Adverse events following immunization: Perception and evidence

Current Opinion in Infectious Diseases

Volumn 20, Issue 3, 2007, Pages 237-246

  Bonhoeffer, Jan ^a   Heininger, Ulrich ^a  

^a UNIVERSITY CHILDREN S HOSPITAL   (Switzerland)

Author keywords

Adverse events; Immunization; Safety

Indexed keywords

ALUMINUM; ALUMINUM DERIVATIVE; ANTHRAX VACCINE; DIPHTHERIA PERTUSSIS TETANUS VACCINE; HAEMOPHILUS INFLUENZAE TYPE B VACCINE; HEPATITIS B VACCINE; IMMUNOLOGICAL ADJUVANT; INFLUENZA VACCINE; MEASLES MUMPS RUBELLA VACCINE; MEASLES VACCINE; MENINGOCOCCUS VACCINE; MUMPS VACCINE; ORAL POLIOMYELITIS VACCINE; PERTUSSIS VACCINE; POLIOMYELITIS VACCINE; ROTAVIRUS VACCINE; RUBELLA VACCINE; SQUALENE; THIOMERSAL;

ANAPHYLAXIS; ASTHMA; ATOPY; AUTISM; BELL PALSY; BRAIN DISEASE; CHRONIC ARTHRITIS; COGNITION; COHORT ANALYSIS; CROHN DISEASE; DRUG SAFETY; EVIDENCE BASED MEDICINE; EYE DISEASE; FASCIITIS; GUILLAIN BARRE SYNDROME; HEALTH CARE ORGANIZATION; HUMAN; HYPOTHESIS; IMMUNIZATION; INSULIN DEPENDENT DIABETES MELLITUS; INTUSSUSCEPTION; LIMB SWELLING; MACROPHAGIC MYOFASCIITIS; MEDICAL SOCIETY; MENINGITIS; MULTIPLE SCLEROSIS; OCULORESPIRATORY SYNDROME; PARALYSIS; RESPIRATORY TRACT DISEASE; REVIEW; THROMBOCYTOPENIA; VACCINATION; VACCINATION REACTION; VACCINE FAILURE;

HUMANS; MASS IMMUNIZATION; ODDS RATIO; PUBLIC OPINION; VACCINATION; VACCINES;

EID: 34247610954     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e32811ebfb0     Document Type: Review

References (94)

1. Rothman KJ, Greenland S. Causation and causal inference in epidemiology. Am J Public Health 2005; 95 (Suppl 1):S144-S150.
2. Folb PI, Bernatowska E, Chen R, et al. A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety. Am J Public Health 2004; 94:1926-1931.
3. Renz H, Blumer N, Virna S, et al. The immunological basis of the hygiene hypothesis. Chem Immunol Allergy 2006; 91:30-48. This review outlines immunoregulatory events potentially involved in the development of allergic disorders in response to environmental triggers.
4. Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy 2006; 36:402-425. This is a comprehensive review on the evolution of the hygiene hypothesis and the pertinent terminology.
5. Nilsson L, Kjellman NI, Bjorksten B. Allergic disease at the age of 7 years after pertussis vaccination in infancy: results from the follow-up of a randomized controlled trial of 3 vaccines. Arch Pediatr Adolesc Med 2003; 157:1184-1189.
6. Anderson HR, Poloniecki JD, Strachan DP, et al. Immunization and symptoms of atopic disease in children: results from the International Study of Asthma and Allergies in Childhood. Am J Public Health 2001; 91:1126-1129.
7. Paunio M, Peltola H, Virtanen M, et al. Acute infections, infection pressure, and atopy. Clin Exp Allergy 2006; 36:634-639. This large study challenged the hygiene hypothesis by showing that atopic constitution is associated with increased susceptibility to acute infections. It also suggests that protection by immunization might be particularly warranted.
8. Nakajima K, Dharmage SC, Carlin JB, et al. Is childhood immunisation associated with atopic disease from age 7 to 32 years? Thorax 2006 Nov 7; [Epub ahead of print]. This large study was unable to demonstrate a causal relation between DTP or polio immunization and atopic disease.
9. Bernsen RM, Koes BW, de Jongste JC, van der Wouden JC. Haemophilus influenzae type b vaccination and reported atopic disorders in 8-12-year-old children. Pediatr Pulmonol 2006; 41:463-469. This large study was unable to show an increased risk of atopic disorders at 8-12 years of age following DTP, DTP-polio (inactivated, IPV) and Haemophilus influenzae type b immunization.
10. Bernsen RM, de Jongste JC, Koes BW, et al. Diphtheria tetanus pertussis poliomyelitis vaccination and reported atopic disorders in 8-12-year-old children. Vaccine 2006; 24:2035-2042. This large study added to the evidence of absence of a relation between DTP-IPV immunization and development of atopic disease.
11. Bergen R, Black S, Shinefield H, et al. Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents. Pediatr Infect Dis J 2004; 23:138-144.
12. Piedra PA, Gaglani MJ, Riggs M, et al. Live attenuated influenza vaccine, trivalent, is safe in healthy children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a community-based, nonrandomized, open-label trial. Pediatrics 2005; 116:e397-e407.
13. Izurieta HS, Haber P, Wise RP, et al. Adverse events reported following live, cold-adapted, intranasal influenza vaccine. JAMA 2005; 294:2720-2725.
14. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, nonspecific colitis, and pervasive developmental disorder in children. Lancet 1998; 351:637-641.
15. Wakefield AJ, Anthony A, Murch SH, et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol 2000; 95:2285-2295.
16. Fombonne E, Zakarian R, Bennett A, et al. Pervasive developmental disorders in Montreal, Quebec, Canada: prevalence and links with immunizations. Pediatrics 2006; 118:e1391-e1450. This study of three birth cohorts provided further evidence, against an association between MMR, ethyl-mercury (thiomersal) and pervasive developmental disorder (including autism) as autism was increasing with decreasing MMR and thiomersal exposure. The highest rates of pervasive developmental disorder were observed in children with no vaccine related thiomersal exposure.
17. Honda H, Shimizu Y, Rutter M. No effect of MMR withdrawal on the incidence of autism: a total population study. J Child Psychol Psychiatry 2005; 46:572-579.
18. Dales L, Hammer SJ, Smith NJ. Time trends in autism and in MMR immunization coverage in California. JAMA 2001; 285:1183-1185.
19. Taylor B, Miller E, Farrington CP, et al. Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. Lancet 1999; 353:2026-2069.
20. Chen W, Landau S, Sham P, Fombonne E. No evidence for links between autism, MMR and measles virus. Psychol Med 2004; 34:543-553.
21. D'Souza Y, Fombonne E, Ward BJ. No evidence of persisting measles virus in peripheral blood mononuclear cells from children with autism spectrum disorder. Pediatrics 2006; 118:1664-1675. This exquisite study uncovered methodological flaws of previous work and refuted the hypothesis of persistence of measles virus in children with autism.
22. Afzal MA, Ozoemena LC, O'Hare A, et al. Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UK. J Med Virol 2006; 78:623-630. This elegant study added microbiological evidence to the rising tide of studies refuting a causal relation between MMR immunization and autism. It could not demonstrate persistence of measles virus in autistic children with development regression.
23. Martin CM, Uhlmann V, Killalea A, et al. Detection of measles virus in children with ileo-colonic lymphoid nodular hyperplasia, enterocolitis and developmental disorder. Mol Psychiatry 2002; 7 (Suppl 2):S47-S48.
24. Kawashima H, Mori T, Kashiwagi Y, et al. Detection and sequencing of measles virus from peripheral mononuclear cells from patients with inflammatory bowel disease and autism. Dig Dis Sci 2000; 45:723-729.
25. Uhlmann V, Martin CM, Sheils O, et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. Mol Pathol 2002; 55:84-90.
26. Ray P, Hayward J, Michelson D, et al. Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study. Pediatr Infect Dis J 2006; 25:768-773. This large case-control study showed no increased relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines.
27. Berkovic SF, Harkin L, McMahon JM, et al. De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study. Lancet Neurol 2006; 5:488-492. This outstanding case series suggests that severe myoclonic epilepsy of infancy (SMEI) due to preexisting mutations in the SCN1A gene represents a considerable part of alleged vaccine encephalopathy.
28. Fourrier A, Begaud B, Alperovitch A, et al. Hepatitis B vaccine and first episodes of central nervous system demyelinating disorders: a comparison between reported and expected number of cases. Br J Clin Pharmacol 2001; 51:489-490.
29. Hernan MA, Jick SS, Olek MJ, Jick H. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2004; 63:838-842.
30. DeStefano F, Weintraub ES, Chen RT. Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study. Neurology 2005; 64:1317.
31. DeStefano F, Verstraeten T, Jackson LA, et al. Vaccinations and risk of central nervous system demyelinating diseases in adults. Arch Neurol 2003; 60:504-509.
32. DeStefano F, Weintraub ES, Chen RT. Determining risk of multiple sclerosis after hepatitis B vaccine: time since vaccination and source of data. Pharmacoepidemiol Drug Saf 2004; 13 (Suppl 1):S143.
33. Hernan MA, Jick SS. Hepatitis B vaccination and multiple sclerosis: the jury is still out. Pharmacoepidemiol Drug Saf 2006; 15:653-655.
34. Piaggio E, Ben Younes A, Desbois S, et al. Hepatitis B vaccination and central nervous system demyelination: an immunological approach. J Autoimmun 2005; 24:33-37.
35. Ozakbas S, Idiman E, Yulug B, et al. Development of multiple sclerosis after vaccination against hepatitis B: a study based on human leucocyte antigen haplotypes. Tissue Antigens 2006; 68:235-238. This was one of the few studies exploring pathophysiologic mechanisms underlying a hypothesized causal relation between hepatitis B immunization and multiple sclerosis: no differences in HLA haplotypes.
36. Safranek TJ, Lawrence DN, Kurland LT, et al. Reassessment of the association between Guillain-Barre syndrome and receipt of swine influenza vaccine in 1976-1977: results of a two-state study. Expert Neurology Group. Am J Epidemiol 1991; 133:940-951.
37. Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barre syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 1998; 339:1797-1802.
38. Centers for Disease Control and Prevention. Update:Guillain-Barre syndrome among recipients of Menactra meningococcal conjugate vaccine-United States, June 2005-September 2006. MMWR Morb Mortal Wkly Rep 2006; 55:1120-1124. This is a comprehensive update on the association between Guillain-Barre syndrome (GBS) and a meningococcal conjugate vaccine (MCV4) concluding that current routine immunization should continue.
39. Hughes RA, Charlton J, Latinovic R, Gulliford MC. No association between immunization and Guillain-Barre syndrome in the United Kingdom, 1992 to 2000. Arch Intern Med 2006; 166:1301-1304. This study suggested no increased risk of GBS following any vaccine.
40. Gherardi RK, Coquet M, Cherin P, et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. Brain 2001; 124:1821-1831.
41. Nevo Y, Kutai M, Jossiphov J, et al. Childhood macrophagic myofasciitis-consanguinity and clinicopathological features. Neuromuscul Disord 2004; 14:246-252.
42. Rivas E, Gomez-Arnaiz M, Ricoy JR, et al. Macrophagic myofasciitis in childhood: a controversial entity. Pediatr Neurol 2005; 33:350-356.
43. Knuf M, Habermehl P, Faber J, et al. Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life. Vaccine 2006; 24:5627-5636. This large study suggested that a reduction of antigen dose correlates with reduced reactogenicity and that entire thigh swelling is most frequently observed in aluminum-free vaccines.
44. Diggle L, Deeks JJ, Pollard AJ. Effect of needle size on immunogenicity and reactogenicity of vaccines in infants: randomised controlled trial. BMJ 2006; 333:563-564. This large study demonstrated that long (25 mm) needles significantly reduce vaccine reactogenicity of infant immunisations compared to (16 mm) needles.
45. Marshall HS, Gold MS, Gent R, et al. Ultrasound examination of extensive limb swelling reactions after diphtheria-tetanus-acellular pertussis or reduced-antigen content diphtheria-tetanus-acellular pertussis immunization in preschool-aged children. Pediatrics 2006; 118:1501-1509. This study furthered the understanding of extensive limb swelling by documenting the localization of the swelling primarily in the subcutaneous tissue.
46. Sekaran NK, Edwards KM. Extensive swelling reaction associated with diphtheria and tetanus toxoids and acellular pertussis vaccine. Pediatr Infect Dis J 2006; 25:374-375. This case report highlights the primarily subcutaneous localization of extensive swelling reactions by computed tomography.
47. Bohlke K, Davis RL, Marcy SM, et al. Risk of anaphylaxis after vaccination of children and adolescents. Pediatrics 2003; 112:815-820.
48. Patja A, Davidkin I, Kurki T, et al. Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up. Pediatr Infect Dis J 2000; 19:1127-1234.
49. Pool V, Braun MM, Kelso JM, et al. Prevalence of antigelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States. Pediatrics 2002; 110:e71.
50. Khakoo GA, Lack G. Recommendations for using MMR vaccine in children allergic to eggs. BMJ 2000; 320:929-932.
51. Goodyear-Smith F, Wong F, Petousis-Harris H, et al. Follow-up of MMR vaccination status in children referred to a pediatric immunization clinic on account of egg allergy. Hum Vaccin 2005; 1:118-122.
52. Kamin W, Staubach P, Klar-Hlawatsch B, et al. Anaphylaxis after vaccination due to hypersensitivity to gelatin. Klin Padiatr 2006; 218:92-94. This well investigated case highlights that MMR immunization is among the medical products potentially triggering gelatin hypersensitivity.
53. Boulianne N, De Serres G, Duval B, et al. Oculo-respiratory syndrome following influenza vaccination: review of postmarketing surveillance through four influenza seasons in Canada. Can Commun Dis Rep 2005; 31:217-225.
54. Scheifele DW, Duval B, Russell ML, et al. Ocular and respiratory symptoms attributable to inactivated split influenza vaccine: evidence from a controlled trial involving adults. Clin Infect Dis 2003; 36:850-857.
55. Grenier JL, Toth E, De Serres G, et al. Safety of revaccination of patients affected by the oculo-respiratory syndrome (ORS) following influenza vaccination. Can Commun Dis Rep 2004; 30:9-16.
56. De Serres G, Boulianne N, Duval B, et al. Oculo-respiratory syndrome following influenza vaccination: evidence for occurrence with more than one influenza vaccine. Vaccine 2003; 21:2346-2353.
57. Skowronski DM, Strauss B, Kendall P, et al. Low risk of recurrence of oculorespiratory syndrome following influenza revaccination. CMAJ 2002; 167:853-858.
58. Skowronski DM, De Serres G, Scheifele D, et al. Randomized, double-blind, placebo-controlled trial to assess the rate of recurrence of oculorespiratory syndrome following influenza vaccination among persons previously affected. Clin Infect Dis 2003; 37:1059-1066.
59. Choudhri Y, Walop W. Influenza vaccine-associated adverse events: results of passive surveillance, Canada 2001-2002. Can Commun Dis Rep 2002; 28:189-196.
60. Skowronski DM, Jacobsen K, Daigneault J, et al. Solicited adverse events after influenza immunization among infants, toddlers, and their household contacts. Pediatrics 2006; 117:1963-1971. This study demonstrated that influenza immunization of infants and toddlers and their household members is well tolerated.
61. Spila-Alegiani S, Salmaso S, Rota MC, et al. Reactogenicity in the elderly of nine commercial influenza vaccines: results from the Italian SVEVA study. Study for the evaluation of adverse events of influenza vaccination. Vaccine 1999; 17:1898-1904.
62. Mutsch M, Zhou W, Rhodes P, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N Engl J Med 2004; 350:896-903.
63. Stowe J, Andrews N, Wise L, Miller E. Bell's palsy and parenteral inactivated influenza vaccine. Hum Vaccin 2006; 2:110-112. This study added to the evidence that currently licensed influenza vaccines are not associated with an increased risk of Bell's palsy.
64. Zhou W, Pool V, DeStefano F, et al. A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: reports to the Vaccine Adverse Event Reporting System (VAERS)-United States, 1991-2001. Pharmacoepidemiol Drug Saf 2004; 13:505-510.
65. Heininger U. An internet-based survey on parental attitudes towards immunization. Vaccine 2006; 24:6351-6355. This study highlighted that misconceptions such as immune overload are still widespread and that intensified public reassurance is needed.
66. Hilton S, Petticrew M, Hunt K. Combined vaccines are like a sudden onslaught to the body's immune system: parental concerns about vaccine 'overload' and 'immune-vulnerability'. Vaccine 2006; 24:4321-4327. This study highlighted the need to more effectively communicate the evidence against overwhelming the immune system of infants by currently licensed vaccines.
67. Gregson AL, Edelman R. Does antigenic overload exist? The role of multiple immunizations in infants. Immunol Allergy Clin North Am 2003; 23:649-664.
68. Offit PA, Quarles J, Gerber MA, et al. Addressing parents' concerns: do multiple vaccines overwhelm or weaken the infant's immune system? Pediatrics 2002; 109:124-129.
69. Cohn M, Langman RE. The protection: the unit of humoral immunity selected by evolution. Immunol Rev 1990; 115:11-147.
70. Shinefield HR, Black SB, Staehle BO, et al. Safety, tolerability and immunogenicity of concomitant injections in separate locations of M-M-R II, VARIVAX and TETRAMUNE in healthy children vs. concomitant injections of M-M-R II and TETRAMUNE followed six weeks later by VARIVAX. Pediatr Infect Dis J 1998; 17:980-985.
71. Heininger U, Sanger R, Jacquet JM, Schuerman L. Booster immunization with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate combination vaccine in the second year of life: Safety, immunogenicity and persistence of antibody responses. Vaccine 2007; 25:1055-1063. This study added to the evidence that this hexavalent vaccine does not weaken or harm the immune system.
72. Tejedor JC, Moro M, Ruiz-Contreras J, et al. Immunogenicity and reactogenicity of primary immunization with a hexavalent diphtheria-tetanus- acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B vaccine coadministered with two doses of a meningococcal C-tetanus toxoid conjugate vaccine. Pediatr Infect Dis J 2006; 25:713-720. This study demonstrated that co-administration of this hexavalent vaccines with a MenC-TT does not weaken or harm the immune system.
73. Halperin SA, Langley JM, Hesley TM, et al. Safety and immunogenicity of two formulations of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae conjugate-hepatitis B vaccine in 15 to 18-month-old children. Hum Vaccin 2005; 1:245-250. This study demonstrates that different formulations of a hexavalent vaccine do not weaken or harm the immune system.
74. Shinefield H, Black S, Thear M, et al. Safety and immunogenicity of a measles, mumps, rubella and varicella vaccine given with combined Haemophilus influenzae type b conjugate/hepatitis B vaccines and combined diphtheria-tetanus-acellular pertussis vaccines. Pediatr Infect Dis J 2006; 25:287-292. This large study added to the evidence that co-administration of MMRV, Hib/HepB and DTaP is safe and represents an effective stimulus rather than weakening, or harm of the immune system.
75. Miller E, Andrews N, Waight P, Taylor B. Bacterial infections, immune overload, and MMR vaccine. Measles, mumps, and rubella. Arch Dis Child 2003; 88:222-223.
76. Centers for Disease Control and Prevention. Withdrawal of rotavirus vaccine recommendation. MMWR Morb Mortal Wkly Rep 1999; 48:1007.
77. Bines J. Intussusception and rotavirus vaccines. Vaccine 2006; 24:3772-3776. This excellent review outlines the effectiveness of the current strategy to detect and react to a postlicensure safety signal and emphasizes that regional immunization safety concerns may have a considerable global impact.
78. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006; 354:11-22. This was one of the largest preclinical vaccine trials demonstrating the safety and efficacy of one of the two recently licensed new generation rotavirus vaccines (HRV).
79. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006; 354:23-33. This was one of the largest preclinical vaccine trials demonstrating the safety and efficacy of one of the two recently licensed new generation rotavirus vaccines (WC3 strain).
80. Bines JE, Kohl KS, Forster J, et al. Acute intussusception in infants and children as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine 2004; 22:569-574.
81. Bouvier-Colle MH, Flahaut A, Messiah A, et al. Sudden infant death and immunization: an extensive epidemiological approach to the problem in France: winter 1986. Int J Epidemiol 1989; 18:121-126.
82. Griffin MR, Ray WA, Livengood JR, Schaffner W. Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine. N Engl J Med 1988; 319:618-623.
83. Hoffman HJ, Hunter JC, Damus K, Pakter J. Peterson DR, van Belle G, et al. Diphtheria-tetanus-pertussis immunization and sudden infant death: results of the National Institute of Child Health and Human Development Cooperative Epidemiological Study of Sudden Infant Death Syndrome risk factors. Pediatrics 1987; 79:598-611.
84. Mitchell EA, Stewart AW, Clements M. Immunisation and the sudden infant death syndrome. New Zealand Cot Death Study Group. Arch Dis Child 1995; 73:498-501.
85. Roberts SC. Vaccination and cot deaths in perspective. Arch Dis Child 1987; 62:754-759.
86. Fleming PJ, Blair PS, Platt MW, et al. The UK accelerated immunisation programme and sudden unexpected death in infancy: case-control study. BMJ 2001; 322:822.
87. Vennemann MM, Butterfass-Bahloul T, Jorch G, et al. Sudden infant death syndrome: No increased risk after immunisation. Vaccine 2007; 25:336-340. This was a timely case-control study on SIDS victims, comprising the 2 years following introduction of hexavalent vaccines in Germany. It could not demonstrate an increased risk of SIDS associated with these vaccines.
88. von Kries R, Toschke AM, Strassburger K, et al. Sudden and unexpected deaths after the administration of hexavalent vaccines (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b): is there a signal? Eur J Pediatr 2005; 164:61-69.
89. Miller E, Waight P, Farrington CP, et al. Idiopathic thrombocytopenic purpura and MMR vaccine. Arch Dis Child 2001; 84:227-229.
90. Rajantie J, Zeller B, Treutiger I, Rosthoj S. Vaccination associated thrombocytopenic purpura in children. Vaccine 2007; 25:1838-1840. This study provided a recent estimate of the incidence of symptomatic thrombocytopenia following MMR. The event is less frequent following immunization compared to the wild virus infection.
91. Imbach P, Kuhne T, Muller D, et al. Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS). Pediatr Blood Cancer 2006; 46:351-356. This is the latest in a series of analyses of a large ITP database. It emphasizes that the acronym ITP is used for a heterogenous group of clinical entities and is ill defined.
92. Asa PB, Cao Y, Garry RF. Antibodies to squalene in Gulf War syndrome. Exp Mol Pathol 2000; 68:55-64.
93. Alving CR, Grabenstein JD. Re: Antibodies to squalene in Gulf War Syndrome. Exp Mol Pathol 2000; 68:196-198.
94. Del Giudice G, Fragapane E, Bugarini R, et al. Vaccines with the MF59 adjuvant do not stimulate antibody responses against squalene. Clin Vaccine Immunol 2006; 13:1010-1013. This study highlighted that adjuvants containing squalene neither elicit nor increase commonly preexisting squalene antibody levels.