Adverse Effects of Vaccines Evidence and Causality (2012) / Chapter Skim
Currently Skimming:
6 Influenza Vaccine
6 Influenza Vaccine
Pages 293-420
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 293... ...
. Occasionally, influenza viruses undergo an abrupt and dramatic change in genome.
|
From page 294... ...
. Influenza viruses have caused epidemics every 1 to 3 years during the past four centuries, and four major pandemics have occurred including the great pandemic of 1918 (Treanor, 2010)
|
From page 295... ...
. Currently, two types of vaccines are available in the United States -- the trivalent, inactivated influenza virus (TIV)
|
From page 296... ...
(2006) were unable to find any cases of encephalopathy or encephalitis following influenza vaccination using a case-crossover or case-control design, so no conclusions could be drawn from these analyses.
|
From page 297... ...
TABLE 6-1 Influenza Vaccines Licensed and Available in the United States Mercury Content Number (mcg Hg/ of Vaccine Trade Name Manufacturer Presentation 0.5 mL dose) Age Group Doses Route TIVa Fluzone Sanofi Pasteur, Inc.
|
From page 298... ...
-like, and B/Brisbane/60/2008-like antigens. e Live attenuated influenza vaccine.
|
From page 299... ...
Viral infection and viral reactivation may contribute to the symptoms of encephalitis; however, the publications did not provide evidence linking these mechanisms to influenza vaccine. The committee assesses the mechanistic evidence regarding an as sociation between influenza vaccine and encephalitis as weak based on knowledge about the natural infection and one case.
|
From page 300... ...
The symptoms described in the publications referenced above are consistent with those leading to a diagnosis of encephalopathy, but the only evidence that could be attributed to the vaccine was recurrence of symptoms upon vaccine rechallenge. Viral infection and viral reactivation may contribute to the symptoms of encephalopathy; however, the publications did not provide evidence linking these mechanisms to influenza vaccine.
|
From page 301... ...
Four studies (D'Heilly et al., 2006; Izurieta et al., 2005; McMahon et al., 2005; Rosenberg et al., 2009) were not considered in the weight of epidemiologic evidence because they provided data from passive surveillance systems and lacked unvaccinated comparison populations.
|
From page 302... ...
. Only discordant pairs were analyzed, and participants that experienced an event during both the risk period and one of the control periods were excluded.
|
From page 303... ...
The relative risk of seizures in children within 7 days of influenza vaccination was 1.35, 0.80, and 0.98 for the 2005–2006, 2006–2007, and 2007–2008 influenza seasons, respectively. The number of vaccine doses administered to adults during the 2005–2006 season was 1,429,974; during the 2006–2007 season it was 1,598,880; and during the 2007–2008 season it was 1,742,858.
|
From page 304... ...
In some instances fever may contribute to the development of seizures; however, the publications did not provide evidence linking this mechanism to influenza vaccine. The committee assesses the mechanistic evidence regarding an as sociation between influenza vaccine and seizures as lacking.
|
From page 305... ...
and in the VSD years of outpatient, 14 days after emergency from 1/1993 inpatient, and influenza department through emergency vaccination visits for 12/1999 department seizures Control period 1: visits for seizures 15 to 28 within 14 days days before of influenza vaccination vaccination Control period 2: 15 to 28 days after vaccination 305 continued
|
From page 306... ...
c Hambidge Outpatient, Eight MCOs Ages 6 to Case-crossover 45,356 cases OR of seizures Serious et al. inpatient, participating 23 months within 14 days Risk period: (2006)
|
From page 307... ...
department in the VSD administered days of influenza ≥ 18 years Risk period: visits for during to children; vaccination 0–7 days seizures 2005–2006, 1,429,974 doses was 1.35 for after TIV 2006–2007, administered to 2005–2006, 0.80 administration and 2007– adults for 2006–2007, for a given 2008 influenza and 0.98 for season 2006–2007: seasons 2007–2008 415,446 doses Control period: influenza seasons administered 8–15 days after to children; RR of seizures in vaccination for 1,598,880 doses adults within 7 the same season administered to days of influenza adults vaccination was 0.99 for 2007–2008: 2005–2006, 0.96 462,998 doses for 2006–2007, administered and 1.09 for to children; 2007–2008 1,742,858 doses influenza seasons administered to adults a The committee assumed statistical significance below the conventional 0.05 level unless otherwise stated by the authors. b The risk/effect estimate for the subgroup/alternate definition of exposure or outcome differs significantly (e.g., is heterogeneous with nonoverlapping 95% confidence intervals)
|
From page 308... ...
Weight of Epidemiologic Evidence The epidemiologic evidence is insufficient or absent to assess an association between influenza vaccine and ADEM. Mechanistic Evidence The committee identified 15 publications reporting the development of ADEM after administration of an influenza vaccine.
|
From page 309... ...
Weight of Epidemiologic Evidence The epidemiologic evidence is insufficient or absent to assess an association between influenza vaccine and transverse myelitis. Mechanistic Evidence The committee identified six publications reporting the development of transverse myelitis after administration of an influenza vaccine.
|
From page 310... ...
. The authors concluded that influenza vaccination did not appear to be associated with an increased risk of optic neuritis in adults.
|
From page 311... ...
The authors performed secondary analyses considering the timing of the influenza vaccination (< 1 year, 1–5 years, and > 5 years) relative to the ON onset, which also showed no significant association, but they did not state how they handled the timing of vaccination for those who had more than one influenza vaccine before the onset of ON or when influenza was given in combination with other vaccines.
|
From page 312... ...
records or telephone neuritis influenza vaccination: participating > 40 years interviews in the VSD 1.2 (95% CI, 0.6–2.3) 228 controls Payne Date of first symptom Defense U.S.
|
From page 313... ...
The symptoms described in the publications referenced above are consistent with those leading to a diagnosis of optic neuritis, but the only evidence that could be attributed to the vaccine was recurrence of symptoms upon vaccine rechallenge. Autoantibodies, T cells, immune complexes, and molecular mimicry may contribute to the symptoms of optic neuritis; however, the publications did not provide evidence linking these mechanisms to influenza vaccine.
|
From page 314... ...
Weight of Epidemiologic Evidence The epidemiologic evidence is insufficient or absent to assess an association between influenza vaccine and NMO. Mechanistic Evidence The committee did not identify literature reporting clinical, diagnostic, or experimental evidence of NMO developing after administration of an influenza vaccine.
|
From page 315... ...
. The authors concluded that influenza vaccination does not appear to be associated with an increased risk of MS onset in adults.
|
From page 316... ...
The committee has limited confidence in the epidemiologic evidence based on two studies that lacked validity and precision to assess an association between influenza vaccine and onset of MS in adults. Mechanistic Evidence The committee identified three publications reporting the onset of MS in adults after administration of an influenza vaccine.
|
From page 317... ...
reported in years control cases within 3 years of described (2004) medical records influenza vaccination: Cases had MS diagnosis 1,604 1.0 (95% CI, 0.5–2.0)
|
From page 318... ...
The difference in MS relapse was not statistically significant for either risk period. The authors concluded that influenza vaccination did not appear to be associated with an increased risk of relapse in MS patients.
|
From page 319... ...
. The relative risk of relapse of MS within 2 months of influenza vaccination was 1.08 (95% CI, 0.37–3.10)
|
From page 320... ...
confirmed by a centers relapsing- randomized difference in MS described 54 received neurologist in the remitting MS controlled trial relapse within 28 placebo United diagnoses days or 6 months States of influenza vaccination Confavreux MS relapse European Case-crossover 643 patients RR of MS None Serious et al. confirmed during Database with definite relapse within described Risk period: (2001)
|
From page 321... ...
(2006) was unable to find any cases of GBS within the defined risk period following influenza vaccination using a case-crossover design, so no conclusions could be drawn from 2 The committee does not include in this review any of the studies of the 1976–1977 swine influenza vaccine and its relationship to GBS.
|
From page 322... ...
The surveillance form listed the patient's date of birth, race, sex, county of residence, date of GBS onset, and date and type of any vaccinations received within 8 weeks of disease onset. Cases of GBS that did not receive an influenza vaccination within 8 weeks of onset were classified as unvaccinated, whereas those that received influenza vaccine during this period were listed at vaccinated.
|
From page 323... ...
The adjusted relative risk of GBS onset within 42 days of influenza vaccination was 0.99 (95% CI, 0.32–3.12)
|
From page 324... ...
The authors also performed an ecological analysis at the population level using a time series in the period between June 1, 1991, and March 31, 2004, to determine if there was an increase in GBS hospitalizations after introduction of universal influenza immunization program. The authors found no significant increase in hospitalization for GBS onset in adults after the mass influenza vaccination program; however, the analysis failed to adequately control for confounding by influenza season.
|
From page 325... ...
A total of 775 episodes occurred in 690 enrolled patients, of which 169 had at least one influenza vaccination. The primary risk period was defined as 0–90 days after vaccination, and 12 and 157 cases occurred within the risk and control periods, respectively (the control period was not defined)
|
From page 326... ...
This retrospective cohort study investigated the occurrence of adverse events after influenza vaccination in children and adults enrolled in eight MCOs participating in the VSD. The authors used a Poisson-based approach (applying a maximized sequential probability ratio test [MaxSPRT]
|
From page 327... ...
In addition, strains of influenza targeted by the vaccine vary each year and associations with GBS also may vary. See Table 6-6 for a summary of the studies that contributed to the weight of epidemiologic evidence.
|
From page 328... ...
weeks of neurologists GBS onset influenza vaccination: unvaccinated vaccination across from 9/1978 1.4 (95% CI, or index date United through 0.7–2.1) States 3/1979 Kaplan GBS onset Reports Cohort 1979–1980 RR of GBS onset None Serious Ages ≥ 18 et al.
|
From page 329... ...
days of with GBS period 42 days of influenza Risk period: vaccination onset from vaccination: 42 days after 225 GBS cases 1/1992 0.99 (95% CI, vaccination in control through 0.32–3.12; p = .99) period 12/2000 Control period: all other time during the study period 329 continued
|
From page 330... ...
7 weeks of Insurance vaccination the 2–7 weeks after Risk period: 141 GBS cases vaccination Plan records influenza vaccination: 2–7 weeks after in control from 4/1993 1.45 (95% CI, vaccination period through 1.05–1.99) 2/2004 Control period: 26–43 weeks after vaccination Tam GBS onset GPRD Patients Nested case 553 patients OR for GBS onset None Serious et al.
|
From page 331... ...
38 GBS through 9–14 weeks cases and RR of GBS onset 12/2000, after vaccination 10,137,566 within 6 weeks of and from person-periods influenza vaccination 9/2001 in control during the 2001 through period season: 12/2001 1.21 (95% CI, 2001 season: 0.79–1.86) 51 GBS cases and 11,972,259 person-periods in risk period 42 GBS cases and 11,895,891 person-periods in control period 331 continued
|
From page 332... ...
1–42 days after 2007–2008 through vaccination in risk period; influenza vaccination influenza 4/2006, current season 15.1 events in during the 2006– seasons from 9/2006 control period 2007 season: 1.13 through Control period: 4/2007, and 1–42 days after 2007–2008: RR of GBS onset (all from 9/2007 vaccination in 23 events in ages) 1–42 days after through previous seasons risk period; influenza vaccination 4/2008 (historical risk 16.7 events in during the 2007– period)
|
From page 333... ...
The antiganglioside antibody-positive mice did not present with clinical disease. Weight of Mechanistic Evidence While rare, infection with influenza viruses A and B have been associated with the development of GBS (Davis, 2008)
|
From page 334... ...
Although the epidemiologic evidence is graded moderate-null, the committee does not feel the evidence is adequate to favor rejection of an association because of the potential for confounding by season and influenza infection and because of the yearly differences in influenza strains included in the vaccine. While the weight of epidemiologic evidence does not support a causal link between influenza vaccinations evaluated over the last 30 years, an association cannot be confidently ruled out, particularly for future vaccine strains.
|
From page 335... ...
Evidence beyond a temporal relationship between administration of the vaccine and development of CIDP after vaccination was not provided in any of the reports. Weight of Mechanistic Evidence The publication described above did not provide evidence sufficient for the committee to conclude the vaccine may be a contributing cause of CIDP.
|
From page 336... ...
This retrospective cohort study investigated the occurrence of adverse events after influenza vaccination in children and adults enrolled in eight MCOs participating in the VSD. The study included cases of Bell's palsy reported during outpatient, inpatient, and emergency department visits after receipt of influenza vaccine from September through April of the 2005–2006, 2006–2007, and 2007–2008 influenza seasons.
|
From page 337... ...
The committee has a high degree of confidence in the epidemiologic evidence based on two studies with validity and precision to assess an association between inactivated influenza vaccine and Bell's palsy; these studies consistently report a null association. Mechanistic Evidence The committee identified two publications reporting Bell's palsy after administration of an influenza vaccine.
|
From page 338... ...
palsy case series days of influenza vaccination: Risk period: 0.92 (95% CI, 1–91 0.78–1.08) days after influenza vaccination Control period: all time not attributed to a risk period excluding 14 days prior to vaccination and day of vaccination
|
From page 339... ...
and administered to within 1–42 participating ≥ 18 years Risk period: emergency in the VSD children; days of influenza 1–42 department during the 1,432,218 doses vaccination was days after visits for 2005–2006, administered to adults 0.67 for 2005– influenza Bell's palsy 2006–2007, 2006, 1.81 for vaccination 2006–2007: and 2006–2007, and for a given 415,446 doses 2007–2008 1.27 for 2007–2008 influenza administered to influenza influenza seasons season children; seasons 1,598,880 doses RR of Bell's palsy in Control administered to adults adults within 1–42 period: days of influenza 15–74 days 2007–2008: vaccination was before 462,998 doses 1.06 for 2005– vaccination administered to 2006, 1.07 for for the same children; 2006–2007, and influenza 1,742,858 doses 0.99 for 2007–2008 season administered to adults influenza seasons a The committee assumed statistical significance below the conventional 0.05 level unless otherwise stated by the authors. b The risk/effect estimate for the subgroup/alternate definition of exposure or outcome differs significantly (e.g., is heterogeneous with nonoverlapping 95% confidence intervals)
|
From page 340... ...
Mechanistic Evidence The committee identified two publications reporting brachial neuritis after administration of an influenza vaccine. The publications did not provide evidence beyond temporality and therefore did not contribute to the weight of mechanistic evidence (Hansen, 2005; Wells, 1971)
|
From page 341... ...
Causality Conclusion Conclusion 6.14: The evidence is inadequate to accept or reject a causal relationship between influenza vaccine and small fiber neuropathy. ANAPHYLAXIS Epidemiologic Evidence The committee reviewed eight studies to evaluate the risk of anaphylaxis after the administration of influenza vaccine.
|
From page 342... ...
of the same season. The relative risk of anaphylaxis in individuals of all ages within 2 days of influenza vaccination was 3.00, 4.00, and 1.00 for the 2005–2006, 2006–2007, and 2007–2008 influenza seasons, respectively.
|
From page 343... ...
(2005) reviewed adverse events, reported to VAERS, after administration of a live attenuated influenza vaccine during the 2003–2004 and 2004–2005 influenza seasons.
|
From page 344... ...
Weight of Mechanistic Evidence The publications, described above, presented clinical evidence sufficient for the committee to conclude the vaccine was a contributing cause of anaphylaxis after administration of influenza vaccines. The clinical descriptions provided in many of the publications establish a strong temporal relationship between administration of the vaccine and anaphylactic reactions.
|
From page 345... ...
The seven remaining controlled studies (Bueving et al., 2004; Castro et al., 2001; Kmiecik et al., 2007; Nicholson et al., 1998; Pedroza et al., 2009; Stenius-Aarniala et al., 1986; Tata et al., 2003) were included in the weight of epidemiologic evidence and are described below.
|
From page 346... ...
over three influenza seasons and three risk periods, no rate ratio showed an increased risk of the outcome following influenza vaccination. The authors concluded that vaccination with TIV does not increase the risk of asthma exacerbations in patients with asthma.
|
From page 347... ...
These small differences were less than the 5 percent difference that the authors considered clinically significant, as well as being less than the study was designed to be able to detect with adequate statistical power. The authors reported that significantly more asthma exacerbations were observed in groups A and B during the first 14-day interval compared to the second 14-day interval; however, results from appropriate repeated measures analyses (required for crossover study designs)
|
From page 348... ...
The committee reviewed four studies evaluating the risk of asthma or reactive airway disease episodes after TIV administration in children without regard to any prior diagnosis of asthma. One study (Rosenberg et al., 2009)
|
From page 349... ...
Under the assumption that a prior asthma diagnosis has no modifying effect (i.e., the influence of inactivated influenza vaccination on a child's risk of an asthma-like episode is the same regardless of any prior diagnosis of asthma) , these reports add to the evidence described in the paragraphs above for asthma episodes in individuals with a prior asthma diagnosis.
|
From page 350... ...
The committee has a high degree of confidence in the epidemiologic evidence based on nine studies with validity and precision to assess an association between inactivated influenza vaccine and asthma exacerbation or reactive airway disease episodes in children and adults; these studies consistently report a null association. Mechanistic Evidence The committee identified 17 publications studying or reporting asthma or reactive airway disease episodes after the administration of an inactivated influenza vaccine.
|
From page 351... ...
within 72 centers and with a controlled crossover received observed in 11 hours of two asthma history of trial TIV and patients after TIV vaccination, clinics in asthma placebo (4.3 percent; 95% Injections separated defined as a the United injections CI, 2.2 to 7.6 by 2 week intervals decrease in Kingdom percent) PEF values Asthma exacerbations observed in 3 patients after placebo (1.2 percent; 95% CI, 0.2 to 3.3 percent)
|
From page 352... ...
codes for during the to 79 series patients an increased risk of described asthma 1991–1992, years with a defined outcome Three risk periods: exacerbation, 1992–1993, asthma or following influenza day of vaccination, asthma and chronic vaccination 1–2 days diagnosis, 1993–1994 obstructive postvaccination, and asthma influenza pulmonary and 3–14 days prescription seasons disease postvaccination use Control period: remaining influenza season from October 1 through April 30
|
From page 353... ...
in the years with controlled trial TIV were reported Netherlands asthma between the TIV and 349 during the placebo groups received 1999–2000 placebo and 2000–2001 influenza seasons Kmiecik Asthma Four centers Ages 18 to Double-blind, 144 Difference in asthma None Serious et al. exacerbations in Poland 65 years randomized patients in exacerbation rates described (2007)
|
From page 354... ...
3–5 days after the Instituto with mild controlled trial TIV changes in FEV1, injection Nacional de intermittent FEV2, or FEV3 31 Pediatria, or among the TIV and received Mexico moderate placebo groups placebo during the persistent 2001–2002 asthma influenza season France Outpatient, Five HMOs Ages under Case-crossover 251,600 Visits for asthma None Serious et al. inpatient, and participating 18 years cases within 14 days of described Risk period: (2004)
|
From page 355... ...
c Studies designated as serious had more methodological limitations than those designated as negligible. Studies assessed as having very serious limitations were not considered in the weight of epidemiologic evidence.
|
From page 356... ...
Causality Conclusion Conclusion 6.16: The evidence favors rejection of a causal relation ship between inactivated influenza vaccine and asthma exacerba tion or reactive airway disease episodes in children and adults. LIVE ATTENUATED INFLUENZA VACCINE AND ASTHMA EXACERBATION OR REACTIVE AIRWAY DISEASE EPISODES IN CHILDREN YOUNGER THAN 5 YEARS OF AGE Epidemiologic Evidence The committee reviewed six studies to evaluate the risk of asthma or reactive airway disease episodes in children younger than 5 years of age with and without a prior diagnosis of asthma after LAIV or CAIV administration.
|
From page 357... ...
The relative risk of asthma or reactive airway disease episodes within 42 days of administration of dose one of CAIV in children aged 12 to 59 months was 3.5 (90% CI, 1.09–15.54) ; however, no statistically significant increased risk was observed for children aged 36 to 59 months.
|
From page 358... ...
. The authors note the lack of temporal clustering of asthma or reactive airway disease episodes within 42 days of vaccination for any age group suggests the observed increased risk of asthma may not be a result of vaccine administration.
|
From page 359... ...
. The authors did not find an increased risk of asthma exacerbation or new onset asthma during the 0-to-14-day or 0-to-42-day risk period after LAIV administration in the 18-month to 4-year age group during any of the 4 study years.
|
From page 360... ...
. Weight of Epidemiologic Evidence In examining evidence for an association of asthma with TIV or LAIV immunization, the committee addressed asthma or wheezing episodes in study populations with and without a prior diagnosis of asthma.
|
From page 361... ...
Mechanistic Evidence The committee did not identify literature reporting clinical, diagnostic, or experimental evidence of asthma or reactive airway disease episodes in children younger than 5 years of age with and without a prior diagnosis of asthma after LAIV or CAIV administration.
|
From page 362... ...
emergency visits, Permanente years randomized months: airway disease episodes statistically (2004) and clinic visits health controlled trial within 42 days of CAIV significant 2,021 for asthma plan from administration among increased risk Reanalysis received 10/2000 ages 12–59 months: observed for of Bergen CAIV through 3.5 (90% CI, children aged et al.
|
From page 363... ...
department, and Health 18 years 0–14 days of LAIV increased risk Risk period 1: hospital visits Plan in administration among of asthma 0–14 days after for asthma Texas ages 18 months to 4 within 15–42 vaccination from 1998 years during all four days of LAIV through Risk period 2: study periods administration 2002 15–42 among ages No significant increased days after 18 months to risk of asthma within vaccination 4 years during 15–42 days of LAIV the first study Control administration among period period: ages 18 months to 4 prevaccination years during the last period from three study periods start date of program to date of vaccination 363 continued
|
From page 364... ...
asthma 2002 0–42 days after four study periods vaccination Control period: prevaccination period from start date of program to date of vaccination and postvaccination period after defined risk periods
|
From page 365... ...
Studies assessed as having very serious limitations were not considered in the weight of epidemiologic evidence.
|
From page 366... ...
LIVE ATTENUATED INFLUENZA VACCINE AND ASTHMA EXACERBATION OR REACTIVE AIRWAY DISEASE EPISODES IN PERSONS 5 YEARS OF AGE OR OLDER Epidemiologic Evidence The committee reviewed six studies to evaluate the risk of asthma or reactive airway disease episodes in persons 5 years of age or older after LAIV or CAIV administration. One study (Izurieta et al., 2005)
|
From page 367... ...
(2004) was described in detail in the section on LAIV and asthma exacerbation or reactive airway disease episodes in children younger than 5 years of age.
|
From page 368... ...
Although preexisting asthma was an exclusion criterion, 8.8 percent of the participants had a record of prior asthma diagnosis or symptoms. In these children receipt of CAIV was not associated with an increased risk of an asthma or reactive airway disease episode in the 42 days after vaccination (RR, 1.11; 90% CI, 0.59–2.14)
|
From page 369... ...
See Table 6-10 for a summary of the studies that contributed to the weight of epidemiologic evidence. The committee has a moderate degree of confidence in the epi demiologic evidence based on five studies with sufficient validity and precision to assess an association between LAIV and asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older; these studies consistently report a null association.
|
From page 370... ...
c Bergen Hospitalizations, Kaiser Ages 1–18 Double-blind, Ages No increased risk None Serious et al. emergency visits, Permanente years randomized 1–8 of asthma episodes described (2004)
|
From page 371... ...
department, and Health Plan 18 years days or 15–42 of 0–14 days after hospital visits in Texas LAIV administration vaccination for asthma during 1998 among ages 5–9 to 2002 Risk period 2: years or 10–18 years 15–42 days after during all four study vaccination periods Control period: prevaccination period from start date of program to date of vaccination 371 continued
|
From page 372... ...
asthma 10–18 years during vaccination all four study periods Control period: prevaccination period from start date of program to date of vaccination and postvaccination period after defined risk periods Fleming Asthma 13 countries Ages 6–17 Randomized 1,114 Percentage point None Serious et al. symptoms during years with controlled trial received difference of asthma described (2006)
|
From page 373... ...
The committee assesses the mechanistic evidence regarding an asso ciation between LAIV and asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older as weak based on knowledge about the natural infection and nine cases. Causality Conclusion Conclusion 6.18: The evidence is inadequate to accept or reject a causal relationship between LAIV and asthma exacerbation or reactive airway disease episodes in persons 5 years of age or older.
|
From page 374... ...
, and were observed in two vaccinated patients and one unvaccinated patient. The authors concluded that influenza vaccination does not adversely influence the disease activity of SLE patients.
|
From page 375... ...
The authors concluded that influenza vaccination does not adversely influence the disease activity of SLE patients, and noted that unvaccinated patients are at higher risk of disease exacerbation resulting from viral and bacterial infections. Weight of Epidemiologic Evidence The studies considered in the epidemiologic evidence consist of one small RCT comparing influenza vaccine and no vaccine in SLE patients (Williams et al., 1978)
|
From page 376... ...
the American randomized influenza vaccinated and Rheumatism controlled vaccine placebo groups Association trial 20 received diagnostic saline injection criteria Abu- SLEDAI score Patients with Cohort 24 vaccinated SLEDAI scores Significant Serious Shakra SLE that met for the vaccinated decrease in 24 unvaccinated et al. the American and unvaccinated SLEDAI scores (2000)
|
From page 377... ...
c Studies designated as serious had more methodological limitations than those designated as negligible. Studies assessed as having very serious limitations were not considered in the weight of epidemiologic evidence.
|
From page 378... ...
It is important to note, however, that not all inflammation is infectious so lupus flare-ups may also be associated with sterile inflammation as would be the case with an inactivated influenza vaccine. Autoantibodies, T cells, complement activation, and immune complexes may contribute to the onset or exacerbation of SLE; however, the publications did not provide evidence linking these mechanisms to influenza vaccine.
|
From page 379... ...
. The authors concluded that influenza vaccination does not increase the occurrence of disease relapse in AAV patients.
|
From page 380... ...
The ANCA titers, fourfold increase in ANCA titers, and VAS did not differ among the vaccinated and control groups during the 4 months of follow-up. The authors concluded that influenza vaccination does not increase the occurrence of disease relapse in Wegener's granulomatosis patients with quiescent disease; however, they noted the study was underpowered to adequately detect this effect.
|
From page 381... ...
titers granulomatosis trial vaccine vaccinated and control groups within 4 months 23 controls of influenza vaccination a The committee assumed statistical significance below the conventional 0.05 level unless otherwise stated by the authors. b The risk/effect estimate for the subgroup/alternate definition of exposure or outcome differs significantly (e.g., is heterogeneous with nonoverlapping 95% confidence intervals)
|
From page 382... ...
Weight of Mechanistic Evidence The publication described above did not provide evidence sufficient for the committee to conclude the vaccine may be a contributing cause of vasculitis. The symptoms described in the publications referenced above are
|
From page 383... ...
Mechanistic Evidence The committee identified one publication reporting the development of PAN after administration of an influenza vaccine. The publication did not provide evidence beyond temporality and therefore did not contribute to the weight of mechanistic evidence (Wharton and Pietroni, 1974)
|
From page 384... ...
Weight of Epidemiologic Evidence The epidemiologic evidence is insufficient or absent to assess an association between influenza vaccine and onset or exacerbation of arthropathy. Mechanistic Evidence The committee identified 12 publications either reporting or studying the onset or exacerbation of arthropathy after administration of an influenza vaccine.
|
From page 385... ...
Autoantibodies, T cells, complement activation, immune complexes, and infection may contribute to the symptoms of arthropathy; however, the publications did not provide evidence linking these mechanisms to the vaccine. The committee assesses the mechanistic evidence regarding an as sociation between influenza vaccine and onset or exacerbation of arthropathy as weak based on one case and knowledge about the natural infection.
|
From page 386... ...
following vaccination. The authors concluded that influenza vaccination is not associated with an increased risk of stroke.
|
From page 387... ...
. The control period consisted of all other time outside the risk period not including the time before a participant's first influenza vaccination, since influenza vaccine is indicated for patients with preexisting cardiovascular disease.
|
From page 388... ...
following vaccination. The authors concluded that influenza vaccination is not associated with an increased risk of a first myocardial infarction.
|
From page 389... ...
to reach a high degree of confidence in the epidemiologic evidence. Only one epidemiologic study with negligible methodological limitations that reports a decreased risk is included in the weight of evidence for this causality conclusion.
|
From page 390... ...
. The authors concluded that influenza vaccination is not associated with an increased risk of death in the short term.
|
From page 391... ...
The committee assesses the mechanistic evidence regarding an as sociation between inactivated influenza vaccine and all-cause mor tality as lacking. Causality Conclusion Conclusion 6.26: The evidence is inadequate to accept or reject a causal relationship between influenza vaccine and all-cause mortality.5 OCULORESPIRATORY SYNDROME Epidemiologic Evidence The committee reviewed seven studies to evaluate the risk of oculorespiratory syndrome (ORS)
|
From page 392... ...
(2003) , and patients who had ORS following influenza vaccination during the 2000–2001 season were included in Skowronski et al.
|
From page 393... ...
during four risk periods (0–2 or 1–3 days, 1–14 days, 15–42 days, and 1–42 days) after influenza vaccination, but were limited to predefined codes in the MCO databases.
|
From page 394... ...
Thus, the evidence is limited to observations following the administration of two particular vaccines used in Canada in the first 3 years of the 21st century, and does not offer useful information as to the risk of ORS following influenza vaccination in the United States. See Table 6-13 for a summary of the studies that contributed to the weight of epidemiologic evidence.
|
From page 395... ...
experienced ORS received symptoms after a placebo previous influenza vaccination 395 continued
|
From page 396... ...
recorded by a Manitoba, ORS following crossover trial Fluviral ORS symptoms team member Alberta, Fluviral S/F S/F within 24 hours Injections were by telephone and British vaccination during influenza of injection with given 5–7 days 24 hours and Columbia) the 2000–2001 vaccine no time limit apart during 6 days after influenza season for the for resolution of September 2001 each injection 2001– symptoms: 2002 4.0 (95% CI, season 1.4–37.8)
|
From page 397... ...
Vaxigrip the 2000–2001 influenza The vaccine influenza vaccine vaccines attributable and were for the risk of ORS revaccinated 2002– symptoms during the 2001– 2003 within 24 hours 2002 influenza season of Vaxigrip season vaccination with 146 Group C: patients no time limit received who had a first for resolution of placebo occurrence of ORS symptoms: after receiving 15 percent the 2001–2002 (95% CI, 2–28 influenza vaccine percent) 397 continued
|
From page 398... ...
c Studies designated as serious had more methodological limitations than those designated as negligible. Studies assessed as having very serious limitations were not considered in the weight of epidemiologic evidence.
|
From page 399... ...
(2003) described six patients presenting with symptoms of ORS developing 1.5 to 12 hours postinfluenza vaccination.
|
From page 400... ...
(2005) conducted a survey of children in British Columbia, Canada, to assess the development of adverse events postinfluenza vaccination in 2000–2001.
|
From page 401... ...
CONCLUDING SECTION Table 6-14 provides a summary of the epidemiologic assessments, mechanistic assessments, and causality conclusions for influenza vaccine. 6 Due to the use of the same sample population in some studies it is likely that some of the cases were presented in more than one publication; thus, it is difficult to determine the number of unique cases.
|
From page 402... ...
Influenza Chronic Inflammatory Disseminated Insufficient None Weak 2 Inadequate Polyneuropathy Influenza Inactivated Influenza Vaccine and Bell's High (null) 2 Lacking None Favors Palsy Rejection Influenza Brachial Neuritis Insufficient None Lacking None Inadequate Influenza Small Fiber Neuropathy Insufficient None Lacking None Inadequate
|
From page 403... ...
Disease Episodes in Children Younger Than 5 Years of Age Influenza Live Attenuated Influenza Vaccine and Moderate 5 Weak 9 Inadequate Asthma Exacerbation or Reactive Airway (null) Disease Episodes in Persons 5 Years of Age or Older Influenza Onset or Exacerbation of Systemic Lupus Limited 4 Lacking None Inadequate Erythematosus (exacerbation)
|
From page 404... ...
(live attenuated influenza vaccine) Lacking None (inactivated influenza vaccine)
|
From page 405... ...
1999. Fatal outcome of systemic vasculitis following influenza vaccination.
|
From page 406... ...
2009. ANCA associated vasculitis following influenza vaccination: Causal association or mere coinci dence?
|
From page 407... ...
2006. Safety of influenza vaccinations admin istered in nontraditional settings.
|
From page 408... ...
2010. Descriptive summary of VAERS reports indicat ing serious adverse events following influenza vaccination discussed in Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring.
|
From page 409... ...
2003. Ophthalmological and biological features of the oculorespiratory syndrome after influenza vaccination.
|
From page 410... ...
2004. Guillain-Barré syndrome following influenza vaccination.
|
From page 411... ...
2003. Rheumatoid vasculitis following influenza vaccination.
|
From page 412... ...
2007. Deaths following influenza vaccination -- background mortality or causal connection?
|
From page 413... ...
2005. Adverse events after inactivated influenza vaccination among children less than 2 years of age: Analysis of reports from the Vaccine Adverse Event Reporting System, 1990-2003.
|
From page 414... ...
2003. Multiple sclerosis after allergen-specific immunotherapy and influenza vaccination.
|
From page 415... ...
1987. Allergic vasculitis and bronchial asthma following influenza vaccination [in Hebrew]
|
From page 416... ...
2003a. Randomized, double-blind, placebo-controlled trial to assess the rate of recurrence of oculorespiratory syndrome following influenza vaccination among persons previously affected.
|
From page 417... ...
1968. A case of transverse myelitis following influenza vaccination [in Japanese]
|
From page 418... ...
2008. Hepatitis B virus-related vasculitis manifesting as severe peripheral neuropathy following influenza vaccination.
|
From page 419... ...
2010. Adult onset Still's disease following influenza vaccination.
|
From page 420... ...
2004. A potential signal of Bell's palsy after parenteral inactivated influenza vaccines: Reports to the Vaccine Adverse Event Reporting System (VAERS)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.