- Email: [email protected]
Conjugate Hib vaccines
COMMENTARY
The Wagner study makes an important argument in favour of CMR in this non-invasive type of approach, but further research is warranted with functional recovery and cardiac events as outcome, and comparison of a comprehensive CMR strategy to nuclear, echocardiographic, and invasive methods. If CMR is ever to become a significant player in cardiology practice, a higher penetration of the technique in routine cardiac imaging is needed, which probably requires not only more magnetic resonance scanners but increased access to existing scanners for cardiac patients and improved collaboration between the radiology and cardiology communities. Frank E Rademakers Department of Cardiology, University Hospitals Leuven, 3000 Leuven, Belgium (e-mail: [email protected]) 1
Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet 2001; 357: 21–28. 2 Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000; 343: 1445–53. 3 Al-Saadi N, Nagel E, Gross M, et al. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. Circulation 2000; 101: 1379–83. 4 Nagel E, Lehmkuhl HB, Bocksch W, et al. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation 1999; 99: 763–70. 5 Klein C, Nekolla SG, Bengel FM, et al. Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography. Circulation 2002; 105: 162–67. 6 Ibrahim T, Nekolla SG, Schreiber K, et al. Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography. J Am Coll Cardiol 2002; 39: 864–70. 7 Wahba FF, Lamb HJ, Bax JJ, et al. Assessment of regional myocardial wall motion and thickening by gated 99Tcm-tetrofosmin SPECT: a comparison with magnetic resonance imaging. Nucl Med Commun 2001; 22: 663–71. 8 Bogaert J, Maes A, Van de Werf F, et al. Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function. Circulation 1999; 99: 36–43. 9 Panting JR, Gatehouse PD, Yang GZ, et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 2002; 346: 1948–53. 10 Schwitter J, Nanz D, Kneifel S, et al. Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography. Circulation 2001; 103: 2230–35. 11 Kim WY, Danias PG, Stuber M, et al. Coronary magnetic resonance angiography for the detection of coronary stenoses. N Engl J Med 2001; 345: 1863–69.
Conjugate Hib vaccines See page 395 Since their introduction in 1988, Haemophilus influenzae type B (Hib) conjugate vaccines have been administered in various schedules worldwide, although most countries use a two-dose or three-dose primary schedule for infants with a booster administered in the second year of life. Rates of Hib disease in individual countries that use these schedules have fallen gradually after implementation and control of Hib disease has been sustained.1,2 Hib conjugate vaccines were introduced into the UK infant immunisation schedule in October, 1992, with some important differences. Three doses were introduced into the infant immunisation campaign with 360
no provision of a booster in the second year of life, plus a catch-up campaign (a single dose given to all children under the age of 5 years within 1 calendar year of introduction) was implemented.3 The rates of Hib disease in all vaccinated children fell rapidly, as did the rates in unvaccinated children. This herd effect was probably due to the documented reduction in nasopharyngeal carriage, which reduced transmission of Hib to the unvaccinated.3 Thus the initial control of Hib disease in the UK has been influenced by the strategy used to introduce the vaccine—ie, additional catch-up immunisation of children less than 5 years of age. In countries such as the Netherlands where the Hib conjugate vaccine was introduced in 1993 but was only provided within the infant immunisation programme (doses at 2, 4, 6, and 12 months) with no catch-up campaign, it has taken longer to control the disease.2 In this issue of The Lancet, David Garner and Vivienne Weston describe their experience in one small region of the UK where Hib disease has increased since 1998. This mirrors an increase nationally in Hib disease since 1998, predominantly in those under age 2 years,4 and other local reports.5 There are several possible reasons for the increase in Hib disease in the UK. First, the cases could represent a random variation in Hib disease occurrence, since the overall rate is still far lower than that before the use of Hib vaccine, although the increasing trend in numbers of cases suggests other causes may be operating. Second, decreasing herd immunity would mean that continuing circulation of Hib leaves children at risk, including the small proportion who may not have adequate antibody levels after immunisation. This experience may be similar to that in Alaska, where adoption of a less immunogenic vaccine did not protect Alaskan native infants who were exposed to continuing Hib circulation.1 Third, the infant vaccination schedule used in the UK is Hib conjugate at 2, 3, and 4 months only. This early and short schedule without a booster seemed to be effective for the initial years in which it was used. If the unique UK infant schedule alone accounts for vaccine failures, the reason the failures are seen only after many years of use of the schedule, and after substantial reduction in the prevalence of Hib disease, may be related to the waning of the initial impact of the catch-up campaign. Countries with other schedules, which include a later booster dose, do not seem to have a similar pattern of Hib disease in vaccinated infants, with the exception of the Alaskan experience. Fourth, a reduced immune response to Hib vaccines in part of the vaccinated population may be occurring, which could be related to the use of a combination acellular pertussis, diphtheria, tetanus, and Hib vaccine during 2000–01, which produces lower Hib antibody levels, compared with whole-cell pertussis and Hib combinations.6 Most studies of vaccine failures show a reduced antibody response as the major factor.7,8 The addition of the meningococcal conjugate vaccine may have had an effect on the Hib antibody response, although studies of one of the meningococcal conjugates have suggested no such effect.9 What evaluations might provide data to explain these vaccine failures? Studies of Hib colonisation rates of different age cohorts of UK children, including those who were immunised as part of the original catch-up programme for Hib vaccine, and those who received the acellular pertussis and Hib conjugate, by comparison with recipients of the whole-cell pertussis and Hib conjugate vaccine would be informative. Current Hib antibody titres of these cohorts would also be of interest. THE LANCET • Vol 361 • February 1, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Given the apparent increasing trend of Hib cases over several years, it would seem prudent to re-evaluate routine immunisation of infants, and consider the most appropriate schedule, based on the spectrum of vaccines now recommended for UK infants. Some authorities might suggest the adoption of a Hib booster, in the second year of life. *Mark Steinhoff, David Goldblatt *Johns Hopkins University School of Medicine, School of Hygiene, Baltimore, MD 21205, USA (MS); and Institute of Child Health, London, UK (DG) (e-mail: [email protected]) 1 2
3 4
5
6
7
8
9
Granoff DM. Assessing efficacy of Haemophilus influenzae type b combination vaccines. Clin Infect Dis 2001; 33: S278–87. van Alphen L, Spanjaard L, van der Ende A, Schuurman I, Dankert J. Effect of nationwide vaccination of 3-month-old infants in The Netherlands with conjugate Haemophilus influenzae type b vaccine: high efficacy and lack of herd immunity. J Pediatr 1997; 131: 869–73. Heath PT, McVernon J. The UK Hib vaccine experience. Arch Dis Child 2002; 86: 396–99. Public Health Laboratory Service. Surveillance of invasive Haemophilus influenzae infections in children. CDR Weekly Jan 24, 2002: 34. Tanner K, Fitzsimmons G, Carrol ED, Flood TJ, Clark JE. Lesson of the week: Haemophilus influenzae type b epiglottitis as a cause of acute upper airways obstruction in children. BMJ 2002; 325: 1099–100. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet 1999; 354: 2063–68. Heath PT, Booy R, Griffiths H, et al. Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood. Clin Infect Dis 2000; 31: 973–80. Breukels MA, Spanjaard L, Sanders LA, Rijkers GT. Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants. Clin Infect Dis 2001; 32: 1700–05. Richmond P, Borrow R, Findlow J, et al. Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains. Infect Immun 2001; 69: 2378–82.
Acrylamide in food In 1997 work on a waterlogged tunnel for the Swedish National Rail Administration ended in disaster when an acrylamide sealant (grout) leaked out.1 There were consequences for some tunnel workers, who had reversible and generally mild peripheral neurotoxicity,2 and economically for local farmers.3 The neurotoxicity has recently been confirmed in cattle exposed to acrylamide while grazing.4 Follow-up studies of the Swedish incident revealed laboratory markers for the presence of acrylamide at unexpectedly high levels in unexposed controls,2 with animal studies hinting at cooking as the source of this background.5 Matters came to a head with the early release of further Swedish research suggesting that some normal cooking processes yield acrylamide,6 a chemical that the International Agency for Research on Cancer (IARC) labelled a probable human carcinogen in 1994.7 Regulatory agencies and the food industry almost immediately had to face independent confirmation that the Swedish data were reliable. In June of last year UN agencies issued an interim response8 in which they conceded that on present knowledge the human cancer risk, if any, could not be calculated directly. It was equally impossible to say what level of exposure could be deemed safe, nor THE LANCET • Vol 361 • February 1, 2003 • www.thelancet.com
could advice be given about avoiding acrylamide in food or eliminating it. The analyses of foodstuffs heated above 120ºC or so in the laboratory yielded acrylamide concentrations up to 1 mg/kg (or 1 part per million) in carbohydrate-rich foodstuffs. Foods prepared or purchased in restaurants had concentrations up to almost 4 mg/kg (in one sample of potato crisps). However, typical adult dietary exposure was estimated as “a daily intake of a few tens of micrograms of acrylamide”6 and, except for those habituated to gargantuan portions of fried potatoes, for example, the confirmatory pooled results of data from Scandinavia, Switzerland, the UK, and the USA point in the same direction.8 Polyacrylamide is widely used to clarify domestic water supplies, and in the European Union the limit for residual monomer is being tightened to 0·1 g/L. Acrylamide from food wrappings is not likely to be the explanation for the levels found in fried foods (but also bread and breakfast cereals); contamination from that source is also controlled, at no more than 10 g/kg. The biggest epidemiological study in chemical workers was essentially negative for a causal association between exposure to acrylamide (by the respiratory route) and cancer at any site,9 and the IARC classification is an extrapolation from laboratory animal studies. A model for cancer risk assessment, involving genotoxicity and the acrylamide metabolite glycidamide, has been devised.10 One of several gaps in knowledge highlighted by the FAO/WHO report8 was the mechanism by which acrylamide could be formed by heating. Work in the UK, Switzerland, and Canada has provided an answer to that.11–13 In 1912 Louis Camille Maillard described a condensation reaction between protein and carbohydrate that has since become almost a subspecialty of organic chemistry. Maillard reactions contribute to the colour and flavour of cooked foods, but UK food scientists found that a reaction between asparagine, an aminoacid strongly represented in potatoes and cereals, and a reducing sugar could yield acrylamide.11 Data from the Nestlé Research Centre in Switzerland point in a similar direction, although this work focuses on N-glycosides formed as early Maillard reaction products, and the Nestlé workers used isotopes to confirm asparagine as a supplier of carbon and nitrogen in acrylamide.12 The sequence of events is not a simple A+B=C.14 The practical consequences of these findings for the Food and Drug Administration (FDA) and others— “nobody wants [acrylamide] in the food supply”, says FDA deputy commissioner Lester Crawford15—are not immediately obvious. Indeed translation of all the acrylamide data into sensible public-health advice is proving very difficult. In early December, 2002, the American Council on Science and Health issued a position paper16 presented as “No credible evidence that acrylamide in foods poses human cancer risk”. New Zealand food safety experts, using a “no observable adverse effect level” for acrylamide of 0·1 mg/kg bodyweight, also estimate that people eating fried potato and crisps are at a very low risk of cancer from this source.17 European Union experts, on the other hand, state that the risk from exposure to acrylamide cannot be determined.18 Similarly, the FDA, with its very public current debate on acrylamide, emphasises what we still do not know.19 David Sharp c/o The Lancet, London NW1 7BY, UK
361
For personal use. Only reproduce with permission from The Lancet Publishing Group.
The Wagner study makes an important argument in favour of CMR in this non-invasive type of approach, but further research is warranted with functional recovery and cardiac events as outcome, and comparison of a comprehensive CMR strategy to nuclear, echocardiographic, and invasive methods. If CMR is ever to become a significant player in cardiology practice, a higher penetration of the technique in routine cardiac imaging is needed, which probably requires not only more magnetic resonance scanners but increased access to existing scanners for cardiac patients and improved collaboration between the radiology and cardiology communities. Frank E Rademakers Department of Cardiology, University Hospitals Leuven, 3000 Leuven, Belgium (e-mail: [email protected]) 1
Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet 2001; 357: 21–28. 2 Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000; 343: 1445–53. 3 Al-Saadi N, Nagel E, Gross M, et al. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. Circulation 2000; 101: 1379–83. 4 Nagel E, Lehmkuhl HB, Bocksch W, et al. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation 1999; 99: 763–70. 5 Klein C, Nekolla SG, Bengel FM, et al. Assessment of myocardial viability with contrast-enhanced magnetic resonance imaging: comparison with positron emission tomography. Circulation 2002; 105: 162–67. 6 Ibrahim T, Nekolla SG, Schreiber K, et al. Assessment of coronary flow reserve: comparison between contrast-enhanced magnetic resonance imaging and positron emission tomography. J Am Coll Cardiol 2002; 39: 864–70. 7 Wahba FF, Lamb HJ, Bax JJ, et al. Assessment of regional myocardial wall motion and thickening by gated 99Tcm-tetrofosmin SPECT: a comparison with magnetic resonance imaging. Nucl Med Commun 2001; 22: 663–71. 8 Bogaert J, Maes A, Van de Werf F, et al. Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function. Circulation 1999; 99: 36–43. 9 Panting JR, Gatehouse PD, Yang GZ, et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med 2002; 346: 1948–53. 10 Schwitter J, Nanz D, Kneifel S, et al. Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography. Circulation 2001; 103: 2230–35. 11 Kim WY, Danias PG, Stuber M, et al. Coronary magnetic resonance angiography for the detection of coronary stenoses. N Engl J Med 2001; 345: 1863–69.
Conjugate Hib vaccines See page 395 Since their introduction in 1988, Haemophilus influenzae type B (Hib) conjugate vaccines have been administered in various schedules worldwide, although most countries use a two-dose or three-dose primary schedule for infants with a booster administered in the second year of life. Rates of Hib disease in individual countries that use these schedules have fallen gradually after implementation and control of Hib disease has been sustained.1,2 Hib conjugate vaccines were introduced into the UK infant immunisation schedule in October, 1992, with some important differences. Three doses were introduced into the infant immunisation campaign with 360
no provision of a booster in the second year of life, plus a catch-up campaign (a single dose given to all children under the age of 5 years within 1 calendar year of introduction) was implemented.3 The rates of Hib disease in all vaccinated children fell rapidly, as did the rates in unvaccinated children. This herd effect was probably due to the documented reduction in nasopharyngeal carriage, which reduced transmission of Hib to the unvaccinated.3 Thus the initial control of Hib disease in the UK has been influenced by the strategy used to introduce the vaccine—ie, additional catch-up immunisation of children less than 5 years of age. In countries such as the Netherlands where the Hib conjugate vaccine was introduced in 1993 but was only provided within the infant immunisation programme (doses at 2, 4, 6, and 12 months) with no catch-up campaign, it has taken longer to control the disease.2 In this issue of The Lancet, David Garner and Vivienne Weston describe their experience in one small region of the UK where Hib disease has increased since 1998. This mirrors an increase nationally in Hib disease since 1998, predominantly in those under age 2 years,4 and other local reports.5 There are several possible reasons for the increase in Hib disease in the UK. First, the cases could represent a random variation in Hib disease occurrence, since the overall rate is still far lower than that before the use of Hib vaccine, although the increasing trend in numbers of cases suggests other causes may be operating. Second, decreasing herd immunity would mean that continuing circulation of Hib leaves children at risk, including the small proportion who may not have adequate antibody levels after immunisation. This experience may be similar to that in Alaska, where adoption of a less immunogenic vaccine did not protect Alaskan native infants who were exposed to continuing Hib circulation.1 Third, the infant vaccination schedule used in the UK is Hib conjugate at 2, 3, and 4 months only. This early and short schedule without a booster seemed to be effective for the initial years in which it was used. If the unique UK infant schedule alone accounts for vaccine failures, the reason the failures are seen only after many years of use of the schedule, and after substantial reduction in the prevalence of Hib disease, may be related to the waning of the initial impact of the catch-up campaign. Countries with other schedules, which include a later booster dose, do not seem to have a similar pattern of Hib disease in vaccinated infants, with the exception of the Alaskan experience. Fourth, a reduced immune response to Hib vaccines in part of the vaccinated population may be occurring, which could be related to the use of a combination acellular pertussis, diphtheria, tetanus, and Hib vaccine during 2000–01, which produces lower Hib antibody levels, compared with whole-cell pertussis and Hib combinations.6 Most studies of vaccine failures show a reduced antibody response as the major factor.7,8 The addition of the meningococcal conjugate vaccine may have had an effect on the Hib antibody response, although studies of one of the meningococcal conjugates have suggested no such effect.9 What evaluations might provide data to explain these vaccine failures? Studies of Hib colonisation rates of different age cohorts of UK children, including those who were immunised as part of the original catch-up programme for Hib vaccine, and those who received the acellular pertussis and Hib conjugate, by comparison with recipients of the whole-cell pertussis and Hib conjugate vaccine would be informative. Current Hib antibody titres of these cohorts would also be of interest. THE LANCET • Vol 361 • February 1, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
COMMENTARY
Given the apparent increasing trend of Hib cases over several years, it would seem prudent to re-evaluate routine immunisation of infants, and consider the most appropriate schedule, based on the spectrum of vaccines now recommended for UK infants. Some authorities might suggest the adoption of a Hib booster, in the second year of life. *Mark Steinhoff, David Goldblatt *Johns Hopkins University School of Medicine, School of Hygiene, Baltimore, MD 21205, USA (MS); and Institute of Child Health, London, UK (DG) (e-mail: [email protected]) 1 2
3 4
5
6
7
8
9
Granoff DM. Assessing efficacy of Haemophilus influenzae type b combination vaccines. Clin Infect Dis 2001; 33: S278–87. van Alphen L, Spanjaard L, van der Ende A, Schuurman I, Dankert J. Effect of nationwide vaccination of 3-month-old infants in The Netherlands with conjugate Haemophilus influenzae type b vaccine: high efficacy and lack of herd immunity. J Pediatr 1997; 131: 869–73. Heath PT, McVernon J. The UK Hib vaccine experience. Arch Dis Child 2002; 86: 396–99. Public Health Laboratory Service. Surveillance of invasive Haemophilus influenzae infections in children. CDR Weekly Jan 24, 2002: 34. Tanner K, Fitzsimmons G, Carrol ED, Flood TJ, Clark JE. Lesson of the week: Haemophilus influenzae type b epiglottitis as a cause of acute upper airways obstruction in children. BMJ 2002; 325: 1099–100. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet 1999; 354: 2063–68. Heath PT, Booy R, Griffiths H, et al. Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood. Clin Infect Dis 2000; 31: 973–80. Breukels MA, Spanjaard L, Sanders LA, Rijkers GT. Immunological characterization of conjugated Haemophilus influenzae type b vaccine failure in infants. Clin Infect Dis 2001; 32: 1700–05. Richmond P, Borrow R, Findlow J, et al. Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains. Infect Immun 2001; 69: 2378–82.
Acrylamide in food In 1997 work on a waterlogged tunnel for the Swedish National Rail Administration ended in disaster when an acrylamide sealant (grout) leaked out.1 There were consequences for some tunnel workers, who had reversible and generally mild peripheral neurotoxicity,2 and economically for local farmers.3 The neurotoxicity has recently been confirmed in cattle exposed to acrylamide while grazing.4 Follow-up studies of the Swedish incident revealed laboratory markers for the presence of acrylamide at unexpectedly high levels in unexposed controls,2 with animal studies hinting at cooking as the source of this background.5 Matters came to a head with the early release of further Swedish research suggesting that some normal cooking processes yield acrylamide,6 a chemical that the International Agency for Research on Cancer (IARC) labelled a probable human carcinogen in 1994.7 Regulatory agencies and the food industry almost immediately had to face independent confirmation that the Swedish data were reliable. In June of last year UN agencies issued an interim response8 in which they conceded that on present knowledge the human cancer risk, if any, could not be calculated directly. It was equally impossible to say what level of exposure could be deemed safe, nor THE LANCET • Vol 361 • February 1, 2003 • www.thelancet.com
could advice be given about avoiding acrylamide in food or eliminating it. The analyses of foodstuffs heated above 120ºC or so in the laboratory yielded acrylamide concentrations up to 1 mg/kg (or 1 part per million) in carbohydrate-rich foodstuffs. Foods prepared or purchased in restaurants had concentrations up to almost 4 mg/kg (in one sample of potato crisps). However, typical adult dietary exposure was estimated as “a daily intake of a few tens of micrograms of acrylamide”6 and, except for those habituated to gargantuan portions of fried potatoes, for example, the confirmatory pooled results of data from Scandinavia, Switzerland, the UK, and the USA point in the same direction.8 Polyacrylamide is widely used to clarify domestic water supplies, and in the European Union the limit for residual monomer is being tightened to 0·1 g/L. Acrylamide from food wrappings is not likely to be the explanation for the levels found in fried foods (but also bread and breakfast cereals); contamination from that source is also controlled, at no more than 10 g/kg. The biggest epidemiological study in chemical workers was essentially negative for a causal association between exposure to acrylamide (by the respiratory route) and cancer at any site,9 and the IARC classification is an extrapolation from laboratory animal studies. A model for cancer risk assessment, involving genotoxicity and the acrylamide metabolite glycidamide, has been devised.10 One of several gaps in knowledge highlighted by the FAO/WHO report8 was the mechanism by which acrylamide could be formed by heating. Work in the UK, Switzerland, and Canada has provided an answer to that.11–13 In 1912 Louis Camille Maillard described a condensation reaction between protein and carbohydrate that has since become almost a subspecialty of organic chemistry. Maillard reactions contribute to the colour and flavour of cooked foods, but UK food scientists found that a reaction between asparagine, an aminoacid strongly represented in potatoes and cereals, and a reducing sugar could yield acrylamide.11 Data from the Nestlé Research Centre in Switzerland point in a similar direction, although this work focuses on N-glycosides formed as early Maillard reaction products, and the Nestlé workers used isotopes to confirm asparagine as a supplier of carbon and nitrogen in acrylamide.12 The sequence of events is not a simple A+B=C.14 The practical consequences of these findings for the Food and Drug Administration (FDA) and others— “nobody wants [acrylamide] in the food supply”, says FDA deputy commissioner Lester Crawford15—are not immediately obvious. Indeed translation of all the acrylamide data into sensible public-health advice is proving very difficult. In early December, 2002, the American Council on Science and Health issued a position paper16 presented as “No credible evidence that acrylamide in foods poses human cancer risk”. New Zealand food safety experts, using a “no observable adverse effect level” for acrylamide of 0·1 mg/kg bodyweight, also estimate that people eating fried potato and crisps are at a very low risk of cancer from this source.17 European Union experts, on the other hand, state that the risk from exposure to acrylamide cannot be determined.18 Similarly, the FDA, with its very public current debate on acrylamide, emphasises what we still do not know.19 David Sharp c/o The Lancet, London NW1 7BY, UK
361
For personal use. Only reproduce with permission from The Lancet Publishing Group.