgence, lequipe de soins intraveineux et les services dietetiques charges de manipuler directement Ia nourriture.
Routine testing of health care personnel for hepatitis B surface antigen (HB1Ag) and restriction of HB.Ag carriers from work with patients are still controversial.lA In 1972 the committee on viral hepatitis of the US Department of Health, Education and Welfare recommended routine testing of all blood donors.5 No restrictions were recommended for any occupational group. Then reports of nonparenteral transmission of HB5Ag appeared. HB1Ag was found in saliva, urine and stool,6 in menstrual blood7 and in mosquitoes.8 Transmission of HB1Ag by human bite was reported.9 Close contact in families seems to play a role in transmitting hepatitis)0 The possibility of sexual transmission exists but is controversial.11'12 In 1974 the committee on viral hepatitis released another statement, which still did not recommend any restrictions on members of any occupational group if they were carriers of HB.Ag.13 In the meantime, laboratory tests for the detection of HB5Ag improved in both sensitivity and specificity and therefore were in reach of many laboratories.14"5 The danger of health care personnel acquiring hepatitis B from blood or direct contact with patients is now well established.16-18 However1 there are few reports of possible transmission of hepatitis B by health care staff to patients,4'19-21 and little was known about such transmission when we began in 1972 a prospective study to determine the feasibility of selective or routine testing of hospital staff for HB5Ag and possible restriction of employment of HB.Ag-positive staff within our hospital. Methods Selective testing At the beginning of the study in September 1972 we decided to test hospital
staff on a selective basis only. In cooperation with the hospital's employee health service we established the following guidelines: 1. Selected hospital staff members from the renal dialysis unit were tested for HB5Ag and serum glutamic oxaloacetic transaminase (SGOT) every 3 months. 2. All staff members with clinical or suspected hepatitis B were tested for HB5Ag, SGOT, serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase and followed up in the gastrointestinal clinic. 3. Staff members exposed to blood or secretions from patients or staff with clinical hepatitis B were tested immediately for HB.Ag and SGOT to establish baseline data and again after 2 months. These contacts were followed up in the employee health service if symptoms developed. 4. No restrictions were imposed on any HB5Ag carriers except renal dialysis staff and dietary staff handling food, who were not allowed to work in their departments. 5. Staff members with clinical hepatitis B were allowed to return to work after full clinical recovery. 6. HB.Ag-positive staff members were instructed as to proper personal hygiene and the possibility of infecting others. Routine testing
In January 1974 we decided to test hospital staff on a routine basis. One of our reasons was that radioimmunoassay tests had become available as convenient and very sensitive procedures for the assay of HB.Ag. The guidelines were changed as follows: 1. All staff members were tested for HB5Ag prior to employment and during periodic health examination. No liver function tests were ordered. The periodic health examination was done, depending on age and other possible clinical conditions, at the discretion of the medical director of the employee health service. Renal dialysis staff was tested every 3 months for HB.Ag and SGOT. 2. HB.Ag-positive staff members were followed up in the gastrointestinal clinic with clinical evaluation and liver function tests. 3. All HB.Ag-positive staff members
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
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were interviewed by the employee health service to assess the possible risk of transmission of HB5Ag to patients or other staff and were instructed to use proper personal hygiene. 4. No restrictions were imposed on any HB8Ag carriers except the renal dialysis staff members, who were not allowed to work in their unit, and dietary staff members handling food, who were employed in other areas in the dietary department where they were not handling food directly. 5. Staff members in close contact with patients with clinical hepatitis B were tested for SGOT and HB5Ag immediately and after 2 months only if exposure to a patient's blood or secretions occurred and transmission of HB.Ag was suspected. 6. Staff members with clinical hepatitis B were allowed to return to work after full clinical recovery. Laboratory investigation
We performed the complement fixation test for HB8Ag for the selected staff in 1972.73,14 and after January 1974 we used a modified Ausria radioimmunoassay test (Abbott Laboratories, North Chicago).22 The employee health service was responsible for the clinical examination, arrangement of tests and interviews of staff and contacts.
Results
Of the 48 staff members tested selectively in 1972-73, 4 (8.3%) were HB8Ag-positive, and of the 1415 staff members tested routinely in 1974-75, 25 (1.8%) were HB.Ag-positive. The 29 HB.Ag-positive staff members included 16 men and 13 women. The mean age was 35.8 years and the median, 35 years. Ten had abnormal results of liver function tests. Details for these people are given in Table I. The first four staff members listed were from the selected group. Two were nurses in whom clinical hepatitis developed in 1973. Follow-up was not possible because both left the hospital. The other two were technologists, one in biochemistry and the other in pathology; the latter took blood samples from patients. Both are still carriers. Of the other 25 staff members 24 were found to be HB5Ag-positive as a result of their pre-employment examination. No further details are available on three hecause they were not hired. Patient 14 was HB8Ag-negative at the time of her pre-employment examination in November 1974 and contracted clinical hepatitis B in February 1975. She is now HB8Ag-negative. Patient 23 has had chronic active hepatitis since 1969 and is a chronic carrier. Of the 29 HB8Ag-positive staff mem-
bers 16 (55.2%) came from Asia (fable II); this proportion was significantly higher (P < 0.05) than those of the other ethnic groups. Staff members from Asia or southern Europe accounted for 86.2% of the HB.Agpositive staff. Nine (31%) came from the Philippines (Table III). No significant difference was found between individual countries of origin, probably because of the small numbers. There was no significant difference between any of the occupational groups in numbers of HB5Ag-positive members (Table IV). Nurses and laboratory technologists each represented 20.7% of the total group. After evaluation of these results in October 1975 we established the following guidelines:
Table Il-Ethnic origin of 29 HB3Ag-positive staff No. (and %) of Region of HB8Ag-positive origin staff North America 2 (6.9) Northwestern Europe 1 (3.4) Eastern Europe 0 (0) Southern Europe 9 (31.0) Asia 16 (55.2)* West Indies 1 (3.4) Africa and Australia 0 (0) *Significantly larger (P < 0.05) than the other proportions.
Table I-Details of HB,Ag-positive staff Patient no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Age (yr) 24 29 36 26 22 48
Date hired 1967 1968 1972 1972 1974 1974 1974 1974 1974 1974 1974 1968 1968 1974 1975 1966 1975 1967 1969 1975 1971 1975 1970
Country or region Liver of origin )ccupation function* Remarkst Italy .h. (biochem.) Carrier n Canada Nu rse Hep., 1973 n Carrier Philippines Tei.h. (path.) n Canada Stiid. nurse Hep., 1973 Philippines DIEitary n Carrier Greece Ho usekeeping a Carrier Asia 31 Philippines Nu rse a Carrier Asia Greece 58 a Carrier Greece Ho usekeeping 42 Greece Ho' usekeeping n Carrier Philippines Te .h. (biochem.) 35 n Carrier 29 Hong Kong Nu rse a Hep., 1975 30 Carrier Philippines Nu rse n 49 Carrier Germany CIE.rk n 21 Philippines Ho usekeeping a Carrier 38 Italy Ma intenance n Carrier 36 Greece Ho usekeeping a Carrier 26 Carrier Hong Kong Nu rse a 29 Philippines Te ch. (radiol.) a Carrier 32 Philippines Tei.h. (biochem.) n Carrier 35 Korea Ph armacist a Chr. act. hep. since 1969 24 40 Korea Ma intenance n Carrier 25 China Teich. (radiol.) 35 n Carrier 26 65 Italy DiE.tary a Carrier 27 44 Portugal Ho sp. asst. n Carrier 28 33 Carrier Trinidad DiEitary 29 39 Philippines Ho sp. asst. n Carrier *Results of tests were normal (n) or abnormal (a). tHep. = hepatitis B. - = no information available. Sex F F F M M M M M F M M M M F F F F M F F M F M
996 CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
Table Ill-Country of origin of 29 HB8Ag-positive staff
Country of origin Canada Germany Greece Italy Portugal Philippines Korea China Other Asian West Indies
No. (and %) of HB.Ag-pesitlve staff 2 (6.9) 1 (3.4) 5 (17.2) 3 (10.3) 1 (3.4) 9 (31.0) 2 (6.9) 3 (10.3) 2 (6.9) 1 (3.4)
Table IV-Occupation of 29 HB.Ag-positive staff Occupation Nurse Lab. technologist Housekeeping Dietary Maintenance Hospital assistant Clerk Pharmacist Not known
No. (and %) of HB.Ag-positive staff 6 (20.7) 6 (20.7) 5 (17.2) 3 (10.3) 2 (6.9) 2 (6.9) 1 (3.4) 1 (3.4) 3 (10.3)
1. Routine testing of hospital staff for HB.Ag was discontinued. 2. Selective testing was continued for the following groups: (a) Renal and peritoneal dialysis staff, intravenous (IV) team and emergency nurses before employment and every 3 months. (b) Dietary staff directly handling food before employment and at the periodic health examination. (c) Any staff having close contact with patients with hepatitis B, but only if exposure to a patient's blood or secretions has occurred and transmission of HB5Ag is suspected. 3. Restrictions of employment for HB8Ag-positive individuals were as follows: (a) Renal and peritoneal dialysis staff, IV team and emergency nurses should not be allowed to work in their units. (b) Staff members directly handling food should be transferred to other areas within the department. 4. All HB.Ag carriers should be informed about their carrier state and the danger of infecting others and instructed to use proper personal hygiene. The guidelines were based on the following facts: (a) in no instance of clinical hepatitis B developing in a staff member could transmission be traced back to any of our HB.Ag-positive staff members, either a carrier or an individual with clinical hepatitis B; (b) no staff member became HB5Agpositive because of exposure to a staff member with HB8Ag, either a carrier or an individual with clinical hepatitis B; and (c) no patients known to us contracted hepatitis B that could be traced to HB8Ag-positive staff, either a carrier or an individual with clinical hepatitis B; however, patients who had been in contact with those staff members were not followed up. Discussion
The high proportion (55.2%) of Asians among the HB,Ag-positive staff members is not surprising since Asians are known to have a high prevalence of hepatitis B surface antibodies (antiHBS).'3 However, it is striking when one considers that the ethnic distribution of our entire staff was as follows: North American, 51.5%; northwestern European, 17.7%; eastern European, 2.5%; southern European, 5.7%; Asian, 13.5%; West Indian, 7.4%; and African, 1.1% . Southern Europeans were the second largest HB8Ag-positive ethnic group, after Asians, among patients tested routinely before admission to another Toronto hospital.24 The proportion of southern Europeans in our HB5Ag-
positive staff (31.0%) was also second largest. Nurses and technologists each accounted for the highest proportion of HB8Ag-positive staff members, 20.7%. This supports the finding that nurses and technologists exposed to patients and specimens were at greater risk of contracting hepatitis B than other staff members, although the difference was not significant.16 However, housekeeping and dietary staff, who are not exposed to blood or specimens and only occasionally to patients, accounted for relatively large proportions of HB,Ag-positive staff members - 17.2 and 10.3%, respectively. This could be explained by the fact that these groups come largely from a lower socioeconomic class, which is known to have a high prevalence of anti-HB8.23'. In addition, four of the five HB.Ag-positive housekeeping staff members were from Greece, where the prevalence of HB.Ag is high.26 Therefore ethnic background seems to be an additional factor. There are few reports of staff-topatient transmission of hepatitis B.4 Dentists have been reported to have transmitted HB8Ag to their patients, causing clinical hepatitis B.20'21 Also, clinical hepatitis B developed in 11 patients who had previously been cared for in hospital by a nurse who was in the late incubation period of hepatitis B.19 Alter and colleagues2 recently reviewed the problem of HB.Ag-positive health care workers as a possible hazard to patients. They concluded that no restriction of employment of such persons was warranted because sufficient convincing data were not yet available. However, others disagree.3 Restriction of our dietary staff from direct food handling may seem overcautious since HB5Ag-contaminated food has so far not been implicated in transmission of hepatitis B.27 But there are still many questions unanswered. The selective testing of dietary staff was decided upon because a high percentage of them come from a lower socioeconomic class, which has a high prevalence of HB.Ag.22 We did not have to restrict any nurse from working in any of the high-risk units because none was found to be HB.Ag-positive. However, we do advise that an HB.Ag carrier not work closely with severely ill patients or those receiving immunosuppressive therapy. The selective testing of staff in high-risk areas would allow us to detect early the occurrence of HB.Ag in a staff member. This staff member could immediately be removed from the unit and would therefore not be a risk to staff or other patients. However, there is no
clear evidence that staff HB8Ag carriers are a source of hepatitis B outbreaks in dialysis units.17 Any HB5Ag carrier should be interviewed before a decision regarding restrictions is made. Obviously no staff member with acute hepatitis B should work in a hospital in any area. The question of routine testing for HB8Ag in physicians, especially urologists, nephrologists and surgeons, is difficult. It is desirable that physicians know if they are HB8Ag carriers, especially if there is evidence of previous infection with HB5Ag from clinical disease or accidental exposure. However, routine screening of physicians would be impractical and expensive. Also, the medical staff is not under the jurisdiction of the employee health service in our hospital. A physician or surgeon should be aware of the implications of being an HB5Ag carrier and the possible risk of transmitting this antigen to patients. Although he would be expected to take the necessary precautions, we do not advise restricting a carrier from practising. Routine laboratory testing of any group for any reason is expensive. Any routine or selective testing requires that some tentative guidelines be established beforehand as to the measures to be taken. Any restriction for staff members should be made only after careful consideration. The question of routine testing for anti-HR8 is being studied. If anti-HB, proves protective it may be feasible in the future to employ in high-risk areas mainly staff with anti-HB,, who would be at lesser risk of contracting hepatitis B from patients. We are aware that our guidelines are conservative. However, before more conclusive evidence is presented it is imperative to protect patients and staff from contracting hepatitis B. The guidelines are meant to be flexible and will be changed in the future as necessary. We are indebted to the technical staff of the virus unit of the department of microbiology. We sincerely thank Mr. M.A. Malkani for statistical analysis of the results and Miss Elizabeth Nimmo for preparation of the manuscript. We also thank Mrs. Karen Hume, PHN for her help in obtaining information and coordination of blood samples. References 1. CHALMERS TC, ALTER HJ: Management of the asymptomatic carrier of the hepatitisassociated (Australia) antigen. N Engi .! Med 285: 613, 1971 2. ALTER HJ, CHALMERS TC, FREEMAN BM. et al: Health-care workers positive for hepatitis B surface antigen. Are their contacts at risk? N Engi I Med 292: 454, 1975 3. GOODINO MK: Risk to contacts of HB5Ag carriers. Ibid. p 1079 4. REDEKER AG: Hepatitis B. Risk of infection from antigen-positive medical personnel and patients. JAMA 233: 1061, 1975 5. Committee on viral hepatitis, division of medical services, US Department of Health,
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6. 7. 8. 9.
Education and Welfare: Public health implications of the presence of hepatitis B antigen in human serum. Morbid Mortal Wkly Rep 21: no 16, 1972 IRwIN GR, ALLEN AM, BANCROFT WH, et al: Hepatitis B antigen in saliva, urine and stool. Inject Immun 11: 142, 1975 MAZZUR S: Menstrual blood as a vehicle of Australia-antigen transmission. Lancet 1: 749, 1973 DIcK SJ, TAMBURRO CH, LEEvY CM: Hepatitis B antigen in urban-caught mosquitoes. JAMA 229: 1627, 1975 MACQUARRIE MB, FOROHANI B, WOLOCHOW DA: Hepatitis B transmitted by a human bite. JAMA 230: 723, 1974
10. SzMUNEss W, PRICE AM, HIRsCH RL, et al:
Familial clustering of hepatitis B infection. N Engi J Med 289: 1162, 1973 II. ADAM E, HOLLINGER FB, MELNICK JL, et al: Type B hepatitis antigen and antibody among prostitutes and nuns: a study of possible venereal transmission. I Inject Dis 129: 317, 1974 12. FAss RJ: Sexual transmission of viral hepatitis? JAMA 230: 861, 1974 13. Committee on viral hepatitis, division of medical sciences, US Department of Health,
14.
15. 16. 17.
Education and Welfare: Public health implications of hepatitis B antigen in human blood. Revised statement. Morbid Mortal Wkly Rep 23: no 14, 1974 KoURoUPIs GM, LEERS W-D: Radioimmunoassay, complement fixation and counterimmunoelectrophoresis in the laboratory diagnosis of hepatitis B. Arch Gesamte Virusjorsch 43: 112, 1973 LEERS W-D, KouRouPIs GM: Comparison of the reversed passive haemagglutination with radioimmunoassay methods for hepatitis B antigen. J Clin Microbiol 2: 8, 1975 Idem: Prevalence of hepatitis B antibodies in hospital personnel. Can Med Assoc 1 113: 844, 1975 POLAKOFF S: Decrease of the incidence of
hepatitis in dialysis units associated with prevention program. Br Med 1 4: 751, 1974 18. WANDS JR, WALKER JA, DAVIS TT, et al: Hepatitis in an oncology unit. N Engi I Med
26: 1371, 1974 et al: Hospital-acquired serum hepatitis. JAMA 219: 1577, 1972 20. RIMLAND D, PARKIN WE: An outbreak of hepatitia B traced to an oral surgeon. Gastroenterology 67: 822, 1974 19. GARIsALDI RA, RASMUS5EN CM, HOLMES AW,
21. LEVIN ML, MADDREY WC, WANDS JR: Hepa-
titis B transmission by dentists. JAMA 228: 1139, 1974 22. KouRoupis GM, LEERS W-D: A rapid radioimmunoassay method for the detection of
hepatitis B antigen. Arch Gesamte Viruslorsch
44: 370, 1974 23. Idem: Prevalence of anti-hepatitis B. antigen
in hospital staff with respect to ethnic origin. Presented at 43rd annual meeting of the laboratory division, Canadian Public Health Association, Joint Meeting of Infectious Diseases, Toronto, Nov. 26-28, 1975
24. FEINMAN SV, KRAS5NITZKY 0, SINCLAIR JC, et al: Prevalence and significance of hepatitis B surface antigen in a general hospital. Can
Med Assoc / 112: 43, 1975 al: Acquisition of antibody to hepatitis B antigen in three socioeconomically different medical populations. Lancet 2: 149, 1972
25. CHERUBIN CE, PURCELL RH, LANDER JJ, et
26. HADZIYANNI5 5, MERIKAS G, PANETSOS 5: Hepatitis associated antigen carriers among
blood donors in Greece. Am J Dis Child 123: 381, 1972 27. PLOTZ PH, ALTER HI, HOLLAND PV: Exposure to a food-handler with hepatitis B (C). Lancet 2: 333, 1972
Detection of core antibody in hepatitis B infection L. SPENCE, FRCP[C]; M. FAUVEL, M Sc
Hepatitis B core antigen (HB.Ag) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HB.Ag prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HB.) by complement fixation. Anti-HB. was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HB,Ag) and from patients with chronic liver or renal disease who were carriers of HB,Ag: It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HB5Ag. La nucleocapside du virus de l'hepatite de type B (HB.Ag) est retrouve sur Ia particule Dane debarrassee de sa game et sur une particule morphologiquement semblable decelee principalement dans le noyau des hepatocytes des patients souffrant d'hepatite de type B. L'HB.Ag prepare a partir du foie d'un chimpanze infect6 avec le virus de l'hepatite de type B a et6 utilis6 afin de d.tecter Ia pr6sence de I'anticorps dirig6 contre I'HB.Ag (anti-HB.) dans le serum humain par fixation du compl6ment. L'anti-HB. a .te retrouve dans les s6rums preleves chez des patients atteints de I'h6patite de type B, From the department of medical microbiology, faculty of medicine, University of Toronto and the department of microbiology, Toronto General Hospital Reprint requests to: Dr. L. Spence, Department of medical microbiology, Banting Institute, 100 College St., Toronto, Ont. M5G 1L5
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aussi bien durant Ia phase aigue que durant Ia convalescence, chez des porteurs de l'antigene de surface de l'hepatite de type B (HB,Ag) et chez des patients souffrant de maladies hepatiques ou r6nales chroniques et porteurs de l'HBAg. L'anti-HB. n'a pas ete decel6 chez des patients souffrant d'hepatite A ou de mononucleose infectieuse, ou chez des personnes saines qui n'etaient pas porteurs de l'HBAg.
In 1970 Dane, Cameron and Briggs1 described in the blood of hepatitis B patients a particle 42 nm in diameter with a complex structure. By negative staining and examination under the electron microscope it was found to have an outer coat 7 nm in thickness surrounding an inner core 28 nm in diameter. The particle shared an antigen, hepatitis B surface antigen (HB.Ag), with the small spherical and tubular particles previously described in association with Australia antigen.1'2 In 1971 Almeida, Rubenstein and Stott3 reported that treatment of the Dane particle with a detergent, polysorbate (Tween) 80, disrupted the particle and released an internal component (the core), 27 nm in diameter, that resembled a particle Almeida and colleagues4 had found previously in homogenates of liver prepared from two patients who had died from hepatitis. Immune electron microscopy (IEM) showed that the internal component reacted with posthepatitis but not prehepatitis serum and that this represented a new antigen-antibody reaction in hepatitis B infection. Similar results were reported by Deutsch and Spence5 in 1972. In this paper we report the results
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
of further studies with hepatitis B core antigen (HB.Ag) on serum of patients with hepatitis B. Patients and methods Patients The patients in the study, all adults, included the following: (a) healthy women admitted to the maternity ward for delivery and found to be HB5Agnegative by routine screening (not matched for age and sex with the other patients); (b) healthy carriers of HB8Ag, including Red Cross blood donors and healthy maternity patients found to be HB8Ag-positive by routine screening; (c) patients with hepatitis B; (d) HB8Agpositive patients with chronic liver or renal disease; (e) patients with hepatitis A, diagnosed from clinical and epidemiologic history, physical examination and biochemical and virologic tests; and (f) patients with infectious mononucleosis. Serum collection Serum was collected from the patients admitted to or visiting a general hospital for the investigation and treatment of acute hepatitis B and again after* HB.Ag was no longer detectable in the blood. Usually the first HB9Agnegative sample obtained was tested for antibodies to HB8Ag (anti-HB.) and to HB.Ag (anti-HB.). Serum was also collected from all other categories of patients. Preparation of HB.Ag The HB.Ag used in these studies was prepared from the liver of a chimpanzee infected with hepatitis B virus at Connaught Laboratories, Toronto.6
