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Vaccination against Hepatitis B
1391
Vaccination
against Hepatitis B
SERUM hepatitis or, as it is now called, hepatitis a serious and common disease, especially in warm countries. It is also a danger for patients repeatedly exposed to blood or certain blood products and for those who care for them in ward or laboratory. Its prevalence is high in institutions, especially those for the mentally retarded. Measures to prevent the disease are therefore urgently sought. MARMION and his colleaguesl have shown how effective simple methods of screening for HBsAg and good housekeeping can be in controlling the disease. Indeed the success of these measures in controlling infection in haemodialysis units in Britain has been very encouraging. Nevertheless, it would be highly desirable to back up preventive measures based on identification of the hazard and good hygiene by active immunisation. There is good reason to believe that a vaccine against hepatitis B could be developed. The infection is known to be an immunising one; and HBsAb in Y-globulin has been shown to prevent the disease, provided its titre is adequate. But there are difficulties surrounding the development of a vaccine as outlined by Professor ZUCKERMAN on p. 1396. Despite these uncertainties, vaccines are being prepared within the limitations of present technology by a number of workers; and the results obtained by Professor MAUPAS and his colleagues in Tours are reported on p. 1367 this week. How can the undoubted advantages of a vaccine be balanced against risks involved? The history of the control of infectious diseases is an impressive record, but there has been some cost—for example, several hundred children were paralysed during the early days of vaccination against poliomyelitis. In March an international meeting3 in Geneva discussed the ethical and technical questions involved in the development of vaccines. The overriding requirement was held to be that the preparation of any vaccine should be technically efficient and open to independent review, which could be secured by national or even international committees. Such committees are often entirely manned by experts and there was a plea for wider public representation. Another valuable form of review is provided by the publication of the results of those workers who are developing a vaccine. Some will say that it is premature to attempt to make an HBsAg vaccine. Because the virus cannot B is
1. Marmion, B. P., Tonkin, R. W. Br. med. Bull. 1972, 28, 169. 2. Wilson, G. S. The Hazards of Immunisation. London, 1967. 3. Sponsored by the World Health Organisation, the World Medical Association, the International Association for Biological Standardisation, the U.S. Public Health Service, and the Council for International Organisations of Medical Sciences.
be grown in the laboratory in cell culture, purity and safety cannot be assured by direct tests. Moreover, HBsAg may not contain the antigen necessary for protection; and it may contain antigens which could cause immunological damage rather than clinical immunity. Strong arguments can also be put for undertaking trials in a highly selective way. HBsAg is readily available from persons carrying it, and donors can be selected by means which reduce risks from the presence of other agents, as is done with blood-donors in many countries. Techniques for purification can employ both affinity chromatography and physical methods to concentrate the 22 nm particles. There is convincing evidence that heat at 60°C for 10 hours destroys hepatitis-B virus in plasma and this treatcombined with another established ment, as such formalin, may be coninactivating agent, sidered to add extra security. To another key question-how important are the dangers of host-specific antigens?-the answer must be that we do not know. There is assurance in the knowledge that blood products have been massively used without this type of hazard becoming apparent. Among the blood products used on a large scale is heated plasma-protein fraction, which, in the U.S.A. at least,4 almost always contained HBsAg until about 1972.4 The most that can be said is that so far the vaccine used by Professor MAUPAS and his colleagues has been associated with none of the possible untoward reactions.
Viral Cross-infections in Children’s Wards ON the children’s ward, hospital-acquired virus infection can be a calamity. Discomforts and dangers apart, such infections complicate management of other ills and may add to distress by prolonging the hospital stay. Thus, a child in hospital who acquires an exanthem such as measles or varicella should at once be discharged or, failing that, isolated. As to the contacts, they should when possible be screened for the presence of antibody to the virus in question (unless there is a clear history of infection or of measles vaccination). Susceptible contacts over the age of 9-12 months may be protected against measles with attenuated measles vaccine, provided that this is given within three days of exposure.5 Probably this works because measles induced by attenuated vaccine has a shorter incubation period than naturally acquired disease; alternatively, the vaccine-induced interferon response may inhibit replication of natural measles virus. It may be useful to check patients for the presence of antibodies after this vaccination, say at 8-10 weeks. Susceptible contacts in 4. Pattison, C. P., et al. Am. J. Epidemiol. 5. Marshall, W. C. Unpublished.
1976, 103, 399.
Vaccination
against Hepatitis B
SERUM hepatitis or, as it is now called, hepatitis a serious and common disease, especially in warm countries. It is also a danger for patients repeatedly exposed to blood or certain blood products and for those who care for them in ward or laboratory. Its prevalence is high in institutions, especially those for the mentally retarded. Measures to prevent the disease are therefore urgently sought. MARMION and his colleaguesl have shown how effective simple methods of screening for HBsAg and good housekeeping can be in controlling the disease. Indeed the success of these measures in controlling infection in haemodialysis units in Britain has been very encouraging. Nevertheless, it would be highly desirable to back up preventive measures based on identification of the hazard and good hygiene by active immunisation. There is good reason to believe that a vaccine against hepatitis B could be developed. The infection is known to be an immunising one; and HBsAb in Y-globulin has been shown to prevent the disease, provided its titre is adequate. But there are difficulties surrounding the development of a vaccine as outlined by Professor ZUCKERMAN on p. 1396. Despite these uncertainties, vaccines are being prepared within the limitations of present technology by a number of workers; and the results obtained by Professor MAUPAS and his colleagues in Tours are reported on p. 1367 this week. How can the undoubted advantages of a vaccine be balanced against risks involved? The history of the control of infectious diseases is an impressive record, but there has been some cost—for example, several hundred children were paralysed during the early days of vaccination against poliomyelitis. In March an international meeting3 in Geneva discussed the ethical and technical questions involved in the development of vaccines. The overriding requirement was held to be that the preparation of any vaccine should be technically efficient and open to independent review, which could be secured by national or even international committees. Such committees are often entirely manned by experts and there was a plea for wider public representation. Another valuable form of review is provided by the publication of the results of those workers who are developing a vaccine. Some will say that it is premature to attempt to make an HBsAg vaccine. Because the virus cannot B is
1. Marmion, B. P., Tonkin, R. W. Br. med. Bull. 1972, 28, 169. 2. Wilson, G. S. The Hazards of Immunisation. London, 1967. 3. Sponsored by the World Health Organisation, the World Medical Association, the International Association for Biological Standardisation, the U.S. Public Health Service, and the Council for International Organisations of Medical Sciences.
be grown in the laboratory in cell culture, purity and safety cannot be assured by direct tests. Moreover, HBsAg may not contain the antigen necessary for protection; and it may contain antigens which could cause immunological damage rather than clinical immunity. Strong arguments can also be put for undertaking trials in a highly selective way. HBsAg is readily available from persons carrying it, and donors can be selected by means which reduce risks from the presence of other agents, as is done with blood-donors in many countries. Techniques for purification can employ both affinity chromatography and physical methods to concentrate the 22 nm particles. There is convincing evidence that heat at 60°C for 10 hours destroys hepatitis-B virus in plasma and this treatcombined with another established ment, as such formalin, may be coninactivating agent, sidered to add extra security. To another key question-how important are the dangers of host-specific antigens?-the answer must be that we do not know. There is assurance in the knowledge that blood products have been massively used without this type of hazard becoming apparent. Among the blood products used on a large scale is heated plasma-protein fraction, which, in the U.S.A. at least,4 almost always contained HBsAg until about 1972.4 The most that can be said is that so far the vaccine used by Professor MAUPAS and his colleagues has been associated with none of the possible untoward reactions.
Viral Cross-infections in Children’s Wards ON the children’s ward, hospital-acquired virus infection can be a calamity. Discomforts and dangers apart, such infections complicate management of other ills and may add to distress by prolonging the hospital stay. Thus, a child in hospital who acquires an exanthem such as measles or varicella should at once be discharged or, failing that, isolated. As to the contacts, they should when possible be screened for the presence of antibody to the virus in question (unless there is a clear history of infection or of measles vaccination). Susceptible contacts over the age of 9-12 months may be protected against measles with attenuated measles vaccine, provided that this is given within three days of exposure.5 Probably this works because measles induced by attenuated vaccine has a shorter incubation period than naturally acquired disease; alternatively, the vaccine-induced interferon response may inhibit replication of natural measles virus. It may be useful to check patients for the presence of antibodies after this vaccination, say at 8-10 weeks. Susceptible contacts in 4. Pattison, C. P., et al. Am. J. Epidemiol. 5. Marshall, W. C. Unpublished.
1976, 103, 399.