Investigation of Zika Virus infection in patients with Guillain-Barré syndrome

Author(s)

Taline Monteiro Klein

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2019-09-27

Examining board members

Benedito Antonio Lopes da Fonseca; Eurico de Arruda Neto; Wilson Marques Júnior

• Advisor: Benedito Antonio Lopes da Fonseca

Abstract

Guillain-Barré Syndrome is a neurologic disease that is characterized as an immunomediated acute inflammatory polyradiculoneuropathy, that is triggered by a previous infection. The clinical manifestations usually present with tingling, progressive weakness, ascending paralysis frequently simetric, arreflexia, autonomic disfunction and pain. More serious manifestations as the respiratory muscle involvement can occur, and about 3% of the patients come to death. GBS incidence increased 20 times in French Polynesia during ZIKV epidemic in 2013-2014. In Ribeirão Preto, it was observed an increase of 3,5 times of this incidence in 2016, when compared with the last three years. Thus, the aim of this study was to investigate and characterize ZIKV infection in patients diagnosed with GBS followed up at the Hospital das Clínicas of Ribeirão Preto - SP. The research had the participation of 75 patients, and 42 presented neurologic manifestations, 31 of whom were diagnosed with GBS. Clinical samples of plasm, serum, urine and CSF were collected and tested for the presence of ZIKV by real time qRT-PCR. Our results demonstrated ZIKV detection in 22 of 31 GBS patients (70,9%), revealing a high incidence of this infection in this syndrome at Ribeirão Preto, and the mean detection time of ZIKV in these patients was 55 days, and in one of the patients the virus was detected up to 186 days after the first detection. The highest percentage of ZIKV detection was in urine with about 56% of the positive results among all the materials collected, corroborating with data from the literature. CSF also presented a high percentage of detection (53%). Among the 22 cases of ZIKV infection, most of them had the diagnosis of PIDA with albumin-cytologic dissociation, and eight presented anti-ZIKV neutralizing antibodies using PRNT50 assay. A negative patient for ZIKV detection was positive for anti-ZIKV neutralizing antibodies. In addition to the characterization of virus kinetics in each patient, it was possible to obtain two viral isolates, from the serum and CSF of two different patients, demonstrating the presence of ZIKV in the CNS of patients with GBS and its viability. The isolates were submitted to complete genome sequencing. Our study is of great relevance for the contribution of greater scientific knowledge about ZIKV as a possible trigger for the development of GBS, as ZIKV behaves in these patients, for how long they persist in this case of acute immune-mediated inflammatory neuropathy, and how such patients are confronted with a rare neurological manifestation, possibly induced by ZIKV infection. (AU)

• FAPESP's process: 16/04320-8 - STUDY OF ZIKA VIRUS INFECTION AND ITS POSSIBLE ASSOCIATION WITH GUILLAIN-BARRÉ SYNDROME
• Grantee: Taline Monteiro Klein
• Support Opportunities: Scholarships in Brazil - Doctorate