Maria Cano

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).

Multidrug-Resistant Tuberculosis Outbreak among US-bound Hmong Refugees, Thailand, 2005

Enhanced pre-immigration screening and program expansion decreased TB importation.

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

BACKGROUND Quadrivalent 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). METHODS We 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. RESULTS In 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. CONCLUSIONS Our 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.

Deaths following vaccination: What does the evidence show?

Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014-2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral poliovirus vaccine. However, making general assumptions and drawing conclusions about vaccinations causing deaths based on spontaneous reports to VAERS - some of which might be anecdotal or second-hand - or from case reports in the media, is not a scientifically valid practice.

Post-Licensure Surveillance of Trivalent Live-Attenuated Influenza Vaccine in Children Aged 2–18 Years, Vaccine Adverse Event Reporting System, United States, July 2005–June 2012

BACKGROUND The first trivalent live-attenuated influenza vaccine (LAIV3) was licensed in 2003 for use in healthy persons 5-49 years of age. In 2007, the US Food and Drug Administration expanded its indication to healthy children 2-4 years of age. METHODS We searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after LAIV3 from July 1, 2005 to June 30, 2012 in children aged 2-18 years. Medical records were requested for nonmanufacturer reports coded as serious (ie, death, hospitalization, prolonged hospitalization, life-threatening illness, disability). We characterized electronic data and clinically reviewed all serious reports and reports of special interest. Empirical Bayesian data mining was used to identify new or unexpected adverse events (AEs). RESULTS During the study period, VAERS received 2619 US LAIV3 reports for children aged 2-18 years; 197 (7.5%) reports were serious, including 5 deaths. The 2 most frequent nonfatal serious reports involved neurological and respiratory systems, with 56 (29.2%) and 43 (22.4%) reports, respectively. The most frequent neurological diagnoses were seizures and Guillain-Barré Syndrome, and the most frequent respiratory conditions were pneumonia and asthma or reactive airway disease. Data mining showed increased proportions for reports of medication errors, most commonly vaccine administration errors not associated with an AE. CONCLUSIONS In this VAERS analysis of reports following LAIV3, we found no new or unexpected AEs patterns. Reports of LAIV3 administration to persons, for whom it is not recommended, including children with a history of asthma or reactive airway disease or wheezing, indicate that ongoing monitoring and education in vaccine indications are needed.

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.

Background Quadrivalent 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. Methods We 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. Results VAERS 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. Conclusions In 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.

Deaths Reported to the Vaccine Adverse Event Reporting System, United States, 1997–2013

BACKGROUND Vaccines are among the safest medical products in use today. Hundreds of millions of vaccinations are administered in the United States each year. Serious adverse reactions are uncommon. However, temporally associated deaths can occur following vaccination. Our aim was to characterize main causes of death among reports submitted to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous vaccine safety surveillance system. METHODS We searched VAERS for US reports of death after any vaccination from 1 July 1997 through 31 December 2013. Available medical records, autopsy reports, and death certificates were reviewed to identify cause of death. RESULTS VAERS received 2149 death reports, most (n = 1469 [68.4%]) in children. Median age was 0.5 years (range, 0-100 years); males accounted for 1226 (57%) reports. The total annual number of death reports generally decreased during the latter part of the study period. Most common causes of death among 1244 child reports with available death certificates/autopsy reports included sudden infant death syndrome (n = 544 [44%]), asphyxia (n = 74 [6.0%]), septicemia (n = 61 [4.9%]), and pneumonia (n = 57 [4.6%]). Among 526 adult reports, most common causes of death included diseases of the circulatory (n = 247 [46.9%]) and respiratory systems (n = 77 [14.6%]), certain infections and parasitic diseases (n = 62 [11.8%]), and malignant neoplasms (n = 20 [3.8%]). For child death reports, 79.4% received >1 vaccine on the same day. Inactivated influenza vaccine given alone was most commonly associated with death reports in adults (51.4%). CONCLUSIONS No concerning pattern was noted among death reports submitted to VAERS during 1997-2013. The main causes of death were consistent with the most common causes of death in the US population.

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

BACKGROUND 23-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. OBJECTIVE To analyze reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following PPSV23 from 1990 to 2013 in order to characterize its safety profile. METHODS We 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. RESULTS During 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. CONCLUSIONS We 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.

Surveillance systems and methods for monitoring the post-marketing safety of influenza vaccines at the Centers for Disease Control and Prevention

ABSTRACT Introduction: Annual influenza vaccine safety monitoring is an important component of the influenza vaccination program in the United States to ensure that vaccines are safe, which is important for maintaining public trust in the national vaccination program. This is specially the case for influenza vaccines since the antigen composition of the viruses of which the vaccine is made often changes from one season to the next, based on the circulating strain of influenza virus. Areas covered: This review describes the two surveillance systems used by the Centers for Disease Control and Prevention (CDC) to monitor the safety of influenza vaccines: 1) the Vaccine Adverse Event Reporting System (VAERS); and 2) the Vaccine Safety datalink (VSD). Expert opinion: VAERS and VSD are used routinely to monitor the safety of influenza vaccines in the United States, and over the years they have demonstrated their value in monitoring vaccine safety since their implementation in 1990. Both systems, although different, complemented each other well to study febrile seizures in young children following influenza vaccination during the 2010–2011 influenza season. Other examples of potential safety concerns after influenza vaccines are also presented and discussed.

Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000® compared with Dryvax®

Background: Routine vaccination against smallpox (variola) ceased in the US in 1976. However, in 2002 limited coverage for military personnel and some healthcare workers was reinstituted. In March 2008, ACAM2000® replaced Dryvax® as the vaccine used in the United States against smallpox. Unintentional transfer of vaccinia virus from a vaccination site by autoinoculation or contact transmission, can have significant public health implications. We summarize unintentional virus transfer AEs associated with ACAM2000® since March 2008 and compare with Dryvax®. Results: We identified 309 reports for ACAM2000® with skin or ocular involvement, of which 93 were autoinoculation cases and 20 were contact transmission cases. The rate for reported cases of autoinoculation was 20.6 per 100,000 vaccinations and for contact transmission was 4.4 per 100,000 vaccinations. Eighteen contact transmission cases could be attributed to contact during a sporting activity (45%) or intimate contact (45%). Of the 113 unintentional transfer cases, 6 met the case definition for ocular vaccinia. The most common locations for all autoinoculation and contact cases were arm/elbow/shoulder (35/113; 31%) and face (24/113; 21%). Methods: We reviewed 753 reports associated with smallpox in the Vaccine Adverse Event Reporting System and CDC Poxvirus consultation log, reported from March 2008 to August 2010. Reports were classified into categories based upon standard case definitions. Conclusion: Overall, unintentional transfer events for ACAM2000® and Dryvax® are similar. We recommend continued efforts to prevent transfer events and continuing education for healthcare providers focused on recognition of vaccinia lesions, proper sample collection, and laboratory testing to confirm diagnosis.