Low frequency of side effects following an incidental 25 times concentrated dose of yellow fever vaccine

Abstract

In August/1999, a group of 14 adults from the staff of a private hospital in Contagem -- Minas Gerais State, Brazil, received unintentionally a 25 times concentrated dose of the 17-DD yellow fever vaccine (Bio-Manguinhos), due to a mistake at the reconstitution step. All patients were clinically and laboratorially evaluated at days 5, 13 and 35 post vaccination. Frequency of side effects and clinical observations of this group of individuals were not different from the observed in recipients immunized with normal doses of the vaccine. At the second and third evaluation none of the subjects reported symptoms. None of the patients presented abnormalities at the physical examination at none of the time points and in all cases the blood examination was normal, except for a reduced number of platelets that was detected in one subject at the first and second evaluation and reverted to normal at third evaluation. At the first evaluation point, 8 subjects were serum negative and 6 serum positive for yellow fever at the plaque reduction neutralization test. In 5 subjects the observed titre was 10 times higher as the baseline of 2.36 Log10 mUI/ml. The samples collected at second and third evaluation (13th and 35th days) demonstrated that all subjects responded to the vaccination with the exception of one that did not present a positive result in any of the samples collected. This evaluation confirms the safety of the 17-DD yellow fever vaccine.

Serious adverse events associated with yellow fever vaccine

“…In a dose-response study viremias by virus isolation, qRT-PCR, and clinical reactogenicity were statistically similar across the different study arms, with deescalating doses from 27,476 IU (approximately 52,000 PFU, the usual dose) to 31 IU (approximately 60 PFU) 32 Mass vaccination campaigns include errors administering vaccines in doses from 10 times to 25 times the recommended dose (n D 163), but there were no serious adverse events. 13,33,34 Moreover, in BioManguinhos/Fiocruz, the release titers are verified for all lots and have been around 70,000 PFU/human dose and within narrow limits of variation across different lots along the last decades, showing a very consistent and homogeneous production. So, this hypothesis seems untenable.…”

17DD yellow fever vaccine

“…The current study has not enough power to define if lower yellow fever vaccine doses may be followed by a decrease in serious adverse events, such as vaccine-associated viscerotropic disease. On the other hand, information about the effect of large doses administered inadvertently is scant, based in few individuals and does not permit conclusions 29 , 30 …”

Review of the risks and benefits of yellow fever vaccination including some new analyses

“…The infectivity assay underestimates the number of genome equivalents (measured by RT-PCR) by approximately 1000-fold [108]. Inadvertant overdose of YF vaccine has occurred occasionally, without any known adverse effects [122], and none would be expected based on the knowledge of virus-host interactions. The problem may, in fact, be the reverse -the administration of very low doses could potentially be associated with high, delayed or prolonged viremia and potentially increase the risk of neuroinvasion.…”