Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil

doi:10.1016/j.vaccine.2014.05.003

Vaccine

Volume 32, Issue 49, 20 November 2014, Pages 6676-6682

https://doi.org/10.1016/j.vaccine.2014.05.003 Get rights and content

Highlights

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Neurological adverse events after yellow fever vaccination have in general a good prognosis but rarely sequel or even death may occur.
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Finding of neurological adverse events is highly dependent on alertness and training.
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The age group from 5 to 9 years is the most vulnerable.
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Despite the occurrence of neurologic adverse events seen following YF vaccination, the risk benefit balance points to its continued use for those who are at risk.

Abstract

Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus.

Section snippets

Background

Yellow fever is an acute infectious disease, transmitted by arthropod vectors of the genus Flavivirus. The prognosis is poor and symptoms include: fever, nausea, vomiting, epigastric pain, hepatitis with jaundice, renal failure, hemorrhage, shock and death in 20–50% of reported cases in Brazil, where the disease is endemic in the North and Mid-West of the country. There is no specific treatment for yellow fever. Within a few years after isolation of the virus by inoculation in monkeys, in 1927,

Methods

This study is based on YFV-17DD neurological adverse events reported in public health units in Brazil from 2007 to 2012. These cases were obtained from the NIP database in January 31st, 2013, and updated until March 31st. All serious neurological adverse events related to YFV were discussed and classified by the national AEFI committee at the Ministry of Health. Reported cases were classified according to a modified CDC criteria for YEL-AND [4].

We modified CDC criteria for neurotropic disease

Results

From 2007 to 2012, a total of 129 neurological cases following the YFV-17DD were reported by the NIP in Brazil. Of these, 62 were excluded as shown in Fig. 1. Cases were excluded for the following reasons: 13 discarded, 37 inconclusive or inconsistent, 8 possible or suspect, and 1 probable. The most common reasons of exclusion were negativity of IgM for yellow fever in CSF, cases with clinical or laboratorial evidences against causality to YFV, and cases with insufficient information for

Discussion

The present study evaluated the features and rates of 67 neurological cases (neurotropic, neurological autoimmune and combined disease) following the administration of YFV-17DD in Brazil. Two scenarios were analyzed: the whole country and the state of Rio Grande do Sul. For most analyses we used first doses as the denominator, as all neurotropic (meningoencephalitis) cases were after the first dose. For the whole country and for the RS state, in 2009, children from 5 to 9 years old had the

Conclusions

The current study analyzed the largest series of neurological adverse events following a 17D yellow fever vaccine in current use and showed that the number of neurological adverse events temporally associated to the vaccine is substantial. However, these events have in general a good prognosis. Yellow fever is a serious condition, of high lethality, and without the yellow fever vaccine we would have large scale epidemics, as the potential vectors of the disease are widespread in Brazil and many

Authors’ contributions

All authors contributed to the discussions on diagnosis and classification of cases, and to the study concept, design, acquisition of data, analysis, interpretation, and to the manuscript; all approved the manuscript final version.

Conflicts of interest

Reinaldo de Menezes Martins, Ana Luiza Braz Pavão, Patrícia Mouta Nunes de Oliveira, Paulo Roberto Gomes dos Santos, Vanessa dos Reis von Doellinger, Maria da Luz Fernandes Leal, Akira Homma and Maria de Lourdes S. Maia work for Bio-Manguinhos, a government-owned and not for profit producer of vaccines for the Brazilian Ministry of Health, including the yellow fever vaccine analyzed on this study

Acknowledgements

Maria Isabel de Moraes Pinto, Sandra A. Moreira G. Monteiro, Solange Dourado, for their participation on the discussions for classification of cases at the national AEFI committee of the Ministry of Health.

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In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.
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View full text

Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil

Highlights

Abstract

Section snippets

Background

Methods

Results

Discussion

Conclusions

Authors’ contributions

Conflicts of interest

Acknowledgements

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

Expert Rev Vaccines

Vaccines and vaccination against yellow fever

Wkly Epidemiol Rec

Yellow fever vaccine

Yellow fever vaccine

MMWR

The effect of prolonged cultivation in vitro upon the pathogenicity of yellow fever virus

J Exp Med

The early use of yellow fever virus strain 17D for vaccine production in Brazil—a review

Mem Inst Oswaldo Cruz

Reactogenicity of yellow fever vaccines in a randomized, placebo-controlled trial

Rev Saude Publica

The phylogeny of yellow fever virus 17D vaccines

Vaccine

Complete nucleotide sequence of yellow fever virus vaccine strains 17DD and 17D-213

Virus Res

Neurovirulence of yellow fever 17DD vaccine virus to rhesus monkeys

Virology

Genetic variability among yellow fever virus 17D substrains

Vaccine

Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vacines: a randomized trial

Rev Saude Publica

Yellow fever vaccine post-marketing surveillance in Brazil

Proc Vaccinol

Phenotypic and molecular analyses of yellow fever 17DD vaccine viruses associated with serious adverse events in Brazil

Virology

Viscerotropic disease following yellow fever vaccination in Peru

Vaccine