Seasonality of birth defects in West Africa: could congenital Zika syndrome be to blame?

Majumder, Maimuna S.; Hess, Rosanna F.; Ross, Ratchneewan; Piontkivska, Helen

doi:10.12688/f1000research.13858.1

Cited by 4 publications

(1 citation statement)

References 37 publications

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“…Our mechanistic explanation suggests potential treatment strategies for intervention in the dysregulation of ADAR editing during or shortly after ZIKV infection with the aim of preventing or diminishing the spectrum of ZIKV pathogenic/neurodevelopmental sequelae. For example, during pregnancy, within 2–3 weeks of diagnosed ZIKV infection, a short course of drugs leading to the suppression of the type I IFN pathway would be expected to result in downregulation of fetal ADAR activity. This could be achieved by administering treatments currently used, e.g., to treat lupus .…”

Section: Other Future Research Prospectsmentioning

confidence: 99%

Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

2019

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Previous studies of Zika virus (ZIKV) pathogenesis have focused primarily on virus‐driven pathology and neurotoxicity, as well as host‐related changes in cell proliferation, autophagy, immunity, and uterine function. It is now hypothesized that ZIKV pathogenesis arises instead as an (unintended) consequence of host innate immunity, specifically, as the side effect of an otherwise well‐functioning machine. The hypothesis presented here suggests a new way of thinking about the role of host immune mechanisms in disease pathogenesis, focusing on dysregulation of post‐transcriptional RNA editing as a candidate driver of a broad range of observed neurodevelopmental defects and neurodegenerative clinical symptoms in both infants and adults linked with ZIKV infections. The authors collect and synthesize existing evidence of ZIKV‐mediated changes in the expression of adenosine deaminases acting on RNA (ADARs), known links between abnormal RNA editing and pathogenesis, as well as ideas for future research directions, including potential treatment strategies.

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Section: Other Future Research Prospectsmentioning

confidence: 99%

Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

2019

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The African strain of Zika virus causes more severe in utero infection than Asian strain in a porcine fetal transmission model

Udenze

Trus

Bérubé

et al. 2019

Emerging Microbes & Infections

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Studies in mice showed that African Zika virus (ZIKV) strains cause more damage in embryos. These studies, however, were limited to the mouse-adapted African MR766 strain or infection at early gestation. Here, we compared infection of Asian and African strains in the fetal pig model at midgestation. Both strains caused fetal infection. ZIKV was detected in placenta, amniotic membrane, amniotic fluid, fetal blood, and brain. The African strain produced more vigorous in utero infection as represented by more efficient virus transmission between siblings, and higher viral loads in fetal organs and membranes. Infection with both strains was associated with reduced fetal brain weight and increased number of placental CD163-positive cells, as well as elevated in utero interferon alpha and cortisol levels. This is the first large animal model study which demonstrated that African strain of ZIKV, with no passage history in experimental animals, can cause persistent infection in fetuses and fetal membranes at midgestation. Our studies also suggest that similar to Asian strains, ZIKV of African lineage might cause silent pathology which is difficult to identify in deceptively healthy fetuses. The findings emphasize the need for further studies to highlight the impact of ZIKV heterogeneity on infection outcomes during pregnancy.

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Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

et al. 2019

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Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I2=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I2=74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.

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Seasonality of birth defects in West Africa: could congenital Zika syndrome be to blame?

Cited by 4 publications

References 37 publications

Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

Explaining Pathogenicity of Congenital Zika and Guillain–Barré Syndromes: Does Dysregulation of RNA Editing Play a Role?

The African strain of Zika virus causes more severe in utero infection than Asian strain in a porcine fetal transmission model

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

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