The reemergence of human rabies and emergence of an Indian subcontinent lineage in Tibet, China

The reemergence of human rabies and emergence of an Indian subcontinent lineage in Tibet, China
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人类狂犬病的重新出现以及印度次大陆谱系在中国西藏的出现

DOI:
10.1371/journal.pntd.0007036
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发表时间:
2019-01-01
影响因子:
3.8
通讯作者:
Zhu, Wu-Yang
Zhu, Wu-Yang
中科院分区:
医学2区
文献类型:
--
作者:
Tao, Xiao-Yan;Li, Mu-Li;Zhu, Wu-Yang

文献摘要

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协调的监测、疫苗接种和公共信息工作使中国的狂犬病流行得到控制,但每年仍有大量死亡病例报告,其中一些病例发生在以前的狂犬病疫区。西藏16年来几乎没有狂犬病,但自2015年以来,每年都报告一例人类狂犬病病例。为了更好地了解这些病例的起源,我们对三个人类样本和2012年从一只狗身上分离出的另一个样本进行了测序。从大脑样本中测序了三个基因组:人类病例1(2015年报告),人类病例3(2017年)和2012年的狗病例。对于人类病例2(2016年),从有限的唾液样本中测序了狂犬病N基因。系统发育分析显示,病例1(CXZ1501H)和犬病例(CXZ1201D)属于中国IV谱系(相当于全球狂犬病中的北极样2),表明与野生动物溢出事件有关。然而,病例2(CXZ1601H)被置于优势谱系中国I中,并且与邻近云南省的最近菌株最相似,表明当前的动物流行病最终到达了西藏。然而,最令人惊讶的是发现病例3(CXZ 1704 H)与其他中国分离株不同。该分离株被置于印度次大陆分支,与最近的尼泊尔菌株相似,表明跨境传播是狂犬病感染的新来源。因此,西藏狂犬病流行的复杂混合物对西藏和全国狂犬病控制提出了新的重大挑战。
Coordinated surveillance, vaccination and public information efforts have brought the Chinese rabies epizootic under control, but significant numbers of fatalities are still reported annually with some cases occurring in previously rabies free regions. Tibet has remained virtually rabies free for 16 years, but since 2015 one human rabies case has been reported each year. To better understand the origins of these cases, we sequenced three human samples and an additional sample isolated from a dog in 2012. Three genomes were sequenced from brain samples: human case 1 (reported in 2015), human case 3 (2017), and the 2012 dog case. For human case 2 (2016), the rabies N gene was sequenced from a limited saliva sample. Phylogenetic analysis shows that Case 1 (CXZ1501H) and the dog case (CXZ1201D) belong to China IV lineage (equivalent to Arctic-like-2 in global rabies), suggesting an association with a wildlife spillover event. However, Case 2 (CXZ1601H) is placed within the dominant lineage China I, and was most similar with recent strains from neighboring Yunnan province, indicating the current epizootic has finally reached Tibet. Most surprisingly however, was the finding that Case 3 (CXZ1704H) is distinct from other Chinese isolates. This isolate is placed in the Indian Subcontinent clade, similar to recent Nepal strains, indicating that cross-border transmission is a new source for rabies infections. Thus, the complex mixture of the rabies epizootic in Tibet represents a major new challenge for Tibet and national rabies control.