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Tuesday, 8 October, 2024
HomeInfectious DiseasesZika virus causes Guillain-Barre Syndrome and birth defects

Zika virus causes Guillain-Barre Syndrome and birth defects

A World Health Organisation evidence analysis confirms that infection with mosquito-borne Zika virus is a cause of the neurological disorder Guillain-Barre Syndrome (GBS), as well as microcephaly and other congenital brain abnormalities. 

This is according to a systematic review published by Nicola Low of the University of Bern, Switzerland, and colleagues in the World Health Organisation (WHO) Zika Causality Working Group.

In March 2016, WHO stated that there was a strong scientific consensus that Zika virus is a cause of GBS, microcephaly, and other neurological disorders. However, decisions about causality must be assessed systematically to guide public health actions. In the new work, the WHO group defined specific questions about the relationship between Zika virus and clinical outcomes, setting a framework of ten dimensions to define causality.

They then reviewed existing literature for studies that addressed the outcomes – either GBS or congenital brain abnormalities – and convened a panel of experts to assess the review findings.

Based on 72 studies published up to 30 May, 2016, that included data on Zika and congenital brain abnormalities, the team concluded that at least eight of the ten criteria for causality were met. Based on 36 studies published in the same time frame with data on Zika and GBS, the researchers concluded that at least seven of the ten criteria for causality were met. In addition, papers published after the initial literature review – between 30 May and 29 July, 2016 – strengthened the initial findings that Zika virus is causative of brain abnormalities and GBS. However, there are remaining questions about the link that will need to be addressed with continuing studies.

“Rapid and systematic reviews with frequent updating and open disseminating are now needed, both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge,” the authors say. “This rapid systematic review found sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.”

Abstract
Background: The World Health Organization (WHO) stated in March 2016 that there was scientific consensus that the mosquito-borne Zika virus was a cause of the neurological disorder Guillain–Barré syndrome (GBS) and of microcephaly and other congenital brain abnormalities based on rapid evidence assessments. Decisions about causality require systematic assessment to guide public health actions. The objectives of this study were to update and reassess the evidence for causality through a rapid and systematic review about links between Zika virus infection and (a) congenital brain abnormalities, including microcephaly, in the foetuses and offspring of pregnant women and (b) GBS in any population, and to describe the process and outcomes of an expert assessment of the evidence about causality.
Methods and Findings: The study had three linked components. First, in February 2016, we developed a causality framework that defined questions about the relationship between Zika virus infection and each of the two clinical outcomes in ten dimensions: temporality, biological plausibility, strength of association, alternative explanations, cessation, dose–response relationship, animal experiments, analogy, specificity, and consistency. Second, we did a systematic review (protocol number CRD42016036693). We searched multiple online sources up to May 30, 2016 to find studies that directly addressed either outcome and any causality dimension, used methods to expedite study selection, data extraction, and quality assessment, and summarised evidence descriptively. Third, WHO convened a multidisciplinary panel of experts who assessed the review findings and reached consensus statements to update the WHO position on causality. We found 1,091 unique items up to May 30, 2016. For congenital brain abnormalities, including microcephaly, we included 72 items; for eight of ten causality dimensions (all except dose–response relationship and specificity), we found that more than half the relevant studies supported a causal association with Zika virus infection. For GBS, we included 36 items, of which more than half the relevant studies supported a causal association in seven of ten dimensions (all except dose–response relationship, specificity, and animal experimental evidence). Articles identified nonsystematically from May 30 to July 29, 2016 strengthened the review findings. The expert panel concluded that (a) the most likely explanation of available evidence from outbreaks of Zika virus infection and clusters of microcephaly is that Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly, and (b) the most likely explanation of available evidence from outbreaks of Zika virus infection and GBS is that Zika virus infection is a trigger of GBS. The expert panel recognised that Zika virus alone may not be sufficient to cause either congenital brain abnormalities or GBS but agreed that the evidence was sufficient to recommend increased public health measures. Weaknesses are the limited assessment of the role of dengue virus and other possible cofactors, the small number of comparative epidemiological studies, and the difficulty in keeping the review up to date with the pace of publication of new research.
Conclusions: Rapid and systematic reviews with frequent updating and open dissemination are now needed both for appraisal of the evidence about Zika virus infection and for the next public health threats that will emerge. This systematic review found sufficient evidence to say that Zika virus is a cause of congenital abnormalities and is a trigger of GBS.

Authors
Fabienne Krauer, Maurane Riesen, Ludovic Reveiz, Olufemi T Oladapo, Ruth Martínez-Vega, Teegwendé V Porgo, Anina Haefliger, Nathalie J Broutet, Nicola Low

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[link url="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002203"]PLOS Medicine abstract[/link]

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