A post-licensure evaluation of the safety of inactivated hepatitis A vaccine (VAQTA, Merck) in children and adults.
BACKGROUND
Hepatitis A is a major cause of epidemic hepatitis in the US. In pre-licensure trials, inactivated hepatitis A vaccine (HAV, VAQTA, Merck) was shown to be generally well-tolerated and effective in inducing immunity to hepatitis A infection in adults and children over 2 years of age. Following the licensure of this vaccine, we began a Phase IV safety evaluation in adults and in children over 2 years of age.


METHODS
Safety was assessed by comparing the rates of diagnoses in clinic, emergency and hospital utilization. From April 1997 to December 1998, rates of diagnoses within 30 days for the clinic and emergency setting and 60 days for hospitalization were compared with unexposed follow-up time in the same individuals both before receipt of vaccine and after the 60 days interval post-vaccination.


RESULTS
There were a total of approximately 2000 comparisons between the risk and "before" or "after" period. Among them, 106 were found to have statistically significant differences in rates (30 elevated, 76 lowered). Among children/adolescents (2-17 year-old), in the hospitalization category, the only statistically significant elevated risk found was "elective procedures", as compared with both "before" and "after" periods. In the outpatient visit category for children and adolescents, elevated risks were found for consultation/general medicine/exam when compared with both "before" and "after" periods, and ganglion and viral warts when compared with either "before" or "after" period. Among adults (> or =18 year-old), in the outpatient visit category, a statistically significant elevated relative risk was seen for diarrhea/gastroenteritis for both "before" and "after" periods. There were additionally 17 diagnostic categories that showed a statistically significantly elevated relative risk compared with either "before" or "after" period. Except for diarrhea/gastroenteritis, the other eight events were elevated only in one comparison (either "before" or "after"). These eight elevated relative risks might be explained by chance resulting from multiple comparison or seasonal variations. There were no serious adverse events judged by the investigator to be associated with HAV.


CONCLUSIONS
In this large Phase IV evaluation of the safety of HAV, the vaccine appeared to be generally well-tolerated. These data support the continued routine use of HAV for vaccination in children and adults.
Black
Steven
S
Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612, USA. steve.black@kp.org
Shinefield
Henry
H
Hansen
John
J
Lewis
Edwin
E
Su
Ling
L
Coplan
Paul
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D004632:Emergency Medical Services; D005260:Female; D022362:Hepatitis A Vaccines / Q000009:adverse effects*; D006760:Hospitalization; D006801:Humans; D008004:Licensure; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D018570:Risk Assessment
D022362:Hepatitis A Vaccines