福州口岸入境船舶上首次发现埃及伊蚊及其携带的病原体

[目的]通过加强入境船舶医学媒介监测,防止新蚊种、蚊媒传染病传入和传播。[方法]对入境船舶的积水容器进行蚊幼虫监测,并采样送实验室进行形态学鉴定,登革热、黄热病、基孔肯雅热等病原检测,对船舶实施灭蚊等卫生处理,对船员施行流行病学调查、体温检测、医学检查等措施。[结果]全船发现9处积水,1处蚊幼虫阳性,积水4000ml,幼虫70条,羽化后经实验室鉴定该蚊幼虫均为埃及伊蚊,未检出登革热、基孔肯雅、西尼罗、乙脑等病毒。对该轮船员进行流行病学调查、医学检查,未发现登革、基孔肯雅热、乙型脑炎、西尼罗热、黄热病等病人。对船舶实施灭蚊等卫生处理措施后,未再发现成蚊和蚊幼虫。[结论]埃及伊蚊属福州地区外来蚊种,是传播黄热病、登革热等热带病的重要媒介。提示福州口岸应提高防范意识,特别应加强来自蚊媒传染病疫区船舶的蚊媒监测、卫生处理工作。     

Zika virus as an emerging arbovirus of international public health concern

Zika virus (ZIKV) was identified in 1947 in a rhesus monkey during an investigation of the yellow fever virus in the Zika Forest of Uganda; it was also isolated later from humans in Nigeria. The main distribution areas of ZIKV were the African mainland and South-East Asia in the 1980s, Micronesia in 2007, and more recently the Americas in 2014. ZIKV belongs to the Flaviviridae family and Flavivirus genus. ZIKV infection, which is transmitted by Aedes mosquitoes, is an emerging arbovirus disease. The clinical symptoms of ZIKV infection are fever, headache, rashes, arthralgia, and conjunctivitis, which clinically resemble dengue fever syndrome. Sometimes, ZIKV infection has been associated with Guillain-Barré syndrome and microcephaly. At the end of 2015, following an increase in cases of ZIKV infection associated with Guillain-Barré syndrome and microcephaly in newborns in Brazil, the World Health Organization declared a global emergency. Therefore, considering the global distribution and pathogenic nature of this virus, the current study aimed at reviewing the virologic features, transmission patterns, clinical manifestations, diagnosis, treatment, and prevention of ZIKV infection.     

A review of successful flavivirus vaccines and the problems with those flaviviruses for which vaccines are not yet available

Genus flavivirus comprises many important human pathogens causing public health problems worldwide. Some flavivirus infections are characterized by a relatively high mortality rate and/or high sequelae rate in survivors. Because most flavivirus life cycles are maintained between arthropod vectors and amplifying/reservoir hosts in the absence of humans, eradication of flaviviruses might be extremely difficult. Flavivirus vaccine development is considered a reasonable method to prevent flavivirus infections. Some vaccines have been successfully developed, but others have not, regardless of much effort. This review article describes currently available flavivirus vaccines against yellow fever, Japanese encephalitis, and tick-borne encephalitis. In addition, the current status of dengue and West Nile virus vaccine development is reviewed and problems regarding their development are discussed.     

Muddying the waters: A political ecology of mosquito-borne disease in coastal Ecuador

The mosquito-borne arboviral diseases dengue, chikungunya, and Zika are major public health burdens in Latin America. To analyze the socio-environmental dynamics of these diseases, we apply a political ecology of health and disease framework that is attentive to local etiological frameworks, structural sociopolitical conditions, processes of identity construction, and the contested, politicized nature of public health work. We use multiple qualitative methods to analyze perceptions and interactions with the local environment in relation to mosquito-borne disease across three small communities in Manabí Province, Ecuador. We find that participants' perceptions and practices are complex and multilayered: subjects possess a mixed theory of causation, where these diseases are caused not only by mosquitoes, but also by people's interactions with a changing environment; most environmental management to control vector mosquitoes is carried out informally by women as part of domestic routines; and contrary to public health messaging that stresses the importance of individual agency, participants prefer some of the most invasive techniques for mosquito control (i.e. fumigation with insecticides). However, individual agency in disease control is constrained by poor water infrastructure and lack of public health coordination. Our approach advocates for recognition of local knowledges and sociopolitical constraints in the development of public health messages and interventions.     

西尼罗热研究进展

西尼罗病毒属黄病毒科,为单股正链RNA病毒。它感染人类导致发展为西尼罗热。主要宿主动物为鸟类,蚊虫为传播媒介。该病在欧洲及中亚地区散发,小规模流行,于1999年在美国暴发流行及随后在北美的流行引起极大关注。另外,蚊虫叮咬以外的传播途径,如输血、器官移植、母婴传播等日益受到人们的重视,且目前还没有预防该病的疫苗。该病具有传染性强,重症病例多和病死率高的特点,对人类健康和生命安全造成较大威胁。现就西尼罗热的病原学、流行病学、临床学、实验室诊断及预防控制的研究进展做一综述。     

一起登革热和一起基孔肯雅热暴发疫情的对比分析

目的 了解登革热和基孔肯雅热这两种伊蚊传播疾病的流行病学特征和临床特征异同点,为预防控制这两种疾病提供依据.方法 采用问卷调查和查阅患者就诊资料的方法,搜集东莞市2010年发生的一起登革热和一起基孔肯雅热社区暴发疫情的流行病学特征和临床特征资料并进行对比分析.结果 两起疫情共同点为:输入性疫情;发生在夏秋季节;具有一定的家庭聚集性;发生疫情的社区蚊媒密度高;采取以杀灭成蚊和清除伊蚊孳生地为主的综合性防控措施可有效控制疫情;登革热和基孔肯雅热临床表现类似,以发热、疼痛为主.两起疫情的不同点:与登革热暴发疫情相比,基孔肯雅热暴发疫情强度更大、扩散范围更广、家庭聚集性更强,但疫情持续时间短;在临床表现方面,基孔肯雅热患者关节痛、皮疹、肌肉痛的发生率高于登革热患者,而登革热患者头痛、白细胞减少、血小板减少的发生率高于基孔肯雅热患者.结论 登革热和基孔肯雅热的流行病学和临床特征类似.但与登革热相比,基孔肯雅热传播能力更强;病人更常见关节痛、皮疹,而白细胞、血小板则多正常.     

应用DPO引物技术同时检测5种蚊媒病毒的多重RT-PCR方法

目的应用双启动寡核苷酸引物(Dual Priming Oligonucleotide,DPO)技术建立同时检测日本脑炎病毒(JapaneseEncephalitisVirus,JEV)、黄热病毒(YellowFeverVirus,YFV)、西尼罗病毒(WestNileVirus,WNV)、圣路易斯脑炎病毒(St.Louis encephalitis virus,SLEV)和登革病毒(Dengue virus,DV)5种蚊媒病毒的多重RT-PCR方法。方法利用Primer Premier5.0软件设计5种病毒的特异性DPO引物,对引物浓度、Mg2+浓度和退火温度进行优化,测定多重RT-PCR反应的特异性和敏感性。结果应用DPO引物技术建立的多重RT-PCR方法可特异性扩增JEV、YFV、WNV、SLEV和DV的142 bp、293 bp、377 bp、630 bp和521 bp基因片段,灵敏度分别为5 000 PFU/ml、4 500 PFU/ml、2.3×105copies/μl、2.6×104copies/μl和1.37×104copies/μl,蚊虫模拟添加实验未发生非特异反应。结论应用DPO引物技术建立的针对5种蚊媒病毒的多重RT-PCR检测方法有良好的敏感性和特异性,可以同时对JEV、YFV、WNV、SLEV和DV进行检测。     

Arbovirus prevalence in mosquitoes, Kenya

Few studies have investigated the many mosquito species that harbor arboviruses in Kenya. During the 2006-2007 Rift Valley fever outbreak in North Eastern Province, Kenya, exophilic mosquitoes were collected from homesteads within 2 affected areas: Gumarey (rural) and Sogan-Godud (urban). Mosquitoes (n = 920) were pooled by trap location and tested for Rift Valley fever virus and West Nile virus. The most common mosquitoes trapped belonged to the genus Culex (75%). Of 105 mosquito pools tested, 22% were positive for Rift Valley fever virus, 18% were positive for West Nile virus, and 3% were positive for both. Estimated mosquito minimum infection rates did not differ between locations. Our data demonstrate the local abundance of mosquitoes that could propagate arboviral infections in Kenya and the high prevalence of vector arbovirus positivity during a Rift Valley fever outbreak.     

Inflammasome signaling pathways exert antiviral effect against Chikungunya virus in human dermal fibroblasts

Arboviruses represent an emerging threat to human. They are transmitted to vertebrates by the bite of infected arthropods. Early transmission to vertebrates is initiated by skin puncture and deposition of virus in this organ. However, events at the bite site remain largely unknown. Here, we report that Chikungunya virus (CHIKV) and West Nile virus (WNV), despite belonging to distinct viral families, elicit a common antiviral signature in primary human dermal fibroblasts, attesting for the up regulation of interferon signaling pathways and leading to an increased expression of IFN-β, interleukins and chemokines. Remarkably, CHIKV and WNV enhance IL-1β expression and induce maturation of caspase-1, indicating the capacity of these pathogens to elicit activation of the inflammasome program in resident skin cells. CHIKV and WNV also induce the expression of the inflammasome sensor AIM2 in dermal fibroblasts, whereas inhibition of caspase-1 and AIM2 with siRNA interferes with both CHIKV- and WNV-induced IL-1β production by these cells. Finally, inhibition of the inflammasome via caspase-1 silencing was found to enhance CHIKV replication in dermal fibroblasts. Together, these results indicate that the skin contributes to the pro-inflammatory and anti-viral microenvironment via the activation of the inflammasome in the early stages following infection with arboviruses.     

Fever versus fever: The role of host and vector susceptibility and interspecific competition in shaping the current and future distributions of the sylvatic cycles of dengue virus and yellow fever virus

Two different species of flaviviruses, dengue virus (DENV) and yellow fever virus (YFV), that originated in sylvatic cycles maintained in non-human primates and forest-dwelling mosquitoes have emerged repeatedly into sustained human-to-human transmission by Aedes aegypti mosquitoes. Sylvatic cycles of both viruses remain active, and where the two viruses overlap in West Africa they utilize similar suites of monkeys and Aedes mosquitoes. These extensive similarities render the differences in the biogeography and epidemiology of the two viruses all the more striking. First, the sylvatic cycle of YFV originated in Africa and was introduced into the New World, probably as a result of the slave trade, but is absent in Asia; in contrast, sylvatic DENV likely originated in Asia and has spread to Africa but not to the New World. Second, while sylvatic YFV can emerge into extensive urban outbreaks in humans, these invariably die out, whereas four different types of DENV have established human transmission cycles that are ecologically and evolutionarily distinct from their sylvatic ancestors. Finally, transmission of YFV among humans has been documented only in Africa and the Americas, whereas DENV is transmitted among humans across most of the range of competent Aedes vectors, which in the last decade has included every continent save Antarctica. This review summarizes current understanding of sylvatic transmission cycles of YFV and DENV, considers possible explanations for their disjunct distributions, and speculates on the potential consequences of future establishment of a sylvatic cycle of DENV in the Americas.     

First report of chikungunya from the Maldives

An outbreak, characterised by fever, arthralgia and myalgia, in Malé and other islands of the Maldives began in December 2006. The illness was suspected as being due to chikungunya virus based on clinical symptoms and the prevailing chikungunya epidemic in the Indian Ocean region. The Department of Public Health initiated an investigation and collected blood samples from 67 patients; 21% were IgM-positive for chikungunya and 96% were PCR-positive. Six percent were positive for dengue by enzyme immunosorbent assay and 4% had evidence of dual infection. This is the first time that chikungunya fever has been confirmed in the Maldives. A total of 11,879 suspected and confirmed cases affecting 61% of inhabited islands (attack rate ranging from 0% to 72% on individual islands) were reported by the end of the epidemic in April 2007.     

Follow-up of 2003 human West Nile virus infections, Denver, Colorado

Tri-County Health Department and Boulder County Public Health conducted a follow-up study of all nonfatal West Nile virus (WNV) cases reported during 2003 in 4 metropolitan Denver, Colorado, counties. Self-reported patient information was obtained approximately 6 months after onset. A total of 656 (81.2%) eligible WNV patients are included in this study.     

Coping and health behaviours in times of global health crises: Lessons from SARS and West Nile

Abstract

We examined perceived threats of Severe Acute Respiratory Syndrome and West Nile Virus using an Internet-based questionnaire. Higher levels of perceived threats of diseases were associated with increases in a variety of ways of coping, including empathic responding and wishful thinking. In turn, we examined how coping with the perceived health threat was related to two specific health related behaviours: taking recommended precautions, and avoiding people in an attempt to avoid disease. The findings from linear regression indicated that empathic responding, in response to the threat of a virulent agent, was related to taking recommended and effective health precautions. On the other hand, wishful thinking was associated with those behaviours that may potentially lead to economic hardship in afflicted areas, such as avoiding people perceived to be at risk for an infectious agent. Implications for health promotion are discussed.     

Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue,West Nile and Japanese encephalitis viruses

Dengue viruses (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV) are major global health and growing medical problems. While a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (YFV), there is an urgent need for vaccines against dengue or West Nile diseases, and for improved vaccines against Japanese encephalitis. Live-attenuated chimeric viruses were constructed by replacing the genes coding for Premembrane (prM) and Envelope (E) proteins from YFV 17D vaccine strain with those of heterologous flaviviruses (ChimeriVax™ technology). This technology has been used to produce vaccine candidates for humans, for construction of a horse vaccine for West Nile fever, and as diagnostic reagents for dengue, Japanese encephalitis, West Nile and St. Louis encephalitis infections. This review focuses on human vaccines and their characterization from the early stages of research through to clinical development. Phenotypic and genetic properties and stability were examined, preclinical evaluation through in vitro or animal models, and clinical testing were carried out. Theoretical environmental concerns linked to the live and genetically modified nature of these vaccines have been carefully addressed. Results of the extensive characterizations are in accordance with the immunogenicity and excellent safety profile of the ChimeriVax™-based vaccine candidates, and support their development towards large-scale efficacy trials and registration.     

A plant-produced vaccine protects mice against lethal West Nile virus infection without enhancing Zika or dengue virus infectivity

West Nile virus (WNV) has caused multiple global outbreaks with increased frequency of neuroinvasive disease in recent years. Despite many years of research, there are no licensed therapeutics or vaccines available for human use. One of the major impediments of vaccine development against WNV is the potential enhancement of infection by related flaviviruses in vaccinated subjects through the mechanism of antibody-dependent enhancement of infection (ADE). For instance, the recent finding of enhancement of Zika virus (ZIKV) infection by pre-exposure to WNV further complicates the development of WNV vaccines. Epidemics of WNV and the potential risk of ADE by current vaccine candidates demand the development of effective and safe vaccines. We have previously reported that the domain III (DIII) of the WNV envelope protein can be readily expressed in Nicotiana benthamiana leaves, purified to homogeneity, and promote antigen-specific antibody response in mice. Herein, we further investigated the in vivo potency of a plant-made DIII (plant-DIII) in providing protective immunity against WNV infection. Furthermore, we examined if vaccination with plant-DIII would enhance the risk of a subsequent infection by ZIKV and Dengue virus (DENV). Plant-DIII vaccination evoked antigen-specific cellular immune responses as well as humoral responses. DIII-specific antibodies were neutralizing and the neutralization titers met the threshold correlated with protective immunity by vaccines against multiple flaviviruses. Furthermore, passive administration of anti-plant DIII mouse serum provided full protection against a lethal challenge of WNV infection in mice. Notably, plant DIII-induced antibodies did not enhance ZIKV and DENV infection in Fc gamma receptor-expressing cells, addressing the concern of WNV vaccines in inducing cross-reactive antibodies and sensitizing subjects to subsequent infection by heterologous flavivirus. This study provides the first report of a WNV subunit vaccine that induces protective immunity, while circumventing induction of antibodies with enhancing activity for ZIKV and DENV infection.     

西尼罗病毒感染的抗体检测方法研究进展

病毒核酸编码3种结构蛋白和7种非结构蛋     

发热伴血小板减少综合征的流行病学研究进展

目的调查苏州市丘陵山地风景区蜱的地理分布及其病原体携带感染率,旨在评估和预警该地区蜱传疾病的传播风险。方法利用人工布旗法和动物体表采集法采集游离蜱和寄生蜱,采用PCR方法检测蜱体内巴贝虫、斑点热群立克次体、伯氏疏螺旋体、蜱传脑炎病毒和发热伴血小板减少综合征布尼亚病毒(SFTSV)核酸。结果共捕蜱148只,隶属于1科3属4种,分别为长角血蜱(占47.3%)、中华血蜱(占49.3%)、血红扇头蜱(占2.0%)及微小牛蜱(占1.4%)。蜱标本中巴贝虫、伯氏疏螺旋体、蜱传脑炎和发热伴血小板减少综合征布尼亚病毒核酸检测均为阴性;斑点热群立克次体核酸检测阳性,最小感染率为2.8%。结论该地区蜱分布广泛,种类以长角血蜱和中华血蜱为主;部分蜱携带有斑点热群立克次体,应加强斑点热群立克次体的监控和研究。     

West Nile fever outbreak in horses and humans, Spain, 2010

TO THE EDITOR: West Nile virus (WNV) is a member of the genus Flavivirus within the Japanese encephalitis antigenic complex. The enzootic virus cycle involves transmission between avian hosts and ornithophilic mosquitoes, whereas humans and horses are considered dead-end hosts. Given the recent increase of WNV infection in humans and horses in Europe, concern has been raised regarding public and animal health.     

Purification of flavivirus VLPs by a two-step chomatographic process

Flaviviruses are enveloped viruses with positive-sense, single-stranded RNA, which are most commonly transmitted by infected mosquitoes. Zika virus (ZIKV) and yellow fever virus (YFV) are flaviviruses that have caused significant outbreaks in the last few years. Since there is no approved vaccine against ZIKV, and since the existing YF attenuated vaccine presents disadvantages related to limited supply and to rare, but fatal adverse effects, there is an urgent need for new vaccines to control these diseases. Virus-like particles (VLPs) represent a recombinant platform to produce safe and immunogenic vaccines. Thus, based on our experience of expressing in recombinant mammalian cells VLPs of most flaviviruses circulating in the Americas, this work focused on the evaluation of chromatographic purification processes for zika and yellow-fever VLPs. The clarified cell culture supernatant was processed by a membrane-based anion-exchange chromatography and then a multimodal chromatographic step. With this process, it was possible to obtain the purified VLPs with a yield (including the clarification step) of 66.4% for zika and 68.1% for yellow fever. DNA clearance was in the range of 99.8–99.9%, providing VLP preparations that meet the WHO limit for this critical contaminant. Correct size and morphology of the purified VLPs were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The promising results obtained for both zika and yellow fever VLPs indicate that this process could be potentially applied also to VLPs of other flaviviruses.     

Understanding social inequalities in Zika infection and its consequences: A model of pathways and policy entry-points

The health consequences of arbovirus infections such as dengue fever (DENV), Chikungunya (CHIKV) and Zika (ZIKV) has in recent years become a public health challenge, due to failure of prevention followed by increased incidence and pronounced social inequality in occurrence and consequences. This motivates a more systematic analysis of the potential mechanisms and pathways that generate these inequalities. We present in the paper a model that delineates five possible mechanisms driving the inequality of ZIKV and congenital Zika syndrome (CZS). They include differential exposure to bad housing and sanitary conditions, differential exposure to vector density and virus, differential vulnerability to the health effects of exposure to virus, differential intrauterine susceptibility to the teratogenic effects of ZIKV infection and differential social consequences of caring for a disabled child. For each mechanism, we present empirical evidence or need for more research as well as a discussion about policy implications.