[Page numbers followed by italic letter n or t refer to footnotes or tables.]
A
Acellular pertussis vaccine
development, 529
formulations, 530
summary of evidence and causality conclusions, 585–588t
Acute disseminated encephalomyelitis definition, 635
DTaP vaccine and, 546–547, 586t
hepatitis A vaccine and, 423–424, 431t
hepatitis B vaccine and, 440–442, 491t
human papillomavirus vaccine and, 507–508, 521t
influenza vaccine and, 308–309, 402t
mechanism(s) that may contribute to symptoms of, 154, 271, 308, 423–424, 441, 507, 547, 604
meningococcal vaccine and, 603–604, 611t
MMR vaccine and, 153–154, 219t
varicella zoster vaccine and, 271, 284t
Acute motor axonal neuropathy (AMAN), 71–72
Adjuvants, 59
mechanism of action, 59
See also Alum; ASO4
Adverse events, generally
animal models, 89–91
brain development alterations, 85–89
definition, 1n, 30n
frequency and rate determinations, 629–632
injection-related, 78–81, 615–624, 625t
limitations of data sources and findings, 629–633
mechanisms of, 57, 65, 67–68, 72–73, 74, 76
methodology for evaluation of evidence, 10–14, 40–48
prior reviews, 1–2, 29–30, 39
recognized risk, 28
reporting requirements, 29
scope of review, 2–10, 30–36
seriousness of, 632
susceptibility, 24, 54, 82–84
See also Causality
Advisory Committee on Immunization Practices
DTaP vaccination recommendations, 530
hepatitis B vaccination recommendations, 437
human papillomavirus vaccination recommendations, 506–507
influenza vaccination recommendations, 295–296
meningococcal vaccination recommendations, 601
MMR vaccination recommendations, 108, 242
varicella vaccination recommendations, 242
Age
as adverse event risk factor, 24, 84
human papillomavirus infection risk, 505–506
Alterations in brain development. SeeBiological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Alum, 59
American Academy of Family Physicians, 437, 530
American Academy of Pediatrics, 437, 530
Amyotrophic lateral sclerosis
definition, 635
human papillomavirus vaccine and, 513–515
mechanism(s) that may contribute to symptoms of, 514
Anaphylaxis
causes, 65, 66, 632
complement-mediated, 65–66
definition, 635
DTaP vaccine and, 563–565, 587t
hepatitis A vaccine and, 428–429, 431t
hepatitis B vaccine and, 18, 20t, 468–469, 492t
human papillomavirus vaccine and, 21t, 515–516, 521t
immunoglobulin E-mediated hypersensitivity in, 64–65
influenza vaccine and, 18, 20t, 341–345, 403t
limitations of data sources, 631–632
mechanism(s) that may contribute to symptoms of, 64–66
meningococcal vaccine and, 18, 20t,608–610, 611t
MMR vaccine and, 18, 20t, 169–174, 219t, 631–632
recognized risks, 28
susceptibility to, 83–84
tetanus toxoid vaccine and, 18, 20t, 565, 587t
varicella zoster vaccine and, 18, 20t, 275–278, 284t
Animal models
application of evidence from, 89–91
contribution to the weight of mechanistic evidence, 14, 45, 47
disease processes affecting the brain, 86
influenza vaccine and Guillain-Barré syndrome, 333–334
MMR vaccine and hearing loss, 153
Antibodies and autoantibodies. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Antigen persistence. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Antigen-presenting cells, 58, 59
Antigenic drift, 293
Antigenic shift, 293
Arthralgia
chronic, in women, MMR vaccine and, 190–195, 220t
definition, 635
mechanism(s) that may contribute to symptoms of, 181, 185, 194, 517
transient, human papillomavirus vaccine and, 516–517, 521t
transient, in children, MMR vaccine and, 18, 21t, 182–190, 220t
transient, in women, MMR vaccine and, 18, 21t, 174–181, 219t
Arthritis, chronic
definition, 635
mechanism(s) that may contribute to symptoms of, 198
in women, MMR vaccine and, 195–199, 220t
Arthritis, juvenile idiopathic
definition, 641
hepatitis B vaccine and, 485–488, 493t
mechanism(s) that may contribute to symptoms of, 488
MMR vaccine and, transient arthralgia in children, 184
Arthritis, psoriatic
definition, 643
hepatitis B vaccine, onset or exacerbation of, 479–480, 492t
Arthritis, reactive
definition, 643
hepatitis B vaccine and, 480–482, 493t
mechanism(s) that may contribute to symptoms of, 481–482
Arthritis, rheumatoid
definition, 644
hepatitis B vaccine, onset or exacerbation of, 482–485, 493t
immune complexes and, 67
mechanism(s) that may contribute to symptoms of, 485
Arthropathy
chronic, in children, MMR vaccine and, 199–200, 220t,
definition, 635
DTaP vaccine and, 567–571, 588t
influenza vaccine, onset or exacerbation of, 384–385, 403t
mechanism(s) that may contribute to symptoms of, 200, 202, 279, 385, 571
in men, MMR vaccine and, 201–204, 220t
varicella vaccine, onset or exacerbation of, 278–279, 284t
ASO4, 59
Assessment of causality
DTaP vaccine
acute disseminated encephalomyelitis, 546–547
anaphylaxis, 563–565
arthropathy, 567–571
ataxia, 544–545
autism, 545–546
Bell’s Palsy, 561–562
chronic inflammatory disseminated polyneuropathy, 558–560
chronic urticaria, 565–566
encephalitis and encephalopathy, 534–537
fibromyalgia, 581
Guillain-Barré syndrome, 557–558
immune thrombocytopenic purpura, 582–584
infantile spasms, 537–539
multiple sclerosis onset in adults, 550–553
multiple sclerosis relapse in adults, 554–555
multiple sclerosis relapse in children, 555–557
myocarditis, 579–580
opsoclonus myoclonus syndrome, 560–561
optic neuritis, 549–550
seizures, 539–544
serum sickness, 566–567
sudden infant death syndrome, 581–582
summary of evidence and causality conclusions, 22t, 585–588t, 683–687t
transverse myelitis, 547–548
type 1 diabetes, 22t, 571–579
hepatitis A vaccine
acute disseminated encephalomyelitis, 423–424
anaphylaxis, 428–429
autoimmune hepatitis, 429–430
Bell’s palsy, 427–428
chronic inflammatory disseminated polyneuropathy, 427
Guillain-Barré syndrome, 426
multiple sclerosis, 425
summary of evidence and causality conclusions, 4311, 680–681t
transverse myelitis, 424–425
hepatitis B vaccine
acute disseminated encephalomyelitis, 440–442
anaphylaxis, 468–469
brachial neuritis, 467–468
chronic inflammatory disseminated polyneuropathy, 466–467
encephalitis and encephalopathy, 437–438
erythema nodosum, 469–471
fibromyalgia, 490
first demyelinating event in adults, 458–464
first demyelinating event in children, 464–465
Guillain-Barré syndrome, 465–466
juvenile idiopathic arthritis, onset or exacerbation, 485–488
multiple sclerosis onset in adults, 447–450, 451–453t
sclerosis onset in children, 454–455
multiple sclerosis relapse in adults, 455–456
multiple sclerosis relapse in children, 457–458
neuromyelitis optica, 446–447
optic neuritis, 443–446
polyarteritis nodosa, onset or exacerbation, 477–479
psoriatic arthritis, onset or exacerbation, 479–480
reactive arthritis, onset or exacerbation, 480–482
rheumatoid arthritis, onset or exacerbation, 482–485
seizures, 438–440
summary of evidence and causality conclusions, 20t, 491–493t, 681–683t
systemic lupus erythematosus, onset or exacerbation, 471–473
transverse myelitis, 442–443
type 1 diabetes, 488–490
vasculitis, onset or exacerbation, 473–477
human papillomavirus vaccine
acute disseminated encephalomyelitis, 507–508
amyotrophic lateral sclerosis, 513–515
anaphylaxis, 515–516
brachial neuritis, 512–513
chronic inflammatory disseminated polyneuropathy, 512
Guillain-Barré syndrome, 511–512
hypercoagulable states, 520
multiple sclerosis, 510
neuromyelitis optica, 509
pancreatitis, 517–518
summary of evidence and causality conclusions, 21t, 521t, 683t
thromboembolic events, 519–520
transient arthralgia, 516–517
transverse myelitis, 508
influenza vaccine
acute disseminated encephalomyelitis, 308–309
all-cause mortality, 390–391
anaphylaxis, 341–345
arthropathy, onset or exacerbation, 384–385
asthma exacerbation or reactive airway disease episodes in children and adults, inactivated influenza vaccine, 345–356
asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age, live attenuated influenza vaccine, 356–366
asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older, live attenuated influenza vaccine, 366–373
Bell’s palsy, 335–337, 338–339t
brachial neuritis, 340
chronic inflammatory disseminated polyneuropathy, 334–335
encephalitis and encephalopathy, 296, 299–301
fibromyalgia, 389
Guillain-Barré syndrome, 321–334
multiple sclerosis onset in adults, 314–318
multiple sclerosis relapse in adults, 318–321
myocardial infarction, 387–389
neuromyelitis optica, 314
oculorespiratory syndrome, 391–401
optic neuritis, 310–313
polyarteritis nodosa, 383–384
seizures, 301–304, 305–307t
small fiber neuropathy, 340–341
stroke, 386–387
summary of evidence and causality conclusions, 20–22t, 402–404t, 678–680t
systemic lupus erythematosus, onset or exacerbation, 373–379
transverse myelitis, 309–310
vasculitis, onset or exacerbation, 379–383
injection-related adverse events
complex regional pain syndrome, 615–617
deltoid bursitis, 618–620
summary of evidence and causality conclusions, 21t, 625t, 687–688t,
syncope, 620–624
meningococcal vaccine
acute disseminated encephalomyelitis, 603–604
anaphylaxis, 608–610
chronic headache, 610
chronic inflammatory disseminated polyneuropathy, 607–608
encephalitis and encephalopathy, 602–603
Guillain-Barré syndrome, 606–607
multiple sclerosis, 605–606
summary of evidence and causality conclusions, 20t, 611t, 687t
transverse myelitis, 604–605
MMR vaccine
acute disseminated encephalomyelitis, 153–154
afebrile seizures, 133–137
anaphylaxis, 169–174
arthropathy in men, 201–204
ataxia, 143–144
autism, 145–153
brachial neuritis, 168–169
chronic arthralgia in women, 190–195
chronic arthritis in women, 195–199
chronic arthropathy in children, 199–200
chronic fatigue syndrome, 212–213
chronic inflammatory disseminated polyneuropathy, 166–167
encephalitis and encephalopathy, 111–119
febrile seizures, 119–132
fibromyalgia, 213–214
Guillain-Barré syndrome, 165–166
hearing loss, 214–217
hepatitis, 211–212
measles inclusion body encephalitis, 108–110
meningitis, 137–143
multiple sclerosis onset in adults, 159–164
multiple sclerosis onset in children, 164–165
neuromyelitis optica, 158–159
opsoclonus myoclonus syndrome, 167–168
optic neuritis, 156–158
summary of evidence and causality conclusions, 20–22t, 218–221t, 674–677t
transient arthralgia in children, 182–190
transient arthralgia in women, 174–181
transverse myelitis, 154–156
type 1 diabetes, 204–211
prior reviews, 1–2, 29–30, 39
process
categorization of findings, 14–18, 23–24, 48–53
contradictory evidence, 23
framework for, 10–18, 23–24, 42–53
weight-of-evidence evaluations, 10–14, 42–48
varicella zoster vaccine
acute disseminated encephalomyelitis, 271
anaphylaxis, 275–278
arthropathy, onset or exacerbation, 278–279
cerebellar ataxia, 269–270
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis, 249–256
disseminated Oka VZV without other organ involvement, 242–249
encephalopathy, 267–268
Guillain-Barré syndrome, 273–274
seizures, 268–269
small fiber neuropathy, 274–275
stroke, 279–280
summary of evidence and causality conclusions, 19–20t, 283–284t, 677–678t
thrombocytopenia, 281–282
transverse myelitis, 272–273
vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis, 261–267
vaccine strain viral reactivation without other organ involvement, 256–261
See also Causality
Asthma and reactive airway disease episodes
definition, 635
inactivated influenza vaccine and, 22t, 23, 345–356, 403t
live attenuated influenza vaccine and, 356–373, 403t
mechanism(s) that may contribute to symptoms of, 356, 366, 369, 373
Ataxia
definition, 636
DTaP vaccine and, 544–545, 585t
mechanism(s) that may contribute to symptoms of, 144
MMR vaccine and, 143–144, 218t
Attribution elements, 13, 46
Autism
definition, 636
diagnosis and biological mechanism, 57, 85–89
DTaP vaccine and, 545–546, 585t
MMR vaccine and, 21t, 23, 145–153, 218t
See also Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Autoimmune hepatitis
definition, 636
hepatitis A vaccine and, 429–430, 431t
mechanism(s) that may contribute to symptoms of, 430
Autoreactivity. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
B
B cell response to antigen exposure, 57–58, 60, 63
Bell’s palsy
definition, 636
DTaP vaccine and, 561–562, 587t
hepatitis A vaccine and, 427–428, 431t
influenza vaccine and, 21t, 23, 335–337, 338–339t, 402t
Benefits of vaccination, 27
Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
alterations in brain development, 85–86
autism, 86–89
coagulation and hypercoagulable states, 81–82
immune mediated mechanisms, 59–76
antigen persistence, 73–74
autoreactivity, 75
bystander activation, 75
complement activation, 62–64
effector functions of antibodies and autoantibodies, 60–62
effector functions of T cells, 59–60
epitope spreading, 74–75
hyperresponsiveness, 75
hypersensitivity reactions, 64–66
complement mediated hypersensitivity, 65–6
immunoglobulin E hypersensitivity, 64–65
immune complexes, 66–68
increased cytokines, 75–76
molecular mimicry, 70–73
superantigens, 76
tissue responses (fever and seizure), 68–70
increased susceptibility, 82–84
injection-related adverse events complex regional pain syndrome, 78–80
deltoid bursitis, 80
syncope, 80–81
latency between antigen exposure and peak adaptive immune response, 57–59
viral activity, 76–78
direct or primary infection, 76–77
persistent infection, 77
viral reactivation, 77–78
Bordatella pertussis
bacteria description, 528
clinical description, 529, 643
complications, 529
encephalitis and encephalopathy and, 529, 536
seizures and, 529, 544
transmission, 529
vaccine development and recommendations, 529, 530
See also Diphtheria toxoid, tetanus toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
Brachial neuritis
definition, 636
hepatitis B vaccine and, 467–468, 492t
human papillomavirus vaccine and, 512–513, 521t
influenza vaccine and, 340, 402t
mechanism(s) that may contribute to symptoms of, 168, 340, 468, 513
MMR vaccine and, 168–169, 219t
Brain development, alterations, 85–86
Bystander activation. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
C
Campylobacter jejuni, 72, 333, 423, 426
Canada, 18, 392–401
Cardiopulmonary disease, complications of influenza infection, 294–295
Case-control study
definition, 636
studies contributing to the weight of epidemiologic evidence, 111–112, 114–115t, 137–138, 140t, 147–148, 151–152t, 156, 160, 162–163t, 164, 201, 203t, 204–206, 208–210t, 310–311, 312t, 315, 317t, 443–444, 445t, 448, 452t, 454, 458–459, 461t, 464, 471, 488–489, 534–535, 537, 549, 550–551, 552t, 567–568, 569–570t, 572–573, 575–577t
Case-crossover study
definition, 636
studies contributing to the weight of epidemiologic evidence, 120–121, 125t, 138–139, 141t, 301–302, 305–306t, 318–319, 320t, 348–349, 354–355t, 393–394, 398t, 455–456, 554
Case-only study, definition, 637
Case reports, 12–13, 46–47, 52, 53
definition, 637
Case series, definition, 637
Causality
adverse effects versus adverse events, 1n
categories and explanations of, 14–24, 48–53
evidence convincingly supports, 15, 17–18, 49, 50–52
evidence favoring acceptance of, 15, 18–23, 49, 52–53
evidence favoring rejection of, 15, 23, 49, 53, 389n
evidence inadequate to accept or reject, 15, 23–24, 49, 53
DTaP vaccine
acute disseminated encephalomyelitis, 547
anaphylaxis, 565
arthropathy, 571
ataxia, 545
autism, 546
Bell’s Palsy, 562
chronic inflammatory disseminated polyneuropathy, 560
chronic urticaria, 566
encephalitis and encephalopathy, 537
fibromyalgia, 581
Guillain-Barré syndrome, 558
immune thrombocytopenic purpura, 584
infantile spasms, 539
multiple sclerosis onset in adults, 553
multiple sclerosis relapse in adults, 555
multiple sclerosis relapse in children, 557
myocarditis, 580
opsoclonus myoclonus syndrome, 561
optic neuritis, 550
seizures, 544
serum sickness, 567
sudden infant death syndrome, 582
summary of evidence and causality conclusions, 22t, 585–588t, 683–687t
transverse myelitis, 548
type 1 diabetes, 579
finding of no causal relationship, 15, 49
hepatitis A vaccine
acute disseminated encephalomyelitis, 424
anaphylaxis, 429
autoimmune hepatitis, 430
Bell’s palsy, 428
chronic inflammatory disseminated polyneuropathy, 427
Guillain-Barré syndrome, 426
multiple sclerosis, 425
summary of evidence and causality conclusions, 431t, 680–681t
transverse myelitis, 425
hepatitis B vaccine
acute disseminated encephalomyelitis, 442
anaphylaxis, 469
brachial neuritis, 468
chronic inflammatory disseminated polyneuropathy, 467
encephalitis and encephalopathy, 438
erythema nodosum, 471
fibromyalgia, 490
first demyelinating event in adults, 463
first demyelinating event in children, 465
Guillain-Barré syndrome, 466
juvenile idiopathic arthritis, onset or exacerbation, 488
multiple sclerosis onset in adults, 450
multiple sclerosis onset in children, 455
multiple sclerosis relapse in adults, 456
multiple sclerosis relapse in children, 458
neuromyelitis optica, 447
optic neuritis, 446
polyarteritis nodosa, onset or exacerbation, 479
psoriatic arthritis, onset or exacerbation, 480
reactive arthritis, onset or exacerbation, 482
rheumatoid arthritis, onset or exacerbation, 485
seizures, 440
summary of evidence and causality conclusions, 20t, 491–493t, 681–683t
systemic lupus erythematosus, onset or exacerbation, 473
transverse myelitis, 443
type 1 diabetes, 490
vasculitis, onset or exacerbation, 477
human papillomavirus vaccine
acute disseminated encephalomyelitis, 508
amyotrophic lateral sclerosis, 515
anaphylaxis, 516
brachial neuritis, 513
chronic inflammatory disseminated polyneuropathy, 512
Guillain-Barré syndrome, 512
hypercoagulable states, 520
multiple sclerosis, 510
neuromyelitis optica, 509
pancreatitis, 518
summary of evidence and causality conclusions, 21t, 521t, 683t
thromboembolic events, 520
transient arthralgia, 517
transverse myelitis, 508
influenza vaccine
acute disseminated encephalomyelitis, 309
all-cause mortality, 391
anaphylaxis, 345
arthropathy, onset or exacerbation, 385
asthma exacerbation or reactive airway disease episodes in children and adults, inactivated influenza vaccine, 356
asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age, live attenuated influenza vaccine, 366
asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older, live attenuated influenza vaccine, 373
Bell’s palsy, 337
brachial neuritis, 340
chronic inflammatory disseminated polyneuropathy, 335
encephalitis, 299
encephalopathy, 301
fibromyalgia, 389
Guillain-Barré syndrome, 334
multiple sclerosis onset in adults, 318
multiple sclerosis relapse in adults, 321
myocardial infarction, 389
neuromyelitis optica, 314
oculorespiratory syndrome, 401
optic neuritis, 313
polyarteritis nodosa, 384
seizures, 304
small fiber neuropathy, 341
stroke, 386
summary of evidence and causality conclusions, 20–22t, 402–404t, 678–680t
systemic lupus erythematosus, onset or exacerbation, 379
transverse myelitis, 310
vasculitis, onset or exacerbation, 383
injection-related adverse events
complex regional pain syndrome, 617
deltoid bursitis, 620
summary of evidence and causality conclusions, 21t, 625t, 678–680t,
syncope, 624
limitations of data sources and findings, 629–633
meningococcal vaccine
acute disseminated encephalomyelitis, 604
anaphylaxis, 610
chronic headache, 610
chronic inflammatory disseminated polyneuropathy, 608
encephalitis and encephalopathy, 603
Guillain-Barré syndrome, 607
multiple sclerosis, 606
summary of evidence and causality conclusions, 20t, 611t, 687t
transverse myelitis, 605
MMR vaccine
acute disseminated encephalomyelitis, 154
afebrile seizures, 137
anaphylaxis, 174
arthropathy in men, 204
ataxia, 144
autism, 153
brachial neuritis, 169
chronic arthralgia in women, 195
chronic arthritis in women, 199
chronic arthropathy in children, 200
chronic fatigue syndrome, 213
chronic inflammatory disseminated polyneuropathy, 167
encephalitis, 118
encephalopathy, 119
febrile seizures, 132
fibromyalgia, 214
Guillain-Barré syndrome, 166
hearing loss, 217
hepatitis, 212
measles inclusion body encephalitis, 110
meningitis, 143
multiple sclerosis onset in adults, 164
multiple sclerosis onset in children, 165
neuromyelitis optica, 159
opsoclonus myoclonus syndrome, 168
optic neuritis, 158
summary of evidence and causality conclusions, 20–22t, 218–221t, 674–677t
transient arthralgia in children, 190
transient arthralgia in women, 181
transverse myelitis, 156
type 1 diabetes, 211
summary of evidence and causality conclusions, 19–221, 674–748t
DTaP vaccine and, 585–588t
hepatitis A vaccine and, 431t
hepatitis B vaccine and, 491–493t
human papillomavirus vaccine and, 521t
influenza vaccine and, 402–404t
injection related adverse events and, 625t
meningococcal vaccine and, 611t
MMR vaccine and, 218–221t
varicella vaccine and, 283–284t
varicella zoster vaccine
acute disseminated encephalomyelitis, 271
anaphylaxis, 278
arthropathy, onset or exacerbation, 279
cerebellar ataxia, 270
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis, 256
disseminated Oka VZV without other organ involvement, 249
encephalopathy, 268
Guillain-Barré syndrome, 274
seizures, 269
small fiber neuropathy, 275
stroke, 280
summary of evidence and causality conclusions, 19–20t, 283–284t, 677–678t,
thrombocytopenia, 282
transverse myelitis, 273
vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis, 267
vaccine strain viral reactivation without other organ involvement, 261
See also Assessment of causality
Centers for Disease Control and Prevention, 2, 29, 30
Cephalic tetanus, 527–528
Cerebellar ataxia
definition, 637
mechanism(s) that may contribute to symptoms of, 270
varicella zoster vaccine and, 269–270, 284t
Chemotherapy, 73, 82, 241, 246–248, 253, 254–255, 260, 264, 265
Chronic fatigue syndrome
definition, 637
MMR vaccine and, 212–213, 221t
Chronic inflammatory disseminated polyneuropathy
definition, 637
DTaP vaccine and, 558–560, 587t
hepatitis A vaccine and, 427, 431t
hepatitis B vaccine and, 466–467, 492t
human papillomavirus vaccine and, 512, 521t
influenza vaccine and, 334–335, 402t
mechanism(s) that may contribute to symptoms of, 167, 335, 427, 467, 512, 560, 608
meningococcal vaccine and, 607–608, 611t
MMR vaccine and, 166–167, 219t
Chronic urticaria
definition, 637
DTaP vaccine and, 565–566, 587t
mechanism(s) that may contribute to symptoms of, 565
Clostridium tetani
bacteria description, 527
Bell’s palsy and, 562
clinical description, 527, 645
complications, 527–528
incidence, 528
transmission, 527
vaccine development and recommendations, 528, 530
See also Diphtheria toxoid, tetanus toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
Coagulation and hypercoagulable states. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Cohort studies
contributing to the weight of epidemiologic evidence, 322–323, 328t, 374, 375, 3761, 377t, 438–439, 535, 540, 542t, 561, 574, 578t,
definition, 637–638
prospective cohort studies contributing to the weight of epidemiologic evidence, 374, 376–377t,482–483
retrospective cohort studies contributing to the weight of epidemiologic evidence, 111, 114t, 120, 121–122, 125–127t, 133–134, 135–136t, 138, 140–141t, 146, 151t, 174–175, 177–178t, 183, 184, 187t, 189t, 190, 192t, 195, 197t, 201, 203t, 206, 210t, 250–251, 262, 268, 275, 279, 303, 307t, 323, 325–326, 329t, 331–332t, 336–337, 339t, 341, 358–359, 363–364t, 367, 371–372t, 379, 381t, 390, 457, 540–541, 543t, 555–556, 573–574, 577t, 606–607, 618
Compensation for adverse events
for effects of vaccines not on Vaccine Injury Table, 29, 30
legislation in support of, 1, 28, 29
Complement activation. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Complement-mediated hypersensitivity. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Complex regional pain syndrome
definition, 638
injection-related, 78–80, 615–617, 625t
See also Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Confounding variables, definition, 638
Consumer education, legislation in support of, 1, 28–29
Contradictory evidence, 23, 53
Convulsion. See Febrile seizures; Seizures
Corynebacterium diphtheriae
bacteria description, 525
Bell’s palsy and, 562
clinical description, 525–526, 638–639
complications, 526
encephalitis and encephalopathy and, 526, 536
myocarditis and, 526, 580
transmission, 525
vaccine development and recommendations, 526, 530
See also Diphtheria toxoid, tetanus toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
Countermeasures Injury Compensation Program, 2n
Critical periods, 84
Crossover experiment, definition, 638
Cytokine storm, 75–76
D
Defense Medical Surveillance System, 310–311, 312t, 444, 445t, 461t
Deltoid bursitis
definition, 80, 638
injection of vaccine and, 18, 21t, 618–620, 625t
See also Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Demyelination, definition, 638
Department of Health and Human Services
National Vaccine Program Office, 29
prior reviews of adverse events, 1–2, 29–30
Developmental problems, brain development, 85–89
Diabetes, type 1
definition, 641
DTaP vaccine and, 22t, 571–579, 588t
evidence favoring rejection of vaccine causality, 23
hepatitis B vaccine and, 488–490, 493t
mechanism(s) that may contribute to symptoms of, 211, 489, 571
MMR vaccine and, 22t, 204–211, 220t
molecular mimicry, 71
mumps and, 105, 211
Diabetes mellitus, insulin-dependent. See Diabetes, type 1
Diphtheria toxoid, tetanus toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
acute disseminated encephalomyelitis, 546–547
anaphylaxis, 563–565
arthropathy, 567–571
ataxia, 544–545
autism, 545–546
Bell’s Palsy, 561–562
booster vaccinations, 530
as cause of adverse events. See Causality, DTaP vaccine
chronic inflammatory disseminated polyneuropathy, 558–560
chronic urticaria, 565–566
development of, 526
effectiveness, 526, 528
encephalitis and encephalopathy, 534–537
fibromyalgia, 581
formulations and dosages, 530, 531–533t
Guillain-Barré syndrome, 557–558
immune thrombocytopenic purpura, 582–584
infantile spasms, 537–539
multiple sclerosis onset in adults, 550–553
multiple sclerosis relapse in adults, 554–555
multiple sclerosis relapse in children, 555–557
myocarditis, 579–580
opsoclonus myoclonus syndrome, 560–561
optic neuritis, 10, 36, 549–550
prior reviews into adverse events, 1–2, 30
seizures, 539–544
serum sickness, 566–567
sudden infant death syndrome, 581–582
transverse myelitis, 547–548
type 1 diabetes, 23, 571–579
summary of evidence and causality conclusions, 20t, 22t, 585–588t, 683–687t
vaccination rates, 530
with whole cell pertussis component, 2, 30, 84, 529, 530
See also Acellular pertussis vaccine; Pertussis vaccine, whole cell; Tetanus toxoid-containing vaccines
Double blind controlled crossover study
studies contributing to the weight of epidemiologic evidence, 182–183, 186t
Double blind randomized controlled crossover trial
studies contributing to the weight of epidemiologic evidence, 345–346, 347, 351–352t, 353t
DTaP. See Diphtheria toxoid, tetanus-toxoid, and acellular pertussis antigen-containing vaccines
E
Egg sensitivity, 83, 170–172, 277, 342–343, 344, 632
Embolism, definition, 639
Encephalitis and encephalopathy autism and, 85, 88–89
as Bordetella pertussis infection complication, 529, 536
as Corynebacterium diphtheriae infection complication, 526, 536
definition, 639
DTaP vaccine and, 534–537, 585t
genetic risk, 84, 85, 88–89
hepatitis B vaccine and, 437–438, 491t
as influenza infection complication, 299
influenza vaccine and, 296, 299–301, 402t
as measles infection complication, 77, 103, 117, 118
mechanism(s) that may contribute to symptoms of, 117, 119, 266, 267, 299, 300, 537, 603
meningococcal vaccine and, 602–603, 611t
MMR vaccine and, 111–119, 218t
as mumps infection complication, 105, 117, 118
as rubella infection complication, 77, 106–107, 117
varicella vaccine and, 262–263, 265–266, 267–268, 283t
as varicella zoster virus complication, 266
See also Measles inclusion body encephalitis
Encephalomyelitis, acute disseminated. See Acute disseminated encephalomyelitis
Epidemiologic evidence
categorization of causality based on, 10, 12, 14–18, 23–24, 42–45, 48–53
DTaP vaccine
acute disseminated encephalomyelitis, 546
anaphylaxis, 563
arthropathy, 567–578, 569–570t,
ataxia, 544–545
autism, 545
Bell’s Palsy, 561–562
chronic inflammatory disseminated polyneuropathy, 558
chronic urticaria, 565
encephalitis and encephalopathy, 534–535
fibromyalgia, 581
Guillain-Barré syndrome, 557
immune thrombocytopenic purpura, 582–583
infantile spasms, 537–538
multiple sclerosis onset in adults, 550–553
multiple sclerosis relapse in adults, 554
multiple sclerosis relapse in children, 555–556
myocarditis, 579
opsoclonus myoclonus syndrome, 560
optic neuritis, 549
seizures, 539–541, 542–543t
serum sickness, 566
sudden infant death syndrome, 581–582
summary of evidence and causality conclusions, 22t, 585–588t, 683–687t
transverse myelitis, 547–548
type 1 diabetes, 571–579
for evaluation of causality, 39–40
hepatitis A vaccine
acute disseminated encephalomyelitis, 423
anaphylaxis, 428
autoimmune hepatitis, 429
Bell’s palsy, 427
chronic inflammatory disseminated polyneuropathy, 427
Guillain-Barré syndrome, 426
multiple sclerosis, 425
summary of evidence and causality conclusions, 431t, 680–681t
transverse myelitis, 424
hepatitis B vaccine
acute disseminated encephalomyelitis, 440
anaphylaxis, 468
brachial neuritis, 467
chronic inflammatory disseminated polyneuropathy, 466–467
encephalitis and encephalopathy, 437
erythema nodosum, 469
fibromyalgia, 490
first demyelinating event in adults, 458–460,461–462t
first demyelinating event in children, 464–465
Guillain-Barré syndrome, 465–466
juvenile idiopathic arthritis, onset or exacerbation, 485–486
multiple sclerosis, onset in adults, 447–450, 451–453t
multiple sclerosis, onset in children, 454
multiple sclerosis, relapse in adults, 455–456
multiple sclerosis, relapse in children, 457
neuromyelitis optica, 446
optic neuritis, 443–444, 445t
polyarteritis nodosa, onset or exacerbation, 477
psoriatic arthritis, onset or exacerbation, 479–480
reactive arthritis, onset or exacerbation, 480
rheumatoid arthritis, onset or exacerbation, 482–483
seizures, 438–439
summary of evidence and causality conclusions, 20t, 491–493t, 681–683t
systemic lupus erythematosus onset or exacerbation, 471–472
transverse myelitis, 442
type 1 diabetes, 488–489
vasculitis, onset or exacerbation, 473
human papillomavirus vaccine
acute disseminated encephalomyelitis, 507
amyotrophic lateral sclerosis, 513
anaphylaxis, 515
brachial neuritis, 512–513
chronic inflammatory disseminated polyneuropathy, 512
Guillain-Barré syndrome, 511
hypercoagulable states, 520
multiple sclerosis, 510
neuromyelitis optica, 509
pancreatitis, 517–518
summary of evidence and causality conclusions, 21t, 521t, 683t
thromboembolic events, 519
transient arthralgia, 516–517
transverse myelitis, 508
influenza vaccine
acute disseminated encephalomyelitis, 308
all-cause mortality, 390
anaphylaxis, 341–342
arthropathy, onset or exacerbation, 384
asthma exacerbation or reactive airway disease episodes in children and adults, inactivated influenza vaccine, 345–350, 351–355t
asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age, live attenuated influenza vaccine, 356–361, 362–365t
asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older, live attenuated influenza vaccine, 366–369, 370–372t
Bell’s palsy, 335–337, 338–339t
brachial neuritis, 340
chronic inflammatory disseminated polyneuropathy, 334
encephalitis and encephalopathy, 296
fibromyalgia, 389
Guillain-Barré syndrome, 321–327, 328–332t
multiple sclerosis, onset in adults, 314–316, 317t
multiple sclerosis, relapse in adults, 318–319, 320t
myocardial infarction, 387–388
neuromyelitis optica, 314
oculorespiratory syndrome, 391–398
optic neuritis, 310–311, 312t
polyarteritis nodosa, 383
seizures, 301–304, 305–307t
small fiber neuropathy, 340–341
stroke, 386
summary of evidence and causality conclusions, 20–221, 402–404t, 678–680t
systemic lupus erythematosus, onset or exacerbation, 373–375, 376–377t
transverse myelitis, 309
vasculitis, onset or exacerbation, 379–380, 381t
injection-related outcomes
complex regional pain syndrome, 615
deltoid bursitis, 618
summary of evidence and causality conclusions, 21t, 625t, 687–688t,
syncope, 620
limitations of current data, 630
meningococcal vaccine
acute disseminated encephalomyelitis, 603–604
anaphylaxis, 608–609
chronic headache, 610
chronic inflammatory disseminated polyneuropathy, 607–608
encephalitis and encephalopathy, 602–603
Guillain-Barré syndrome, 606–607
multiple sclerosis, 605
summary of evidence and causality conclusions, 20t, 611t, 687t
transverse myelitis, 604
MMR vaccine
acute disseminated encephalomyelitis, 153
afebrile seizures, 133–134, 135–136t
anaphylaxis, 169
arthropathy in men, 201–202, 203t
ataxia, 143
autism, 145–148, 149–152t
brachial neuritis, 168
chronic arthralgia in women, 190–191, 192t
chronic arthritis in women, 195–196, 197t
chronic arthropathy in children, 199
chronic fatigue syndrome, 212–213
chronic inflammatory disseminated polyneuropathy, 166–167
encephalitis and encephalopathy, 111–113, 114–115t
febrile seizures, 119–124, 125–130t,
fibromyalgia, 213
Guillain-Barré syndrome, 165
hearing loss, 214
hepatitis, 211
measles inclusion body encephalitis, 108
meningitis, 137–139, 140–141t
multiple sclerosis, onset in adults, 159–161,162–163t
multiple sclerosis, onset in children, 164
neuromyelitis optica, 158
opsoclonus myoclonus syndrome, 167
optic neuritis, 156
summary of evidence and causality conclusions, 20–22t, 218–221t, 674–677t
transient arthralgia in children, 182–185,186–189t
transient arthralgia in women, 174–176, 177–179t
transverse myelitis, 154
type 1 diabetes, 204–207, 208–210t
varicella zoster vaccine
acute disseminated encephalomyelitis, 271
anaphylaxis, 275
arthropathy, onset or exacerbation, 278
cerebellar ataxia, 269–270
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis, 250–251
disseminated Oka VZV without other organ involvement, 243
encephalopathy, 267
Guillain-Barré syndrome, 273
seizures, 268
small fiber neuropathy, 274
stroke, 279–280
summary of evidence and causality conclusions, 19t, 20t, 283–284t, 677–678t
thrombocytopenia, 281
transverse myelitis, 272
vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis, 262–263
vaccine strain viral reactivation without other organ involvement, 256–257
weight-of-evidence evaluations, 10, 12, 42–45
Epilepsy, myoclonic, definition, 642
Epitope spreading. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events Erythema nodosum
definition, 639
hepatitis B vaccine and, 10, 36, 469–471, 492t
mechanism(s) that may contribute to symptoms of, 470
F
Febrile seizures
clinical significance, 630
definition, 639
influenza infection, 294
mechanism(s) that may contribute to symptoms of, 132
MMR vaccine and, 18, 20t, 119–132, 218t, 630
tissue responses, 68–70
Fibromyalgia
DTaP vaccine and, 581, 588t
hepatitishepatitis B vaccine and, 490, 493t
influenza vaccine and, 389, 404t
MMR vaccine and, 213–214, 221t
First demyelinating event
hepatitis B vaccine and, in adults, 458–460, 461–462t, 491t
hepatitis B vaccine and, in children, 464–465, 492t
mechanism(s) that may contribute to symptoms of, 463, 465
Food and Drug Administration, 29
Food hypersensitivity reactions, 65, 171–173
See also Egg sensitivity; Gelatin
G
Gelatin, 83, 171–173, 276–277, 342–344, 632
Gender differences
as susceptibility factor, 84
General Practice Research Database, 147, 151t, 315, 317t, 323–325, 329–330t, 336, 338t, 344, 346, 352t, 386, 387–388, 448–449, 452t, 551, 552t
Genetic risk factors
autism, 87–88
febrile seizures, 69–70
neuronal development, 85, 86
susceptibility to adverse events, 24, 83–84
German measles. See Rubivirus (rubella infection)
Guillain-Barré syndrome
acute motor axonal neuropathy in, 71–72
definition, 639
DTaP vaccine and, 557–558, 587t
evaluation of adverse event data, 47
hepatitis A vaccine and, 426, 431t
hepatitis B vaccine and, 465–466, 492t
human papillomavirus vaccine and, 511–512, 521t
influenza vaccine and, 321–334, 402t
mechanism(s) that may contribute to symptoms of, 166, 274, 334, 426, 466, 511, 558, 607
meningococcal vaccine and, 606–607, 611t
MMR vaccine and, 165–166, 219t
swine influenza vaccine and, 321n
varicella zoster vaccine and, 273–274, 284t
H
H1N1 vaccine, 2n, 30
H5N1 vaccine, 294
Haemophilus influenzae type B vaccine, 2, 30
Health Resources and Services Administration, 2, 29, 30, 36
Hearing loss
definition, 639
mechanism(s) that may contribute to symptoms of, 217
MMR vaccine and, 214–217, 221t
Hemagglutinin surface proteins, 294
Hepatitis, as an adverse event of vaccination
definition, 639
mechanism(s) that may contribute to symptoms of, 212, 256
MMR vaccine and, 211–212, 221t
varicella vaccine and, 251, 254–256, 283t
Hepatitis A infection
acute disseminated encephalomyelitis and, 423
autoimmune hepatitis and, 421–422, 430
clinical description, 421–422, 640
complications, 421–422
Guillain-Barré syndrome and, 426
transmission, 422
transverse myelitis and, 424
vaccine development, 422
virus description, 421
Hepatitis A vaccine
acute disseminated encephalomyelitis, 423–424
anaphylaxis, 428–429
autoimmune hepatitis, 429–430
Bell’s palsy, 427–428
as cause of adverse events. See Causality, hepatitis A vaccine
chronic inflammatory disseminated polyneuropathy, 427
development, 422
formulations, 422–423
Guillain-Barré syndrome, 426
multiple sclerosis, 425
summary of evidence and causality conclusions, 431t, 680–681t
transverse myelitis, 424–425
Hepatitis B infection
clinical description, 435–436, 640
complications, 435–436
onset or exacerbation of juvenile idiopathic arthritis and, 435, 487
onset or exacerbation of polyarteritis nodosa and, 435, 478–479
onset or exacerbation of rheumatoid arthritis and, 435, 484
onset or exacerbation of vasculitis and, 435, 476
transmission, 435
vaccine development and recommendations, 436–437
virus description, 435
Hepatitis B vaccine
acute disseminated encephalomyelitis, 440–442
anaphylactic reactions, 18
anaphylaxis, 468–469
brachial neuritis, 467–468
as cause of adverse events. See Causality, hepatitis B vaccine
chronic inflammatory disseminated polyneuropathy, 466–467
cytokine imbalance and, 76
development, 436
encephalitis and encephalopathy, 437–438
erythema nodosum, 10, 36, 469–471
fibromyalgia, 490
first demyelinating event in adults, 458–464
first demyelinating event in children, 464–465
formulations, 436–437
Guillain-Barré syndrome, 465–466
immune complex-mediated effects, 68
injection-related adverse events, 616
juvenile idiopathic arthritis, onset or exacerbation, 485–488
multiple sclerosis onset in adults, 447–450, 451–453t
multiple sclerosis onset in children, 454–455
multiple sclerosis relapse in adults, 455–456
multiple sclerosis relapse in children, 457–458
neuromyelitis optica, 446–447
optic neuritis, 10, 36, 443–446
polyarteritis nodosa, onset or exacerbation, 477–479
prior reviews into adverse events, 2, 30
psoriatic arthritis, onset or exacerbation, 479–480
reactive arthritis, onset or exacerbation, 480–482
rheumatoid arthritis, onset or exacerbation, 482–485
seizures, 438–440
summary of causality studies and conclusions, 20t, 491–493t, 681–683t
systemic lupus erythematosus onset or exacerbation, 471–473
transverse myelitis, 442–443
type 1 diabetes, 488–490
vasculitis, onset or exacerbation, 473–477
Herd immunity, 28
Herpes zoster
cause, 240
definition, 640
mechanism(s) that may contribute to symptoms of, 261
rate, 631
varicella vaccine and, 256–267, 283t
Human papillomavirus infection clinical description, 506, 640
complications, 506
nomenclature, 505
transmission, 505
vaccine development and recommendations, 506–507
virus description, 505, 640
Human papillomavirus vaccine
acute disseminated encephalomyelitis, 507–508
amyotrophic lateral sclerosis, 513–515
anaphylaxis, 18, 515–516
brachial neuritis, 512–513
as cause of adverse events. See Causality, human papillomavirus vaccine
chronic inflammatory disseminated polyneuropathy, 512
current formulations, 506
cytokine imbalance and, 76
development, 506
Guillain-Barré syndrome, 511–512
hypercoagulable states, 520
multiple sclerosis, 510
neuromyelitis optica, 509
pancreatitis, 517–518
prevalence of use, 507
recommendations for, 506–507
summary of evidence and causality conclusions, 21t, 521t, 683t
thromboembolicthromboembolic events, 519–520
transient arthralgia, 516–517
transverse myelitis, 508
Hypercoagulable states
definition, 640
mechanismhuman papillomavirus vaccine and, 520, 521t
mechanism(s) that may contribute to symptoms of, 520
Hyperresponsiveness. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Hypersensitivity reactions. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
I
Immune complexes. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Immune thrombocytopenic purpura
definition, 640
DTaP vaccine and, 582–584, 588t
mechanism(s) that may contribute to symptoms of, 583
Immunocompromised individuals complications of varicella zoster infection, 240
influenza vaccine recommendations in, 296
measles inclusion body encephalitis and MMR vaccine, 109–110
meningococcal disease, 600
treatment of varicella zoster infection in, 241
varicella vaccine and, 241–242, 244–249, 252–256, 258–262, 264–265, 630–631
Immunoglobulin E hypersensitivity. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Increased cytokines. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Increased susceptibility. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Infant mortality, historical evolution, 27
Infantile spasms
definition, 640
DTaP vaccine and, 537–539, 585t
Influenza infection
acute disseminated encephalomyelitis, 308
all-cause mortality, 391
asthma exacerbation and, 295, 356, 366, 369
clinical description, 294–295, 641
complications, 294–295
encephalitis and, 299
Guillain-Barré syndrome, 333
mutagenesis, 293
myocardial infarction, 388
nomenclature, 293–294
onset or exacerbation of arthropathy and, 385
transmission, 294
transverse myelitis and, 309
vaccine development and recommendations, 295–296
virus description, 293–294
Influenza vaccine
acute disseminated encephalomyelitis, 308–309
all-cause mortality, 390–391
anaphylaxis, 18, 341–345
arthropathy, onset or exacerbation, 384–385
asthma exacerbation or reactive airway disease episodes in children and adults, inactivated influenza vaccine, 23, 345–356
asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age, live attenuated influenza vaccine, 356–366
asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older, live attenuated influenza vaccine, 366–373
Bell’s palsy, 23, 335–337, 338–339t
brachial neuritis, 340
Campylobacter jejuni contamination, 333
as cause of adverse events. See Causality, influenza vaccine chronic inflammatory disseminated polyneuropathy, 334–335
development of, 295
encephalitis and encephalopathy, 296, 299–301
fibromyalgia, 389
formulations, 295
Guillain-Barré syndrome, 321–334
H1N1, 2n
multiple sclerosis onset in adults, 314–318
multiple sclerosis relapse in adults, 318–321
myocardial infarction, 387–389
neuromyelitis optica, 314
oculorespiratory syndrome, 18, 391–401, 632
optic neuritis, 18, 36, 310–313
polyarteritis nodosa, 383–384
recommendations for administration, 295–296
seizures, 2, 36, 301–304, 305–307t
small fiber neuropathy, 340–341
stroke, 386–387
summary of evidence and causality conclusions, 20–221, 402–404t, 678–680t
systemic lupus erythematosus onset or exacerbation, 373–379
transverse myelitis, 309–310
trivalent, definition, 295–296
vaccination rates, 296
vasculitis, onset or exacerbation, 379–383
Injection of vaccine,
as cause of adverse event, evidence convincingly supporting, 18
as cause of adverse events. See Causality, injection-related adverse events
complex regional pain syndrome, 78–80, 615–617
deltoid bursitis, 80, 618–620, 632
summary of evidence and causality conclusions, 21t, 625t, 687–688t
syncope, 80–81, 620–624, 632
Institute of Medicine, 1–2, 29–30, 39
L
Latency between antigen exposure and peak adaptive immune response. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Lockjaw, 527
M
Manufacturers of vaccine, legislative relief from tort liablity, 1, 28
Measles, mumps, and rubella (MMR) vaccine
acute disseminated encephalomyelitis, 153–154
afebrile seizures, 133–137
anaphylaxis, 18, 169–174, 631–632
arthropathy in men, 201–204
ataxia, 143–144
autism, 23, 88, 145–153
brachial neuritis, 168–169
causality conclusions. See Causality, MMR vaccine
chronic arthralgia in women, 190–195
chronic arthritis in women, 195–199
chronic arthropathy in children, 199–200
chronic fatigue syndrome, 212–213
chronic inflammatory disseminated polyneuropathy, 166–167
cytokine imbalance and, 76
encephalitis and encephalopathy, 111–119
febrile seizures, 18, 119–132, 630
fibromyalgia, 213–214
formulation, 107–108
Guillain-Barré syndrome, 165–166
hearing loss, 214–217
hepatitis, 211–212
measles inclusion body encephalitis, 18, 108–110
measles virus strain, 104
meningitis, 10, 36, 137–143
multiple sclerosis onset in adults, 159–164
multiple sclerosis onset in children, 164–165
mumps virus strain, 106
neuromyelitis optica, 10, 36, 158–159
opsoclonus myoclonus syndrome, 167–168
optic neuritis, 2–10, 36, 156–158
prior reviews into adverse events, 1–2, 30
rubella virus strain, 107
summary of evidence and causality conclusions, 20–221, 218–221t, 674–677t
transient arthralgia in children, 18, 182–190
transient arthralgia in women, 174–181
transverse myelitis, 154–156
type 1 diabetes, 23, 204–211
Measles, mumps, rubella, and varicella vaccine, 108, 242
Measles inclusion body encephalitis
definition, 641
mechanism(s) that may contribute to symptoms of, 110
MMR vaccine and, 18, 20t, 108–110, 218t
Measles infection
acute disseminated encephalomyelitis, 154
ataxia and, 144
clinical description, 103, 641
complications, 103
encephalitis and, 103, 117
encephalopathy and, 118
febrile seizures and, 132
Guillain-Barré syndrome and, 166
hearing loss and, 216
hepatitis and, 104, 212
measles inclusion body encephalitis and, 110
optic neuritis and, 157
transmission, 103
transverse myelitis and, 155
vaccine development and recommendations, 104, 108
virus description, 103
See also Measles, mumps, and rubella (MMR) vaccine
Mechanistic evidence
categorization of causality based on, 12–14,45–48
DTaP vaccine
acute disseminated encephalomyelitis, 546–547
anaphylaxis, 563–565
arthropathy, 571
ataxia, 545
autism, 546
Bell’s Palsy, 562
chronic inflammatory disseminated polyneuropathy, 559–560
chronic urticaria, 565–566
encephalitis and encephalopathy, 536–537
fibromyalgia, 581
Guillain-Barré syndrome, 557–558
immune thrombocytopenic purpura, 583
infantile spasms, 538
multiple sclerosis onset in adults, 553
multiple sclerosis relapse in adults, 554–555
multiple sclerosis relapse in children, 556–557
myocarditis, 580
opsoclonus myoclonus syndrome, 561
optic neuritis, 549–550
seizures, 541, 544
serum sickness, 566–567
sudden infant death syndrome, 582
summary of evidence and causality conclusions, 22t, 585–588t, 683–687t
transverse myelitis, 548
type 1 diabetes, 579
hepatitis A vaccine
acute disseminated encephalomyelitis, 423–424
anaphylaxis, 428–429
autoimmune hepatitis, 429–430
Bell’s palsy, 428
chronic inflammatory disseminated polyneuropathy, 427
Guillain-Barré syndrome, 426
multiple sclerosis, 425
summary of evidence and causality conclusions, 4311, 680–681t
transverse myelitis, 424
hepatitis B vaccine
acute disseminated encephalomyelitis, 440–441
anaphylaxis, 468–469
brachial neuritis, 467–468
chronic inflammatory disseminated polyneuropathy, 467
encephalitis and encephalopathy, 438
erythema nodosum, 470
fibromyalgia, 490
first demyelinating event in adults, 460, 463
first demyelinating event in children, 465
Guillain-Barré syndrome, 466
juvenile idiopathic arthritis, onset or exacerbation, 486–488
multiple sclerosis onset in adults, 450
multiple sclerosis onset in children, 455
multiple sclerosis relapse in adults, 456
multiple sclerosis relapse in children, 457–458
neuromyelitis optica, 446–447
optic neuritis, 444, 446
polyarteritis nodosa, onset or exacerbation, 477–479
psoriatic arthritis, onset or exacerbation, 480
reactive arthritis, onset or exacerbation, 480–482
rheumatoid arthritis, onset or exacerbation, 483–485
seizures, 439
summary of evidence and causality conclusions, 20t, 491–493t, 681–683t
systemic lupus erythematosus, 472–473
transverse myelitis, 442–443
type 1 diabetes, 489
vasculitis, onset or exacerbation, 473–476
human papillomavirus vaccine
acute disseminated encephalomyelitis, 507
amyotrophic lateral sclerosis, 514
anaphylaxis, 515–516
brachial neuritis, 513
chronic inflammatory disseminated polyneuropathy, 512
Guillain-Barré syndrome, 511
hypercoagulable states, 520
multiple sclerosis, 510
neuromyelitis optica, 509
pancreatitis, 518
summary of evidence and causality conclusions, 21t, 521t, 683t
thromboembolic events, 519
transient arthralgia, 517
transverse myelitis, 508
influenza vaccine
acute disseminated encephalomyelitis, 308
all-cause mortality, 390–391
anaphylaxis, 342–344
arthropathy, onset or exacerbation, 384–385
asthma exacerbation or reactive airway disease episodes in children and adults, inactivated influenza vaccine, 350, 356
asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age, live attenuated influenza vaccine, 361, 366
asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older, live attenuated influenza vaccine, 369, 373
Bell’s palsy, 337
brachial neuritis, 340
chronic inflammatory disseminated polyneuropathy, 334–335
encephalitis and encephalopathy, 299–300
fibromyalgia, 389
Guillain-Barré syndrome, 327, 333–334
multiple sclerosis onset in adults, 316
multiple sclerosis relapse in adults, 319, 321
myocardial infarction, 388
neuromyelitis optica, 314
oculorespiratory syndrome, 399–401
optic neuritis, 311, 313
polyarteritis nodosa, 383–384
seizures, 304
small fiber neuropathy, 341
stroke, 386–387
summary of evidence and causality conclusions, 20–221, 401–404t, 678–680t
systemic lupus erythematosus, onset or exacerbation, 375, 378–379
transverse myelitis, 309
vasculitis, onset or exacerbation, 380, 382–383
injection-related outcomes
complex regional pain syndrome, 615–617
deltoid bursitis, 618–620
summary of evidence and causality conclusions, 21t, 625t, 687–688t,
syncope, 620–624
meningococcal vaccine
acute disseminated encephalomyelitis, 604
anaphylaxis, 609
chronic headache, 610
chronic inflammatory disseminated polyneuropathy, 608
encephalitis and encephalopathy, 603
Guillain-Barré syndrome, 607
multiple sclerosis, 605–606
summary of evidence and causality conclusions, 20t, 611t, 687t
transverse myelitis, 605
MMR vaccine
acute disseminated encephalomyelitis, 153–154
afebrile seizures, 134, 137
anaphylaxis, 169–174
arthropathy in men, 202
ataxia, 143–144
autism, 148, 153
brachial neuritis, 168–169
chronic arthralgia in women, 191, 193–194
chronic arthritis in women, 196, 198
chronic arthropathy in children, 199–200
chronic fatigue syndrome, 213
chronic inflammatory disseminated polyneuropathy, 167
encephalitis and encephalopathy, 116–119
febrile seizures, 124, 131–132
fibromyalgia, 213
Guillain-Barré syndrome, 165–166
hearing loss, 214–217
hepatitis, 212
measles inclusion body encephalitis, 109–110
meningitis, 139, 142–143
multiple sclerosis onset in adults, 161
multiple sclerosis onset in children, 165
neuromyelitis optica, 158–159
opsoclonus myoclonus syndrome, 167–168
optic neuritis, 156–157
summary of evidence and causality conclusions, 20–22t, 218–221t, 674–677t
transient arthralgia in children, 185, 190
transient arthralgia in women, 176, 180–181
transverse myelitis, 154–156
type 1 diabetes, 207, 211
varicella zoster vaccine
acute disseminated encephalomyelitis, 271
anaphylaxis, 276–278
arthropathy, onset or exacerbation, 278–279
cerebellar ataxia, 270
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis, 251–256
disseminated Oka VZV without other organ involvement, 243–249
encephalopathy, 267
Guillain-Barré syndrome, 273–274
seizures, 269
small fiber neuropathy, 274–275
stroke, 280
summary of evidence and causality conclusions, 19–20t, 283–284t, 677–678t
thrombocytopenia, 281–282
transverse myelitis, 272–273
vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis, 263–266
vaccine strain viral reactivation without other organ involvement, 257–261
weight-of-evidence evaluations, 12–14, 45–48
Meningitis
definition, 641
mechanism(s) that may contribute to symptoms of, 143, 256, 266
MMR vaccine and, 10, 36, 137–143, 218t
varicella vaccine and, 19t, 251, 253, 255–256, 262, 263–267, 283t
Meningococcal disease, 599–600
as cause of adverse events. See Causality, meningococcal vaccine
See Neisseria meningitides
Meningococcal vaccine
acute disseminated encephalomyelitis, 603–604
anaphylactic reactions, 18
anaphylaxis, 608–610
chronic headache, 610
chronic inflammatory disseminated polyneuropathy, 607–608
development, 600–601
encephalitis and encephalopathy, 602–603
formulations, 601
Guillain-Barré syndrome, 606–607
multiple sclerosis, 605–606
summary of evidence and causality conclusions, 20t, 611t, 687t
transverse myelitis, 604–605
vaccination rate, 601–602
Meningococcemia, 599
Meningoencephalitis
definition, 641
influenza vaccine and, 299
MMR. See Measles, mumps, and rubella vaccine
Molecular mimicry. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Mortality
infant, 27
influenza vaccine and all-cause mortality, 390–391
Multiple sclerosis
definition, 641
DTaP vaccine and, 550–557, 586–587t
hepatitis A vaccine and, 425, 431t
hepatitis B vaccine and, 447–458, 491t
human vaccine and, 510, 521t
influenza vaccine and, 314–321, 402t
mechanism(s) that may contribute to symptoms of, 161, 165, 316, 321, 425, 450, 455, 456, 458, 510, 553, 555, 556, 606
meningococcal vaccine and, 605–606, 611t
MMR vaccine and, 159–165, 219t
molecular mimicry, 71
onset in adults
DTaP vaccine, 550–553, 586t
hepatitis B vaccine and, 447–450, 451–453t, 491t
influenza vaccine and, 314–318, 402t
MMR vaccine and, 159–164, 219t
oneset in children
hepatitis B vaccine and, 454–455, 491t
MMR vaccine and, 164–165, 219t
relapse in adults
DTaP vaccine, 554–555, 586t
hepatitis B vaccine and, 455–456, 491t
influenza vaccine and, 318–321, 402t
relapse in children DTaP vaccine, 555–557, 587t
hepatitis B vaccine and, 457–458, 491t
Mumps infection
acute disseminated encephalomyelitis, 154
ataxia and, 144
clinical description, 105, 641–642
complications, 105
encephalitis and, 105, 117
encephalopathy and, 118
febrile seizures and, 132
Guillain-Barré syndrome and, 166
meningitis and, 105, 142
hearing loss and, 105, 216
hepatitis and, 212
optic neuritis and, 157
transmission, 104–105
transverse myelitis and, 105, 155
type 1 diabetes and, 105, 211
vaccine development and recommendations, 105–106, 108
virus description, 104
See also Measles, mumps, and rubella (MMR) vaccine
Myocardial infarction
definition, 642
influenza vaccine and, 387–389, 404t
mechanism(s) that may contribute to symptoms of, 388
Myocarditis
definition, 642
DTaP vaccine and, 579–580, 588t
mechanism(s) that may contribute to symptoms of, 580
Myoclonic epilepsy, 84, 642
N
National Childhood Vaccine Injury Act, 1, 28–29
National Vaccine Injury Compensation Program
purpose, 29
scientific basis for adjudication under, 30
scope of coverage, 1–2, 2n, 30n
structure, 29
National Vaccine Program Office, 29
Neisseria meningitides
bacteria description, 599
clinical description, 599
complications, 599, 600
nomenclature, 600
transmission, 599
vaccine development and recommendations, 600–602
Nested case-control studies
definition, 642
studies contributing to the weight of epidemiologic evidence, 302–303, 306t, 315, 317t, 324–325, 330t, 447–449, 451t, 452t, 551, 552t
Neuraminidase surface proteins, 294
Neuritis, definition of, 642
Neuromyelitis optica
definition, 642
hepatitis B vaccine and, 446–447, 491t
human papillomavirus vaccine and, 509, 521t
influenza vaccine and, 314, 402t
mechanism(s) that may contribute to symptoms of, 158–159, 314, 447, 509
MMR vaccine and, 10, 36, 158–159, 219t
Neuropathy, definition of, 642
Northern California Kaiser Permanente Patients, 133–134, 135t, 175, 178t, 192t, 197t, 250, 268, 275, 438–439, 574, 578t, 618
Nurses’Health Study, 447–448, 451t
O
Oculorespiratory syndrome
definition, 642
influenza vaccine and, 18, 21t, 391–401, 404t, 632
mechanism(s) that may contribute to symptoms of, 400
Opsoclonus myoclonus syndrome
definition, 642–643
DTaP vaccine and, 560–561, 587t
mechanism(s) that may contribute to symptoms of, 168, 561
MMR vaccine and, 167–168, 219t
Optic neuritis
definition, 643
DTaP vaccine and, 549–550, 586t
hepatitis B vaccine and, 443–446, 491t
influenza vaccine and, 310–313, 402t
mechanism(s) that may contribute to symptoms of, 157, 313, 446, 550
MMR vaccine and, 156–158, 219t
scope of review into vaccine events, 2, 10, 36
Orthomyxoviridae, 293
P
Pancreatitis
definition, 643
human papillomavirus vaccine and, 517–518, 521t
mechanism(s) that may contribute to symptoms of, 518
Pertussis vaccine, acellular. See Acellular pertussis vaccine
Pertussis vaccine, whole cell
adverse event review, 1–2, 30, 530
development, 529
susceptibility to adverse events, 84
See also Diphtheria toxoid, tetanus-toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
Pneumonia
definition, 643
influenza infection and, 294–295
meningococcal infection and, 599
varicella vaccine and, 250–253, 255–256, 283t
varicella vaccine and mechanism(s) contributing to symptoms of, 256
Polio vaccine, 2, 28, 30
Polyarteritis nodosa
definition, 643
hepatitis B infection and, 67
hepatitis B vaccine and onset or exacerbation of, 477–479, 492t
influenza vaccine and, 383–384, 403t
mechanism(s) that may contribute to symptoms of, 67, 383–384, 479
Pregnancy, rubella infection in, 106–107
Preventive interventions
accomplishments, 27
evolution of vaccination programs, 27
ProQuad, 107–108, 242
Psychogenic factors in complex regional pain syndrome, 79
Purpura. See Immune thrombocytopenic purpura
R
Randomized clinical trials, 43–44
Randomized controlled crossover trials, studies contributing to the weight of epidemiologic evidence, 392–393, 395–397t
Randomized controlled trials
contributing to the weight of epidemiologic evidence, 359–360, 365t, 367–368, 372t, 379–380, 381t
definition, 643
double blind randomized controlled trials contributing to the weight of epidemiologic evidence, 175–176, 178–179t, 183–184, 188t, 190, 192t, 195, 197t, 318, 320t, 345, 347–348, 351t, 353t, 354t, 357–358, 362t, 367, 370–371t, 373–374, 376t, 516–517
Rechallenge reports as an attribution element, 13, 46–47, 84
Research and development, vaccine, 28
Retrospective studies, 644
Rubivirus (rubella infection)
acute disseminated encephalomyelitis, 154
arthropathy in men and, 106, 202
chronic arthralgia in women and, 106, 194
chronic arthritis in women and, 106, 198
chronic arthropathy in children and, 106, 200
clinical description, 106–107, 644
encephalitis, 106, 117
Guillain-Barré syndrome and, 106, 166
hepatitis and, 212
optic neuritis and, 157
neuromyelitis optica, 158
transient arthralgia in children and, 106, 185
transient arthralgia in women and, 106, 181
transmission, 106
transverse myelitis and, 155
vaccine development and recommendations, 107, 108
virus description, 106
See also Measles, mumps, and rubella (MMR) vaccine
S
Seizures
afebrile, definition, 635
definition, 644
DTaP vaccine and, 537–544, 585t
hepatitis B vaccine and, 438–440, 491t
influenza infection and, 294
influenza vaccine and, 2, 36, 301–304, 305–307t, 402t
mechanism(s) that may contribute to symptoms of, 68–70, 132, 269, 304, 439, 544
MMR vaccine and, 18, 20t, 119–137, 218t
varicella vaccine and, 268–269, 283t
See also Febrile seizures; Infantile spasms
Self-controlled case-series study
definition, 644
studies contributing to the weight of epidemiologic evidence, 112, 115t, 121, 122–124, 128–130t, 145–146, 149–150t, 184, 188t, 323–324, 325, 329–330t, 336, 338t, 346, 352t, 386, 387–388, 449, 453t, 459, 462t, 539–540, 542t, 602
Sequential vaccination, 36
Serum sickness
definition, 644
DTaP vaccine and, 566–567, 587t
mechanism(s) that may contribute to symptoms of, 566–567
Shingles. See Herpes zoster
Shoulder pain and stiffness, 80
See also Deltoid bursitis
Small fiber neuropathy
definition, 644
influenza vaccine and, 340–341, 402t
mechanism(s) that may contribute to symptoms of, 274–275, 341
varicella vaccine and, 10, 36, 274–275, 284t
Smallpox, 27
Special Masters, 2, 29, 30
Streptococcal infection
immune complexes, 67
molecular mimicry, 71
superantigens, 76
Streptococcus pneumoniae, 61
Stroke
definition, 645
influenza vaccine and, 386–387, 403t
mechanism(s) that may contribute to symptoms of, 280, 386–387
varicella vaccine and, 10, 36, 279–280, 284t
Subunit vaccines, 59
Sudden infant death syndrome
definition, 645
DTaP vaccine and, 581–582, 588t
Superantigens. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Surveillance system for adverse events
definition and features, 645
legislation in support of, 1, 28–29
See also Vaccine Adverse Event Reporting System (VAERS)
Susceptible individuals and populations
application to adverse event review, 24, 54
hypersensitivity mechanisms, 64–66
predispositions in, 82–84
See also Genetic risk factors
Swine influenza vaccine, 321n
Syncope
clinical features, 80–81
definition, 645
injection-related adverse events, 620–624, 625t
mechanism(s) that may contribute to symptoms of, 623–624
as result of vaccine injection, 18
See also Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Systemic lupus erythematosus
definition, 645
hepatitis B vaccine and, 471–473, 492t
immune complexes in, 67
influenza vaccine and, 373–379, 403t
mechanism(s) that may contribute to symptoms of, 67, 378, 473
T
T cells. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Tetanospasm, 527
Tetanus infection, 527–528, 562, 645
Tetanus toxoid-containing vaccines
anaphylactic reactions, 18
development, 528
effectiveness, 528
non-whole cell pertussis, 1n, 2
summary of evidence and causality conclusions, 20t, 22t, 585–588t, 683–687t
See also Diphtheria toxoid, tetanus-toxoid, and acellular pertussis antigen-containing (DTaP) vaccines
Thrombocytopenia
definition, 645
mechanism(s) that may contribute to symptoms of, 282
varicella zoster vaccine and, 281–282, 284t
Thromboembolic events
definition, 645
human papillomavirus vaccine and, 519–520, 521t
mechanism(s) that may contribute to symptoms of, 519
Thromboembolism, definition of, 645
Time interval between vaccine administration and adverse event
case report evaluations, 13
Vaccine Injury Table reporting requirements, 29
Tissue responses. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
Transverse myelitis
definition, 646
DTaP vaccine and, 547–548, 586t
hepatitis A vaccine and, 424–425, 431t
hepatitis B vaccine and, 442–443, 491t
human papillomavirus vaccine and, 508, 521t
influenza vaccine and, 309–310, 402t
mechanism(s) that may contribute to symptoms of, 155, 273, 309, 424, 443, 508, 548, 605
meningococcal vaccine and, 604–605, 611t
MMR vaccine and, 154–156, 219t
varicella zoster vaccine and, 272–273, 284t
Trismus, 527
Type 1 autoimmune chronic hepatitis, 421–422
U
Urticaria
definition, 646
See also Chronic urticaria
V
Vaccine Adverse Event Reporting System (VAERS), 29, 171–172, 215, 244–245, 257–258, 263, 276, 277, 281, 313, 335, 343–344, 382, 469, 474, 477, 515, 618–619, 622, 623, 631, 646
Vaccine information statement (VIS), 29
Vaccine Injury Table
purpose, 29
Vaccine Safety Datalink (VSD), 111–112, 121, 156, 160, 170, 205–206, 262, 279, 301, 302, 303, 310, 315, 326, 336, 342, 348–349, 428, 443, 448, 458–459, 488, 535, 540, 551, 573, 646
Vaccines, general
historical evolution, 27
mechanism of action, 28, 57–59
public health benefits, 28
recognized risks, 28
See also Adverse events, generally; specific vaccines
Varicella Vaccine Collaborative Study, 241–242
Varicella zoster vaccine
acute disseminated encephalomyelitis, 271
anaphylaxis, 18, 20t, 275–278
arthropathy, onset or exacerbation, 278–279
causality conclusions. See Causality, varicella zoster vaccine
as cause of adverse events. See Causality, varicella zoster vaccine
cerebellar ataxia, 269–270
development of, 241–242
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis, 249–256
disseminated Oka VZV without other organ involvement, 242–249
dosage, 242
encephalopathy, 267–268
Guillain-Barré syndrome, 273–274
in immunodeficient individuals, 241–242, 245–248, 255, 630–631
limitations of data sources, 631
seizures, 268–269
small fiber neuropathy, 10, 36, 274–275
stroke, 10, 36, 279–280
summary of evidence and causality conclusions, 19–20t, 283–284t, 677–678t
thrombocytopenia, 281–282
transverse myelitis, 272–273
vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis, 78, 261–267
vaccine strain viral reactivation without other organ involvement, 18, 78, 256–261
Varicella zoster virus infection
acute disseminated encephalomyelitis and, 271
cerebellar ataxia and, 240, 270
clinical description, 239–240, 646
complications, 239–241
disseminated Oka VZV without other organ involvement and, 239, 248
disseminated Oka VZV with subsequent infection resulting in pneumonia, meningitis, or hepatitis and, 239–240, 255
Guillain-Barré syndrome and, 240, 274
incidence, 240–241
stroke and, 280
thrombocytopenia, 239, 282
transmission, 239
transverse myelitis and, 240, 272
vaccine development and recommendations, 241–242
vaccine-strain viral reactivation with subsequent infection resulting in meningitis or encephalitis and, 240, 266
vaccine-strain viral reactivation without other organ involvement and, 240, 260
virus description, 239
Vasculitis
definition, 646
hepatitis B vaccine and onset or exacerbation of, 473–477, 492t
influenza vaccine and onset or exacerbation of, 379–383, 403t
mechanism(s) that may contribute to symptoms of, 383, 476
Viral activity. See Biological mechanisms, pathophysiologies, and susceptibilities with the potential to contribute to adverse events
W
Weight-of-evidence evaluations, 10–14, 42–48
Worldwide Adverse Event System, 244–245, 257, 258, 263, 277