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Fieldwork in the tropics: duplicate frozen samples
THE LANCET
We vigorously contest the assertion that parents living outside the immediate vicinity of a regional paediatric ICU would settle for a compromise in standards in order to be closer to home. Experience suggests exactly the opposite; parents will go to any lengths to get the best for their children and they require us to do the same.
have been worth the small extra effort of dividing each sample into two and storing them in different freezers? A not uncommon but avoidable disaster and the stuff of nightmares. It has not happened to me but it easily could have. R David G Theakston Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
reflects the effect of a two-dose schedule in the first year or the use of other vaccines in Germany where there is a lower vaccination coverage of about 78%.3 In populations with different vaccination programmes and coverage, it may be unwise to follow the UK example and switch to no Hib booster vaccinations. *O Böhm, R von Kries
Gale Pearson The Birmingham Children’s Hospital NHS Trust, Ladywood Middleway, Ladywood, Birmingham B16 8ET, UK
Are Hib booster vaccinations redundant?
1
SIR—Robert Booy and co-workers (April 26, p 1197)1 challenge the assumption that a booster dose of Haemophilus influenzae type b (Hib) vaccine is required in the second year of life to ensure protection until school age. This conclusion seems justified in the UK, with a high vaccination coverage, a three-dose vaccination schedule within the first year, and the use of a highly immunogenic vaccine2 for all primary vaccinations. For financial reasons, it may be tempting to abandon Hib booster vaccinations in other populations as well, but in some populations, Hib booster vaccination is mandatory. We have shown3 that the risk for systemic H influenzae infections for infants of 18 months or older was increased by a factor of 25 in those who did not receive a booster dose of Hib before the age of 18 months.3 In accordance with German recommendations, these children had only received two doses of a mono-Hib vaccine or three doses of the combined Hib-DPT vaccine in the first year of life, most were given two doses of the monovaccine. Subgroup analyses of the UK data1 suggested a lower efficacy for children in whom the third dose had been omitted. We therefore reanalysed our data with respect to that subgroup (two vaccinations only in first year of life: nine cases, 15 controls; two vaccinations in first year of life plus booster: one case, 39 controls). The risk of systemic H influenzae infection in children older than 18 months was increased by a factor of 23·4 in children with two vaccinations only, compared with children given the recommended booster vaccination before the 18th month (odds ratio 23·40 [95% CI 2·7–200·9]). The figures are based on all cases with confirmed systemic H influenzae infection. For two of these cases, typing confirmed the Hib serotype. For the remaining eight patients in whom serotyping was not done, type b is most likely because 80% of typed cases were of Hib serotype.3 Our data do not show whether the increased risk associated with the absence of the booster vaccinations
2
3
4
Shann F, Pearson G, Slater A, Wilkinson K. Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care. Intens Care Med 1997; 23: 201–07. Haines L, Pollock J. A retrospective survey of paediatric intensive care provision and utilisation in the North West Region. Manchester, UK: North West Regional Health Authority, February, 1996. Haines L, Pollock J, Scrivener R. Report on a prospective study of intensive care utilisation in the North West Region. Manchester, UK: North West Regional Health Authority, December, 1996. Shann F. A critical appraisal of “the care of critically ill children”. In: Which way forward for the care of critically ill children?.York, UK: NHS Centres for Reviews and Dissemination, 1994.
Fieldwork in the tropics: duplicate frozen samples SIR—How many times has it happened? You have spent hundreds of hours writing grant applications to a wide range of funding bodies. After as many rejections as a budding novelist you finally get the money for a clinical trial of say, a new antivenom against snakebite. The protocol is approved, the team selected, the antivenoms delivered to the site, and the study begins. Accurately timed serial blood samples are obtained from patients meeting the stringent entry criteria who have been randomised to treatment with one of two or three antivenoms. The samples are unique, a thousand times more valuable than gold or platinum. At first, they are stored in a hospital in the rural tropics where the power supply for the freezer is unreliable so you have had to get hold of a back-up generator at great expense, and you have had to beg, borrow, or steal fuel to keep it running. Finally, you manage to transport the samples to your laboratory in the UK, after considerable effort in organising an efficient cold chain from rural northern Nigeria, central Sri Lanka, or the Brazilian Amazon. Then your freezer breaks down over the weekend; no one hears the alarm and all those priceless samples are lost for ever. Would it not
68
Institute for Social Paediatrics and Adolescent Medicine, Ludwig Maximilians University, D-81377 Munich, Germany
1
2
3
Booy R, Heath PT, Slack MPE, et al.Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster. Lancet 1997; 349: 1197–202. Booy R,Taylor SA, Dobson SRM, et al. Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule. Arch Dis Child 1992; 67: 475–78. von Kries R, Böhm O,Windfuhr A. Haemophilus influenzae b-vaccination: the urgency for timely vaccination. Eur J Pediatr 1987; 156: 282–87.
Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy SIR—Andrew Hill and colleagues (Jan 11, p 99)1 report that both immunohistochemistry and Western blotting revealed the presence of abnormal replication of proteaseresistant prion protein (PrP) within the tonsillar germinal centres of a patient with new variant Creutzfeldt-Jakob disease (nvCJD). David J Evans (May 3, p 1323)2 points out that examination of the immunohistochemistry of other sites that contain dendritic reticulum cells is needed. We found that no abnormal deposition of PrP could be detected by immunohistochemistry, western blot, or both in various lymphoreticular tissues in 11 Japanese patients with CJD or Gerstmann-Sträussler-Scheinker syndrome. The diagnoses were confirmed by immunohistochemistry and western blotting for PrP in the brains, and analysis of prion-protein gene (PRNP). We identified follicular dendritic cells in the formalin-fixed tissues by immunohistochemistry with anti-CD35 monoclonal antibody (BerMAC-DRC, DAKO),3 and PrP was detected by anti-PrP monoclonal antibody. Ten of the 11 patients had homozygous methionine at codon 129 of PRNP. One patient had heterozygous valine and methionine. In seven patients, immunohistochemistry with anti-CD35 monoclonal antibody revealed the characteristic features of the follicular dendritic cells with multiple dendritic processes encasing the surrounding lymphocytes, located in the white pulp of the spleen or the germinal centres of
Vol 350 • July 5, 1997
We vigorously contest the assertion that parents living outside the immediate vicinity of a regional paediatric ICU would settle for a compromise in standards in order to be closer to home. Experience suggests exactly the opposite; parents will go to any lengths to get the best for their children and they require us to do the same.
have been worth the small extra effort of dividing each sample into two and storing them in different freezers? A not uncommon but avoidable disaster and the stuff of nightmares. It has not happened to me but it easily could have. R David G Theakston Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
reflects the effect of a two-dose schedule in the first year or the use of other vaccines in Germany where there is a lower vaccination coverage of about 78%.3 In populations with different vaccination programmes and coverage, it may be unwise to follow the UK example and switch to no Hib booster vaccinations. *O Böhm, R von Kries
Gale Pearson The Birmingham Children’s Hospital NHS Trust, Ladywood Middleway, Ladywood, Birmingham B16 8ET, UK
Are Hib booster vaccinations redundant?
1
SIR—Robert Booy and co-workers (April 26, p 1197)1 challenge the assumption that a booster dose of Haemophilus influenzae type b (Hib) vaccine is required in the second year of life to ensure protection until school age. This conclusion seems justified in the UK, with a high vaccination coverage, a three-dose vaccination schedule within the first year, and the use of a highly immunogenic vaccine2 for all primary vaccinations. For financial reasons, it may be tempting to abandon Hib booster vaccinations in other populations as well, but in some populations, Hib booster vaccination is mandatory. We have shown3 that the risk for systemic H influenzae infections for infants of 18 months or older was increased by a factor of 25 in those who did not receive a booster dose of Hib before the age of 18 months.3 In accordance with German recommendations, these children had only received two doses of a mono-Hib vaccine or three doses of the combined Hib-DPT vaccine in the first year of life, most were given two doses of the monovaccine. Subgroup analyses of the UK data1 suggested a lower efficacy for children in whom the third dose had been omitted. We therefore reanalysed our data with respect to that subgroup (two vaccinations only in first year of life: nine cases, 15 controls; two vaccinations in first year of life plus booster: one case, 39 controls). The risk of systemic H influenzae infection in children older than 18 months was increased by a factor of 23·4 in children with two vaccinations only, compared with children given the recommended booster vaccination before the 18th month (odds ratio 23·40 [95% CI 2·7–200·9]). The figures are based on all cases with confirmed systemic H influenzae infection. For two of these cases, typing confirmed the Hib serotype. For the remaining eight patients in whom serotyping was not done, type b is most likely because 80% of typed cases were of Hib serotype.3 Our data do not show whether the increased risk associated with the absence of the booster vaccinations
2
3
4
Shann F, Pearson G, Slater A, Wilkinson K. Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care. Intens Care Med 1997; 23: 201–07. Haines L, Pollock J. A retrospective survey of paediatric intensive care provision and utilisation in the North West Region. Manchester, UK: North West Regional Health Authority, February, 1996. Haines L, Pollock J, Scrivener R. Report on a prospective study of intensive care utilisation in the North West Region. Manchester, UK: North West Regional Health Authority, December, 1996. Shann F. A critical appraisal of “the care of critically ill children”. In: Which way forward for the care of critically ill children?.York, UK: NHS Centres for Reviews and Dissemination, 1994.
Fieldwork in the tropics: duplicate frozen samples SIR—How many times has it happened? You have spent hundreds of hours writing grant applications to a wide range of funding bodies. After as many rejections as a budding novelist you finally get the money for a clinical trial of say, a new antivenom against snakebite. The protocol is approved, the team selected, the antivenoms delivered to the site, and the study begins. Accurately timed serial blood samples are obtained from patients meeting the stringent entry criteria who have been randomised to treatment with one of two or three antivenoms. The samples are unique, a thousand times more valuable than gold or platinum. At first, they are stored in a hospital in the rural tropics where the power supply for the freezer is unreliable so you have had to get hold of a back-up generator at great expense, and you have had to beg, borrow, or steal fuel to keep it running. Finally, you manage to transport the samples to your laboratory in the UK, after considerable effort in organising an efficient cold chain from rural northern Nigeria, central Sri Lanka, or the Brazilian Amazon. Then your freezer breaks down over the weekend; no one hears the alarm and all those priceless samples are lost for ever. Would it not
68
Institute for Social Paediatrics and Adolescent Medicine, Ludwig Maximilians University, D-81377 Munich, Germany
1
2
3
Booy R, Heath PT, Slack MPE, et al.Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster. Lancet 1997; 349: 1197–202. Booy R,Taylor SA, Dobson SRM, et al. Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule. Arch Dis Child 1992; 67: 475–78. von Kries R, Böhm O,Windfuhr A. Haemophilus influenzae b-vaccination: the urgency for timely vaccination. Eur J Pediatr 1987; 156: 282–87.
Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy SIR—Andrew Hill and colleagues (Jan 11, p 99)1 report that both immunohistochemistry and Western blotting revealed the presence of abnormal replication of proteaseresistant prion protein (PrP) within the tonsillar germinal centres of a patient with new variant Creutzfeldt-Jakob disease (nvCJD). David J Evans (May 3, p 1323)2 points out that examination of the immunohistochemistry of other sites that contain dendritic reticulum cells is needed. We found that no abnormal deposition of PrP could be detected by immunohistochemistry, western blot, or both in various lymphoreticular tissues in 11 Japanese patients with CJD or Gerstmann-Sträussler-Scheinker syndrome. The diagnoses were confirmed by immunohistochemistry and western blotting for PrP in the brains, and analysis of prion-protein gene (PRNP). We identified follicular dendritic cells in the formalin-fixed tissues by immunohistochemistry with anti-CD35 monoclonal antibody (BerMAC-DRC, DAKO),3 and PrP was detected by anti-PrP monoclonal antibody. Ten of the 11 patients had homozygous methionine at codon 129 of PRNP. One patient had heterozygous valine and methionine. In seven patients, immunohistochemistry with anti-CD35 monoclonal antibody revealed the characteristic features of the follicular dendritic cells with multiple dendritic processes encasing the surrounding lymphocytes, located in the white pulp of the spleen or the germinal centres of
Vol 350 • July 5, 1997