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Zika virus: assessing causality and consequences of emerging infectious diseases

English title Zika virus: assessing causality and consequences of emerging infectious diseases
Applicant Low Nicola Minling
Number 170069
Funding scheme Project funding (Div. I-III)
Research institution Institut für Sozial- und Präventivmedizin Universität Bern
Institution of higher education University of Berne - BE
Main discipline Infectious Diseases
Start/End 01.10.2016 - 31.10.2017
Approved amount 117'500.00
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All Disciplines (2)

Discipline
Infectious Diseases
Methods of Epidemiology and Preventive Medicine

Keywords (8)

Autoimmune diseases; Congenital abnormalities; Causality; Zika virus; Systematic review; Living systematic review; Emerging infectious diseases; Guillain-Barré syndrome

Lay Summary (German)

Lead
Zika ist ein von Mücken übertragenes Virus und hat in Brasilien sowie anderen lateinamerikanischen Ländern und der Karibik grosse Epidemien verursacht. Mitte bis Ende 2015 haben Ärzte in Brasilien darauf hingewiesen, dass es möglicherweise einen Zusammenhang geben könnte zwischen Zika, der unerwarteten Zunahme von Babys, welche mit viel zu kleinen Köpfen geboren werden (Mikrozephalie) und Erwachsenen mit dem Guillan-Barré Syndrom (GBS), einer Lähmung ausgelöst durch bestimmte Infektionen.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Wir haben, gestützt auf einer selektiven Literaturrecherche, eine systematische Übersichtsarbeit (Review) zum Thema Zika-Virus und dessen Auswirkungen durchgeführt. Die Ergebnisse wurden in einem „Causality Framework“ strukturiert dargestellt. Basierend auf unseren Erkenntnissen hat die Weltgesundheitsorganisation (WHO) im September 2016 die Schlussfolgerung gezogen, dass das Zika-Virus angeborene Gehirnanomalien verursachen und der Auslöser für GBS sein könnte. Es gibt jedoch noch viele ungeklärte Fragen. Neue Forschungsergebnisse zum Zika-Virus und dessen Auswirkungen werden fast täglich veröffentlicht. Im aktuellen Projekt entwickeln wir eine „lebende systematische Übersichtsarbeit“ zum Zika-Virus. Eine web-basierte Plattform geht die Forschungsergebnisse systematisch durch und ermöglicht eine der Echtzeit entsprechende online Aktualisierung des „Causality frameworks“. Wissenslücken zum Zika-Virus und dessen Auswirkungen auf eine Schwangerschaft, auf neurologische Störungen und zu sexueller Übertragbarkeit können so geschlossen werden. Wir entwickeln zudem Protokolle, um verschiedenen Studienleitern das Zusammentragen ihrer Daten zu ermöglichen und unsere Einschätzung des relativen Risikos der durch das Zika-Virus angeborene Anomalien und neurologische Krankheiten zu verbessern.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Der Ausbruch angeborener Anomalien, einschliesslich Mikrozephalie und GBS ist eine gesundheitliche Notsituation von internationaler Bedeutung. Das Zika-Virus wurde seit 2015 in 67 Ländern übertragen. Wir arbeiten mit der WHO zusammen, um Instrumente für die rasche laufende systematische Beurteilung bereitzustellen und die neusten Erkenntnisse zum Zika-Virus und dessen gesundheitliche Auswirkungen zusammentragen. In der Zukunft können die Methoden, welche wir entwickeln, auf verschiedene neue epidemische Infektionskrankheiten angepasst werden.
Direct link to Lay Summary Last update: 01.11.2016

Lay Summary (English)

Lead
Zika, a mosquito-borne virus, has caused large epidemics in Brazil and other countries in Latin America and the Caribbean. In mid to late 2015, doctors in Brazil suggested that Zika might be linked to unexpected increases in the numbers of babies born with abnormally small heads (microcephaly) and of adults with Guillain-Barré syndrome (GBS), a paralytic condition triggered by certain infections.
Lay summary

Inhalt und Ziele des Forschungsprojekts

We did a systematic review of the literature about Zika virus and its effects, structured in a ‘causality framework’. Based on our findings, the World Health Organization (WHO) concluded in September 2016 that Zika virus is a cause of congenital brain abnormalities and is a trigger of GBS, but many open questions remain. New research about Zika virus and its effects is being published almost daily. In this project, we will develop a ‘living systematic review’ for Zika virus. A web-based platform will track the expanding research evidence systematically and allow real-time online updates of the causality framework to fill gaps in our knowledge about Zika virus and its effects in pregnancy, on neurological disorders and on sexual transmission. We will also develop protocols to allow investigators from different studies to pool their data and improve our estimates of the relative risks of congenital abnormalities and neurological disease caused by Zika virus.  

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

The outbreaks of congenital abnormalities, including microcephaly and of GBS are a Public Health Emergency of International Concern. Zika virus has been transmitted in 67 countries since 2015. We are working with WHO to provide the tools for ongoing rapid systematic appraisal and synthesis of evidence about Zika virus and its effects on health. In future, the methods that we develop can be adapted to future emerging infectious disease epidemics.

Direct link to Lay Summary Last update: 01.11.2016

Responsible applicant and co-applicants

Employees

Publications

Publication
Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review
Counotte Michel Jacques, Meili Kaspar Walter, Taghavi Katayoun, Calvet Guilherme, Sejvar James, Low Nicola (2019), Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review, in F1000Research, 8, 1433-1433.
Sexual transmission of Zika virus and other flaviviruses: A living systematic review
Counotte Michel Jacques, Kim Caron Rahn, Wang Jingying, Bernstein Kyle, Deal Carolyn D., Broutet Nathalie Jeanne Nicole, Low Nicola (2018), Sexual transmission of Zika virus and other flaviviruses: A living systematic review, in PLOS Medicine, 15(7), e1002611-e1002611.
Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: From systematic review to living systematic review
Counotte Michel Jacques, Egli-Gany Dianne, Riesen Maurane, Abraha Million, Porgo Teegwendé Valérie, Wang Jingying, Low Nicola (2018), Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: From systematic review to living systematic review, in F1000Research, 7, 196-196.
Investigating the sexual transmission of Zika virus
Kim Caron R, Counotte Michel, Bernstein Kyle, Deal Carolyn, Mayaud Philippe, Low Nicola, Broutet Nathalie (2018), Investigating the sexual transmission of Zika virus, in The Lancet Global Health, 6(1), e24-e25.
Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control?
Bernstein Kyle, Bowen Virginia B., Kim Caron R., Counotte Michel J., Kirkcaldy Robert D., Kara Edna, Bolan Gail, Low Nicola, Broutet Nathalie (2017), Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control?, in PLOS Medicine, 14(12), e1002474-e1002474.
Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review
Krauer Fabienne, Riesen Maurane, Reveiz Ludovic, Oladapo Olufemi, Martinez-Vega Ruth, Porgo Teegwende, Haefliger Anina, Broutet Nathalie, Low Nicola (2017), Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review, in PLoS Medicine, 14(1), e1002203.

Collaboration

Group / person Country
Types of collaboration
World Health Organization Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Medical librarianship in the data age: transforming research data into clinical insight Talk given at a conference Living systematic reviews – from theory to implementation 31.08.2017 Bern, Switzerland Nguyen Phi Hung; Counotte Michel;
STI & HIV World Congress Talk given at a conference Sexual transmission of flaviviruses – a living systematic review 12.07.2017 Rio de Janeiro, Brazil Counotte Michel;
WHO meeting on sexual transmission of Zika Individual talk Sexual transmission of Zika virus and other flaviviruses 20.03.2017 Geneva, Switzerland Counotte Michel;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Zika causality statement. World Health Organization website International 2016

Associated projects

Number Title Start Funding scheme
176233 Zika virus: causality, open science and risks of emerging infectious diseases 01.11.2017 Project funding (Div. I-III)
160320 Epidemiology and Mathematical Modelling for Infectious disease Control (EpideMMIC) 01.08.2015 Project funding (Div. I-III)

Abstract

Background: An explosive pandemic of Zika virus infection has caught the research world by surprise. On February 1 2016, barely a year after the introduction of a new arbovirus infection in Brazil, a Public Health Emergency of International Concern was triggered by clusters of Guillain-Barré syndrome and microcephaly. By the end of March 2016, scientific opinion about the causal role of Zika virus in these conditions had increased. This project started in February 2016 to systematically appraise the evidence for causality in a theoretically grounded framework.Objectives: 1) To establish a “living systematic review” to assess and continuously update evidence about causal links between Zika virus infection and: a) auto-immune mediated disorders such as Guillain-Barré syndrome and idiopathic thrombocytopaenia purpura; b) acute central nervous system disorders and c) congenital anomalies, and 2) To determine incidence and factors associated with congenital anomalies and adverse pregnancy outcomes in pregnant women infected with Zika virus.Methods: 1) We have developed a causality framework, based on the Bradford Hill list of dimensions of causation, to define specific questions about causal links between Zika virus and neurological and congenital conditions. We apply state-of-the-art systematic review methods to search, select and appraise the literature about each causality dimension and each condition in the rapidly evolving field of Zika research. We will develop the specification for a platform for “living systematic reviews” that can be continuously updated to track causal research in future emerging infectious diseases. 2) We will develop a protocol for a cohort study of pregnant women in Brazil and a protocol for an individual patient data meta-analysis that will allow pooled analyses of data from this and other ongoing cohort studies. These analyses will allow us to examine risk factors for Zika virus transmission in pregnancy and to develop and validate criteria that could define a congenital Zika syndrome.Timeline: This is a one year project. The next research objectives will depend on the results of this project and the spread of Zika in this emergency situation.Importance and impact: The Zika virus pandemic has presented new challenges for infectious disease control. There is no other known mosquito-borne flaviviral infection that is very probably teratogenic. Without a vaccine or treatment, Zika will be a continuing problem and new complications may emerge. This project has already had an impact, by providing rapid systematic appraisals to the WHO Director General about the status of research into causal associations between Zika virus and neurological complications. The project is urgent because of the need for ongoing rapid systematic appraisal and synthesis of the emerging and enlarging evidence base. The project is important because our approach will provide sustainable methods, in collaboration with international agencies, that will be transferable to future emerging infectious disease epidemics.
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