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Efficacy of Haemophilus influenzae type B conjugate vaccine in Oxford region
847
LETTERS to the EDITOR
Efficacy of Haemophilus influenzae type conjugate vaccine in Oxford region
B
SIR,-The Haemophilus influenzae type B (Hib) conjugate vaccine that has been introduced as routine immunisation throughout the UK (starting Oct 1, 1992) has been piloted during the past eighteen months in four health districts in the Oxford region (Oxfordshire, Northampton, Kettering, and West Berkshire). In these districts, conjugate vaccine (PRP-T, Pasteur-Merieux) was given by separate injection in addition to the standard diphtheria/pertussis/tetanus and polio vaccines at age 2, 3, and 4 months. Four control districts were also selected in which Hib vaccine was not given. At least 90% of the 29 600 children who were offered the Hib vaccine have been immunised. Cases of systemic Hib infection were identified by systematic reporting from microbiology laboratories throughout the region. The vaccine was well tolerated and no serious adverse reactions occurred. In the control districts, 11 cases would have been expected on past experience; 12 were observed, 8 of which were meningitis. In the districts where Hib vaccine was offered, 11cases would have been expected among vaccinees, but none occurred. There were 2 cases, but both were in unimmunised children. These findings cannot be attributed to chance or bias. With the evidence from Finland of virtually complete protection, albeit by a somewhat different immunisation schedule, these results suggest that the inclusion of an Hib conjugate vaccine in the routine immunisation schedule for UK infants will, if generally accepted, almost eliminate Hib disease in early childhood. Since such immunisation has now been introduced into the control districts, the comparative part of our study is ending. Monitoring of Hib infection in all eight districts will continue to be informative about long-term control.
Departments of Paediatrics, Public Health, and Bacteriolology, John Radcliffe Hospital, Oxford 0X3 9DU, UK
R. BOOY E. R. MOXON J. A. MACFARLANE R. T. MAYON-WHITE M. P. E. SLACK
Creutzfeldt-Jakob legacy for Australian women treated with human pituitary
gonadotropins derived from cadaver donors, were administered between 1963 and 1985, as pituitary gonadotropins (hPG) to infertile woman and as growth hormone (hGH) to children with pituitary insufficiency. This source of pituitary hormones was abandoned in most countries in 1985 when 2 hGH recipients died in the USA from Creutzfeldt-Jakob disease (CJD). The lethal threat of CJD from hormones prepared from cadaveric pituitary glands was subsequently confirmed by a further 18 cases. 16 had received hGH but the other 2, both treated in Australia, were in infertile women given hPG as a source of follicle-stimulating hormone. The symptoms of CJD associated with hPG/hGH appear earlier than they do with sporadic CJD, for example, the 2 Australian women were aged 40 and 44 at onset of neurological
SIR,-Pituitary hormones,
symptoms’ and the first 6 UK victims died aged 20-34.2 Although psychometric testing may reveal subclinical impairment, dementia is notably absent as a presenting symptom of iatrogenic CJD and the electroencephalographic abnormalities of sporadic CJD are often absent too. CJD from pituitary gland treatments has a more rapid downhill course (4-11 months from presentation to death). These differences may even mean that a diagnosis of iatrogenic CJD is missed.3 In its 1976 report,4the Australian National Pituitary Advisory Committee (NPAC) noted that experts had drawn up guidelines for the selection of patients for treatment with hPG. Furthermore "Investigation of the infertile couple must indicate that anovulation is the only factor requiring treatment". However, the article that followed that one from the NPAC and the Australian Department of Health reports that hPG "supplied by the Australian Pituitary Advisory Committee" was used in 14 infertile ovulatory women with total tubal destruction who were candidates for IVF.’ How many other ovulatory women were conditioned for IVF with hPG between 1976 and 1985? Information provided to the Australian Federal Parliament6 indicates that about 1500 infertile Australian women received hPG but the proportion who were ovulatory remains unknown. By 1988, despite the emergence of further cases, it was being suggested that the threat of an epidemic of iatrogenic CJD had passed.’ That claim was supported by a 1988 report that CJD had not occurred in 1698 hGH-treated individuals in France. By mid1991, however, 3 French cases had been reported; a year later, 2 more had been confirmed and, as Dr Brown and his colleagues note in their latest review (July 4, p 24), at least another 6 suspected cases amongst that French cohort await confirmation. Iatrogenic CJD remains a threat in the UK2 and USAtoo. The 1991 US review points out that "the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD". The interval between the mid-point of hGH treatment and the onset of CJD symptoms had averaged 15 years. In Australia only 104 of 2003 known Australian treatments (many women had more than one) were administered between 1964 and 1969.6 In the USA, monitoring, surveillance, and counselling of individuals at risk began immediately after the first CJD death in 1985. In the UK, the past 4 years have been spent tracing hGH-treated individuals8 but it was only after the sixth UK death in 1991 that the Department of Health agreed to a complete programme of information. Even though 90% of British recipients have been traced, less than half have been notified. Those involved have unsuccessfully sought compensation from the Government and are now pursuing litigation.9 In 1985, the Australian Department of Health wrote to the clinicians who had used hPG advising them to tell patients of the risk of CJD and this advice was reissued in 1991 and again this year. However, by mid-1992 only one-quarter of the women had been contacted.6 We are aware of 10 women who suspect that they were so treated in the 1970s but who cannot find out whether they were exposed to hPG or not. To the psychological stress of this uncertainty must be added the risk not
LETTERS to the EDITOR
Efficacy of Haemophilus influenzae type conjugate vaccine in Oxford region
B
SIR,-The Haemophilus influenzae type B (Hib) conjugate vaccine that has been introduced as routine immunisation throughout the UK (starting Oct 1, 1992) has been piloted during the past eighteen months in four health districts in the Oxford region (Oxfordshire, Northampton, Kettering, and West Berkshire). In these districts, conjugate vaccine (PRP-T, Pasteur-Merieux) was given by separate injection in addition to the standard diphtheria/pertussis/tetanus and polio vaccines at age 2, 3, and 4 months. Four control districts were also selected in which Hib vaccine was not given. At least 90% of the 29 600 children who were offered the Hib vaccine have been immunised. Cases of systemic Hib infection were identified by systematic reporting from microbiology laboratories throughout the region. The vaccine was well tolerated and no serious adverse reactions occurred. In the control districts, 11 cases would have been expected on past experience; 12 were observed, 8 of which were meningitis. In the districts where Hib vaccine was offered, 11cases would have been expected among vaccinees, but none occurred. There were 2 cases, but both were in unimmunised children. These findings cannot be attributed to chance or bias. With the evidence from Finland of virtually complete protection, albeit by a somewhat different immunisation schedule, these results suggest that the inclusion of an Hib conjugate vaccine in the routine immunisation schedule for UK infants will, if generally accepted, almost eliminate Hib disease in early childhood. Since such immunisation has now been introduced into the control districts, the comparative part of our study is ending. Monitoring of Hib infection in all eight districts will continue to be informative about long-term control.
Departments of Paediatrics, Public Health, and Bacteriolology, John Radcliffe Hospital, Oxford 0X3 9DU, UK
R. BOOY E. R. MOXON J. A. MACFARLANE R. T. MAYON-WHITE M. P. E. SLACK
Creutzfeldt-Jakob legacy for Australian women treated with human pituitary
gonadotropins derived from cadaver donors, were administered between 1963 and 1985, as pituitary gonadotropins (hPG) to infertile woman and as growth hormone (hGH) to children with pituitary insufficiency. This source of pituitary hormones was abandoned in most countries in 1985 when 2 hGH recipients died in the USA from Creutzfeldt-Jakob disease (CJD). The lethal threat of CJD from hormones prepared from cadaveric pituitary glands was subsequently confirmed by a further 18 cases. 16 had received hGH but the other 2, both treated in Australia, were in infertile women given hPG as a source of follicle-stimulating hormone. The symptoms of CJD associated with hPG/hGH appear earlier than they do with sporadic CJD, for example, the 2 Australian women were aged 40 and 44 at onset of neurological
SIR,-Pituitary hormones,
symptoms’ and the first 6 UK victims died aged 20-34.2 Although psychometric testing may reveal subclinical impairment, dementia is notably absent as a presenting symptom of iatrogenic CJD and the electroencephalographic abnormalities of sporadic CJD are often absent too. CJD from pituitary gland treatments has a more rapid downhill course (4-11 months from presentation to death). These differences may even mean that a diagnosis of iatrogenic CJD is missed.3 In its 1976 report,4the Australian National Pituitary Advisory Committee (NPAC) noted that experts had drawn up guidelines for the selection of patients for treatment with hPG. Furthermore "Investigation of the infertile couple must indicate that anovulation is the only factor requiring treatment". However, the article that followed that one from the NPAC and the Australian Department of Health reports that hPG "supplied by the Australian Pituitary Advisory Committee" was used in 14 infertile ovulatory women with total tubal destruction who were candidates for IVF.’ How many other ovulatory women were conditioned for IVF with hPG between 1976 and 1985? Information provided to the Australian Federal Parliament6 indicates that about 1500 infertile Australian women received hPG but the proportion who were ovulatory remains unknown. By 1988, despite the emergence of further cases, it was being suggested that the threat of an epidemic of iatrogenic CJD had passed.’ That claim was supported by a 1988 report that CJD had not occurred in 1698 hGH-treated individuals in France. By mid1991, however, 3 French cases had been reported; a year later, 2 more had been confirmed and, as Dr Brown and his colleagues note in their latest review (July 4, p 24), at least another 6 suspected cases amongst that French cohort await confirmation. Iatrogenic CJD remains a threat in the UK2 and USAtoo. The 1991 US review points out that "the great majority of potentially exposed patients have not yet attained the requisite incubation period for expression of CJD". The interval between the mid-point of hGH treatment and the onset of CJD symptoms had averaged 15 years. In Australia only 104 of 2003 known Australian treatments (many women had more than one) were administered between 1964 and 1969.6 In the USA, monitoring, surveillance, and counselling of individuals at risk began immediately after the first CJD death in 1985. In the UK, the past 4 years have been spent tracing hGH-treated individuals8 but it was only after the sixth UK death in 1991 that the Department of Health agreed to a complete programme of information. Even though 90% of British recipients have been traced, less than half have been notified. Those involved have unsuccessfully sought compensation from the Government and are now pursuing litigation.9 In 1985, the Australian Department of Health wrote to the clinicians who had used hPG advising them to tell patients of the risk of CJD and this advice was reissued in 1991 and again this year. However, by mid-1992 only one-quarter of the women had been contacted.6 We are aware of 10 women who suspect that they were so treated in the 1970s but who cannot find out whether they were exposed to hPG or not. To the psychological stress of this uncertainty must be added the risk not