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. 2024 Mar 1;31(2):taad160.
doi: 10.1093/jtm/taad160.

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights

Anne Le Hir  1 , Guillaume A Durand  2   3 , José Boucraut  4   5 , Annabelle Garnier  6 , Marie Mura  6   7 , Sylvain Diamantis  8   9 , Michel Carles  10 , Claire Durand  10 , Cyril Schweitzer  11   12 , Claire Audouard  11 , Véronique Decroix  13 , Romain Boyez  14 , Anne Van Dendriessche  15 , Alexandre Leclancher  16 , Elsa Kaphan  17 , Luce Barbat du Closel  18 , Renaud Verdon  19 , Damien du Cheyron  20 , Astrid Vabret  21 , Delphine Vergnon  22 , Gilda Grard  2   3 , Rémi Charrel  2   23   24 , Xavier de Lamballerie  2   3 , Carole Eldin  23
Affiliations

Yellow fever vaccine-associated neurologic and viscerotropic disease: a 10-year case series of the French National Reference Center for Arboviruses with clinical and immunological insights

Anne Le Hir et al. J Travel Med. .

Abstract

Background: Immunization against the Yellow fever virus (YFV) with the 17D live-attenuated vaccine is the most effective way to prevent the disease. However, unexpected severe adverse events can occur. They consist in a neurological impairment - neurological disease (YEL-AND), a YF-like illness - viscerotropic disease (YEL-AVD) or anaphylaxis. In this article, we describe the epidemiology, clinical and biological features of YEL-AND and YEL-AVD cases reported to the French National Reference Center for Arboviruses (NRCA) in the past 10 years.

Methods: We conducted a national, retrospective study using the database of the NRCA from June 2012 to June 2022. All patients whose biological samples were sent to the NRCA for detection of YFV by serology and/or RT-qPCR for a suspected vaccine-associated adverse event were included. We collected data by reading medical records and conducted complementary neuro-immunological analysis, followed by a search for autoimmunity against type-1-interferon when samples were available at the NRCA.

Results: There were 10 cases of YEL-AND and 2 cases of YEL-AVD reported to the NRCA in the past 10 years, which represented an overall incidence of 0.6 for 100 000 doses. A total of 6/12 cases were previously healthy patients (50%, mean age 31 years), and 4/12 cases had cardiovascular co-morbidities (42%, mean age 56 years). The majority of YEL-AND had a favourable outcome at 6 months of follow up. One YEL-AVD patient passed. In secondary analyses, we evidenced a significant blood cerebrospinal fluid (CSF) barrier dysfunction, without intrathecal synthesis of immunoglobulin and without argument for a neuron damage. We further detected a significant rate of anti-type-1alpha interferon antibodies in 3/10 tested patients (2 YEL-AND and 1 YEL-AVD).

Conclusion: YEL-AND and YEL-AVD are rare events that can underlie defect in the innate immunity of apparently healthy or mild co-morbid subjects. Outcome was generally favourable in the YEL-AND cases of our series, but still life-threatening or even fatal in the YEL-AVD cases.

Keywords: YEL-AND; YEL-AVD; Yellow fever; adverse event; anti-interferon autoantibodies; interferon; vaccine.

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