Immunization Safety Review Influenza Vaccines and Neurological Complications (2004) / Chapter Skim
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Contents of Report
Contents of Report
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From page 23... ...
The committee's mandate also includes assessing the broader significance for society of these immunization safety issues. This seventh report from the committee examines the hypothesis that influenza vaccines are associated with an increased risk of neurological complications, particularly Guillain-Barre syndrome (GBS)
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In 1999, because of IOM's previous work and its access to independent scientific experts, CDC and NIH began a year of discussions with IOM to develop the Immunization Safety Review project, which would address both emerging and existing vaccine safety issues. The Immunization Safety Review Committee is responsible for examining a broad variety of immunization safety concerns.
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For its evaluation of the question concerning influenza vaccines and neurological complications, the committee held an open scientific meeting in March 2003 (see Appendix B) to hear presentations on issues germane to the topic.
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does or does not cause the adverse event in question. The weight of the available clinical and epidemiologic evidence determines whether it is possible to shift from that neutral position to a finding for causality ("the evidence favors acceptance of a causal relationship")
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That is, the data are specifically related to the effects of the vaccines under review and the adverse health outcomes) under review in this report, the effects of influenza vaccination on the risk of neurological complications.
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But this committee is often faced with circumstances in which the epidemiologic evidence is judged inadequate to accept or reject a causal association between a vaccine exposure and an adverse event of concern. It is then left with the task of examining proposed or conceivable biological mechanisms that might be operating if an epidemiologically sound association could be shown between a vaccine exposure and an adverse event.
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From page 30... ...
For example, the wild-type infection causes the adverse health outcome associated with the vaccine, or another vaccine has been demonstrated to cause the same adverse outcome by the same or a similar mechanism. Data from populationbased studies of the risk of adverse outcomes following vaccination constitute evidence regarding causality, not biological mechanisms.
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From page 31... ...
~ UNDER REVIEW: INFLUENZA VACCINES AND NEUROLOGICAL COMPLICATIONS The Immunization Safety Review Committee was asked to examine the hypothesis that a causal relationship might exist between receipt of influenza vaccines and neurological complications. In the United States, concern about such adverse neurological events is most prominently linked to cases of Guillain
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From page 32... ...
This federally funded immunization program was aimed at averting the possibility of an outbreak of a type of influenza "swine flu" thought to be related to the virus that caused a massive global epidemic in 1918-1919. Although production of a vaccine was slowed by technical problems as well as by negotiations between the government and manufacturers over the purchase contracts and liability protections, ultimately, the production, distribution, and administration of the swine influenza vaccine was successfully implemented.
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From page 33... ...
A temporal association between neurological complications such as encephalitis, transverse myelitis, and GBS has also been reported (Dolin, 2001~. Encephalitis/ encephalopathy has been reported as a complication primarily of influenza type A (H3N2)
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From page 34... ...
For example, the type A swine influenza virus that prompted the 1976 immunization program in the United States is referred to as A/New Jersey/76 (HlNl)
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Since 1977, H3N2 and HlN1 subtypes have been co-circulating in humans. Antigenic drift occurs often, leading the need for annual influenza vaccination.
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ACIP also encourages that children aged 6-23 months receive the influenza vaccine. A recommendation for universal routine influenza immunization in that age group may be made in the near future (CDC, 2003d)
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The influenza vaccines that were used in the 1976 swine influenza vaccination program were produced using similar methods, except that both whole-cell and subunit vaccines were manufactured. Some of the vaccine produced in 1976 was monovalent, using only the influenza A(HlNl)
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In the CNS (the brain, spinal cord, and optic nerves) , myelin is synthesized by oligodendrocytes; in the
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From page 39... ...
This difference is probably related to the respective tissue environments, with peripheral nerves exposed to growth factors and other mediators that are not present in or are less accessible to the CNS (Waubant and Stuve, 2002~. Several other neurological complications have been reported following receipt of influenza vaccines, including transverse myelitis, hypoglossal nerve paralysis, hemiparesis, meningoencephalitic syndrome, and ADEM (acute disseminated encephalomyelitis)
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From page 40... ...
published after the release of that IOM report suggests to some that the relationship with the oral polio vaccine is not, in fact, causal (Sutter et al., 1999~. The potential association between GBS and influenza vaccines, most notably the 1976 swine influenza vaccines, has been widely studied and is the principle focus of this report.
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INFLUENZA VACCINES AND NEUROLOGICAL COMPLICATIONS 41 Diagnosis of GBS is based primarily on clinical evaluation (Joseph and Tsao,2002~. Diagnostic criteria have varied over time and were made more strict in the wake of the concern about GBS raised by the 1976 swine influenza vaccination program (Asbury, 2000~.
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Multiple Sclerosis MS affects between 250,000 and 350,000 people in the United States and is the most common inflammatory demyelinating disease of the CNS (Keegan and Noseworthy, 2002~. Its incidence and manifestations vary within the population.
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Optic neuritis can occur as an isolated monophasic disease, or it may be a symptom of other demyelinating diseases such as acute disseminated encephalomyelitis (ADEM)
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For other neurological complications that have been observed following influenza vaccination, only case reports were found. Concluding the assessment of these outcomes is a brief review of reports regarding neurological complications following administration of influenza vaccines to children.
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1976 Swine Influenza Vaccines Controlled Observational Studies United States: Initial Analyses. Expanding on the preliminary report by Langmuir (1979)
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Of these, 532 were considered vaccinated with the A/New Jersey/76 influenza vaccine prior to their GBS onset and 543 were not vaccinated. The 15 patients who received the vaccine after onset of GBS were considered unvaccinated.
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From page 47... ...
Among the fatal cases, 32 had received a swine influenza vaccine. The overall case fatality rate of 5.3 percent was described as similar to the rate of 7 percent reported for an earlier 14-year period.
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They also were not permitted to interview personnel who had been involved in the National Influenza Immunization Program. However, one former CDC staff member from the immunization program was responsible for preparing the computerized data reviewed for the study.
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From page 49... ...
They calculated that the number of GBS cases attributable to the influenza vaccine was 211 with the higher baseline estimate and 246 with the lower baseline. The authors concluded that that there was no epidemiological basis for linking the vaccinated cases with "limited" motor involvement to the swine influenza vaccine since those cases occurred without a discernable pattern.
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From page 50... ...
examined the association between swine influenza vaccination and GBS cases in Ohio with onset between October 1, 1976, and January 31, 1977. Cases were identified by contacting all neurologists in the state who could be identified from listings of the Ohio State Medical Association or the telephone books of major metropolitan areas.
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Breman and Hayner (1984) examined the incidence of GBS in Michigan between July 1, 1976, and April 30, 1977, a period that included the swine influenza vaccination program.
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Swine influenza vaccination were based on state and national data. Overall, 2.2 million out of a population of 6.2 million persons 18 years of age and older were vaccinated in Michigan.
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Michigan and Minnesota. To address persistent questions about previous analyses that had found an association between GBS and receipt of the swine influenza vaccine, Safranek and colleagues (1991)
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received the swine influenza vaccine before onset of GBS. Four cases that had been classified as unvaccinated in the CDC records were reclassified as vaccinated.
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From page 55... ...
Army, Navy, Marine Corps, and Air Force. Although it was not clear what sources were used to obtain the number of vaccinations administered and the number of active duty personnel serving in the military, the authors calculated that for this period an average of 80.5 percent of 2.1 million military personnel on active duty received an influenza vaccine each year.
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to obtain GBS cases and does not focus solely on GBS cases occurring in 1976, the committee notes the study's limited ability in assessing GBS cases related to swine influenza vaccination.
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The committee concludes that the evidence favors acceptance of a causal relationship between 1976 swine influenza vaccines and Guillain-Barre syndrome in adults. Concerns that the evidence of increased risk found in the original analysis of the national data might have been a reflection of inaccuracies in ascertainment of GBS cases have been addressed in subsequent studies by detailed and systematic reviews of clinical data to verify GBS diagnoses.
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58 IMMUNIZATION SAFETY REVIEW TABLE 3 Evidence Table: Exposure to 1976 Swine Influenza Vaccines and Guillain-Barre Syndrome Citation Design Population Assessment of Vaccine Exposure Outcomes Schonberger et Cohort al.
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GBS onset, with influenza vaccines by patient by a physician and cases clustered and GBS in adults. on sought objective evidence of Attributable Risk within within the first urination muscle involvement.
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60 TABLE 3 Continued IMMUNIZATION SAFETY REVIEW Citation Design Population Assessment of Vaccine Exposure Outcomes Langmuir et al. Cohort (1984)
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curing first page, computer- association ported GBS cases six 7-day intervals after generated between exposure NIIP categorized as receipt of the influenza summaries for to the 1976 swine having "extensive" vaccine: each of the 1098 influenza vaccines r. motor involvement cases in the and GBS in adults.
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GBS cases (onset 9/15/76-1/31/77) : Total = 56 Vaccinated= 36 Unvaccinated = 20 A short epidemiologic form including information about influenza vaccination history, was completed for each case.
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From page 63... ...
between exposure ing 1 to 7 days after Onset within 5 weeks of About 75 percent to the 1976 swine outacted initial symptoms, influenza vaccination: of all cases influenza vaccines the form. marked symmetrical 4.09 experienced and GBS in adults.
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64 TABLE 3 Continued IMMUNIZATION SAFETY REVIEW Citation Design Population Assessment of Vaccine Exposure Outcomes Marks and Halpin Cohort (1980) Ohio population, based on 1970 census data.
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INFLUENZA VACCINES AND NEUROLOGICAL COMPLICATIONS 65 Contribution to Outcomes Results Comment Causality Argument s of GBS GBS case defined as Relative risk for GBS Possible The study provides by diagnosis with after vaccination: ascertainment evidence of an nt. Copy physical evidence of 5.1 bias if physicians association used as bilateral, but not were more likely between exposure necessarily Attributable risk: to report GBS to the 1976 swine symmetrical, 10.7 cases/million cases in vaccine influenza vaccine l included lower-motor neuron vaccinations recipients than and GBS in adults.
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From page 66... ...
Vaccination status of GBS cases determined by review of medical records by epidemiologists and .
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From page 67... ...
: showed an association s of GBS bilateral muscle Unvaccinated: 0.36 per increased between exposure by review weakness of lower million person-weeks incidence of GBS to the 1976 swine s by motor neuron type during the swine influenza vaccine nd with or without Onset before vaccination: influenza and GBS in adults. cranial nerve or 0.19 per million vaccination sensory person-weeks program and that abnormalities; the increased risk acute or subacute Onset 1-6 weeks after occurred for onset and evolution vaccination: 2.31 per only 6 weeks of signs and million person-weeks after vaccination.
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From page 68... ...
: Total: 73 Vaccinated: 45 Unvaccinated: 28 Michigan: Numbers of vaccinations administered each week during the immunization program determined from National Center for Health Statistics estimates. Minnesota: Numbers of vaccinations administered each week were based on data released under 1981 court order that prompted the reanalysis of the national data (Langmuir et al., 1984)
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From page 69... ...
between exposure National records using vaccination: Nonrandom to the 1976 swine Statistics modification of Michigan: 7.94 clustering of influenza vaccine previously published Minnesota: 5.23 cases in the and GBS in adults. criteria.
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Influenza vaccine given to all active-duty military personnel in October. Recruits immunized on entry into active duty.
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Study lacked a control group. The study design limits the study's contribution to the causality argument.
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military personnel Military personnel on active Analysis l (1986) trolled 1974-1978 duty routinely receive hospitaliz observa- influenza vaccine each year.
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In addition, because of the well-publicized association between swine influenza vaccine and GBS, it was possible that GBS cases among persons who had been vaccinated were more likely to be reported. United States, 1979-1980, 1980-1981.
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From page 74... ...
examined the association between GBS and exposure to influenza vaccines administered during 1992-1993 and 1993-1994. Data on GBS cases were obtained from hospital discharge databases from Illinois, Maryland, North Carolina, and Washington.
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From page 75... ...
Vaccine-related GBS was defined as cases with onset of GBS within 6 weeks after receipt of the influenza vaccine. The estimated population 2 18 years of age in the four states was 21.2 million in 1992-1993 and 21.4 million in 1993-1994.
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From page 76... ...
GBS cases were identified from physician diagnoses in records for patients hospitalized at Army medical-treatment facilities. Army personnel are expected to receive influenza vaccine during the last week in October; the Army Surgeon General estimated a compliance rate of 80 percent for the period covered by the study.
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From page 77... ...
Chen (2003) presented unpublished data on the association between GBS and the influenza vaccine administered in the 19901991 season.
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From page 78... ...
For the age group 18-64 years, there was an indication of increased risk for GBS following influenza vaccination, but the data on timing of GBS onset and antecedent illness did not provide clear support for a causal link with vaccination. In addition, interpretation of the study is limited by the lack of validation of vaccination status in the 18-64 year age group and the small number of cases.
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From page 79... ...
presented data on reports related to influenza vaccines that were submitted to VAERS between July 1990 and March 13, 2003. Using the indexing term "Guillain-Barre Syndrome," 565 reports of GBS were identified.5 In a follow-up of these reports, the diagnosis of GBS was verified in 81 percent of cases, and 59 percent were reported to have occurred within 1 to 2 weeks after vaccination.
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From page 80... ...
, that only the first two of these four reports are suggestive of cases of GBS associated with influenza vaccination. In neither of these cases, however, was the documentation sufficient to confirm GBS in response to a rechallenge with influenza vaccine.
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From page 81... ...
All these studies concerned influenza vaccines used in various years, including the swine influenza vaccines of 1976. The committee was also provided with information that 24 reports of MS7 following influenza vaccination had been submitted to VAERS from January 1990 through March 2003 (Haber, 2003~.This information did not indicate whether these reports concerned the onset of MS or relapses.
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From page 82... ...
Unknown age = 15 Unknown vaccination status = 21 Vaccinations between 8/1978 and 1/1979 estimated from 1979 national immunization survey. For GBS cases, neurologists provided vaccination history.
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From page 83... ...
than influenza vaccine the causality cases in the vaccinated (33%) and GBS may argument.
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From page 84... ...
Vaccinations between 9/1980 and 1/1981 estimated from 1981 national immunization survey. For GBS cases, neurologists provided vaccination history.
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From page 85... ...
: cases across the association ation 1.4 (0.80-1.76) 8-week period between exposure Cases reported to following to influenza CDC as part of GBS Relative Risk of GBS vaccination.
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From page 86... ...
86 TABLE 4 Continued IMMUNIZATION SAFETY REVIEW Citation Design Population Assessment of Vaccine Exposure Outcomes Lasky et al.
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, of GBS, or requiring Relative Risk (95%CI) period, age less review.
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From page 88... ...
to tional Part B bills) for influenza beneficial Immunization Total influenza vaccine vaccinations administered of any die Safety Review recipients: 9.8 million 9/1/1993-12/31/1993 and coded as Committee 9/1/1994-12/31/1994.
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From page 89... ...
. influenza vaccination findings are between exposure ah random Neurologists (95%CI)
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From page 90... ...
Receipt of influenza vaccine as reported to VAERS. Severe Gl as a case GBS with partial rec .
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From page 91... ...
diagnostic criteria, and inadequate denominator data (Ellenberg and Chen, 1997; Singleton et al., 1999)
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From page 92... ...
~2 TABLE 4 Condnucd C1t~on Design Population Assessment of Vaccine Exposure Ounces VAERS: Possible cb~lenge~cb~lenge Case- Case reports subm1Ued to Receipt of 1nOuenza vaccine repods VAERS, July 1990-~cb 2003. listed in record.as repoded Four report of GBS 1dendOed in VAERS as possible ~cb~l~ge.
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From page 93... ...
In neither of these cases, however, was the documentation sufficient to confirm GBS in response to a rechallenge with influenza vaccine. The nature of VAERS reports limits their contribution to the causality argument.
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From page 94... ...
Myers and colleagues (1977) conducted a randomized controlled trial to examine the safety and efficacy of the 1976 swine influenza vaccine in MS patients.
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From page 95... ...
Miller and colleagues (1997) conducted a multicenter, randomized controlled trial to examine the association between receipt of influenza vaccine and exacerbation of relapsing-remitting MS.
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From page 96... ...
examined the effect of the 1976 swine influenza vaccine on MS patients receiving care at the MS clinic of the Arizona Health Sciences Center. These patients were examined on a regular basis at the clinic, and their disability rated with the Kurtzke Disability Status Scale.
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From page 97... ...
. The authors concluded that the study provided no indication that influenza vaccine was associated with exacerbation of MS in patients with an EDSS of less than 6.5, but the effectiveness of the vaccine in preventing influenza illness was unclear.
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From page 98... ...
A conditional regression analysis was used to calculate the relative risk of MS relapse associated with exposure to the influenza vaccine or to other vaccines. For influenza vaccination, the relative risk of relapse was 1.08 (95% CI, 0.37-3.10~; the relative risk of relapse associated with any vaccine exposure was 0.71 (95% CI, 0.40-1.26~.
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From page 99... ...
Thus, during the risk period of interest, MS patients may be receiving the influenza vaccine and experiencing respiratory illness. The relative risk reported by the study may be an overestimate of the risk of MS relapse associated with influenza vaccine, as it is based on a risk interval when both influenza vaccination and acute illnesses may occur.
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From page 100... ...
. Patients were clinically evaluated every 3 months during the year preceding vaccination with trivalent inactivated influenza vaccine and the year following receipt.
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From page 101... ...
participated in the study. Influenza vaccine exposure was determined on the basis of medical chart reviews and telephone interviews (for those vaccinated outside the HMO)
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From page 102... ...
The number of new cases occurring following administration of the swine influenza vaccine in autumn of 1976 was compared with the number occurring at other times during the 1975-1979 period. Influenza vaccinations are administered to active duty personnel each year in October and are administered to new recruits throughout the year when they begin service.
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From page 103... ...
With a case definition based on the presence in the medical record of a physician's diagnosis of optic neuritis, the odds ratio for optic neuritis following influenza vaccination was 1.2 (95% CI 0.6-2.3~. The authors concluded that the results did not support the hypothesis that influenza vaccine causes the development of optic neuritis.
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From page 104... ...
trial Vaccinated: 23 Placebo: 23 Untreated controls: 22 Patients from two Los Angeles MS clinics and from private practice of UCLA neurologist Randomization to receive either 1976 influenza vaccine (bivalent, whole virus) or placebo (vaccine diluent)
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From page 105... ...
Frequency of relapse within 3 months following injection Vaccine group: 4 Myelopathy: 3 Mild relapse: 3 Moderate relapse: 1 Relapse Rate: 0.5 case/ patient/year Placebo group: 4 Myelopathy: 3 Moderate relapse: 2 Severe relapse: 1 Relapse Rate: 0.5 case/ patient/year Untreated group: 4 Myelopathy: 1 Mild relapse: 4 Relapse Rate: 0.7 case/ patient/year Based on the similar relapse The study provides evidence of no rates among the association groups, the between exposure authors concluded to the influenza that vaccination vaccines and against influenza relapse of MS in is safe for adults. patients with MS.
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From page 106... ...
706 TABLE ~ Condnucd Nation Design Population Assessment of Vaccine Exposure Ounces Bam~rd ~ at. Cobod (1978)
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From page 107... ...
INFLUENZA VACCINES AND NEUROLOGICAL COMPLICATIONS 107 Contribution to Outcomes Results Comment Causality Argument rts elected New or recurrent Frequency of outcomes: The authors noted The study provides rt influenza necrologic symptoms Vaccinated group: that the evidence of no fiber or or increase in rate of Systemic toxic reactions: 2 occurrence of association deterioration Onset of necrologic symptoms was between exposure observed during the symptoms: 1 similar to findings to influenza month following Increased severity of from other studies vaccines and vaccination. preexisting dysfunction: 1 and concluded relapse of MS; Episodes of deterioration: that the vaccine weaknesses in the Vaccinated patients 0.031 per patient-month did not seem to study limit its were asked about of exposure adversely affect contribution to the any allergic or toxic individuals causality reactions to the Unvaccinated group: already diagnosed argument.
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From page 108... ...
trolled Age range = 23-60 years. received either 1993 Neurologi trial trivalent influenza vaccine participan Vaccinated: 11 prepared by a single inoculatio Placebo: 8 manufacturer or placebo inoculatio (vaccine diluent)
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From page 109... ...
They adults; weaknesses concluded that the in the study limit study provided no its contribution to the causality argument. indication that influenza vaccine was associated with exacerbation of MS in patients with an EDSS of less than 6.5.
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From page 110... ...
Controls: Same patients during the first 8 months of the 12-month period before the index relapse. European Database for Multiple Sclerosis Network; France, Spain, Switzerland.
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From page 111... ...
Study strengths included limited confounding by nature of study design, high response rates and validation of vaccine exposures, limited recall bias, and results unaffected by change in length of effect periods. The committee notes that the 1.08 RR may reflect not only the effect of the influenza vaccine on MS relapse, but also the adverse effect of acute illness.
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From page 112... ...
Patients received polyvalent influenza vaccine between 1962- 1975. Patients were asked if they received influenza vaccine in autumn 1996 (trivalent product for the 1996- 1996 influenza season)
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From page 113... ...
Patients Primary progressive group: were also asked if 4 they had experienced Relapsing MS patients: 36 influenza illness. Exacerbations: 12 (33%)
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From page 114... ...
Received influenza vaccine. Receipt of influenza vaccine as reported to VAERS.
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From page 115... ...
if they also included such problems as Guillain-Barre as an underreporting, indexing term. lack of detail, inconsistent diagnostic criteria, and inadequate denominator data (Ellenberg and Chen, 1997; Singleton et al., 1999)
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From page 116... ...
tional Study Exposed 85% received the swine influenza vaccine Cases occurring in 1976 compared to cases occurring in 1975-1979 Receipt of influenza vaccine before index date. Influenza vaccine exposure was determined on the basis of medical chart reviews and telephone interviews for those vaccinated outside the HMO.
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From page 117... ...
cases: interpret the data limits the study's fiber. Average per calendar year: as indicating that contribution to the 6.55 the 1976 causality vaccine influenza vaccine argument.
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From page 118... ...
Children and In;fluenza Vaccines Influenza vaccine is generally administered to adults, and relatively few studies have reported data concerning any neurological complications observed in children. Currently, ACIP encourages influenza immunization for healthy children aged 6-23 months when feasible (CDC, 2003d)
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From page 119... ...
, in their study of GBS and the swine influenza vaccine, reported two cases of GBS occurring in vaccinated children in the age group 0-17 years, compared with 120 cases occurring during the same period (October 1, 1976-January 31, 1977) in unvaccinated children.
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From page 120... ...
Receipt of influenza vaccine before index date. Influenza vaccine exposure was determined on the basis of medical chart reviews and telephone interviews for those vaccinated outside the HMO.
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From page 121... ...
ma Optic neuritis; cases Number of optic neuritis The analytical The nature of d to identified on the reports: value of data VAERS reports basis of inclusion of 26 from passive limits their optic neuritis as surveillance contribution to the indexing term. systems is limited causality Cases were excluded by such problems argument.
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From page 122... ...
In its assessment of the possibility of a relationship between influenza vaccines and neurological complications, the committee hypothesized two general ways vaccine could lead to neurological complications: immune-mediated processes and neurotoxic effects. Before discussing these mechanisms, there is the issue of year-to-year variability in influenza vaccine and the role this could play in explaining variability in adverse effects (e.g.
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From page 123... ...
The committee also reviewed evidence from animal models as to whether influenza vaccines might be expected to induce relevant immune-system responses. Because the influenza vaccine uses antigens that are produced by the influenza viruses, evidence regarding neurological complications following influenza infections was also considered relevant.
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From page 124... ...
Evidence from Animal Models for a Possible Role of Influenza Vaccines in Neurological Complications. The most studied animal model for GBS and its peripheral demyelination is experimental allergic neuritis (EAN)
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From page 125... ...
In this model, the swine influenza vaccine was shown to trigger autoimmune responses and peripheral demyelination (Hjorth et al., 1984~. The presence of the vaccine was important for the development of neuritis when low doses of nerve homogenate were injected.
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From page 126... ...
There is inconclusive evidence that molecular mimicry between influenza vaccine glycoprotein antigens and PNS or CNS antigens plays a role in the pathogenesis of GBS, MS, or other neurological complications. As discussed above, immunization of rats with the myelin protein P2 or neuritogenic peptides derived from P2 can cause EAN, an experimental equivalent of GBS.
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From page 127... ...
Thus, there is no evidence supporting the notion of molecular mimicry between myelin proteins and components of influenza vaccines. The use of embryonated chicken eggs in the production of virus for influenza vaccines raises the prospect of another possible source of antigens with structural similarities to PNS antigens.
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From page 128... ...
It is not prominent in the discussions of viral triggers for the onset of MS, however. In terms of the implications for risks that might be associated with influenza vaccines, one study has shown that the risk of relapse is substantially greater following influenza-like illness9 than after influenza vaccination (De Keyser et al., 1998~.
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From page 129... ...
The following biological evidence relates to the theory that influenza vaccines could be associated with neurological complications: · Bystander activation. Animal models (Hjorth et al., 1984; Ziegler et al., 1983)
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From page 130... ...
The committee concludes that there is weak evidence for biological mechanisms related to immune-mediated processes, including molecular mimicry and bystander activation, by which receipt of any influenza vaccine could possibly influence an individual's risk of developing the neurological complications of GBS, MS, or other demyelinating conditions such as optic neuritis. Neurotoxic Effects Neurotoxin The FDA requires pre-release testing of samples of each lot of every vaccine used in the United States to ensure that the vaccine meets specifications for potency and purity.
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From page 131... ...
In the present case, the committee considered the significance of the concern that influenza vaccines might increase the risk of developing neurological complications such as GBS or MS. The scientific assessment provided support for a link between GBS and the 1976 influenza vaccines, but the evidence for other outcomes or for vaccines for other years was inadequate to support a conclusion or favored no association.
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From page 132... ...
jejuni (Buzby et al., 1997~. In 1976, the incidence of GBS within 6 weeks influenza vaccination that was considered attributable to vaccination was estimated at 0.488 to 0.567 case per 100,000 vaccinations (Langmuir et al., 1984~.
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From page 133... ...
, adverse events such as congestive heart failure, urinary retentions, dyspnea, optic nerve palsy and others occur. Rarely (< 0.1%)
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From page 134... ...
Cost-effectiveness studies show that vaccination reduces both the cost of medical care and the productivity losses associated with illness among the working-age population (Bridges et al., 2000; CDC, 2003d; Nichol, 2001~. Influenza vaccine must be given every year and is recommended for large segments of the population, making it the one of the most widely used vaccines in the United States.
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From page 135... ...
Direct transmission was suspected, however, when avian H9N2 infected two children in Hong Kong in 1999 (tin et al., 2000~. New Vaccine Approaches Since influenza vaccine was first introduced, the United States has relied on vaccine products based on inactivated influenza virus.
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From page 136... ...
These "virosomal" vaccine preparations are given intranasally.l2 12One virosomal influenza vaccine licensed for use in Switzerland in 2000 was withdrawn a year later because of unresolved concerns about an association between the vaccine and Bell's palsy (temporary facial paralysis) (Berna Biotech, 2002)
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From page 137... ...
To date there has not been a comprehensive effort to organize current knowledge and evaluate these models and theories using the results for various populations. Knowledge of the key factors that predict and/or influence influenza vaccination decisions remains constrained, thereby limiting the basis on which sound risk communication strategies can be designed.
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From page 138... ...
, the severity of the complications that may arise from influenza, · the degree to which individual actions (e.g., hand washing, taking vitamins, etc.) can reduce the risk of getting the disease, · the unique role of the vaccine as a preventive measure, and · the health impacts and side effects related to the influenza vaccine.
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From page 139... ...
The committee found no evidence bearing on a causal relationship between influenza vaccines and demyelinating neurological disorders in children aged 6-23 months. GBS is a serious condition, but it is rare and the additional risk related to vaccination in 1976 translated into fewer than 6 cases per million vaccinee (Langmuir et al., 1984~.
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From page 140... ...
With a vaccine as widely used as influenza vaccine, the committee considers it important to pursue research and research-related activities aimed at ensuring that any risk of GBS or other neurological complications is minimized. Surveillance and Epidemiologic Studies Influenza vaccine is not only widely used but is recommended for even wider use than is routinely achieved.
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From page 141... ...
. In preparation for this change in influenza immunization practices, the committee recommends increased surveillance of adverse events associated with influenza vaccination of children, with particular attentiveness to detecting and assessing potential neurological complications.
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From page 142... ...
There is a need to better understand the immunological responses in recipients of the 1976 swine influenza vaccine who experienced GBS. One avenue of inquiry should be the pathogenesis of influenza viruses in general and the swine influenza strain (A/New Jersey/76)
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From page 143... ...
have provided at least some basis for considering bystander activation as a potential mechanism by which influenza vaccines could cause GBS or related neurological complications. Under contrived experimental conditions, influenza vaccines had adjuvant properties in the presence of neural antigens.
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From page 144... ...
The Immunization Safety Review committee reviewed the data on influenza vaccine and neurological conditions and concluded that the evidence favored acceptance of a causal relationship between the 1976 swine influenza vaccine and GBS in adults. The evidence about GBS for other years' influenza vaccines is not clear one way or the other (that is, the evidence is inadequate to accept or reject a causal relationship)
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