Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data.
Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data.
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DOI：
10.1371/journal.pntd.0004687
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发表时间：
2016-04
影响因子：
3.8
通讯作者：
Morris JG Jr
中科院分区：
文献类型：
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作者：
Lednicky J;Beau De Rochars VM;El Badry M;Loeb J;Telisma T;Chavannes S;Anilis G;Cella E;Ciccozzi M;Rashid M;Okech B;Salemi M;Morris JG Jr
寨卡病毒（ZIKV）于1947年首次在乌干达分离出来，目前正在南美洲和加勒比地区迅速蔓延。在巴西，感染与小头症和其他严重并发症有关，导致宣布为国际关注的突发公共卫生事件;然而，目前关于加勒比地区该病毒（及其可能的来源和表现）的数据有限。从2014年5月至2015年2月，结合基孔肯雅（CHIKV）和登革热（DENV）病毒感染的研究，从海地格雷西耶/Leogane地区的儿童中收集血液样本，这些儿童因未分化的发热性疾病而到学校诊所就诊。首先通过RT-PCR筛选样品的CHIKV和DENV，通过病毒培养进一步筛选这些测定中阴性的样品。在筛选的177个样品中，通过病毒测序证实，三个对ZIKV呈阳性;还在来自三个阳性病例患者之一的培养物中鉴定出DENV-1。患者来自两所不同的学校和三个不同的城镇，所有三例病例都发生在一周内，与该地区暴发的情况一致。已知全基因组病毒序列的系统发育分析表明与来自巴西的ZIKV有密切关系;对NS 5基因的额外分析（目前有更多序列可供使用）显示，海地菌株聚类在一个不同于巴西、波多黎各和危地马拉序列的单系进化枝内，一个更大进化枝的所有部分包括来自复活节岛的分离株。系统地理学还澄清了至少存在三个主要的非洲亚系，并证实南美流行病最有可能起源于最初的ZIKV从法属波利尼西亚引入复活节岛，然后再到美洲的其余部分。ZIKV在南美洲和非洲的流行显示出复杂的传播模式。该病毒似乎在巴西首次报告病例之前就已在海地传播。导致传播的因素以及海地早期疫情与小头畸形症的可能联系仍有待确定。寨卡病毒目前正在包括加勒比在内的美洲迅速蔓延，由于与包括小头畸形在内的出生缺陷有关，寨卡病毒已成为一个主要的公共卫生问题。我们报告了2014年12月从海地农村的3名儿童中分离出寨卡病毒，作为我们研究小组正在进行的急性未分化发热性疾病研究的一部分;从其中一名儿童中，我们还分离出登革热病毒血清型1。在对这些和来自其他地区的寨卡病毒株的核苷酸序列数据进行分析后，南美洲/海地序列在亚洲分支中聚类，并且明显地从复活节岛上流传的序列中分支出来，而复活节岛又起源于法属波利尼西亚。在进一步分析一个特定的基因序列时，有更多的数据可用，海地菌株和来自巴西，苏里南，波多黎各和危地马拉的菌株似乎略有分离，分子钟分析表明，寨卡病毒早在2013年年中就存在于海地。这些发现提出了关于寨卡病毒在加勒比地区起源的问题，以及该病毒随后在美洲传播的模式。
Zika virus (ZIKV), first isolated in Uganda in 1947, is currently spreading rapidly through South America and the Caribbean. In Brazil, infection has been linked with microcephaly and other serious complications, leading to declaration of a public health emergency of international concern; however, there currently are only limited data on the virus (and its possible sources and manifestations) in the Caribbean. From May, 2014-February, 2015, in conjunction with studies of chikungunya (CHIKV) and dengue (DENV) virus infections, blood samples were collected from children in the Gressier/Leogane region of Haiti who presented to a school clinic with undifferentiated febrile illness. Samples were initially screened by RT-PCR for CHIKV and DENV, with samples negative in these assays further screened by viral culture. Of 177 samples screened, three were positive for ZIKV, confirmed by viral sequencing; DENV-1 was also identified in culture from one of the three positive case patients. Patients were from two different schools and 3 different towns, with all three cases occurring within a single week, consistent with the occurrence of an outbreak in the region. Phylogenetic analysis of known full genome viral sequences demonstrated a close relationship with ZIKV from Brazil; additional analysis of the NS5 gene, for which more sequences are currently available, showed the Haitian strains clustering within a monophyletic clade distinct from Brazilian, Puerto Rican and Guatemalan sequences, with all part of a larger clade including isolates from Easter Island. Phylogeography also clarified that at least three major African sub-lineages exist, and confirmed that the South American epidemic is most likely to have originated from an initial ZIKV introduction from French Polynesia into Easter Island, and then to the remainder of the Americas. ZIKV epidemics in South America, as well as in Africa, show complex dissemination patterns. The virus appears to have been circulating in Haiti prior to the first reported cases in Brazil. Factors contributing to transmission and the possible linkage of this early Haitian outbreak with microcephaly remain to be determined. Zika virus is currently spreading rapidly through the Americas, including the Caribbean, where it has emerged as a major public health problem due to the linkage with birth defects, including microcephaly. We report the isolation of Zika virus from 3 children in rural Haiti in December, 2014, as part of a study of acute undifferentiated febrile illness that was being conducted by our research group; from one of these children, we also isolated dengue virus serotype 1. On analysis of nucleotide sequence data from these and Zika strains from other locales, the South American/Haitian sequences cluster within the Asian clade and clearly branch out from a sequence circulating in Easter Island, which originated, in turn, from French Polynesia. On further analysis of one specific gene sequence for which more data were available, there appeared to be slight separation of Haitian strains and the strains from Brazil, Suriname, Puerto Rico and Guatemala, with molecular clock analysis suggesting that Zika virus was present in Haiti as early as mid-2013. These findings raise questions about the origin of Zika virus in the Caribbean, and subsequent patterns of circulation of the virus within the Americas.