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Australia antigen and hepatitis
Publ. Htth, LomL (1972,~87, 33-38
Australia Antigen and Hepatitis Y. E. C O S S A R T B.SC., M.B., B.S., M.¢.Path., D.c.P.
Virus Rcferem'e Laboratory, Central Public Health Lahorato~3", Col#Male A venue, London N. HL9.
UNTIL recently viral hepatitis was classified as 'infectious' or 'serum' hepatitis on the basis of differences in the length of the incubation period and the mode of transmission (Table !t. TAItI.t~ ]
hlfi, ctioas hepatitis Incubation period Agent present in Mode of transmission Age affected Clinical course Features other than liver damage
3--6 weeks Blood, faeces Oral & parenteral Young people, especially children Short, rarely fatal Rare
Serum hepatitis 6 wks-6 months Blood Parentcral Any age Longer and more severe Joint pains and rash common
Krugman, Giles & Hammond (1967) however, suggested that this scheme was not entirely satisfactory because they found that there were two differcnt types of viral hepatitis circulating in the Willowbrook State School for mentally defective persons. The first lyFe, MS-I. had the features expected of "infectious' hepatitis. The second type, MS-2. had the long incubation period characteristic of 'serum' hepatitis, but was shown to spread to close contacts and to be transmissible by the oral as well as the parenteral route. The discovery of Australia antigen by Blumberg, Alter & Visnich (1965)and the realization that it occurred in the serum of individuals who were hepatitis carriers as well as in patients during the viraemic phase of "serum' hepatitis (Prince, 1968) has provided a useful marker for epidemiological studies. The nature of the antigen remains obscure. It consists of small virus-like particles of 3 morphological types (Bayer, Blumberg & Werner, 1968; Aimeida et al., 1969; Dane, Cameron & Briggs, 1970). The smallest of these is roughly the size expected for the hepatitis virus itself. The rather variable size of these particles and the general failure to find nucleic acid in purified preparations suggests that these particles are not themselves viruses. Nevertheless, blood containing the antigen seems always to be infectious, producing hepatitis and antigen formation in recipients. The particles are also present in the serum in vi~ry large quantities. Their concentration has been estimated in some preparations as about 1012 particles/ml. Although the infectivity titre of such preparations is also high it is only about 106 ID/50ml (Barker et al., 1970). It might be expected that such a large amount of foreign protein in the circulation would readily stimulate antibody formation. This is not the case and anti-Australia antibody is rare, usually occurring in individuals such as haemophiliacs who have received many blood transfusions. Antibody does not usually appear during convalescence from an acute attack of hepatitis,
34
PUBLIC HEALTIt VOL. 87 NOS. 1 & 2
This means that tests for the presence of Australia antigen in the sertun are useful in identifying: (1) "i'he type of hepatitis during the acute stage of illness e.g. the antigen is regularly present in *MS-2' hepatitis at Willowbrook, but is not found in the °MS-I' type (Giles et al, 1969). (2) Hepatitis carriers e.g. blood donors, In the laboratory Australia antigen may be detected either by serological methods using antisera derived from multiply transfused patients or animals immunized with purified antigen, or by electron microscopy. The commonly used serological methods are the gel diffusion test, the complement fixation test and immunoelectrophoresis. In epidemiological work a balance between sensitivity and economy has to be strtlck. The gel test is simple, inexpensive and gives few false positive results. Complement fixation is nmch more sensitive, detecting antigen about 100 times more dilute than reacts in the gel test. It is haore likely to give false positive results. Electrophoresis is rapid and relatively simple. It is nearly as sensitive as complement fixation, but also gives a proportion of false positive results. The subject is reviewed in detail elsewhere (Cossart, 1971). For survey work gel diffusion is probably the test of choice as direct comparison (Table 2) with CFT and electrophoresis showed the more sensitive tests improved the detection rate in serum hepatitis specimens by only 10~. The improvement for carriers is even less.
TABLE2 Comparison of testing methods on consecutive "scram hepatitis" specimens (1970)
Total received Positive by gel Negative by gel Insufficient specimen for further study 56 negative specimens retested: By C.F.T. By electrophoresis i.e. 107,~of positives missed by the Gel Test
95 32 63 7 3 additional positive 4 additional positive
For diagnostic work no single test is ideal. Both electrophoresis and gel diffusion tests depend on the passage of antigen particles through a gel matrix, Should the particles be clumped, as may occur in the acute phase of hepatitis, such tests may be negative despite a high concentration of antigen (Cossart & Vahrman, 1970). Using the gel test a number of surveys have been conducted in the Virus Reference Laboratory. These have aimed to identify areas where further work would be profitable. Table 3 shows the carrier rate in several groJ,Ips of patients. In healthy adults in England, the rate (I/800) approximates that of blood donors (Wallace, 1970) although the latter group excludes persons who have ever experienced an attack of clinical hepatitis. The carrier rate is more than ten-fold higher in groups who receive many blood transfusions such as patients with blood dyscrasias or haemophilia, and also in drug addicts and in patients with chronic renal failure. In mo~gol and other mentally defective patients in a large institution, the Australia antigen c~¢~r~er rate is almost ten-fold higher still and this group forms a very substarttial reservoir ~ infection.
35
A U S T R A L I A A N T I G E N A N D itEPATITIS TABLE 3 Australia antigen carriers
Category
Number positive :
Healthy adult Male (air force) Female (antenatal) Blood dyscrasia Drug addict Haemophilia Chronic renal failure Mongol Other mental defective
Number tested
(',0 0"1
1/1200 3/2048 3/72 1/49 4/l 0 I 1/101 26/123 t0/125
4 2 4
(8 antibody) (2 antibody)
I
2 8
Table 4 compares the number of 'serum hepatitis' patients in whom Australia antigen was found during 1970 and 1971 and also divides them into groups according to the likely mode of transmission of the infection. It is gratifying to notice a substantial decrease in the number of post-transfusion cases, due almost entirely to the reduction in the antigen positive type. This followed the introduction by the principal supplier in the area of Australia antigen screening tests of blood before issue. In contrast the proportion of addicts with Australia antigen positive hepatitis remained almost constant over this period.
TABLE 4
Australia antigen ht 'serum hepatitis' Category
Number positive : Number tested 1970 t 971
Post transfusion
19/50 38~/o 6/20 30~o 3/3
6/35 17~ I 0/31 31 ,o; 3/5
100%
60%
Drug addict Tattoo
Table 5 shows that addicts are likely to contract hepatitis of both antigen positive and negative types, and that multiple attacks are not uncommon. In Table 6, patients are grouped according to age and sex. The concentration of cases in young men corresponds ,vith that already described from tlle United States (Prince et al., 1970).
TABLE 5
Australia antigen hJ drug addicts (1971) Clinical group
Gel diffusion test Number positive Number tested
Hepatitis when tested Previous hepatitis* No hepatitis *I attack 3 patients; 2 attack 2 patients.
6 1 2
21 27
PUBLIC HEALTH VOL. 87 NOS. I & 2
36
T~IIL£6 Australia antigen in drttg addicts with hepatitis (1971)
Age group < 15 16-30 31-45 46+ Overall
Number positive : Number tested Male Female o/i 0/0 5/8 i/2 5/7 0/0 2/'4 010 60% 50%
Table 7 gives the resttlts of testing patien!ts adlllitted to three infectious disease hospitals in London with a diagnosis of acute viral hepatitis during 1970. Patients where parenteral transmission was suspected are excluded. The age and sex composition of this sample includes fewer children and fewer women than would be expected from the age and sex composition of officially notified cases of 'infective jaundice' where more than half the patients are under 15 years of age and there is only a slight preponderance of males. There is an unexpectedly high proportion of antigen positive cases and these are concentrated i n y o u n g adult males. This tendency has been observed in sporadic hepatitis in London (Cossart & Vahrman, 1970) as well as in New York (Prince, 1968). The extent to which concealed drug abuse contributes to this situation is unknown. Some believe it is tile main factor (Gregg, 1972); others point out that even in known addicts with hepatitis, Australia antigen can only be detected in about half the patients, so that the parenteral drug use would have to be practised by more than half the pat/eats to account for the observed situation (Cherub/n, 197I). TABLE7 Australia antigen in sporadic hepatitis (I971)
Hospital A B C
Number positive : Number tested by gel diffusion Patients age 0--15 16-30 31 + Male Female Male Female Male Female 0/6 0/6 15t40 4/15 4/12 0/2 0112 0!21 7•28 1/21 3/9 I1'5 0/6 011 3/16 |/6 2/6 1/3
It seems most likely that antigen positive hepatitis does circulate in the community by some 'natural' route, which is at present unrecognized. Conversely, the contribution of Australia antigen negative hepatitis to post-transfusion and post-inoculation jaundice is much larger than might have been expected in purely epidemiological grounds. So far no c o m m o n source, food or water-borne outbreaks of hepatitis has been associated with Australia antigen. Hepatitis has long been a problem in institutions for mentally defective persons. It is often classical infectious hepatitis, and epidemics can be prevented by the prophylactic use of normal human immunoglobulin (P.H.L.S., 1968). However Australia antigen positive hepatitis does occur in these hospitals and substantial numbers of carriers are likely to be
AUSTRALIA ANTIGEN AND HEPATITIS
37
found especially amongst the mongols who are predisposed to develop the carrier state because of their immunodeficient state (Blumberg et at., 1970). In one British institution there was great concentration of Australia antigen carriers, 7 0 ~ residing in 3 o f the 15 villas. N o correlation could be found between the age of the individuals or their length of residence and antigen carriage, but it was more c o m m o n in males (20 ~o) than females (8 ~). In these institutions there is relatively little opportunity for parenteral transmission of infection, and close personal contact between the patients seems the most likely mode of spread. In renal dialysis units the hepatitis carrier rate may be o f the same order as that amongst mongols in institutions (Polakoffet aL, 1972), but the intermittent haemodialysis produces a substantial risk of transmitting the disease and large outbreaks have occurred in many centres. In less dramatic fashion, hepatitis carriers admitted to general hospitals may constitute a risk both to those who care for them or handle their blood, or less often to other patients. This risk has probably been exaggerated, but it is likely to ri',e with the increasing applicati on o f intensive methods of treatment, and the widespread use of chemical immunosuppressive drugs and corticosteroids (Lous, Olesen & Skinhoj, 1970). Hepatitis in pregnancy is of some interest because transplacental transmission of the virus to the foetus might occur and give rise either to neonatal liver disease or to the long term carrier state in the infant. Table 8 summarizes the consequences of antigen positive hepatitis and of antigen carriage in 8 patients. Transmission o f infection to the infant occurred in 2 o f the 4 instances where acute hepatitis occurred close to the time of delivery. Both these infants have developed long term Australia antigen carriage and subclinical chronic !tiepatitis,. In the 3 antigen carriers detected in a survey of ante-natal clinic sera, and in the instance of hepatitis early in pregnancy, the infants were quite unaffected and Australia antigen could not be detected in their serum.
TABLE 8
Australian attligen ht mother and infant
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6
Mother Antigen Hepatitis Clinical present or carrier details |st trimester Carrier Normalbaby negative at delivery delivered at term & later 1st trimester Carrier Normalbaby negative later delivered at term 1st & 3rd trimester Carrier Nomaal baby negative at delivery delivered at term positive later 1st trimester Hepatitis Normal baby negative later delivered at term Positive at term Hepatitis Premature'labour infant normal 3rd trimester Hepatitis Baby with cleft palate & talipes
Case 7 3rd trimester
Hepatitis
Normal baby born
Baby Antigen in Antigen cord blood subsequently Hepatitis No No No No
No
No
No
No
No
No
No
No
No
No
No
No
Yes chronic carrier
No
No
Yes chronic active No
Not tested
Yes chronic carrier
Yes chronic active
at t e n l l
Case 8 Puerperium
Hepatitis
Normal baby born at term
38
PUBLIC HEALTH VOL. 87 NOS. 1 & 2
From these surveys it seems that Australia antigen-positive hepatitis corresponds Io serum hepatitis in having a long incubation period, in producing many healthy carriers and in its clinical features, but that some non-parenteral mode of transmission is likely to be responsible for its comparatively wide dissemination in the community.
Acknowledgements The technical help of Miss Sandra March is gratefully acknowledged and thanks are also due to the clinicians who submitted such interesting specimens for testing.
References ALME|DA, J, D., ZUCKERMAN,A. J., TAYLOR, P. E. i~. WA'IERSON, A. P. (1969). Microbios. 2, 117. BARKER, L. F,, SHULMAN,N. J., MURRAV, R., HIRSCHMAN,R., RA'I'NER, F., Dr~'~NaACH, W. C. & GELI_ER, H. M. (1970). J. Ant. reed. Ass. 211, 1509o BAYER, M. E., BLUMBERG,B. S. & WERNER, B. (1968). Natta:e, LomL 218, 1057. BLUMBERG,B. S.~ ALTER, H. J. & VISNICH, S. 1. (1965). J. Am. meal. Ass. 191,541. BLUMBERG, B. S., GERSTLEY, i3. J. S., SOTNICK, A. I., MILLMAN,I, & LONI:~ON,W. T. (1970). Ann. N, Y, Acad. Sci. 171,486. CHERtJBIN, C, E. (1971). Lancet i, 627. COSSART, Y. E, (t971). J. olin. Path. 24, 394. COSSART, Y. E., FIELD, A. M., HARGREAVES,F. D. & PORTER, A. A. (1971). Microbios. 3, (9), 5. COSSART, Y. E. & VAHRM.~,N,J. (1970). Br. reed. J. i, 403. DANE, D. S., CAMI~RON,C. H. & BRIGGS, M. (1970). Lam'et i, 695. GILES, J. P., MCCOLLUM, R. W., BERNDSTON, L. W. & KRUGMAN, S. (1969). New Eng. J. Med. 281, 119~ GREGG, M. B. (1972). Proc. Int. Childrens Centre--Seminar on viral hepatitis. Am. J. Dis'. Child 23, 350. KRUGMAN, S., GILES, J. P. & HAMMOND,J. (1967). J. Ant. reed. Ass. 200, 365. Lous, P., OLESEN, H. & SKINHOJ, P. (1970). Lancet ii, ! 19. P.H.L.S. (1968). Br. reed. J. 3, 451. POLAgOFF, S. et aL (1972). Br. reed. J. ii, 94. PRINCE, A. M. (1968). Proc. Natn Acad. Sci. U.S.A. 60, 814. PRINCE, A. M., HARGROVE,R. L., SZMONESS,W., CHERUaIN,C. E., FON'rANA, J. &. JEFFRIES, (3. H. 0970). New Eng. J. Meal 282, 987. WALLACE, J. (1970). Lancet ii, 609, (Letter).
Australia Antigen and Hepatitis Y. E. C O S S A R T B.SC., M.B., B.S., M.¢.Path., D.c.P.
Virus Rcferem'e Laboratory, Central Public Health Lahorato~3", Col#Male A venue, London N. HL9.
UNTIL recently viral hepatitis was classified as 'infectious' or 'serum' hepatitis on the basis of differences in the length of the incubation period and the mode of transmission (Table !t. TAItI.t~ ]
hlfi, ctioas hepatitis Incubation period Agent present in Mode of transmission Age affected Clinical course Features other than liver damage
3--6 weeks Blood, faeces Oral & parenteral Young people, especially children Short, rarely fatal Rare
Serum hepatitis 6 wks-6 months Blood Parentcral Any age Longer and more severe Joint pains and rash common
Krugman, Giles & Hammond (1967) however, suggested that this scheme was not entirely satisfactory because they found that there were two differcnt types of viral hepatitis circulating in the Willowbrook State School for mentally defective persons. The first lyFe, MS-I. had the features expected of "infectious' hepatitis. The second type, MS-2. had the long incubation period characteristic of 'serum' hepatitis, but was shown to spread to close contacts and to be transmissible by the oral as well as the parenteral route. The discovery of Australia antigen by Blumberg, Alter & Visnich (1965)and the realization that it occurred in the serum of individuals who were hepatitis carriers as well as in patients during the viraemic phase of "serum' hepatitis (Prince, 1968) has provided a useful marker for epidemiological studies. The nature of the antigen remains obscure. It consists of small virus-like particles of 3 morphological types (Bayer, Blumberg & Werner, 1968; Aimeida et al., 1969; Dane, Cameron & Briggs, 1970). The smallest of these is roughly the size expected for the hepatitis virus itself. The rather variable size of these particles and the general failure to find nucleic acid in purified preparations suggests that these particles are not themselves viruses. Nevertheless, blood containing the antigen seems always to be infectious, producing hepatitis and antigen formation in recipients. The particles are also present in the serum in vi~ry large quantities. Their concentration has been estimated in some preparations as about 1012 particles/ml. Although the infectivity titre of such preparations is also high it is only about 106 ID/50ml (Barker et al., 1970). It might be expected that such a large amount of foreign protein in the circulation would readily stimulate antibody formation. This is not the case and anti-Australia antibody is rare, usually occurring in individuals such as haemophiliacs who have received many blood transfusions. Antibody does not usually appear during convalescence from an acute attack of hepatitis,
34
PUBLIC HEALTIt VOL. 87 NOS. 1 & 2
This means that tests for the presence of Australia antigen in the sertun are useful in identifying: (1) "i'he type of hepatitis during the acute stage of illness e.g. the antigen is regularly present in *MS-2' hepatitis at Willowbrook, but is not found in the °MS-I' type (Giles et al, 1969). (2) Hepatitis carriers e.g. blood donors, In the laboratory Australia antigen may be detected either by serological methods using antisera derived from multiply transfused patients or animals immunized with purified antigen, or by electron microscopy. The commonly used serological methods are the gel diffusion test, the complement fixation test and immunoelectrophoresis. In epidemiological work a balance between sensitivity and economy has to be strtlck. The gel test is simple, inexpensive and gives few false positive results. Complement fixation is nmch more sensitive, detecting antigen about 100 times more dilute than reacts in the gel test. It is haore likely to give false positive results. Electrophoresis is rapid and relatively simple. It is nearly as sensitive as complement fixation, but also gives a proportion of false positive results. The subject is reviewed in detail elsewhere (Cossart, 1971). For survey work gel diffusion is probably the test of choice as direct comparison (Table 2) with CFT and electrophoresis showed the more sensitive tests improved the detection rate in serum hepatitis specimens by only 10~. The improvement for carriers is even less.
TABLE2 Comparison of testing methods on consecutive "scram hepatitis" specimens (1970)
Total received Positive by gel Negative by gel Insufficient specimen for further study 56 negative specimens retested: By C.F.T. By electrophoresis i.e. 107,~of positives missed by the Gel Test
95 32 63 7 3 additional positive 4 additional positive
For diagnostic work no single test is ideal. Both electrophoresis and gel diffusion tests depend on the passage of antigen particles through a gel matrix, Should the particles be clumped, as may occur in the acute phase of hepatitis, such tests may be negative despite a high concentration of antigen (Cossart & Vahrman, 1970). Using the gel test a number of surveys have been conducted in the Virus Reference Laboratory. These have aimed to identify areas where further work would be profitable. Table 3 shows the carrier rate in several groJ,Ips of patients. In healthy adults in England, the rate (I/800) approximates that of blood donors (Wallace, 1970) although the latter group excludes persons who have ever experienced an attack of clinical hepatitis. The carrier rate is more than ten-fold higher in groups who receive many blood transfusions such as patients with blood dyscrasias or haemophilia, and also in drug addicts and in patients with chronic renal failure. In mo~gol and other mentally defective patients in a large institution, the Australia antigen c~¢~r~er rate is almost ten-fold higher still and this group forms a very substarttial reservoir ~ infection.
35
A U S T R A L I A A N T I G E N A N D itEPATITIS TABLE 3 Australia antigen carriers
Category
Number positive :
Healthy adult Male (air force) Female (antenatal) Blood dyscrasia Drug addict Haemophilia Chronic renal failure Mongol Other mental defective
Number tested
(',0 0"1
1/1200 3/2048 3/72 1/49 4/l 0 I 1/101 26/123 t0/125
4 2 4
(8 antibody) (2 antibody)
I
2 8
Table 4 compares the number of 'serum hepatitis' patients in whom Australia antigen was found during 1970 and 1971 and also divides them into groups according to the likely mode of transmission of the infection. It is gratifying to notice a substantial decrease in the number of post-transfusion cases, due almost entirely to the reduction in the antigen positive type. This followed the introduction by the principal supplier in the area of Australia antigen screening tests of blood before issue. In contrast the proportion of addicts with Australia antigen positive hepatitis remained almost constant over this period.
TABLE 4
Australia antigen ht 'serum hepatitis' Category
Number positive : Number tested 1970 t 971
Post transfusion
19/50 38~/o 6/20 30~o 3/3
6/35 17~ I 0/31 31 ,o; 3/5
100%
60%
Drug addict Tattoo
Table 5 shows that addicts are likely to contract hepatitis of both antigen positive and negative types, and that multiple attacks are not uncommon. In Table 6, patients are grouped according to age and sex. The concentration of cases in young men corresponds ,vith that already described from tlle United States (Prince et al., 1970).
TABLE 5
Australia antigen hJ drug addicts (1971) Clinical group
Gel diffusion test Number positive Number tested
Hepatitis when tested Previous hepatitis* No hepatitis *I attack 3 patients; 2 attack 2 patients.
6 1 2
21 27
PUBLIC HEALTH VOL. 87 NOS. I & 2
36
T~IIL£6 Australia antigen in drttg addicts with hepatitis (1971)
Age group < 15 16-30 31-45 46+ Overall
Number positive : Number tested Male Female o/i 0/0 5/8 i/2 5/7 0/0 2/'4 010 60% 50%
Table 7 gives the resttlts of testing patien!ts adlllitted to three infectious disease hospitals in London with a diagnosis of acute viral hepatitis during 1970. Patients where parenteral transmission was suspected are excluded. The age and sex composition of this sample includes fewer children and fewer women than would be expected from the age and sex composition of officially notified cases of 'infective jaundice' where more than half the patients are under 15 years of age and there is only a slight preponderance of males. There is an unexpectedly high proportion of antigen positive cases and these are concentrated i n y o u n g adult males. This tendency has been observed in sporadic hepatitis in London (Cossart & Vahrman, 1970) as well as in New York (Prince, 1968). The extent to which concealed drug abuse contributes to this situation is unknown. Some believe it is tile main factor (Gregg, 1972); others point out that even in known addicts with hepatitis, Australia antigen can only be detected in about half the patients, so that the parenteral drug use would have to be practised by more than half the pat/eats to account for the observed situation (Cherub/n, 197I). TABLE7 Australia antigen in sporadic hepatitis (I971)
Hospital A B C
Number positive : Number tested by gel diffusion Patients age 0--15 16-30 31 + Male Female Male Female Male Female 0/6 0/6 15t40 4/15 4/12 0/2 0112 0!21 7•28 1/21 3/9 I1'5 0/6 011 3/16 |/6 2/6 1/3
It seems most likely that antigen positive hepatitis does circulate in the community by some 'natural' route, which is at present unrecognized. Conversely, the contribution of Australia antigen negative hepatitis to post-transfusion and post-inoculation jaundice is much larger than might have been expected in purely epidemiological grounds. So far no c o m m o n source, food or water-borne outbreaks of hepatitis has been associated with Australia antigen. Hepatitis has long been a problem in institutions for mentally defective persons. It is often classical infectious hepatitis, and epidemics can be prevented by the prophylactic use of normal human immunoglobulin (P.H.L.S., 1968). However Australia antigen positive hepatitis does occur in these hospitals and substantial numbers of carriers are likely to be
AUSTRALIA ANTIGEN AND HEPATITIS
37
found especially amongst the mongols who are predisposed to develop the carrier state because of their immunodeficient state (Blumberg et at., 1970). In one British institution there was great concentration of Australia antigen carriers, 7 0 ~ residing in 3 o f the 15 villas. N o correlation could be found between the age of the individuals or their length of residence and antigen carriage, but it was more c o m m o n in males (20 ~o) than females (8 ~). In these institutions there is relatively little opportunity for parenteral transmission of infection, and close personal contact between the patients seems the most likely mode of spread. In renal dialysis units the hepatitis carrier rate may be o f the same order as that amongst mongols in institutions (Polakoffet aL, 1972), but the intermittent haemodialysis produces a substantial risk of transmitting the disease and large outbreaks have occurred in many centres. In less dramatic fashion, hepatitis carriers admitted to general hospitals may constitute a risk both to those who care for them or handle their blood, or less often to other patients. This risk has probably been exaggerated, but it is likely to ri',e with the increasing applicati on o f intensive methods of treatment, and the widespread use of chemical immunosuppressive drugs and corticosteroids (Lous, Olesen & Skinhoj, 1970). Hepatitis in pregnancy is of some interest because transplacental transmission of the virus to the foetus might occur and give rise either to neonatal liver disease or to the long term carrier state in the infant. Table 8 summarizes the consequences of antigen positive hepatitis and of antigen carriage in 8 patients. Transmission o f infection to the infant occurred in 2 o f the 4 instances where acute hepatitis occurred close to the time of delivery. Both these infants have developed long term Australia antigen carriage and subclinical chronic !tiepatitis,. In the 3 antigen carriers detected in a survey of ante-natal clinic sera, and in the instance of hepatitis early in pregnancy, the infants were quite unaffected and Australia antigen could not be detected in their serum.
TABLE 8
Australian attligen ht mother and infant
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6
Mother Antigen Hepatitis Clinical present or carrier details |st trimester Carrier Normalbaby negative at delivery delivered at term & later 1st trimester Carrier Normalbaby negative later delivered at term 1st & 3rd trimester Carrier Nomaal baby negative at delivery delivered at term positive later 1st trimester Hepatitis Normal baby negative later delivered at term Positive at term Hepatitis Premature'labour infant normal 3rd trimester Hepatitis Baby with cleft palate & talipes
Case 7 3rd trimester
Hepatitis
Normal baby born
Baby Antigen in Antigen cord blood subsequently Hepatitis No No No No
No
No
No
No
No
No
No
No
No
No
No
No
Yes chronic carrier
No
No
Yes chronic active No
Not tested
Yes chronic carrier
Yes chronic active
at t e n l l
Case 8 Puerperium
Hepatitis
Normal baby born at term
38
PUBLIC HEALTH VOL. 87 NOS. 1 & 2
From these surveys it seems that Australia antigen-positive hepatitis corresponds Io serum hepatitis in having a long incubation period, in producing many healthy carriers and in its clinical features, but that some non-parenteral mode of transmission is likely to be responsible for its comparatively wide dissemination in the community.
Acknowledgements The technical help of Miss Sandra March is gratefully acknowledged and thanks are also due to the clinicians who submitted such interesting specimens for testing.
References ALME|DA, J, D., ZUCKERMAN,A. J., TAYLOR, P. E. i~. WA'IERSON, A. P. (1969). Microbios. 2, 117. BARKER, L. F,, SHULMAN,N. J., MURRAV, R., HIRSCHMAN,R., RA'I'NER, F., Dr~'~NaACH, W. C. & GELI_ER, H. M. (1970). J. Ant. reed. Ass. 211, 1509o BAYER, M. E., BLUMBERG,B. S. & WERNER, B. (1968). Natta:e, LomL 218, 1057. BLUMBERG,B. S.~ ALTER, H. J. & VISNICH, S. 1. (1965). J. Am. meal. Ass. 191,541. BLUMBERG, B. S., GERSTLEY, i3. J. S., SOTNICK, A. I., MILLMAN,I, & LONI:~ON,W. T. (1970). Ann. N, Y, Acad. Sci. 171,486. CHERtJBIN, C, E. (1971). Lancet i, 627. COSSART, Y. E, (t971). J. olin. Path. 24, 394. COSSART, Y. E., FIELD, A. M., HARGREAVES,F. D. & PORTER, A. A. (1971). Microbios. 3, (9), 5. COSSART, Y. E. & VAHRM.~,N,J. (1970). Br. reed. J. i, 403. DANE, D. S., CAMI~RON,C. H. & BRIGGS, M. (1970). Lam'et i, 695. GILES, J. P., MCCOLLUM, R. W., BERNDSTON, L. W. & KRUGMAN, S. (1969). New Eng. J. Med. 281, 119~ GREGG, M. B. (1972). Proc. Int. Childrens Centre--Seminar on viral hepatitis. Am. J. Dis'. Child 23, 350. KRUGMAN, S., GILES, J. P. & HAMMOND,J. (1967). J. Ant. reed. Ass. 200, 365. Lous, P., OLESEN, H. & SKINHOJ, P. (1970). Lancet ii, ! 19. P.H.L.S. (1968). Br. reed. J. 3, 451. POLAgOFF, S. et aL (1972). Br. reed. J. ii, 94. PRINCE, A. M. (1968). Proc. Natn Acad. Sci. U.S.A. 60, 814. PRINCE, A. M., HARGROVE,R. L., SZMONESS,W., CHERUaIN,C. E., FON'rANA, J. &. JEFFRIES, (3. H. 0970). New Eng. J. Meal 282, 987. WALLACE, J. (1970). Lancet ii, 609, (Letter).