Adverse events following quadrivalent meningococcal diphtheria toxoid conjugate vaccine (Menactra®) reported to the Vaccine Adverse Event Reporting System (VAERS), 2005–2016

BackgroundPost marketing safety evaluations of quadrivalent meningococcal diphtheria-toxoid conjugate vaccine (MenACWY-D) have focused on post-vaccination risk of Guillain Barré syndrome (GBS), adverse events (AEs) after maternal vaccination, and comparative studies with the newer quadrivalent meningococcal CRM₁₉₇ conjugate vaccine (MenACWY-CRM). To provide an updated general safety assessment, we reviewed reports of AEs following MenACWY-D submitted to the Vaccine Adverse Event Reporting System (VAERS).MethodsVAERS is a national spontaneous reporting vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the U.S. Food and Drug Administration. We searched the VAERS database for U.S. reports of AEs after administration of MenACWY-D from January 2005 through June 2016. We conducted clinical reviews of serious reports after MenACWY-D administered alone, reports of MenACWY-D use during pregnancy, and reports of selected pre-specified outcomes. We screened for disproportionate reporting of AEs after MenACWY-D using empirical Bayesian data mining.ResultsVAERS received 13,075 U.S. reports after receipt of MenACWY-D; most (86%) described vaccination in adolescents, were classified as non-serious (94%), and described AEs consistent with pre-licensure studies. We did not find any evidence that reported deaths were related to vaccination. In serious reports, GBS and meningococcal infection were the most commonly reported medical conditions. Many reports of MenACWY-D use during pregnancy described inadvertent vaccination; most (61%) did not report any AE.ConclusionsFindings from our comprehensive review of reports to VAERS following MenACWY-D are consistent with data from pre-licensure studies and provide further reassurance on the safety of MenACWY-D.     

Adverse events after Fluzone Intradermal vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), 2011–2013

Background

In May 2011, the first trivalent inactivated influenza vaccine exclusively for intradermal administration (TIV-ID) was licensed in the US for adults aged 18–64 years.

Objective

To characterize adverse events (AEs) after TIV-ID reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.

Methods

We searched VAERS for US reports after TIV-ID among persons vaccinated from July 1, 2011–February 28, 2013. Medical records were requested for reports coded as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis. Clinicians reviewed available information and assigned a primary clinical category to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following TIV-ID. Causality was not assessed.

Results

VAERS received 466 reports after TIV-ID; 9 (1.9%) were serious, including one reported fatality in an 88-year-old vaccinee. Median age was 43 years (range 4–88 years). The most common AE categories were: 218 (46.8%) injection site reactions; 89 (19.1%) other non-infectious (comprised mainly of constitutional signs and symptoms); and 74 (15.9%) allergy. Eight reports (1.7%) of anaphylaxis were verified by the Brighton criteria or a documented physician diagnosis. Disproportional reporting was identified for three AEs: ‘injection site nodule’, ‘injection site pruritus’, and ‘drug administered to patient of inappropriate age’. The findings for the first two AEs were expected. Twenty-four reports of vaccinees <18 years or ≥65 years were reported, and 14 of 24 were coded with the AE ‘drug administered to patient of inappropriate age’.

Conclusions

Review of VAERS reports did not identify any new or unexpected safety concerns after TIV-ID. Injection site reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Use of TIV-ID in younger and older individuals outside the approved age range highlights the need for education of healthcare providers regarding approved TIV-ID use.     

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009–2015

BackgroundThe Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9–26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination.MethodsWe searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions.FindingsVAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death.InterpretationNo new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data.     

Surveillance of adverse events after the first trivalent inactivated influenza vaccine produced in mammalian cell culture (Flucelvax®) reported to the Vaccine Adverse Event Reporting System (VAERS), United States, 2013–2015

BackgroundIn November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax^®, ccIIV3), was approved in the US for adults aged ≥18 years.ObjectiveTo assess adverse events (AEs) after ccIIV3 reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.MethodsWe searched VAERS for US reports after ccIIV3 among persons vaccinated from July 1, 2013–March 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain–Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category using MedDRA system organ classes (SOC) to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following ccIIV3.ResultsVAERS received 629 reports following ccIIV3 of which 313 were for administration of vaccine to persons <18 years. Among 309 reports with an AE documented, 19 (6.1%) were serious and the most common categories were 152 (49.2%) general disorders and administration site conditions (mostly injection site and systemic reactions) and 73 (23.6%) immune system disorders with two reports of anaphylaxis. Four reports of GBS were submitted. Disproportional reporting was identified for ‘drug administered to patient of inappropriate age.’ConclusionsReview of VAERS reports did not identify any concerning pattern of AEs after ccIIV3. Injection site and systemic reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Reports following ccIIV3 in persons <18 years highlight the need for education of healthcare providers regarding approved ccIIV3 use.     

Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States,Vaccine Adverse Event Reporting System (VAERS), July 2013–June 2014

BackgroundQuadrivalent live attenuated influenza vaccine (LAIV4) was approved in 2012 for healthy persons aged 2–49 years. Beginning with the 2013–2014 influenza season, LAIV4 replaced trivalent live attenuated influenza vaccine (LAIV3).MethodsWe analyzed LAIV4 reports to VAERS, a national spontaneous reporting system. LAIV4 reports in 2013–2014 were compared to LAIV3 reports from the previous three influenza seasons. Medical records were reviewed for non-manufacturer serious reports (i.e., death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability) and reports of selected conditions of interest. We conducted Empirical Bayesian data mining to identify disproportional reporting for LAIV4.ResultsIn 2013–2014, 12.7 million doses of LAIV4 were distributed and VAERS received 779 reports in individuals aged 2–49 years; 95% were non-serious. Expired drug administered (42%), fever (13%) and cough (8%) were most commonly reported in children aged 2–17 years when LAIV4 was administered alone, while headache (18%), expired drug administered (15%) and exposure during pregnancy (12%) were most common in adults aged 18–49 years. We identified one death report in a child who died from complications of cerebellar vascular tumors. Among non-death serious reports, neurologic conditions were common in children and adults. In children, seizures (3) and Guillain-Barré syndrome (2) were the most common serious neurologic outcomes. We identified three serious reports of asthma/wheezing following LAIV4 in children. Data mining detected disproportional reporting for vaccine administration errors and for influenza illness in children.ConclusionsOur analysis of VAERS reports for LAIV4 did not identify any concerning patterns. The data mining finding for reports of influenza illness is consistent with low LAIV4 vaccine effectiveness observed for influenza A disease in children in 2013–2014. Reports of LAIV4 administration to persons in whom the vaccine is not recommended (e.g., pregnant women) indicate the need for education, training and screening regarding indications.     

Who is unlikely to report adverse events after vaccinations to the Vaccine Adverse Event Reporting System (VAERS)?

Background

Healthcare provider (HCP) reporting to the Vaccine Adverse Event Reporting System (VAERS) is important to assuring the safety of U.S. licensed vaccines. HCP awareness of and practices regarding reporting of adverse events following immunization (AEFI) is understudied.

Methods

A large, nationally representative sample of U.S. office-based HCP across three occupational groups (physicians, mid-level providers [physician assistants, advanced practice nurses] and nurses) and three primary care practice areas (pediatrics, family medicine, internal medicine) were surveyed utilizing standardized methodology. We assessed HCP familiarity with VAERS, the situations under which they were likely to report an AEFI, and the methods they used and preferred for reporting. We used logistic regression to determine factors associated with HCP not reporting AEFI to VAERS.

Results

Our survey response rate was 54.9%. The percentage of HCP aware of VAERS (71%) varied by occupation and primary care practice area. About 37% of HCP had identified at least one AEFI with only 17% of these indicating that they had ever reported to VAERS. More serious events were more likely to be reported. Factors associated with HCP not reporting AEFI included: HCP not familiar versus very familiar with filing a paper VAERS report (OR = 12.84; p < 0.0001), primary care practice area of internal medicine versus pediatrics (OR = 4.22; p = 0.0005), and HCP not familiar versus very familiar with when it was required to file a VAERS report (OR = 5.52; p = 0.0013).

Conclusions

Specific educational interventions targeted to HCP likely to see AEFI but not currently reporting may improve vaccine safety reporting practices.     

Safety of quadrivalent human papillomavirus vaccine (Gardasil®) in pregnancy: Adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006–2013

BackgroundIn 2006, quadrivalent human papillomavirus (HPV4; Gardasil, Merck & Co., Inc.) vaccine was licensed in the US for use in females aged 9–26 years. HPV4 is not recommended during pregnancy; however, inadvertent administration during pregnancy may occur.ObjectivesTo evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received HPV4 vaccine and assess for potentially concerning adverse events among non-manufacturer reports.MethodsWe searched the VAERS database for non-manufacturer reports of adverse events (AEs) in pregnant women who received HPV4 vaccine from 6/1/2006 to 12/31/2013. We conducted clinical review of reports and available medical records.ResultsWe found 147 reports after HPV4 vaccine administered to pregnant women. The most frequent pregnancy-specific AE was spontaneous abortion in 15 (10.2%) reports, followed by elective terminations in 6 (4.1%). Maternal fever was the most frequent non-pregnancy-specific AE in 3 reports. Two reports of major birth defects were received. No maternal deaths were noted. One hundred-three (70.1%) reports did not describe an AE.ConclusionsThis review of VAERS non-manufacturer reports following vaccination with HPV4 in pregnancy did not find any unexpected patterns in maternal or fetal outcomes.     

Is there any harm in administering extra-doses of vaccine to a person? Excess doses of vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), 2007–2017

BackgroundThe administration of an extra dose of a vaccine may occur due to a programmatic error (e.g., vaccination error) when there is need to provide one of the antigens of a combination vaccine not readily available as a single antigen, or when there is need to provide immunization in a person with uncertain vaccination histories (e.g., refugees). There is little data available on the safety of an extra dose of vaccine.ObjectiveTo assess for the presence of adverse events (AEs) most commonly reported following the administration of excess doses of vaccine in the Vaccine Adverse Event Reporting System (VAERS).MethodsWe searched VAERS for US reports where an excess dose of vaccine was administered to a person received from 1/1/2007 through 1/26/2018. We reviewed medical records for all serious reports and a random sample of non-serious reports. The most common AEs among reports of excess dose of vaccine administered were compared with the corresponding AEs for all vaccines reported to VAERS during the same period.ResultsOut of 366,815 total VAERS reports received, 5067 (1.4%) reported an excess dose of vaccine was administered; 3898 (76.9%) did not describe an adverse health event (AHE). The most common vaccines reported were trivalent inactivated influenza (15.4%), varicella (13.9%), hepatitis A (11.4%), and measles, mumps, rubella, varicella (11.1%). Among reports where only AHEs were reported, the most common were pyrexia (12.8%), injection site erythema (9.7%), injection site pain (8.9%), and headache (6.6%). The percentage of AHEs among these reports was comparable to all reports submitted to VAERS during the same study period.ConclusionMore than three-fourths of reports of an excess dose of vaccine did not describe an AHE. Among reports where an AHE event was reported, we did not observe any unexpected conditions or clustering of AEs.     

Reports of cell-based influenza vaccine administered during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2013–2020

BackgroundIn November 2012, the first cell cultured influenza vaccine, a trivalent subunit inactivated influenza vaccine (Flucelvax(®), ccIIV3), was approved in the United States for adults aged ≥18 years. A quadrivalent version (ccIIV4) was later approved in 2016 and replaced ccIIV3. The safety of ccIIV3 or ccIIV4 (ccIIV) was not assessed for pregnant women or their infants during pre-licensure studies.ObjectiveTo assess the safety of ccIIV administered during pregnancy in pregnant women and their infants whose reports were submitted to VAERS during 2013–2020.Material and methodsWe searched VAERS for United States reports of adverse events (AEs) in pregnant women who received ccIIV from 1 July 2013 through 31 May 2020. Clinicians reviewed reports and available medical records and assigned a primary clinical category for each report. Reports were coded as serious based on the Code of Federal Regulations definition.ResultsVAERS received 391 reports following ccIIV administered to pregnant women. Twenty-four (6.1%) were serious. Two neonatal deaths were reported. No maternal deaths occurred. Among reports with trimester information (n = 340), ccIIV was administered during the second trimester in 170 (50%). The most frequent pregnancy-specific AE was premature delivery in 85 (21.7%) reports, followed by dysmature placenta in 13 (3.3%) and pre-eclampsia/eclampsia in ten (2.3%). The most common non-pregnancy specific conditions were infectious conditions in 32 (8.2%). Among infant conditions, low birth weight was reported in 62 (15.9%) reports. Fifteen birth defects were reported; in 12 with gestational age information, administration of the vaccine occurred late in the second trimester or later.ConclusionsReview of maternal ccIIV reports in VAERS was not unexpectedly different from other maternal influenza vaccine safety VAERS reviews.     

Adverse events following adenovirus type 4 and type 7 vaccine,live, oral in the Vaccine Adverse Event Reporting System (VAERS), United States,October 2011–July 2018

BackgroundIn March 2011, the U.S. Food and Drug Administration licensed adenovirus type 4 and type 7 vaccine, live, oral (Barr Labs, Inc.) (adenovirus vaccine) for use in military personnel 17 through 50 years of age. The vaccine was first universally administered to U.S. military recruits in October 2011. We investigated adverse event (AE) reports following the adenovirus vaccine submitted to the Vaccine Adverse Event Reporting System (VAERS).MethodsWe searched the VAERS database for U.S. reports among persons who received adenovirus vaccine during October 2011 through July 2018 including participants in a military observational study. We reviewed all serious reports and accompanying medical records. We compared the proportion of serious reports in a proxy military recruit population and reviewed all reports of suspected allergic reactions following adenovirus vaccination.ResultsDuring the analytic period, VAERS received 100 reports following adenovirus vaccination; 39 (39%) were classified as serious and of these, 17 (44%) were from the observational study. One death was reported. Males accounted for 72% of reports. Median age of vaccinees was 19 years (range 17–32). The most frequently reported serious AEs were Guillain Barré syndrome (GBS) (n = 12) and anaphylaxis (n = 8); of these, two GBS and all the anaphylaxis reports were reported in the observational study. Reports documented concurrent receipt of multiple other vaccines (95%) and penicillin G (IM Pen G) or other antibiotics (50%).ConclusionsThe reporting rate for serious AEs was higher than with other vaccines administered in the comparison military recruit population (39% vs 18%); however, we identified no unexpected or concerning pattern of adenovirus vaccine AEs. Co-administration of vaccines and IM Pen G was commonly reported in this military population. These exposures may have contributed to the GBS and anaphylaxis outcomes observed with the adenovirus vaccine. Future adenovirus vaccine safety studies in a population without these co-administrations would be helpful in clarifying the vaccine’s safety profile.     

Post-licensure safety surveillance of 23-valent pneumococcal polysaccharide vaccine in the Vaccine Adverse Event Reporting System (VAERS), 1990–2013

Background23-Valent pneumococcal polysaccharide vaccine, trade name Pneumovax^®23 (PPSV23), has been used for decades in the Unites States and has an extensive clinical record. However, limited post-licensure safety assessment has been conducted.ObjectiveTo analyze reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following PPSV23 from 1990 to 2013 in order to characterize its safety profile.MethodsWe searched the VAERS database for US reports following PPSV23 for persons vaccinated from 1990 to 2013. We assessed safety through: automated analysis of VAERS data, crude adverse event (AE) reporting rates based on PPSV23 doses distributed in the US market, clinical review of death reports and reports involving vaccine administered to pregnant women, and empirical Bayesian data mining to assess for disproportional reporting.ResultsDuring the study period, VAERS received 25,168 PPSV23 reports; 92% were non-serious, 67% were in females and 86% were in adults aged ≥19 years. When PPSV23 was administered alone, fever (43%), injection site erythema (28%) and injection site pain (25%) were the most commonly reported non-serious AEs in children. Injection site erythema (32%), injection site pain (27%) and injection site swelling (23%) were the most commonly reported non-serious AEs in adults. Of serious reports (2129, 8% of total), fever was most commonly reported in both children (69%) and adults (39%). There were 66 reports of death, four in children and 62 in adults. Clinical review of death reports did not reveal any concerning patterns that would suggest a causal association with PPSV23. No disproportional reporting of unexpected AEs was observed in empirical Bayesian data mining.ConclusionsWe did not identify any new or unexpected safety concerns for PPSV23. The VAERS data are consistent with safety data from pre-licensure clinical trials and other post-licensure studies.     

Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 1990–2016

BackgroundThe safety of hepatitis B vaccination during pregnancy has not been well studied.ObjectiveWe characterized adverse events (AEs) after hepatitis B vaccination of pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system.MethodsWe searched VAERS for AEs reports involving pregnant women who received hepatitis B vaccine from January 1, 1990–June 30, 2016. All reports and available medical records were reviewed by physicians. Observed AEs were compared to expected AEs and known rates of pregnancy outcomes to assess for any unexpected safety concern.ResultsWe found 192 reports involving pregnant women following hepatitis B vaccination of which 110 (57.3%) described AEs; 12 (6.3%) were classified as serious; one newborn death was identified in a severely premature delivery, and there were no maternal deaths. Eighty-two (42.7%) reports did not describe any AEs. Among pregnancies for which gestational age was reported, most women were vaccinated during the first trimester, 86/115 (74.7%). Among reports describing an AE, the most common pregnancy-specific outcomes included spontaneous abortion in 23 reports, preterm delivery in 7 reports, and elective termination in 5 reports. The most common non-pregnancy specific outcomes were general disorders and administration site conditions, such as injection site and systemic reactions, in 21 reports. Among 22 reports describing an AE among infants born to women vaccinated during pregnancy, 5 described major birth defects each affecting different organ systems.ConclusionOur analysis of VAERS reports involving hepatitis B vaccination during pregnancy did not identify any new or unexpected safety concerns.     

Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States,Vaccine Adverse Event Reporting System (VAERS), July 1, 2013−May 31, 2015

BackgroundQuadrivalent inactivated influenza vaccines (IIV4) were first available for use during 2013−14 influenza season for individuals aged ≥6 months. IIV4 is designed to protect against four different flu viruses; two influenza A viruses and two influenza B viruses.MethodsWe searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after IIV4 and trivalent inactivated influenza vaccine (IIV3) from 7/1/2013–5/31/2015. Medical records were requested for non-manufacturer reports classified as serious (i.e. death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability). The review included automated data analysis, clinical review of all serious reports, reports of special interest, and empirical Bayesian data mining.ResultsVAERS received 1,838 IIV4 reports; 512 (28%) in persons aged 6 months–17 years of which 42 (8.2%) were serious reports; 1,265 (69%) in persons aged >18 years of which 84 (6.6%) were serious reports; two in children <6 months and 59 in persons of unknown age. Injection site erythema (24%), fever (14%) and injection site swelling (17%) were the most frequent adverse events among persons aged 6 months–17 years, while injection site pain (16%), pain (15%) and pain in extremity (13%) were the most frequent among persons aged 18−64 years given the vaccine alone. Among non-death serious reports, injection site reactions, constitutional symptoms, Guillain-Barré syndrome, seizures, and anaphylaxis were the most frequently reported adverse events. Data mining detected disproportional reporting for incorrect vaccine administration with no associated adverse events. Adverse events following IIV4 reported to VAERS were similar to those following IIV3.ConclusionsIn our review of VAERS reports, IIV4 had a similar safety profile to IIV3. Most of the reported AEs were non-serious. Our findings are consistent with data from pre-licensure studies of IIV4.     

Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System,United States,October 1, 2009–January 31, 2010

The United States (US) influenza A (H1N1) 2009 monovalent (2009-H1N1) vaccination program began in October 2009. Reports to the vaccine adverse event reporting system (VAERS), a US spontaneous reporting system, were reviewed to identify potential rare events or unusual adverse event (AE) patterns after 2009-H1N1 vaccination. The adverse event profile after 2009-H1N1 vaccine in VAERS (∼10,000 reports) was consistent with that of seasonal influenza vaccines, although the reporting rate was higher after 2009-H1N1 than seasonal influenza vaccines, this may be, at least in part, a reflection of stimulated reporting. Death, Guillain–Barré syndrome and anaphylaxis reports after 2009-H1N1 vaccination were rare (each <2 per million doses administered).     

Safety of vaccines that have been kept outside of recommended temperatures: Reports to the Vaccine Adverse Event Reporting System (VAERS), 2008–2012

BackgroundVaccines should be stored and handled according to manufacturer specifications. Inadequate cold chain management can affect potency; but, limited data exist on adverse events (AE) following administration of vaccines kept outside of recommended temperatures.ObjectiveTo describe reports to the Vaccine Adverse Event Reporting System (VAERS) involving vaccines inappropriately stored outside of recommended temperatures and/or exposed to temperatures outside of manufacturer specifications for inappropriate amounts of time.MethodsWe searched the VAERS database (analytic period 2008–2012) for reports describing vaccines kept outside of recommended temperatures. We analyzed reports by vaccine type, length outside of recommended temperature and type of temperature excursion, AE following receipt of potentially compromised vaccine, and reasons for cold chain breakdown.ResultsWe identified 476 reports of vaccines kept outside of recommended temperatures; 77% described cluster incidents involving multiple patients. The most commonly reported vaccines were quadrivalent human papillomavirus (n = 146, 30%), 23-valent pneumococcal polysaccharide (n = 51, 11%), and measles, mumps, and rubella (n = 45, 9%). Length of time vaccines were kept outside of recommended temperatures ranged from 15 mins to 6 months (median 51 h). Most (n = 458, 96%) reports involved patients who were administered potentially compromised vaccines; AE were reported in 32 (7%), with local reactions (n = 21) most frequent. Two reports described multiple patients contracting diseases they were vaccinated against, indicating possible influenza vaccine failure. Lack of vigilance, inadequate training, and equipment failure were reasons cited for cold chain management breakdowns.ConclusionsOur review does not indicate any substantial direct health risk from administration of vaccines kept outside of recommended temperatures. However, there are potential costs and risks, including vaccine wastage, possible decreased protection, and patient and parent inconvenience related to revaccination. Maintaining high vigilance, proper staff training, regular equipment maintenance, and having adequate auxiliary power are important components of comprehensive vaccine cold chain management.