Antecedent infections in Guillain-Barré syndrome in endemic areas of arbovirus transmission: A multinational case-control study

Abstract

Half of the world's population is at risk of arthropod-borne virus (arbovirus) infections. Several arbovirus infections have been associated with Guillain-Barré syndrome (GBS). We investigated whether arboviruses are driving GBS beyond epidemic phases of transmission and studied the antibody response to glycolipids. The protocol of the International Guillain-Barré syndrome Outcome Study (IGOS), an observational prospective cohort study, was adapted to a case-control design. Serum samples were tested for a recent infection with Zika virus (ZIKV), dengue virus (DENV), chikungunya (CHIKV) virus, hepatitis E virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), Campylobacter jejuni, and Mycoplasma pneumoniae, and for antibodies to glycolipids. Forty-nine patients were included from Brazil (63%), Argentina (14%), and Malaysia (22%). Evidence of a recent infection was found in 27/49 (55%) patients: C jejuni (n = 15, 31%), M pneumoniae (n = 5, 10%), CHIKV (n = 2, 4%), EBV (n = 1, 2%), C jejuni and M pneumoniae (n = 2, 4%), CMV and DENV (n = 1, 2%), and C jejuni and DENV (n = 1, 2%). In 22 patients, 35 paired controls were collected. Odds ratio for recent infections did not significantly differ between cases and controls. No typical anti-ganglioside antibody binding was associated with recent arbovirus infection. We conclude that arbovirus infections occur in GBS patients outside of epidemic viral transmission, although not significantly more than in controls. Broad infection and anti-ganglioside antibody serology are important to establish the most likely pathogenic trigger in GBS patients. Larger studies are necessary to determine the association between arboviruses and GBS.

Keywords: Guillain-Barré syndrome; Zika virus; anti-ganglioside antibodies; anti-glycolipid antibodies; chikungunya virus; dengue virus.

FIGURE 1

Flowchart of inclusions in cohort and case‐control part of the analysis. *Family control (brother) instead of hospital control (n = 1), hospital control admitted with Alzheimer's and chikungunya fever (n = 1)

FIGURE 2

Heatmap of IgG antibody binding to glycolipids as assessed by glycoarray. Each row presents one patient (P1‐P49) or control (C1‐C23); each column presents one of the tested glycolipid antibodies (single or in complex). Raw data were was clustered based on a distance matrix using Pearson's correlation and hierarchical cluster algorithm, and clipped at a 10 000 upper limit