Background: Yellow fever vaccine (YFV) was considered safe until 1998, when two deaths following vaccination were reported and YFV-associated neurotropic and viscerotropic diseases were identified.
Methods: Data came from the Vaccine Safety Datalink (VSD) and the U.S. Department of Defense (DoD). VSD subjects, with and without exposure to YFV, were compared in a retrospective matched cohort study. DoD subjects were studied using a risk-interval design. ICD-9 codes were analyzed for signs and symptoms related to acute, viscerotropic and neurotropic adverse events.
Findings: VSD cohorts received 47,159 YFV doses during 1991-2006 and DoD cohorts received 1路12 million during 1999-2007. Acute adverse outpatient events occurred more frequently in YFV exposed subjects in the VSD pediatric (Odds Ratio (OR) 18路0, 2路17-149路51, Attributable risk (AR) 59/100,000 doses), VSD adult (OR 3路75; 1路94-7路24, AR 4/100,000 doses) and DoD cohorts (Rate ratio (RR) 3路85; 3路35,4路41, AR 19路7/100,000 doses). Viscerotropic outpatient codes occurred more frequently in the exposed VSD pediatric (OR 1路54, 95% CI 1路02-2路36, AR 121/100,000 doses) and the military cohorts (RR, 1路93; 95% CI, 1路90-1路96, AR 1018/100,000 doses,). Neurotropic outpatient codes occurred more frequently in the exposed DoD (RR, 1路88; 95% CI, 1路84-1路92, AR 656/100,000 doses), but were not different in the VSD pediatric cohort. In the VSD adult cohort, vaccinated subjects had decreased rates of viscerotropic and neurotropic diagnoses. Inpatient events were rare and not increased following YFV. One YFV-associated death occurred in the DoD population and none in the VSD. Estimated death rate for the DoD cohort was 0路89/1,000,000 YFV doses.
Interpretation: Modest increases in outpatient visits for acute, neurotropic and viscerotropic related events were observed after YFV. No increase in hospitalizations following YFV occurred and the death rate was consistent with previous reports. YFV has an acceptable risk profile.