柳叶刀:更多证据指向寨卡病毒引发小头症

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目前在美洲多国肆虐的寨卡病毒与新生儿小头症之间是否存在因果关系，是医学界当前研究热点。一项对几年前法属波利尼西亚寨卡疫情的回顾性评估显示，孕妇在孕期前3月感染寨卡病毒后，出现小头症等出生缺陷的风险约为1%，大大高于通常情况。相比之下，通常情况下医学界记录到的新生儿小头症比率大约为万分之二。研究负责人、法国巴斯德研究所西蒙·科舍梅在新闻公报中说：“我们的分析强烈支持目前的假设，即新生儿小头症与孕期前3个月感染寨卡病毒有关。”

研究小组在最新一期英国《柳叶刀》杂志上报告说，他们对2013年至2014年间法属波利尼西亚暴发的寨卡疫情进行了统计分析，当时有高达三分之二的当地人口感染了寨卡病毒，但大多数人仅出现了温和症状或甚至无症状。研究人员试图对当时的孕妇感染者及新生儿情况进行追踪调查，来量化寨卡病毒引发小头症的风险，以期对目前的美洲寨卡疫情提供参考。

研究人员对当时记录的孕妇感染及新生儿出生缺陷情况进行了调查，并进行数学建模。模型综合评估显示，孕妇在孕期前3个月内感染寨卡病毒后，新生儿出现小头症的风险为1%。科舍梅说，“（孕期）前3个月是最为关键的”。

他们认为，这一风险虽然与其他孕期感染导致出生缺陷的风险相比并不高，但由于寨卡暴发期间，孕妇感染寨卡病毒的风险相对较高，因此掌握出生缺陷的风险仍然意义重大。

这一风险比研究人员预想中要低得多，比目前在巴西观察到的小头症风险也明显要低。在这次寨卡疫情中，仅巴西就已确诊了700多例小头症病例。一些医学专家评价说，这很可能是因为，自2013年法属波利尼西亚的寨卡疫情以来，病毒本身也出现了变异，毒性变得更强。

并未参与上述研究的英国帝国理工学院纳塔莉·麦克德莫特评价说，这一研究结果是否适用于目前在美洲等地暴发的寨卡疫情还很难说，毕竟法属波利尼西亚人口构成较单一，基因多样性不高。

尽管这项新研究还未能最终确证寨卡病毒与小头症之间的因果关系，但医学界仍认为调查得出的数据十分重要。英国兰开斯特大学研究人员德里克·盖思勒尔说，这一研究让医学界进一步相信孕妇感染寨卡病毒可能会导致小头症，而且首次明确了孕期前3月这一风险期，这对于提醒孕妇感染风险十分关键。

近期多项医学研究都指向寨卡病毒与小头症之间的直接关联。例如此前一项研究发现，寨卡病毒能够“选中并攻击”那些对胎儿大脑发育关键的细胞。

寨卡病毒在全球数十个国家和地区流行，其中巴西、哥伦比亚等美洲国家疫情最重。15日，古巴卫生部也报告说，该国出现了首例本土感染的寨卡病例。

来源：新华社

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Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study

Dr Simon Cauchemez, PhDcorrespondenceemail, Marianne Besnard, MD, Priscillia Bompard, MPH, Timothée Dub, MPH, Prisca Guillemette-Artur, MD, Dominique Eyrolle-Guignot, MD, Henrik Salje, PhD, Maria D Van Kerkhove, PhD, Prof Véronique Abadie, MD, Catherine Garel, MD, Prof Arnaud Fontanet, DrPh†, Henri-Pierre Mallet, MD†

Background
The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified.

Methods
We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk.

Findings
The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62–70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0–8) per 10 000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34–191) per 10 000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data.

Interpretation
Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00651-6/abstract