Guillain-Barré syndrome is a major complication of Zika virus and occurs in 1 in 4,000 or 5,000 cases, which makes it potentially a huge burden to healthcare providers and systems. Central nervous system disease is also being recognised increasingly. A series of clinical studies in ZikaPLAN are devoted to analysing the serious neurological complications in adults associated ZIKV infection.

“We want to study how the virus causes neurological complications and see how much is due to the virus and how much the body’s own immune response is contributing. Understanding these risk factors will hopefully lead to being able to do something about Zika.”

Prof. Tom Solomon, The University of Liverpool

Overall Objectives

This group aims to define the spectrum of neurological diseases associated with Zika virus (ZIKV) infection, in both the central nervous system (CNS) and peripheral nervous system (PNS) of adults and children. This includes immunologically mediated illness, for example Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM), and direct viral invasion of the nervous system for example meningoencephalitis and neuropathies. 

Specific Objectives

An association between ZIKV infections and GBS will be defined by comparing the proportions of infected persons among GBS patients and the controls collected in the IGOS-ZIKA protocol. Researchers in this group are working to:

  • describe the clinical phenotype of GBS related to Zika and its long-term prognosis according to validated outcome measures and long-term follow-up protocols of IGOS,
  • study the association of ADEM, encephalitis and peripheral neuritis/neuropathies with Zika infections,
  • identify rare and unusual neurological manifestations of Zika infections,
  • strengthen the diagnostic capacity of neurological Zika disease,
  • establish a biobank of materials (cerebrospinal fluid, blood, etc.) – including control samples,
  • enhance understanding of disease mechanisms of neurological Zika disease by providing clinical information and biomaterials,
  • improve clinical management of neurological Zika disease.

Results and Achievements

The results from this work have furthered understanding of the spectrum of ZIKV-associated neurological disease and provided valuable information on diagnostic assays, viral epidemiology, characteristic systemic and neurological features, responses to treatment and clinical outcomes. This will inform guideline development and support further educational work that will greatly improve the management of neurological disease associated with ZIKV and other arboviruses globally.

Key Achievements

  • Strengthened diagnostic capacity for ZIKV: this work has been led by Fundação Oswaldo Cruz (Fiocruz) in collaboration with ZikAction and has informed the selection of the most accurate available assays for subsequent clinical and seroepidemiological studies.
  • Recognition of the co-circulation of other arboviruses that may cause neurological disease: the importance of investigating for Chikungunya (CHIKV) or dengue virus (DENV) in patients with suspected arbovirus-associated neurological disease was identified, as a high number of patients in the retrospective studies in Rio de Janeiro and Recife had evidence of infection with one of more of these viruses.
  • Enhanced understanding of the spectrum of ZIKV-associated neurological disease: the Rio de Janeiro study identified that patients infected with ZIKV may have a mixed picture of simultaneous central and peripheral neurological disease, which had not been seen in previous case series.
  • Initiation and continued running of case control studies in Latin America and Asia: case control studies were set up in Colombia, Brazil and across Latin American sites belonging to the IGOS-Zika network, with incorporation of pre-existing Asian IGOS sites into the IGOS-Zika study. Active recruitment of patients is taking place in these locations.
  • Utilization of online platforms for data collection to build capacity for clinical research into neurological disease: this includes use of the REDCap platform by University of Liverpool, Fiocruz and Universidad del Valle and the development of a web-based data entry support system by Erasmus Universitair Medisch Centrum (EMC) for the IGOS study, where local investigators can upload and organize their research data. This system is free for local institutes to use (visit IGOS-Zika).
  • Establishment of biobanks in Colombia and Brazil with ongoing sample collection and in addition to the pre-existing IGOS biobank in EMC: these samples will be used for diagnostic purposes and for other research into the neuropathogenesis of ZIKV performed by NEURO-ZIKA Pathogenesis.
  • Production of practical recommendations on GBS supporting clinical practice in Latin America and aiming to improve patient management.
  • Publication of collaborative work on clinical and diagnostic studies and a review of the understanding of Zika-associated neurological disease in returning travelers, to enhance preparedness in countries where Zika is currently not endemic.
  • Increased awareness of the potential for ZIKV to cause neurological disease through development of training resources and dissemination activities facilitating accurate diagnosis and improved management of patients.

NEURO-ZIKA builds upon ongoing studies in both Brazil and Colombia creating close collaboration through a large network of hospitals

MERG and NEURO-ZIKA Networks

MERG and NEURO-ZIKA Networks

Participating Organisations

Group leader: Prof. Tom Solomon, The University of Liverpool

  • Umeå University
  • University of Glasgow
  • University of Oxford
  • Erasmus Universitair Medisch Centrum Rotterdam
  • Universidad del Valle
  • Fundação de Apoio à Universidade de São Paulo
  • Fundação Oswaldo Cruz (Fiocruz)