Figure 1.
Workflow of the CODAE integrative AE bioinformatics analysis.
A generalized version of CODAE for detection of significant AE terms for one vaccine or one group of vaccines is outlined in (A). See details in the text. An expanded CODAE solution to analyze and compare AEs associated with the two vaccination groups is shown in (B). VAERS records were retrieved based on the query criteria of 4 TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) year 1990–2011 and 1 LAIV (FluMist) year 2003–2011. Parallel analyses of the Proportional Reporting Ratios and Chi-square significant test were performed on individual AEs to identify enriched and significant AEs in each group. Base level filtration of 0.2% of total number of reports was also applied to each AEs. AEs that were identified to have PRR > = 2, Chi-square > = 4, and number of reports > = 0.2% of total reports were then classified based on OAE hierarchical structure. Classification of AEs filtered out AEs that overlapped between the 2 groups.
Figure 2.
Venn diagram summary of the three filtering criteria in each group of vaccines from the pool of 3,582 AEs analyzed in TIV and LAIV and the universe of 7,520 AEs in the entire VAERS database.
Chi-square value of > = 4 – χ2(+), or <4 – χ2(−); PRR > = 2 – PRR(+), or PRR <2 – PRR(−); and number of reports >0.2% of total reported cases (i.e., > = 75 in TIV or > = 8 in LAIV) – count(+), or else – count(−).
Figure 3.
Diagram of AE counts grouped by related symptoms.
Behavior/neurological system contains the most adverse events distributed in two groups of vaccines (40 adverse events; 25 in TIV, 15 in LAIV) but the clusters are significantly different in processes. TIV's behavior/neurological AEs are much more closely related to those of muscle and movement disorder while LAIV's behavior/neurological AEs cluster around pain in the head. Respiratory system AEs is listed as the most significant cluster in LAIV group with 16 AEs. Full listing can be found in Table 1 (TIV) and Table 2 (LAIV).
Table 1.
TIV-specific adverse events. 37,621 TIV-induced AE cases were reported.
Table 2.
LAIV-specific adverse events. 3,707 TIV-induced AE cases were reported.
Figure 4.
Comparison of reporting rates of GBS cases associated with TIV and LAIV administrations.
The Y-axis is the number of GBS cases per 1000 case reports for either TIV or LAIV group. The comparison starts the year when both groups have available data in VAERS.
Figure 5.
Comparison of yearly report distributions of GBS and GBS-related adverse events associated with TIV and LAIV.
LAIV was recently released and therefore data available are from 2003 onward. The raw number of occurrences was scaled to percentages by the number of reports in each year. The percentages of yearly case reports of GBS and other GBS-related symptoms associated with TIV and LAIV are displayed in (A) and (B), respectively. The combined percentages of GBS and related AEs associated with TIV and LAIV are depicted in (C).
Figure 6.
Comparison of case report distributions of GBS and GBS-related adverse events associated with TIV and LAIV based on age using the data from 2003.
(A) In TIV, all but one selected AEs (paraesthesia) followed the expected age range of the populations who were more at risk of GBS (young children and the elderly). (B) In LAIV recipients, age distribution is scattered across all age ranges.
Table 3.
Summary of statistical analysis testing if GBS and GBS-related AEs occur independently of vaccine type.
Table 4.
Summary of association of GBS to influenza vaccines in peer-reviewed literature.