Addressing Parents' Concerns: Do Vaccines Contain Harmful Preservatives, Adjuvants, Additives, or Residuals?

Pediatrics

Volumn 112, Issue 6 I, 2003, Pages 1394-1401

  Offit, Paul A ^a,b   Jew, Rita K ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Aluminum; Egg proteins; Formaldehyde; Gelatin; Thimerosal; Vaccine safety; Yeast proteins

Indexed keywords

ADJUVANT; ALUMINUM; ANTIBIOTIC AGENT; BIAVAX II; CHICKENPOX VACCINE; DIPHTHERIA PERTUSSIS TETANUS HAEMOPHILUS INFLUENZAE TYPE B VACCINE; DIPHTHERIA PERTUSSIS TETANUS VACCINE; DIPHTHERIA TETANUS VACCINE; DIPLOID CELL VACCINE; DRUG ADDITIVE; DRUG PRESERVATIVE; DRUG RESIDUE; DT; EGG PROTEIN; ENGERIX; FORMALDEHYDE; FUNGAL PROTEIN; GELATIN; HAEMOPHILUS INFLUENZAE TYPE B HEPATITIS B VACCINE; HAEMOPHILUS INFLUENZAE TYPE B VACCINE; HEPATITIS A HEPATITIS B VACCINE; HEPATITIS A VACCINE; HEPATITIS B VACCINE; HUMAN SERUM ALBUMIN; INACTIVATED VACCINE; INFLUENZA VACCINE; IPOL; JAPANESE ENCEPHALITIS VACCINE; MEASLES VACCINE; MENINGOCOCCUS VACCINE; MERCURY; MMR II; MRVAX II; MUMPS VACCINE; PEDIARIX; PEDVAX HIB; PNEU IMMUNE 23; PNEUMOCOCCUS POLYSACCHARIDE; PNEUMOCOCCUS VACCINE; POLIOMYELITIS VACCINE; RABIES VACCINE; RECOMBINANT HEPATITIS B VACCINE; RUBELLA VACCINE; THIOMERSAL; TYPHOID VACCINE; UNINDEXED DRUG; VACCINE;

DRUG INFORMATION; DRUG MANUFACTURE; DRUG SAFETY; HUMAN; IMMEDIATE TYPE HYPERSENSITIVITY; INTERNET; PARENT; PRIORITY JOURNAL; REVIEW; VACCINATION;

ADJUVANTS, PHARMACEUTIC; ANIMALS; BIOLOGICAL PRODUCTS; DRUG CONTAMINATION; DRUG STORAGE; HUMANS; PHARMACEUTIC AIDS; PRESERVATIVES, PHARMACEUTICAL; RISK; VACCINES;

EID: 0346220247     PISSN: 00314005     EISSN: None     Source Type: Journal    
DOI: 10.1542/peds.112.6.1394     Document Type: Review

References (97)

1. Wilson GS. The Hazards of Immunization. New York, NY: The Althone Press; 1967:75-84
2. General Biologics Product Standards; Constituent materials. Ingredients, preservatives, diluents, and adjuvants. 21 CFR: 610.15 (a)
3. 21 USC 397 Section 413
4. Stratton K, Gable A, McCormick MC, eds. Immunization Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental Disorders. Washington, DC: National Academy Press; 2001
5. Goldstein BD. The precautionary principle also applies to public health actions. Am J Public Health. 2001;91:1358-1361
6. Hay WJ, Rickerts AG, McMenemey WH, Cumings JN. Organic mercurial encephalopathy. Neurol Neurosurg Psychiatry. 1963;26:199-202
7. Axton JHM. Six cases of poisoning after a parenteral organic mercury compound (Merthiolate). Postgrad Med J. 1972;48:417-421
8. Fagan DG, Pritchard JS, Clarkson TW, Greenwood MR. Organ mercury levels in infants with omphaloceles treated with organic mercury antiseptic. Arch Dis Child. 1977;52:962-964
9. Cinca I, Dumitrescu I, Onaca P, et al. Accidental ethyl mercury poisoning with nervous system, skeletal muscle, and myocardium injury. J Neurol Neurosurg Psychiatry. 1979;43:143-149
10. Rohyans J, Walson PD, Wood GA, MacDonald WA. Mercury toxicity following merthiolate ear irrigations. J Pediatr. 1984;104:311-313
11. Pfab R, Muckter H, Roider G, Zilker T. Clinical course of severe poisoning with thiomersal. Clin Toxicol. 1996;34:453-460
12. Marsh DO, Clarkson TW, Cox C, et al. Fetal methylmercury poisoning: relationship between concentration in single strands of maternal hair and child effects. Arch Neurol. 1987;44:1017-1022
13. Pichichero ME, Cernichiari E, Lopreiato J, Treanor J. Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study. Lancet. 2002;360:1737-1741
14. Strömland K, Nordin V, Miller M, et al. Autism in thalidomide embryopathy: a population study. Dev Med Child Neurol. 1994;36:351-356
15. Rodier PM. The early origins of autism. Sci Am. 2000;February:56-63
16. Chess S, Fernandez P, Korn S. Behavioral consequences of congenital rubella. J Pediatr. 1978;93:699-703
17. Deykin EY, MacMahon B. Viral exposure and autism. Am J Epidemiol. 1979;109:628-638
18. American Academy of Pediatrics. Committee on Infectious Diseases and Committee on Environmental Health. Thimerosal in vaccines - an interim report to clinicians. Pediatrics. 1999;104:570-574
19. Centers for Disease Control and Prevention. Impact of the 1999 AAP/USPHS joint statement on thimerosal in vaccines on infant hepatitis B vaccination practices. MMWR Morb Mortal Wkly Rep. 2001;50:94-97.
20. Hurie MB, Saari TN, Davis JP. Impact of the joint statement by the American Academy of Pediatrics/US Public Health Service on thimerosal in vaccines on hospital infant hepatitis B vaccination practices. Pediatrics. 2001;107:755-758
21. Brayden RM, Pearson KA, Jones JS, et al. Effect of thimerosal recommendations on hospitals' neonatal hepatitis B vaccination policies. J Pediatr. 2001;138:752-755
22. Watson B. Comment. In: Transcript of the National Vaccine Advisory Committee Workshop on Thimerosal in Vaccines. Bethesda, MD: US Government Printing Office; August 12, 1999
23. Centers for Disease Control and Prevention. Recommendations regarding the use of vaccines that contain thimerosal as a preservative. MMWR Morb Mortal Wkly Rep. 1999;48:996-998
24. Freed GL, Andreae M. Presentation to Immunization Safety Review Committee. History of Thimerosal Concern and Comparative Policy Actions; Cambridge, Massachusetts; July 16, 2001
25. Shirodkar S, Hutchinson RL, Perry DL, et al. Aluminum compounds used as adjuvants in vaccines. Pharm Res. 1990;7:1282-1288
26. Glenny AT, Pope CG, Waddington H, Wallace U. The antigenic value of toxoid precipitated by potassium alum. J Pathol Bacteriol. 1926;29:38-39
27. Volk VK, Bunney WE. Diphtheria immunization with fluid toxoid and alum-precipitated toxoid. Am J Public Health. 1942;32:690-699
28. Barr M, Glenney AT, Hignett S, et al. Antigenic efficiency of fluid and precipitated diphtheria prophylactics in very young babies and lambs. Lancet. 1952;2:803-805
29. Barr M, Glermy AT, Butler NR. Immunization of babies with diphtheriatetanus-pertussis prophylactic. Br Med J. 1955;2:635-639
30. Greenberg L, Benoit R. Control of potency and the dosage of diphtheria and tetanus toxoids. JAMA. 1956;160:108-113
31. Glenny AT, Butler AH, Stevens MF. Rate of disappearance of diphtheria toxoid injected into rabbits and guinea pigs: toxoid precipitated with alum. J Pathol Bacteriol. 1931;34:267-275
32. Mannhalter JW, Neychev HO, Zlabinger GJ, et al. Modulation of the immune response by the non-toxic and non-pyrogenic adjuvant aluminum hydroxide: effect on antigen uptake and antigen presentation. Clin Exp Immunol. 1985;61:143-151
33. Ulanova M, Tarkowsi A, Hahn-Zoric M, Hanson LA. The common vaccine adjuvant ahtminum hydroxide upregulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun. 2001;69:1151-1159
34. Ramanathan VD, Badenoch-Jones P, Turk JL. Complement activation by aluminum and zirconium compounds. Immunology. 1979;37:881-888
35. Gupta RK, Rost BE, Relyveld E, Siber GR. Adjuvant properties of aluminum and calcium compounds. In: Powell MF, Newman MJ, eds. Vaccine Design: The Subunit and Adjuvant Approach. New York, NY: Plenum Press; 1995:229-248
36. Koo WWK, Kaplan LA, Krug-Wispe SK. Aluminum contamination of infant formulas. J Parenteral Nutr. 1988;12:170-173
37. Weintraub R, Hams G, Meerkin M, Rosenberg AR. High aluminum content of infant milk formulas. Arch Dis Child. 1986;61:914-916
38. Simmer K, Fudge A, Teubner J, James SL. Aluminum concentrations in infant milk formulae. J Paediatr Child Health. 1990;26:9-11
39. Hawkins NM, Coffey S, Lawson MS, Delves HT. Potential aluminum toxicity in infants fed special infant formula. J Paediatr Gastroenterol Nutr. 1994;19:377-381
40. Mandic ML, Grgic J, Grgic Z, et al. Aluminum levels in human milk. Sci Total Environ. 1995;170:165-170
41. Keith LS, Jones DE, Chou C. Aluminum toxicokinetics regarding infant diet and vaccination. Vaccine. 2002;20:S13-S17
42. Golub MS, Donald JM, Gershwin ME, Keen CL. Effects of aluminum ingestion on spontaneous motor activity of mice. Neurotoxicol Teratol. 1989;11:231-235
43. Toxicological Profile for Aluminum. Atlanta, GA: US Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry; 1999
44. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol. 1993;91:867-872
45. Herman JJ, Radin R, Schneiderman R. Allergic reactions to measles (rubeola) vaccine in patients hypersensitive to egg proteins. J Pediatr. 1983;102:196-199
46. Sakaguchi M, Ogura H, Inouye S. IgE antibody to gelatin in children with immediate-type reactions to measles and mumps vaccines. J Allergy Clin Immunol. 1995;96:563-565
47. Centers for Disease Control and Prevention. Update: vaccine side effects, adverse reactions, contraindications, and precautions. MMWR Morb Mortal Wkly Rep. 1996;45:1-35
48. Sakaguchi M, Nakayama T, Fujita H, et al. Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin. Vaccine. 2001;19:431-436
49. Sakai Y, Yamoto R, Onuma M, et al. Non-antigenic and low allergic gelatin produced by specific digestion with enzyme-coupled matrix. Biol Pharm Bull. 1998;21:330-334
50. Nakayama T, Aizawa C. Change in gelatin content of vaccines associated with reduction in reports of allergic reactions. J Allergy Clin Immunol. 2000;106:591-592
51. Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol. 1996;98:1058-1061
52. Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated systemic reactions to gelatin included in the varicella vaccine. J Allergy Clin Immunol. 1997;99:263-264
53. Sakaguchi M, Hori H, Ebihara T, et al. Reactivity of the immunoglobulin E in bovine gelatin-sensitive children to gelatins from other animals. Immunology. 1999;96:286-290
54. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP). MMWR Morb Mortal Wkly Rep. 2002;51:17
55. Tyler KL. Prions and prion diseases of the central nervous system (transmissible neurodegenerative diseases). In Mandell GL, Bennett JE, Dolin R, eds. Principles and Practices of Infectious Diseases. Philadelphia, PA: Churchill Livingstone; 2000
56. Britton TC, Al-Sarraj S, Shaw C, et al. Sporadic Creutzfeld-Jacob disease in a 16-year-old in the UK. Lancet. 1995;346:1155
57. Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeld-Jacob disease in the UK. Lancet. 1996;347:921-925
58. Zeidler M, Stewart GE, Barraclough CR, et al. New variant Creutzfeld-Jacob disease: neurologic features and diagnostic tests. Lancet. 1997;350:903-907
59. Schonberger L, New variant Creutzfeld-Jacob disease and bovine spongiform encephalopathy. Infect Dis Clin North Am. 1998;12:111-121
60. Anderson RM, Donnelly CA, Ferguson NM, et al. Transmission dynamics and epidemiology of BSE in British cattle. Nature. 1996;382:779
61. Delys J-P, Lasmexas CI, Streichenberger N, et al. New variant Creutzfeld-Jacob disease in France. Lancet. 1997;349:30-31
62. Collinge J, Sidle KCL, Meads J, et al. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature. 1996;383:685-690
63. Parchi P, Capellari S, Chen SG, et al. Typing prion isoforms. Nature. 1997;386:232
64. Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that 'new variant' CJD is caused by BSE agent. Nature. 1997;389:498-501
65. Marwick C. FDA calls bovine-based vaccines currently safe. JAMA. 2000;284:1231-1232
66. Petersen M, Winter G. 5 drug makers use material with possible mad cow link. New York Times. 2001;February 8:C1
67. Brown P. Can Creutzfeld-Jacob disease be transmitted by transfusion? Curr Opin Hematol. 1995;2:472-477
68. Collins S, Law MG, Fletcher A, et al. Surgical treatment and risk of sporadic Creutzfeld-Jacob disease: a case-control study. Lancet. 1999;353:693-697
69. Esmonde TF, Will RG, Slattery JM, et al. Creutzfeld-Jacob disease and blood transfusion. Lancet. 1993;341:205-207
70. Minor PD, Will RG, Salisbury D. Vaccines and variant CJD. Vaccine. 2001;19:409-410
71. Goldmacher VS, Thilly WG. Formaldehyde is mutagenic for cultured human cells. Mutat Res. 1983;116:417-422
72. Ragan DL, Boreiko CJ. Initiation of C3H/10T1/2 cell transformation by formaldehyde. Cancer Lett. 1981;13:325-331
73. Epidemiology of chronic occupational exposure to formaldehyde: report of the ad hoc panel on health aspects of formaldehyde. Toxicol Ind Health. 1988;4:77-90
74. Natarajan AT, Darroudi F, Bussman CJM, van Kesteren-van Leeuwen AC. Evaluation of the mutagenicity of formaldehyde in mammalian cytogenetic assays in vivo and in vitro. Mutat Res. 1983;122:355-360
75. Til HP, Woutersen RA, Feron VJ, et al. Two-year drinking-water study of formaldehyde in rats. Food Chem Toxicol. 1989;27:77-87
76. Huennekens FM, Osborne MJ. Fotic acid coenzymes and one-carbon metabolism. Adv Enzymol. 1959;21:369-446
77. 2O under controlled conditions. Am Ind Hyg Assoc J. 1985;;46:1-3
78. Anderson JA, Adkinson NF. Allergic reactions to drugs and biologic agents. JAMA. 1987;258:2891-2899
79. Yunginger JW. Anaphylaxis. Curr Probl Pediatr. 1992;22:130-146
80. Goh CL. Anaphylaxis from topical neomycin and bacitracin. Aust J Dermatol. 1986;27:125-126
81. Kwittken PL, Rosen S, Sweinberg SK. MMR vaccine and neomycin allergy. Am J Dis Child. 1993;147:128-129
82. Leyden JJ, Kligman AM. Contact dermatitis to neomycin sulfate. JAMA. 1979;242:1276-1278
83. MacDonald RH, Beck M. Neomycin: a review with particular reference to dermatological usage. Clin Exp Dermatol. 1983;8:249-258
84. Ratner B, Untracht S. Egg allergy in children. Am J Dis Child. 1952;83:309-316
85. Bierman CW, Shapiro GG, Pierson WE, et al. Safety of influenza vaccination in allergic children. J Infect Dis. 1977;136:S652-S655
86. James JM, Zeiger RS, Lester MR, et al. Safe administration of influenza vaccine to patients with egg allergy. J Pediatr. 1998;133:624-628
87. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25-44
88. Glezen WP, Greenberg SB, Atmar RL, et al. Impact of respiratory virus infection on persons with underlying conditions. JAMA. 2000;283:499-505
89. Murphy KR, Strunk RC. Safe administration of influenza vaccine in asthmatic children hypersensitive to egg proteins. J Pediatr, 1985;106:931-933
90. Zieger RS. Current issues with influenza vaccination in egg allergy. J Allergy Clin Immunol 2002;110:834-840
91. Fasano MB, Wood RA, Cooke SK, Sampson HA. Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine. J Pediatr. 1992;120:878-881
92. James JM, Burks AW, Roberson PK, Sampson HA. Safe administration of the measles vaccine to children allergic to eggs. N Engl J Med. 1995;332:1262-1266
93. Lear JT, English JS. Anaphylaxis after hepatitis B immunization. Lancet. 1995;345:1249
94. Hudson TJ, Newkirk M, Gervais F, Shuster J. Adverse reaction to the recombinant hepatitis B vaccine. J Allergy Clin Immunol. 1991;88:821-822
95. Barbaud A, Tréchot P, Reichert-Pénétrat S, et al. Allergic mechanisms and urticaria/angioedema after hepatitis B immunization. Br J Dermatol. 1998;139:916-941
96. Brightman CA, Scadding GK, Dumbreck LA, et al. Yeast-derived hepatitis B vaccine and yeast sensitivity. Lancet. 1989;i:903
97. Wiederman G, Scheiner O, Ambrosch F, et al. Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines. Int Arch Allergy Appl Immunol. 1988;85:130-132