Combination vaccines: postlicensure safety evaluation.

The success of immunizations in nearly eliminating many vaccine-preventable diseases has resulted in an increase in the need to study risks from vaccines, combination or otherwise. The well-known limitations associated with prelicensure trials have led many to hope that postlicensure studies can address safety issues. This article reviews measures that have been or should be taken to meet this expectation: establishment of clinical immunization safety assessment centers, standardization of case definitions for vaccine adverse events, use of the Vaccine Identification Standards Initiative to improve the accuracy and efficiency with which vaccination records are transferred, integration of vaccine safety monitoring into immunization registries, establishment (and enlargement) of the Vaccine Safety Datalink project, use of innovative analytic tools for better signal detection, and implementation of various methods to overcome confounding by contraindication. Only by investing in vaccine safety infrastructure at a level commensurate with investments in vaccine development can we hope to retain the public's confidence in immunization.

[Reactivation of herpes virus infections by vaccination: evidence or coincidence?]. / Reaktivierung von Herpesviren-Infektionen durch Impfungen: Evidenz oder Koinzidenz?

Varicella zoster and herpes simplex viruses cause latent infections by persisting in human cells. Reactivation has been associated with increasing age, immunosuppression, cancer, stress, fever, exposure to ultraviolet light, and tissue damage. Based on three cases reported to the Swiss Drug Monitoring Centre SANZ, we postulated previously that vaccinations may trigger reactivation of herpes virus infections due to vaccine-induced immunomodulation. In the meantime, 10 new cases of reactivated herpes virus infections soon after vaccinations have been reported. They involved 5 women and 5 men with an age range between 16 and 60. In only one case had a trauma preceded, otherwise healthy subjects with no known relevant comorbidity were vaccinated. The clustering of reports after publication points to a previous underreporting of similar cases. This may be explained by the fact that both vaccinations and reactivations of herpes virus infections are frequent, and a causal link is not suspected. However, these new cases do not prove causality, and extensive epidemiological or experimental studies are needed to elucidate the possible link between vaccination and reactivation of herpes virus infections.

Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group.

We determined the reporting rates for adverse events following the administration of inactivated mouse-brain derived Japanese encephalitis vaccine (JEV) based on post-marketing surveillance data from Japan and the United States. The rate of total adverse events per 100,000 doses was 2.8 in Japan and 15.0 in the United States. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 for a rate of 0.2 per 100,000 doses. In the United States, no serious neurological adverse events temporally associated with JEV were reported from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100,000 doses in Japan and the United States, respectively. Passively collected VAERS surveillance data indicate that characteristic hypersensitivity reactions with a delayed onset continue to occur among JEV recipients and that conservative recommendations limiting its use to travelers at high risk of infection with Japanese encephalitis are appropriate.

A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team.

BACKGROUND: We investigated a large, foodborne outbreak of hepatitis A that occurred in February and March 1997 in Michigan and then extended the investigation to determine whether it was related to sporadic cases reported in other states among persons who had consumed frozen strawberries, the food suspected of causing the outbreak. METHODS: The cases of hepatitis A were serologically confirmed. Epidemiologic studies were conducted in the two states with sufficient numbers of cases, Michigan and Maine. Hepatitis A virus RNA detected in clinical specimens was sequenced to determine the relatedness of the virus from outbreak-related cases and other cases. RESULTS: A total of 213 cases of hepatitis A were reported from 23 schools in Michigan and 29 cases from 13 schools in Maine, with the median rate of attack ranging from 0.2 to 14 percent. Hepatitis A was associated with the consumption of frozen strawberries in a case-control study (odds ratio for the disease, 8.3; 95 percent confidence interval, 2.1 to 33) and a cohort study (relative risk of infection, 7.5; 95 percent confidence interval, 1.1 to 53) in Michigan and in a case-control study in Maine (odds ratio for infection, 3.4; 95 percent confidence interval, 1.0 to 14). The genetic sequences of viruses from 126 patients in Michigan and Maine were identical to one another and to those from 5 patients in Wisconsin and 7 patients in Arizona, all of whom attended schools where frozen strawberries from the same processor had been served, and to those in 2 patients from Louisiana, both of whom had consumed commercially prepared products containing frozen strawberries from the same processor. CONCLUSIONS: We describe a large outbreak of hepatitis A in Michigan that was associated with the consumption of frozen strawberries. We found apparently sporadic cases in other states that could be linked to the same source by viral genetic analysis.