Potential impact of climate change on emerging vector-borne and other infections in the UK

Climate is one of several causes of disease emergence. Although half or more of infectious diseases are affected by climate it appears to be a relatively infrequent cause of human disease emergence. Climate mostly affects diseases caused by pathogens that spend part of their lifecycle outside of the host, exposed to the environment. The most important routes of transmission of climate sensitive diseases are by arthropod (insect and tick) vectors, in water and in food. Given the sensitivity of many diseases to climate, it is very likely that at least some will respond to future climate change. In the case of vector-borne diseases this response will include spread to new areas. Several vector-borne diseases have emerged in Europe in recent years; these include vivax malaria, West Nile fever, dengue fever, Chikungunya fever, leishmaniasis, Lyme disease and tick-borne encephalitis. The vectors of these diseases are mosquitoes, sand flies and ticks. The UK has endemic mosquito species capable of transmitting malaria and probably other pathogens, and ticks that transmit Lyme disease. The UK is also threatened by invasive mosquito species known to be able to transmit West Nile, dengue, chikungunya and Zika, and sand flies that spread leishmaniasis. Warmer temperatures in the future will increase the suitability of the UK’s climate for these invasive species, and increase the risk that they may spread disease. While much attention is on invasive species, it is important to recognize the threat presented by native species too. Proposed actions to reduce the future impact of emerging vector-borne diseases in the UK include insect control activity at points of entry of vehicles and certain goods, wider surveillance for mosquitoes and sand flies, research into the threat posed by native species, increased awareness of the medical profession of the threat posed by specific diseases, regular risk assessments, and increased preparedness for the occurrence of a disease emergency.     

Epidemiological processes involved in the emergence of vector-borne diseases: West Nile fever, Rift Valley fever, Japanese encephalitis and Crimean-Congo haemorrhagic fever

Over the past few decades, the geographical distribution of arthropod-borne zoonoses has dramatically expanded. The influence of human-induced or ecological changes on the risk of disease outbreaks is undeniable. However, few hypotheses have been proposed which address the re-emergence of these diseases, the spread of these viruses to previously uninfected areas and their establishment therein. Host and vector movements play an important role in the dissemination of pathogens, and the ability of these diseases to colonise previously uninfected areas may be explained by the diversity of hosts and vectors, the presence of favourable ecological conditions, and the successful adaptations of vectors or pathogens to new ecosystems. The objective of this paper is to describe the epidemiological processes of the vector-borne diseases Rift Valley fever, West Nile fever, Japanese encephalitis and Crimean-Congo haemorrhagic fever.     

Potential arbovirus emergence and implications for the United Kingdom

Arboviruses have evolved a number of strategies to survive environmental challenges. This review examines the factors that may determine arbovirus emergence, provides examples of arboviruses that have emerged into new habitats, reviews the arbovirus situation in western Europe in detail, discusses potential arthropod vectors, and attempts to predict the risk for arbovirus emergence in the United Kingdom. We conclude that climate change is probably the most important requirement for the emergence of arthropodborne diseases such as dengue fever, yellow fever, Rift Valley fever, Japanese encephalitis, Crimean-Congo hemorrhagic fever, bluetongue, and African horse sickness in the United Kingdom. While other arboviruses, such as West Nile virus, Sindbis virus, Tahyna virus, and Louping ill virus, apparently circulate in the United Kingdom, they do not appear to present an imminent threat to humans or animals.     

Climate change and animal diseases in South America

Climate strongly affects agriculture and livestock production and influences animal diseases, vectors and pathogens, and their habitat. Global warming trends predicted in the 2007 Intergovernmental Panel on Climatic Change (IPCC) report for South America are likely to change the temporal and geographical distribution of infectious diseases, including those that are vector-borne such as bluetongue, West Nile fever, vesicular stomatitis and New World screwworm. Changes in distribution will be partially modulated by El Ni?o Southern Oscillation events, which will become more frequent and lead to a greater frequency of droughts and floods. Active disease surveillance for animal diseases in South America, particularly for vector-borne diseases, is very poor. Disease reporting is often lacking, which affects knowledge of disease distribution and impact, and preparedness for early response. Improved reporting for animal diseases that may be affected by climate change is needed for better prevention and intervention measures in susceptible livestock, wildlife and vectors in South America. This requires contributions from multidisciplinary experts, including meteorologists, epidemiologists, biologists and ecologists, and from local communities.     

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.     

Wichtige,durch Vektoren übertragene Infektionskrankheiten beim Menschen in Deutschland

Vector-borne infections pathogenic to humans play an important role in Germany. The relevant zoonotic pathogens are either endemic throughout Germany (e.g. Borrelia burgdorferi sensu latu) or only in specific regions, e.g. tick-borne encephalitis (TBE) virus and hantavirus. They cause a substantial burden of disease. Prevention and control largely rely on public advice and the application of personal protective measures (e.g. TBE virus vaccination and protection against vectors). High quality surveillance and targeted epidemiological studies are fundamental for the evaluation of temporal and spatial risks of infection and the effectiveness of preventive measures. Aside from endemic pathogens, vector-borne infections acquired abroad, mostly transmitted by mosquitoes, have to be systematically and intensively monitored as well, to assess the risk of infection for German residents traveling abroad and to adequately evaluate the risk of autochthonous transmission. Related issues, such as invasive species of mosquitoes in Germany and climate change, have to be taken into consideration. Such pathogens include West Nile, dengue and chikungunya viruses, as well as malaria parasites (Plasmodium species). The article presents an overview of the epidemiological situation of selected relevant vector-borne infections in Germany.     

蓖麻提取物在病媒生物防治中的应用进展

病媒生物可传播鼠疫、黄热病、疟疾和登革热／登革出血热等多种重要的虫媒传染病,对人类的健康安全构成巨大威胁,因此,病媒生物的防制意义重大。蓖麻提取物具有良好的杀虫效果,有望作为一种生物农药应用于农业虫害的防治,但其在病媒生物防制中的应用研究甚少。本文就蓖麻提取物在病媒生物防制中的应用进行简要论述,并阐明其目前存在的主要问题。     

天津市主要媒介生物传播相关疾病风险评估

目的应用风险识别与评估方法,评估天津市病媒生物传播疾病发生的风险,避免媒介生物性传染病的发生或流行。方法通过综合分析风险性事件发生的概率和事件发生后造成的后果,对风险进行分级。结果2008--2012年天津市蚊和鼠密度监测结果显示,鼠密度呈逐年下降（0．64％~0．19％）,捕获鼠鼠疫F1抗体间接血凝试验检测均为阴性,检测肾综合征出血热（HFRS）病毒2011年为0．85％,2012年为阴性;蚊密度年平均密度分别为14．11、15．04、16．64、18．82和11．09只／（灯·h）,近年来蚊虫携带病原微生物检测均为阴性。天津市蚊媒传播的主要疾病疟疾、登革热、流行性乙型脑炎及鼠类传播的疾病鼠疫、HFRS的发生流行尚属低风险级别。结论天津市存在发生媒介生物性传染病的风险,日常应加强媒介生物密度及主要媒介病原生物携带的监测,对居民加强相关知识的宣传,适量储备相关药械,以预防和控制传染病发生与流行。     

广州市2006-2012年重点媒介传染病流行特征分析

目的 探讨广州市重点媒介传染病流行病学特征,为媒介传染病防控提供科学依据.方法 从国家疾病监测信息报告管理信息系统中收集广州市2006-2012年重点媒介传染病报告病例基本信息以及个案调查流行病学信息,用描述性流行病学方法分析广州市重点媒介传染病的流行病学特征.结果 2006-2012年,广州市共报告6种媒介传染病5828例,其中肾综合征出血热（HFRS）、登革热、钩端螺旋体（钩体）病、疟疾、流行性乙型脑炎（乙脑）和恙虫病年平均发病率分别为1.01/10万、1.37/10万、0.10/10万、0.18/10万、0.02/10万和4.72/10万.登革热和恙虫病发病季节性特征明显,中心城区HFRS和登革热发病构成比较大,钩体病、疟疾、乙脑和恙虫病发病以城乡结合部和农村区域为主,除乙脑发病以儿童为主外,其余各媒介传染病发病职业分布广泛,年龄以中老年为主.结论 广州市媒介传染病发病整体相对平稳,但近年来有小幅上升趋势,发病风险仍然存在,应加强监测和预防控制工作.     

气候变暖对虫媒传染病影响的研究进展

全球气候变暖对虫媒的影响主要表现在改变虫媒的地区分布,增加虫媒繁殖速度与侵袭力和缩短病原体的外潜伏期。大量资料显示,全球气候变暖的趋势使得许多热带生物不断扩大分布范围,过去仅在热带地区出现的虫媒传染病,也频频出现在亚热带地区。媒介生物性疾病近年在全球呈上升趋势,一些原有的虫媒传染病再度暴发,新的虫媒传染病流行范围不断扩大。受气候变化影响较大的虫媒传染病包括疟疾、血吸虫病、鼠疫、登革热和其他及新发虫媒传染病。提示要面对气候变暖的趋势,努力减缓和控制地球气温的上升,保护好自然环境,加强气候与虫媒传染病传播关系的研究,做好虫媒传染疾病的预防控制工作。     

Fièvre jaune,dengue, encéphalite japonaise et virose West Nile, 4 arboviroses majeures

Yellow fever, Dengue, Japanese encephalitis, and West Nile virus infection are induced by 4 strongly epidemic major arboviruses. Despite its vaccine, yellow fever remains very active in tropical Africa and in South America. The insufficient immunization coverage and population mobility explain the permanence of the epidemics. Vaccination is essential for travelers going to endemic regions. The prevalence of dengue has increased considerably in the last decades. The number of countries concerned with its hemorrhagic forms is also increasing. It is the most frequently observed arbovirus disease in travelers. Widespread in Asia, Japanese encephalitis can be prevented by a specific vaccination. The development of tourism to endemic areas raises the issue of risks for travelers and what preventive measures may be available. The West Nile virus has been present in North America since 1999. There, it caused the most severe epidemic ever observed, in the summer 2002. The clinical expression of the disease has changed over the last 10 years. Initially regarded as a benign virus, it is now considered as being able to cause neurological forms with a high death rate, particularly in elderly people.     

Durch Zecken übertragene humanpathogene und bisher als apathogen geltende Mikroorganismen in Europa

The importance of tick-borne encephalitis (TBE) and Lyme borreliosis-the main European tick-borne diseases-is steadily growing. This fact is due to many different factors including climate changes. However, across Europe many other human pathogenic viruses, bacteria, and parasites are found in ticks. This article gives an overview of tick-borne human pathogenic viruses present in Europe as well as those considered nonpathogenic. It also deals with the various species of vector-competent ticks. Among these ticks, viruses from 6 families encompassing 8 genera and 35 species are found,whereby the families Flaviviridae, Bunyaviridae, and Reoviridae with the genera flavivirus, nairovirus, and orbivirus are the most prevalent. Because of their special importance Omsk hemorrhagic fever, louping-ill disease, tick-borne encephalitis, and Crimean-Congo hemorrhagic fever are discussed in detail. Although West Nile virus is mainly transmitted to man by mosquitoes, it is discussed in detail, because West Nile fever has become a good example for a new and rapidly spreading vector-borne disease in the USA and for a recurrent one in Europe. Secondly, besides the mosquito-bird cycle an interesting tick--bird cycle is emerging. The overview clearly demonstrates that in Europe (particularly in Germany) tick-borne viruses, with the exception of TBE, constitute an extremely ignored research subject. This lack of attention is in contrast to their importance and results in a lack of necessary scientific data.     

The Effect of Global Warming on Infectious Diseases

Global warming has various effects on human health. The main indirect effects are on infectious diseases. Although the effects on infectious diseases will be detected worldwide, the degree and types of the effect are different, depending on the location of the respective countries and socioeconomical situations.Among infectious diseases, water- and foodborne infectious diseases and vector-borne infectious diseases are two main categories that are forecasted to be most affected. The effect on vector-borne infectious diseases such as malaria and dengue fever is mainly because of the expansion of the infested areas of vector mosquitoes and increase in the number and feeding activity of infected mosquitoes. There will be increase in the number of cases with water- and foodborne diarrhoeal diseases.Even with the strongest mitigation procedures, global warming cannot be avoided for decades. Therefore, implementation of adaptation measures to the effect of global warming is the most practical action we can take. It is generally accepted that the impacts of global warming on infectious diseases have not been apparent at this point yet in East Asia. However, these impacts will appear in one form or another if global warming continues to progress in future. Further research on the impacts of global warming on infectious diseases and on future prospects should be conducted.Key words: dengue fever, global warming, Japanese encephalitis, vector-borne infectious diseases, water- and foodborne infectious diseases     

Climate change influences the incidence of arthropod-borne diseases in the Netherlands

Climate change is associated with changes in the occurrence of arthropod-borne diseases. It is difficult to foresee which arthropod-borne diseases will appear in the Netherlands due to climate change. Climate change influences the prevalence of ticks and may lead to a further increase in Lyme disease and an increased risk of the introduction of rickettsioses. With further warming of the climate there is a real possibility of settlement of the mosquito Aedes albopictus and introduction of the sandfly in the Netherlands. Whether this will lead to circulation of micro-organisms transmitted by these vectors (e.g. West Nile virus, Dengue virus, Leishmania) is not clear. Continued vigilance is necessary, even for vector-borne diseases that appear to be less relevant for the Netherlands.     

6种虫媒病毒微孔膜芯片检测方法的研制与应用

目的研制能同时检测6种口岸重要虫媒病毒的微孔膜芯片。方法针对包括1—4型登革病毒、乙型脑炎病毒、西尼罗病毒、黄热病毒、基孔肯雅病毒和裂谷热病毒等6种虫媒病毒,选择合适的保守基因,设计特异性的PCR引物（5’端标记生物素）和检测探针,通过参数优化建立单管多重RT—PCR扩增体系;然后按每个阵列5X5的格式,并确保点样区域为96孔板的微孔大小,将探针喷点到处理后的尼龙膜上,通过条件优化建立稳定的PCR产物与固化探针的杂交体系;采用碱性磷酸酯酶标记链亲和素和化学显色底物NBT／BCIP来检测特异性的PCR杂交产物。选取2012年1—6月份从口岸输入的疑似登革热发热病例的临床血清标本,提取RNA后,直接采用本研究建立的微孔膜芯片进行未知虫媒病毒的快速检测。结果用1～4型登革病毒、乙型脑炎病毒、西尼罗病毒和基孔肯雅病毒等7种毒株、1种黄热病毒疫苗株和1种裂谷热病毒核酸体外转录的RNA模板验证已建立的微孔膜芯片,获得比较特异和稳定的实验结果。应用该研究建立的方法,从3份疑似登革热发热病例的临床血清标本中检出了1例登革1型病毒和2例登革2型病毒,与实时荧光PCR检测结果相符。结论该研究建立的6种虫媒病毒微孔膜芯片检测方法,具有快速、准确、自动化和高通量等特点,为快速应对口岸输入性发热病例提供了非常有价值的检测手段,也为进一步开发更多指标的病原体检测方法提供良好的示范作用。     

Vorkommen und Verhütung vektorassoziierter Erkrankungen des Menschen in Deutschland unter Berücksichtigung zoonotischer Aspekte

Overall, 24 known or potentially human-pathogenic vector-borne disease agents are transmitted in Germany, 13 of them by hard ticks, 5 by commensal rodents (rats and mice), 3 by mosquitoes, and one by body lice, respectively. Regarding vector-borne disease agents that are suspected to be present or hypothetically are transmissible in Germany, additionally 4 disease agents are vectored by hard ticks, 4 by mosquitoes, and one by fleas, and possibly sandflies, respectively. Among vector-borne diseases proven to be endemic in Germany, tick-borne diseases prevail significantly, both in the number of disease agents transmitted as well as in the resulting annual case-load of human diseases. Lyme-borreliosis is by far the most frequent vector-borne disease showing an estimated incidence between 20.000 and 60.000 cases annually. Serologic studies conducted recently for the determination of anti-Ehrlichia- and anti-Babesia-antibodies in human populations indicate that these newly detected disease agents are present and thus the burden of tick-borne diseases may be underestimated in Germany. Currently, Central European tick-borne encephalitis, Mediterranean spotted fever, West Nile fever, and Murine typhus are reportedly spreading across Europe. Available measures for disease prevention mainly base on different principles of personal protection and vector control further discussed herein. Strong efforts in the field of medical entomology must be taken in Germany to improve the health support required to deal with the global disease threat and reach an international standard in this area.     

Flaviviruses and flavivirus vaccines

Several human-pathogenic flaviviruses (including yellow fever, dengue, Japanese encephalitis, West Nile and tick-borne encephalitis viruses) have a significant public health impact in different parts of the world and the potential of emerging in previously non-endemic regions. For some viruses, the structure of the most important immunogen, the envelope protein E, has been determined to atomic resolution by X-ray crystallography, and the architecture of virus particles has been resolved by cryo-electron microscopy. Through the combination of structural and immunological investigations, we now have a detailed understanding of the mechanisms of virus neutralization and antibody-dependent enhancement (ADE) of infectivity at a molecular level. The latter phenomenon has been proposed to play an important role in the immunopathology of severe forms of dengue virus infections (hemorrhagic dengue fever and dengue shock syndrome) and is therefore of special relevance in the context of dengue vaccines. Effective human vaccines are in use for the prophylaxis of yellow fever (live attenuated), Japanese encephalitis (live attenuated and inactivated whole virus), and tick-borne encephalitis (inactivated whole virus). Although dengue is the most important flavivirus with respect to global disease incidence, the development and use of vaccines has been hampered so far by the theoretical risk of vaccine-related adverse events such as immune enhancement of infection and the requirement to induce a long-lasting protective immune response against all four dengue serotypes simultaneously. Currently, several kinds of dengue vaccines are in development, but only one of these candidates (a chimeric dengue-yellow fever live attenuated vaccine) has reached the stage of phase 3 clinical trials.     

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.     

Flavivirus vaccines

Diseases caused by flavivirus infection have been a scourge of mankind for over three centuries; with yellow fever, dengue fever and Russian spring-summer encephalitis causing epidemics resulting in thousands of fatalities. Due to the development of a safe and efficacious live-attenuated vaccine against yellow fever, this disease is no longer such a threat in countries where adequate vaccination is practised. A similarly safe and efficacious inactivated vaccine against central-European tick-borne encephalitis has also been developed and this has drastically reduced the incidence of this disease in many countries where it is endemic. In spite of these successes, the development of vaccines against other pathogenic flaviviruses, causing diseases such as dengue fever and Russian spring-summer encephalitis, have not been successful. This review attempts to summarize the development of flavivirus vaccines to date and identify areas for future improvements. Problems associated with designing flavivirus vaccines are discussed and the advantages and disadvantages of future strategies for vaccine development are considered.     

沃尔巴克氏体应用于蚊媒病控制的研究概况

蚊媒病每年均会造成人类大量的病例数或死亡人数,例如登革热、疟疾、流行性乙型脑炎、西尼罗河病毒病和基孔肯雅热等。全球气候变暖、交通的快速便捷和人类旅游活动的增加,促使蚊虫在全球范围的快速扩张,从而易导致蚊媒病的暴发流行及传播扩散。目前因缺乏蚊媒病相应的高效疫苗,且传统化学杀虫剂的蚊媒控制方法造成了抗药性蚊虫的产生及对环境造成污染等问题,所以经济环保可持续的防治方法成为了研究热点。沃尔巴克氏体( Wolbachia )可诱导两性配子结合时的胞质不亲和从而控制蚊虫种群数量,还可抑制蚊媒病毒增殖,在生物防治方面具有经济环保可持续等优点,已成为部分国家蚊媒及蚊媒病的防治策略。本文主要对 Wolbachia 的分型、人工转染、传播扩散特征、对蚊媒生殖和抗病毒的影响及其应用于实践的研究现状进行综述。