[Neurotropic disease after vaccination against yellow fever]. / Neurotropische ziekte na vaccinatie tegen gele koorts.

Millions of people are vaccinated each year to prevent morbidity and mortality by numerous bacterial and viral infections. Safety of vaccines is an important topic of discussion, especially because of the prophylactic nature of vaccination. Luckily, serious adverse events are rare. However, low incidence results in low awareness, and thus can make identification of these post-vaccination diseases difficult for healthcare workers. In the Netherlands, serious adverse events caused by travel vaccinations are especially rare, because of the low immunisation coverage compared to endemic countries. We present two Dutch cases that were diagnostically challenging. Both turned out to suffer from a serious adverse event of vaccination with live attenuated yellow fever virus, so-called yellow fever associated neurotropic disease (YEL-AND). With this article we hope to improve awareness of post-vaccination diseases, and YEL-AND in particular.

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study.

BACKGROUND: Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects. METHOD: We vaccinated young volunteers (18-28 yrs, N = 30) and elderly travelers (60-81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination. RESULTS: Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8-4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1-2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants. CONCLUSIONS: We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD. TRIAL REGISTRATION: Trialregitser.nl NTR1040.