Penina Haber

The Guillain–Barré Syndrome and the 1992–1993 and 1993–1994 Influenza Vaccines

BACKGROUND The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk. METHODS Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey. RESULTS We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12. CONCLUSIONS There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.

Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring

In preparation for pandemic vaccine safety monitoring, we assessed adverse events reported to the Vaccine Adverse Event Reporting System following receipt of trivalent inactivated influenza vaccines among adults from 1990 through 2005. We calculated reporting rates for nonserious, serious, and neurological adverse events. We reviewed reports of recurrent events and deaths, as well as reports identified through advanced signal detection. The most frequently reported events were local reactions and systemic symptoms. Guillain-Barré syndrome was the most frequently reported serious event (0.70 reports per million vaccinations). Adverse event reporting rates have been reasonably constant over time. No new safety concerns emerged after our review of 15 years of post-licensure surveillance data. These findings provide useful information if pandemic vaccine is rapidly distributed and pre-licensure data are limited.

Vaccines and Guillain-Barré Syndrome

Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis in developed countries and is characterized by various degrees of weakness, sensory abnormalities and autonomic dysfunction. Although the underlying aetiology and pathophysiology of GBS are not completely understood, it is broadly believed that immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an effect on the immune system it is biologically plausible that immunizations may be associated with subsequent GBS.The objective of this article is to review the current body of evidence that either supports or does not support a causal, rather than just temporal, association between various vaccines and GBS, and to provide an evidence-based review of this issue. The scope of the article includes published reports that, regardless of method of case ascertainment, appeared in peer-reviewed literature between 1950 and 2008.Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal association with most vaccines. The evidence for a causal association is strongest for the swine influenza vaccine that was used in 1976–77. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of GBS.Older formulations of rabies vaccine cultured in mammalian brain tissues have been found to have an increased risk of GBS, but newer formulations of rabies vaccine, derived from chick embryo cells, do not appear to be associated with GBS at a greater than expected rate.In an earlier review, the Institute of Medicine concluded that the evidence favoured a causal association between oral polio vaccine and tetanus toxoid-containing vaccines and GBS. However, recent evidence from large epidemiological studies and mass immunization campaigns in different countries found no correlation between oral polio vaccine or tetanus toxoid-containing vaccines and GBS.Spontaneous reports to the US Vaccine Adverse Events Reporting System shortly after the introduction of quadrivalent conjugated meningococcal vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons with expected rates of GBS, however, were inconclusive for an increased risk, and lack of controlled epidemiological studies makes it difficult to draw conclusions about a causal association.For other vaccines, available data are based on isolated case reports or very small clusters temporally related to immunizations, and no conclusion about causality can be drawn.There are certain circumstances in which immunizing individuals, particularly those with a prior history of GBS, may require caution. However, the benefit of vaccines in preventing disease and decreasing morbidity and mortality, particularly for influenza, needs to be weighed against the potential risk of GBS.

Adverse events in pregnant women following administration of trivalent inactivated influenza vaccine and live attenuated influenza vaccine in the Vaccine Adverse Event Reporting System, 1990-2009

OBJECTIVE The objective of the study was to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received seasonal influenza vaccines to assess for potential vaccine safety concerns. STUDY DESIGN We searched VAERS for reports of adverse events (AEs) in pregnant women who received trivalent inactivated influenza vaccine (TIV) from July 1, 1990 through June 30, 2009, or live attenuated influenza vaccine (LAIV) from July 1, 2003, through June 30, 2009. RESULTS A total of 148 reports after TIV and 27 reports after LAIV were identified. Twenty TIV (13.5%) and 1 LAIV (4%) reports were classified as serious. No specific AEs were reported in 30 TIV (20.3%) and 16 LAIV (59%) reports. The most common pregnancy-specific AE was spontaneous abortion: 17 after TIV (11.5%) and 3 after LAIV (11%). The reporting rate of spontaneous abortion was 1.9 per million pregnant women vaccinated. CONCLUSION No unusual patterns of pregnancy complications or fetal outcomes were observed in the VAERS reports of pregnant women after the administration of TIV or LAIV.

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).

Postlicensure Monitoring of Intussusception After RotaTeq Vaccination in the United States, February 1, 2006, to September 25, 2007

BACKGROUND. In 1999, a previous rotavirus vaccine (RotaShield; Wyeth Laboratories, Marietta, PA) was withdrawn from the US market after postlicensure monitoring identified an association with intussusception. Although the new rotavirus vaccine (RotaTeq; Merck, West Point, PA) introduced in 2006 was not associated with intussusception in prelicensure trials, additional monitoring is important to ensure a complete safety profile. METHODS. We assessed intussusception reports after RotaTeq vaccination by using data from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink, a cohort of children enrolled in managed care. Observed versus expected rate ratios were determined by using vaccine dose distribution data and Vaccine Safety Datalink background intussusception rates. RESULTS. Between February 1, 2006, and September 25, 2007, the Vaccine Adverse Event Reporting System received 160 intussusception reports after RotaTeq vaccination. With the assumptions that reporting completeness was 75% and that 75% of the distributed doses of RotaTeq were administered, the observed versus expected rate ratios were 0.53 and 0.91 for the 1–21 and 1–7 day interval after vaccination, respectively. In the Vaccine Safety Datalink, 3 intussusception cases occurred within 30 days after 111521 RotaTeq vaccinations, compared with 6 cases after 186722 non–RotaTeq vaccinations during the same period. If, like RotaShield, RotaTeq had a 37-fold increased risk of intussusception within 3 to 7 days after vaccination, then 8 intussusception cases would be expected within 3 to 7 days among the ∼84000 infants vaccinated with the first dose of RotaTeq in the Vaccine Safety Datalink (N = 49902) and the prelicensure trial (N = 34035) combined, whereas no cases have been observed. CONCLUSIONS. Available data do not indicate that RotaTeq is associated with intussusception. Although an intussusception risk similar in magnitude to that of RotaShield can be excluded, continued monitoring is necessary for complete assessment of the safety profile of RotaTeq.

Adverse event reports after tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines in pregnant women

OBJECTIVE We sought to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). STUDY DESIGN We searched VAERS for reports of pregnant women who received Tdap from Jan. 1, 2005, through June 30, 2010. We conducted a clinical review of reports and available medical records. RESULTS We identified 132 reports of Tdap administered to pregnant women; 55 (42%) described no adverse event (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified. CONCLUSION During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant, or fetal outcomes.

Safety of Varicella Vaccine after Licensure in the United States: Experience from Reports to the Vaccine Adverse Event Reporting System, 1995–2005

Widespread use of varicella vaccine in the United States could enable detection of rare adverse events not identified previously. We reviewed data from 1995 to 2005 from the Vaccine Adverse Event Reporting System, including data from laboratory analyses, to distinguish adverse events associated with wild-type varicella-zoster virus (VZV) versus those associated with vaccine strain. Almost 48 million doses of varicella vaccine were distributed between 1995 and 2005. There were 25,306 adverse events reported (52.7/100,000 doses distributed); 5.0% were classified as serious (2.6/100,000 doses distributed). Adverse events associated with evidence of vaccine-strain VZV included meningitis in patients with concurrent herpes zoster. Patients with genetic predispositions may rarely have disease triggered by receipt of varicella vaccine. Overall, serious adverse events reported after varicella vaccination continue to be rare and must be considered relative to the substantial benefits of varicella vaccination. Ongoing safety surveillance and further studies may shed light on some of the hypothesized associations.

Adverse events following administration to pregnant women of influenza A (H1N1) 2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System

OBJECTIVE The objective of the study was to evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, in pregnant women who received influenza A (H1N1) 2009 monovalent vaccine to assess for potential vaccine safety problems. STUDY DESIGN We reviewed reports of adverse events (AEs) in pregnant women who received 2009-H1N1 vaccines from Oct. 1, 2009, through Feb. 28, 2010. RESULTS VAERS received 294 reports of AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6 after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95 spontaneous abortions (<20 weeks); 18 stillbirths (≥20 weeks); 7 preterm deliveries (<37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia; and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth retardation, and cleft lip. CONCLUSION Review of reports to VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes.

Intussusception After Rotavirus Vaccines Reported to US VAERS, 2006–2012

BACKGROUND: In 2006 and 2008, 2 new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. METHODS: We assessed intussusception events reported to the Vaccine Adverse Event Reporting System from February 2006 through April 2012 for RV5 and from April 2008 through April 2012 for RV1. For RV5, we conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception comparing average daily reports 3 to 6 versus 0 to 2 days after vaccination. We calculated reporting rate differences based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. Few reports were submitted after RV1, allowing only a descriptive analysis. RESULTS: The Vaccine Adverse Event Reporting System received 584 confirmed intussusception reports after RV5 and 52 after RV1, with clustering 3 to 6 days after both vaccines. The DRR comparing the 3- to 6-day and the 0- to 2-day periods after RV5 dose 1 was 3.75 (95% confidence interval = 1.90 to 7.39). There was no significant increase in reporting after dose 2 or dose 3. Over all 3 doses, the excess risk of intussusception was 0.79 events (95% confidence interval = –0.04 to 1.62) per 100 000 vaccinations. From the sensitivity analyses, we conclude that under a worst-case scenario, the DRR could be 5.00 and excess risk per 100 000 doses could be 1.36. CONCLUSIONS: We observed a persistent clustering of reported intussusception events 3 to 6 days after the first dose of RV5 vaccination. This clustering could translate to a small increased risk of intussusception, which is outweighed by the benefits of rotavirus vaccination.