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, I 2=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I 2=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I 2=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, I 2=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I 2=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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Zika Virus Infection as a Cause of Congenital Brain Abnormalities and Guillain-Barré Syndrome: Systematic Review.

Zika Virus and Its Associated Diseases Zika is a mosquito-borne flavivirus that can cause congenital defects, including microcephaly. Although most Zika virus infections are asymptomatic, rash, fev...

https://www.nejm.org/doi/pdf/10.1056/NEJMra1808246?listPDF=true

Zika Virus Infection — After the Pandemic

1.in my book照我看;依我的观点 A:Do you think I should trust Tom and let him do it? 你认为我可以相信汤姆,让他干那份工作吗? B:In my book, Tom is not a responsible person to betrusted 依我看,汤姆不是一个值得信赖的认真负责的人. ……

How to Use It

Zika virus (ZIKV) is an arboviral infection that may be sexually transmitted. The present study aims to determine if accessory sex glands are a potential source of infectious virus and important in sexual transmission. Male interferon type I receptor knockout (Ifnar−/−) mice were challenged subcutaneously with a Puerto Rican ZIKV isolate. Reproductive tissues were harvested seven days after viral challenge and artificial insemination fluid derived from epididymis or homogenized accessory sex glands (seminal plasma) was obtained. Naive interferon type I and II receptor knockout (AG129) females were pre-treated with progesterone, and inoculated intravaginally with either epididymal flush or seminal plasma from ZIKV-infected males. ZIKV RNA was demonstrated in the artificial insemination fluid and ZIKV antigen was detected in epididymal epithelial cells but not within seminiferous tubules at the time of artificial insemination fluid collection. Peripheral viremia, demonstrated by ZIKV RNA in whole blood samples of females from each challenge group was observed. Infectious virus was present in both epididymal fluid and seminal plasma. These studies provide evidence of passage of virus from epididymal flush and seminal plasma to naive females via artificial insemination and provides a model for the study of sexual transmission of ZIKV.

/pdf/coitus-free-sexual-transmission-of-zika-virus-in-a-mouse-45q9f6gs0o.pdf

Coitus-Free Sexual Transmission of Zika Virus in a Mouse Model

Interactions between the host and viruses during the course of their co-evolution have not only shaped cellular function and the immune system, but also the counter measures employed by viruses. Relatively small genomes and high replication rates allow viruses to accumulate mutations and continuously present the host with new challenges. It is therefore, no surprise that they either escape detection or modulate host physiology, often by redirecting normal cellular pathways to their own advantage. Viruses utilize a diverse array of strategies and molecular targets to subvert host cellular processes, while evading detection. These include cell-cycle regulation, major histocompatibility complex-restricted antigen presentation, intracellular protein transport, apoptosis, cytokine-mediated signaling, and humoral immune responses. Moreover, viruses routinely manipulate the host cell cycle to create a favorable environment for replication, largely by deregulating cell cycle checkpoints. This review focuses on our current understanding of the molecular aspects of cell cycle regulation that are often targeted by viruses. Further study of their interactions should provide fundamental insights into cell cycle regulation and improve our ability to exploit these viruses.

/pdf/breaking-bad-how-viruses-subvert-the-cell-cycle-16314193i2.pdf

Breaking Bad: How Viruses Subvert the Cell Cycle.

BACKGROUND:
The risk of congenital neurologic defects related to Zika virus (ZIKV) infection has ranged from 6 to 42% in various reports. The aim of this study was to estimate this risk among pregnant women with symptomatic ZIKV infection in French territories in the Americas.
METHODS:
From March 2016 through November 2016, we enrolled in this prospective cohort study pregnant women with symptomatic ZIKV infection that was confirmed by polymerase-chain-reaction (PCR) assay. The analysis included all data collected up to April 27, 2017, the date of the last delivery in the cohort.
RESULTS:
Among the 555 fetuses and infants in the 546 pregnancies included in the analysis, 28 (5.0%) were not carried to term or were stillborn, and 527 were born alive. Neurologic and ocular defects possibly associated with ZIKV infection were seen in 39 fetuses and infants (7.0%; 95% confidence interval, 5.0 to 9.5); of these, 10 were not carried to term because of termination of pregnancy for medical reasons, 1 was stillborn, and 28 were live-born. Microcephaly (defined as head circumference more than 2 SD below the mean for sex and gestational age) was detected in 32 fetuses and infants (5.8%), of whom 9 (1.6%) had severe microcephaly (more than 3 SD below the mean). Neurologic and ocular defects were more common when ZIKV infection occurred during the first trimester (24 of 189 fetuses and infants [12.7%]) than when it occurred during the second trimester (9 of 252 [3.6%]) or third trimester (6 of 114 [5.3%]) (P=0.001).
CONCLUSIONS:
Among pregnant women with symptomatic, PCR-confirmed ZIKV infection, birth defects possibly associated with ZIKV infection were present in 7% of fetuses and infants. Defects occurred more frequently in fetuses and infants whose mothers had been infected early in pregnancy. Longer-term follow-up of infants is required to assess any manifestations not detected at birth. (Funded by the French Ministry of Health and others; ClinicalTrials.gov number, NCT02916732 .).

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1709481

Arnaud Fontanet

Papers

Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas