基孔肯雅热的流行现况及其研究进展

基孔肯雅病毒（chikungunyavirus，CHIKV）是1种动物源性、昆虫媒介传播的病原体．自20世纪50年代被发现以来导致了大规模的基孔肯雅热的暴发。掌握该病流行特点，防止该病在我国广泛流行是当前面临的重要任务。现就基孔肯雅热全球流行情况以及临床学、媒介生物学和基孔肯雅病毒的分子流行病学等方面的研究进展作一综述。     

基孔肯雅热的流行现况及其研究进展

基孔肯雅病毒(chikungunya virus,CHIKV)是1种动物源性、昆虫媒介传播的病原体,自20世纪50年代被发现以来导致了大规模的基孔肯雅热的暴发.掌握该病流行特点,防止该病在我国广泛流行是当前面临盏的重要任务.现就基孔肯雅热全球流行情况以及临床学、媒介生物学和基孔肯雅病毒的分子流行病学等方面的研究进展作一...     

全球基孔肯雅热流行现状及分子流行病学研究进展

近几年,基孔肯雅热在东非海岸、印度洋岛屿、印度及东南亚地区广泛流行,导致数百万人感染发病,且流行地区不断扩大,发病数不断上升,成为该地区重要的公共卫生问题。掌握该病流行特点,防止该病传入我国并引起流行是当前面临的重要任务。现就基孔肯雅热全球流行情况以及临床学、媒介生物学和基孔肯雅病毒的分子流行病学等方面的研究进展做一综述。     

一例基孔肯雅病毒和寨卡病毒混合感染病例的发现

目的 对来自菲律宾的入境旅客（1例发热病例）进行病原体鉴定。方法 采集病例血液样本,提取核酸后进行基孔肯雅病毒和寨卡病毒荧光RT-PCR检测,进而接种Vero细胞分离培养病毒,细胞培养上清用荧光RT-PCR方法和宏基因组序列测定分析法进行病毒鉴定。结果 荧光RT-PCR检测结果显示,该病例存在基孔肯雅病毒和寨卡病毒感染,Ct值分别为20和26;血清样本接种Vero细胞72 h后可观察到明显的细胞病变效应,细胞培养上清的荧光RT-PCR检测和病毒宏基因组测序分析结果显示,Vero细胞中有基孔肯雅病毒和寨卡病毒。结论 该病例为基孔肯雅病毒和寨卡病毒混合感染病例。     

1例输入性基孔肯雅病例的实验室检测

目的通过系统的实验室检测发现并确认1例输入性基孔肯雅病例。方法根据基孔肯雅病毒基因序列设计引物和荧光标记探针,利用实时荧光RT-PCR和常规RT-PCR检测方法对广东出入境检验检疫局发现的1例入境发热患者的血清样本进行检测,并对RT-PCR扩增产物进行核苷酸序列测定。结果通过实时荧光RT-PCR和常规RT-PCR 2种实验方法在该病例标本中检出基孔肯雅病毒核酸;对RT-PCR扩增产物进行序列测定,测出的521个碱基与GeneBank数据库公布的基孔肯雅病毒核酸序列进行比对,结果显示同源性高达99%。结论结合该患者临床症状、实验室检测结果及流行病学调查结果,判断该病例为输入性基孔肯雅病例。     

基孔肯雅病研究进展

基孔肯雅病是由基孔肯雅病毒(Chikungunya virus,CHIKV)感染所致.该病主要经蚊虫吸血传播,其主要临床表现为发热、关节剧烈疼痛、皮疹和轻度出血体征,称为"基孔肯雅热".人群对基孔肯雅热普遍易感,任何年龄均可感染发病,当基孔肯雅热初次暴发时,可使大量人群发病[1].     

我国基孔肯雅热的流行状况

2010年10月,广东省东莞市暴发了我国首起基孔肯雅热社区聚集性疫情,打破了其长期以来以散在输入性病例为特征的流行现状。基孔肯雅热是一种由基孔肯雅病毒引起的急性传染病,伊蚊是其主要传播媒介。而我国大多数地区拥有其主要传播媒介埃及伊蚊和白纹伊蚊,一旦病原体侵入,可能暴发基孔肯雅热疫情。如何控制该疫情,防止疫情的进一步扩散,是摆在我们面前的当务之急。现就基孔肯雅病毒的病原学特征以及基孔肯雅热在我国历年的流行状况做一概述,以便更好地认识基孔肯雅热,为有效地监测和防治提供科学依据。     

基孔肯雅热诊断和治疗方案

基孔肯雅热是由基孔肯雅病毒引起，经伊蚊传播，以发热、皮疹及关节疼痛为主要特征的急性传染病。1952年首次在坦桑尼亚证实了基孔肯雅热流行，1956年分离到病毒。本病主要流行于非洲和东南亚地区，近年在印度洋地区造成了大规模流行。     

2例马来西亚籍输入性基孔肯雅热病例的实验室诊断

[目的]通过系统的实验室检测发现并确认2例输入性基孔肯雅病例。[方法]采用实时荧光逆转录（Realtime RT-PCR）、逆转录PCR（RT—PCR）检测方法对病人血清进行检测,并对RT-PGR扩增产物进行核苷酸序列测定。[结果]通过实时荧光RT—PCR、RT—PCR 2种实验方法在该病例标本中检出基孔肯雅病毒核酸;对RT-PCR扩增产物进行测序,测出的521个碱基与基孔肯雅病毒核酸序列比对,结果同源性高达99％。[结论]2病例为输入性基孔肯雅实验室确诊病例。     

基孔肯雅病毒的实时荧光RT-PCR检测方法研究

目的:建立基孔肯雅病毒的荧光定量PCR检测方法.方法:人工合成基孔肯雅病毒部分有代表性的序列核酸作为阳性对照模板,设计几组实时荧光PCR引物、探针及反应体系,摸索出最佳反应体系条件.结果:建立的基孔肯雅病毒的实时荧光PCR检测方法最佳反应体系为:正向引物CHIK-FP终浓度500 nM,反向引物CHIK-RP终浓度1000 nM,探针CHIK-Probe终浓度250 nM;扩增程序为:50℃10 min,95℃ 10 min,95℃10 s→62℃30 S 45次循环.结论:该方法灵敏度高、特异性强,适用于基孔肯雅病毒的快速检验.     

A complex adenovirus vaccine against chikungunya virus provides complete protection against viraemia and arthritis

Chikungunya virus, a mosquito-borne alphavirus, recently caused the largest epidemic ever seen for this virus. Chikungunya disease primarily manifests as a painful and debilitating arthralgia/arthritis, and no effective drug or vaccine is currently available. Here we describe a recombinant chikungunya virus vaccine comprising a non-replicating complex adenovirus vector encoding the structural polyprotein cassette of chikungunya virus. A single immunisation with this vaccine consistently induced high titres of anti-chikungunya virus antibodies that neutralised both an old Asian isolate and a Réunion Island isolate from the recent epidemic. The vaccine also completely protected mice against viraemia and arthritic disease caused by both virus isolates.     

基孔肯雅病毒与基孔肯雅热

基孔肯雅热是一种人兽共患病,是由基孔肯雅病毒（chikungunya virus,CHIKV）引起,以发热、皮疹、关节疼痛和轻度出血为主要特征的急性传染病。这种病毒病主要分布在非洲、南亚、东南亚热带和亚热带地区。近年来在印度洋地区造成大规模流行,并波及我国南方,疫区在不断扩大。埃及伊蚊和白纹伊蚊是主要传播媒介。通过携带病毒的伊蚊叮咬而传播。在实验室内可通过气溶胶传播,目前尚无直接人传人的报道。多数病人能完全痊愈,但有些病人关节疼痛持续较长时间。     

实时荧光PCR检测基孔肯雅病毒方法的建立及初步应用

目的 建立基孔肯雅病毒的荧光定量PCR检测方法.方法 针对基孔肯雅病毒的基因序列,设计、合成引物、探针及反应体系,摸索出最佳反应条件,建立TaqMan荧光探针法和SYBR荧光染料法.利用建立的方法对30例基孔肯雅热病标本和10份基孔肯雅病毒保存液进行扩增、检测和结果分析,并与常规RT - PCR方法的检测结果进行比对.结果 实时荧光定量PCR法比常规RT - PCR法快速、灵敏.40份标本TaqMan荧光探针法、SYBR荧光染料法和常规RT - PCR方法的阳性率分别为:17.5％、17.5％、15％.统计分析表明,3种方法差异不具有统计学意义.结论 实时荧光定量PCR方法快速且具有较好的特异性、敏感性、重复性,适用于基孔肯雅病毒的快速检验.     

2010年广州市越秀区首例输入性基孔肯雅热病例的调查与处理

[目的]分析广州市越秀区首例输入性基孔肯雅热病例的临床特点和流行病学特征,为预防控制基孔肯雅热提供科学依据。[方法]2010年采用描述性流行病学方法对广州市越秀区首例输入性基孔肯雅热病例的发现、诊断和应急处置等进行回顾分析和效果评价。[结果]该病例在非洲乘坐埃塞俄比亚至广州的ET606航班时发病,血液标本经广东出入境检验检疫局P3实验室检测基孔肯雅热病毒核酸阳性,为实验室确诊病例。[结论]流行病学证据显示此起疫情为输入性,防控措施及时有效,未出现二代病例。     

US Military contributions to the global response to pandemic chikungunya

Chikungunya virus, transmitted by mosquitoes to man, causes an acute illness characterized by fever, rash and striking joint symptoms. US Military investigators developed, manufactured at The Salk Institute-Government Services Division (TSI-GSD), and tested the live, attenuated Chikungunya Vaccine TSI-GSD-218. The manufacturing facility stopped production in 1994. The Chikungunya Vaccine TSI-GSD-218 development effort was terminated in 1998, and materials were archived. In 2005, an alarming outbreak of chikungunya disease began in Africa and spread to islands in the Indian Ocean and throughout much of Asia. Abrupt epidemics with high attack rates and serious, even fatal, complications were reported, and travelers carried the virus to Europe and the Americas. In response to urgent requests, the US Military offered assistance by providing non-exclusive access to the previously stored vaccine production seed materials, bulk vaccine, regulatory documentation, and reports of previous clinical trials. Five companies requested technology transfers.     

Reemergence of endemic Chikungunya, Malaysia

Chikungunya virus infection recently reemerged in Malaysia after 7 years of nondetection. Genomic sequences of recovered isolates were highly similar to those of Malaysian isolates from the 1998 outbreak. The reemergence of the infection is not part of the epidemics in other Indian Ocean countries but raises the possibility that chikungunya virus is endemic in Malaysia.     

基孔肯雅病毒荧光定量PCR检测方法的建立

目的建立一种快速、敏感、特异的实时荧光定量PCR方法,检测基孔肯雅病毒。方法通过序列比对挑选出基孔肯雅病毒基因组中高度保守的序列,在此序列上设计引物及TaqMan探针,建立实时荧光定量PCR反应体系。结果经优化的荧光定量PCR方法有较好的灵敏度和特异性,对阳性对照质粒标准品的灵敏度可达21拷贝/μl,通过检测与传播媒介相似的流行性乙型脑炎病毒、黄热病毒、登革热病毒无交叉反应。结论该方法的建立在基孔肯雅热的疾病防控方面有较好的应用前景。     

Genetic characterization of Chikungunya virus in the Central African Republic

Chikungunya virus (CHIKV) is an alphavirus transmitted by the bite of mosquito vectors. Over the past 10 years, the virus has gained mutations that enhance its transmissibility by the Aedes albopictus vector, resulting in massive outbreaks in the Indian Ocean, Asia and Central Africa. Recent introduction of competent A. albopictus vectors into the Central African Republic (CAR) pose a threat of a Chikungunya fever (CHIKF) epidemic in this region. We undertook this study to assess the genetic diversity and background of CHIKV strains isolated in the CAR between 1975 and 1984 and also to estimate the ability of local strains to adapt to A. albopictus. Our results suggest that, local CHIKV strains have a genetic background compatible with quick adaptation to A. albopictus, as previously observed in other Central African countries.Intense surveillance of the human and vector populations is necessary to prevent or anticipate the emergence of a massive CHIKF epidemic in the CAR.     

Status of research and development of vaccines for chikungunya

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during the last decade has significantly expanded its geographical range and caused large outbreaks of human disease around the world. Although mortality rates associated with CHIKV outbreaks are low, acute and chronic illnesses caused by CHIKV represent a significant burden of disease largely affecting low and middle income countries. This report summarizes the current status of vaccine development for CHIKV.