云南省虫媒病毒与虫媒病毒病研究进展

云南省为南亚热带气候,适于各类吸血节肢动物的生存繁殖及某些虫媒病毒的保存和传播。迄今,云南已分离到至少8科10属28种虫媒病毒,其中包括能引起人和/或家畜严重疾病的流行性乙型脑炎、登革、基孔肯雅、蜱媒脑炎、寨卡、辛德毕斯、巴泰、马亚罗、肯科伊、盖塔、蓝舌、坦布苏、阿卡斑和曼扎尼拉等病毒;还发现可能导致人、畜感染的新病毒如版纳病毒、云南环状病毒、芒市病毒,以及昆虫特异性病毒如浓核病毒、库蚊黄病毒、伊蚊黄病毒、伊蚊弹状病毒等,为国内已发现虫媒病毒种类最多的省份。加强虫媒病毒和虫媒病毒病调查研究及防控仍是云南省当前面临的重要任务。本文对近20年(2001-2020年)云南省虫媒病毒及其相关疾病研究进展及公共卫生意义做一综述。     

Transfusion‐transmitted arboviruses

There exists considerable risk for transfusion transmission of arboviruses due to short periods of asymptomatic viraemia in populations with variable and sometimes extremely high incidence of arboviral infections. Aside from West Nile virus, few arbovirus transfusion transmissions have been proven, mostly due to difficulties in ruling out vector‐borne transmission in recipients with arbovirus disease. Nevertheless, arbovirus transfusion risk models and assessments of viraemia prevalence in blood donations indicate substantial transfusion transmission of dengue and Chikungunya viruses in epidemic areas. Many other arboviruses, several of which are importation risks in the Americas, Europe and Asia, also cause large outbreaks and threaten transfusion safety. Prevention largely depends on excluding donors from outbreak areas or implementation of highly sensitive nucleic acid amplification tests. Because of the increasing emergence of arboviral disease globally, it is prudent to prepare for both endemic and exotic arboviruses capable of producing large epidemics and subsequent transfusion transmission risk.     

Arbovirus investigations in Argentina, 1977-1980. IV. Serologic surveys and sentinel equine program

Serologic surveys of wild and domestic birds, wild mammals, and horses were conducted during arbovirus field studies in Argentina from 1977 through 1980, a non-epizootic interval. The prevalence of neutralizing antibodies to eastern equine encephalitis (EEE) was consistently higher than to western equine encephalitis (WEE) virus in all species and all areas. The presence of antibodies in short-lived avian species and in young unvaccinated horses and the demonstration of seroconversions in horses during the period, indicated that these viruses are either enzootic in, or annually reintroduced into, Argentina. Antibodies to AG80-646, a new subtype of WEE virus isolated in the subtropical north (Chaco Province) from Culex (Melanoconion) mosquitoes, were found in horses and rodents in that region. Antibodies to the TC-83 strain of Venezuelan equine encephalitis (VEE) virus were found in all areas studied. The presence of antibodies in some horses was probably related to vaccination, but the demonstration of seroconversions in sentinel horses and of antibodies in birds and wild mammals indicates active transmission of VEE virus. In 1980 a new enzootic subtype of VEE virus (AG80-663) was isolated from mosquitoes in Chaco; neutralizing antibodies to this virus were prevalent in horses and rodents in this area. Infections with Aura and Una viruses were most common in the subtropical northern provinces. Infection with St. Louis encephalitis was prevalent and widespread, and birds, principally passerine and columbiform species, appear to be the principal hosts. An interesting and unexplained finding was the absence of arbovirus antibodies, in particular SLE antibodies in house sparrows (Passer domesticus). Antibody prevalences in horses exceeded 50% in all areas, and 12% of horses surveyed in Santa Fe Province developed antibody in a 17-month period. Antibodies to other flaviviruses were rare. A high prevalence of immunity to Maguari virus was found in horses; this agent is considered to be a potential equine pathogen. Antibodies to 2 new viruses, Barranqueras and Resistencia, which had been isolated from Cx. (Melanoconion) in Chaco Province, were found in rodents there. Immunity to Gamboa group viruses was prevalent, and birds were implicated as principal hosts.     

Short report: detection probability of arbovirus infection in mosquito populations

An important component of arbovirus surveillance is monitoring the vector for presence of the pathogen. Intervention and preventive programs need early detection of arboviral activity in mosquito populations. In this report, we examine the factors affecting the probability of detection of mosquito infections. Since arbovirus infection rates in mosquito populations are very low, observations of zero-infected mosquito samples are common. Using statistical models, we describe methods to estimate the probability of detection and upper bounds of confidence intervals of mosquito infection rates as measures of confidence for observations of zero infection. Our results show that detection of low levels of mosquito infections requires large samples (greater than 1,600 individuals) for a high probability (0.8) of detection. Due to focal transmission of arboviruses, grouping samples over different sampling sites and times is often inappropriate for detection of mosquito infection. We emphasize sample size as a key determinant in detection of mosquito infections and recommend intensified entomologic surveys at sentinel sites to detect arboviral activity.     

Comparison of haemagglutination inhibition (HI) and indirect fluorescent antibody (IFA) techniques for the serological diagnosis of certain flavivirus infections

Paired serum samples from 25 patients having clinical evidence of arboviral infections and 15 controls were examined for antibodies against dengue, Japanese encephalitis and West nile viruses by haemagglutination inhibition (HI) and indirect fluorescent antibody (IFA) methods. The two tests were comparable in specificity but the IFA test was found to be more sensitive than the HI test. Like the HI test, the antibodies detected by IFA test cross-reacted within the flavivirus group under test. Use of IFA test is recommended to detect flavivirus infections as the test is simple, sensitive and can be carried out rapidly.     

Seroprevalence of West Nile virus in wild birds in far eastern Russia using a focus reduction neutralization test

West Nile (WN) virus has been spreading geographically to non-endemic areas in various parts of the world. However, little is known about the extent of WN virus infection in Russia. Japanese encephalitis (JE) virus, which is closely related to WN virus, is prevalent throughout East Asia. We evaluated the effectiveness of a focus reduction neutralization test in young chicks inoculated with JE and WN viruses, and conducted a survey of WN infection among wild birds in Far Eastern Russia. Following single virus infection, only neutralizing antibodies specific to the homologous virus were detected in chicks. The neutralization test was then applied to serum samples from 145 wild birds for WN and JE virus. Twenty-one samples were positive for neutralizing antibodies to WN. These results suggest that WN virus is prevalent among wild birds in the Far Eastern region of Russia.     

Arbovirus evolution in vivo is constrained by host alternation

The intrinsic plasticity of RNA viruses can facilitate host range changes that lead to epidemics. However, evolutionary processes promoting cross-species transfers are poorly defined, especially for arthropod-borne viruses (arboviruses). In theory, cross species transfers by arboviruses may be constrained by their alternating infection of disparate hosts, where optimal replication in one host involves a fitness tradeoff for the other. Accordingly, freeing arboviruses from alternate replication via specialization in a single host should accelerate adaptation. This hypothesis has been tested by using cell culture model systems with inconclusive results. Therefore, we tested it using an in vivo system with Venezuelan equine encephalitis virus (VEEV), an emerging alphavirus of the Americas. VEEV serially passaged in mosquitoes exhibited increased mosquito infectivity and vertebrate-specialized strains produced higher viremias. Conversely, alternately passaged VEEV experienced no detectable fitness gains in either host. These results suggest that arbovirus adaptation and evolution is limited by obligate host alternation and predict that arboviral emergence via host range changes may be less frequent than that of single host animal RNA viruses.     

Geographic distribution of arbovirus antibodies in indigenous human populations in the Indo-Australian archipelago.

Sera from lifetime residents in 16 localities of the Indo-Australian archipelago and adjacent areas were tested for hemagglutination-inhibition antibody against four alpha-viruses (Sindbis, Getah, chikungunya, and Ross River) and for neutralizing antibody against six flaviviruses (dengue 2 and 3, Japanese encephalitis, Murray Valley encephalitis, Kunjin, and Edge Hill). Mosquito collections were carried out in some of the localities to study vector relationships to distribution of the arbovirus antibodies. Antibodies specific to Sindbis and Getah viruses were rare except in north Australia. Chikungunya virus-specific antibody was highly prevalent in localities of the Oriental zoogeographic region and Wallacea, rare in west New Guinea, and absent in north Australia. Age distribution of chikungunya antibody suggested that the antibody last occurred in most Indonesian localities about 30 years ago. Ross River virus-specific antibody was confined to localities of the Australian zoogeographic region. Antibodies reacting to dengue 2 and 3 viruses occurred in high frequency in the entire area of the archipelago. Antibodies specific to Murray Valley encephalitis and Kunjin viruses were also widespread although at a very low frequency. Japanese encephalitis virus-specific antibody was highly prevalent in areas west of Wallace's Line while it was absent in areas east of the line with the exception of Lombok. Antibody to Edge Hill virus was rare and confined to the Australian zoogeographic region. The distribution of arthropod vectors, vertebrate hosts, and of arboviruses are discussed in relation to zoogeographic divisions.     

Mosquito Immunity against Arboviruses

Arthropod-borne viruses (arboviruses) pose a significant threat to global health, causing human disease with increasing geographic range and severity. The recent availability of the genome sequences of medically important mosquito species has kick-started investigations into the molecular basis of how mosquito vectors control arbovirus infection. Here, we discuss recent findings concerning the role of the mosquito immune system in antiviral defense, interactions between arboviruses and fundamental cellular processes such as apoptosis and autophagy, and arboviral suppression of mosquito defense mechanisms. This knowledge provides insights into co-evolutionary processes between vector and virus and also lays the groundwork for the development of novel arbovirus control strategies that target the mosquito vector.     

Comparative susceptibility of five species of Toxorhynchites mosquitoes to parenteral infection with dengue and other flaviviruses

Five species of colonized Toxorhynchites mosquitoes were compared for relative susceptibility to parenteral infection with the four dengue serotypes and St. Louis and Japanese encephalitis viruses. Tx. amboinensis, Tx. brevipalpis, Tx. rutilus, and Tx. splendens were equally susceptible to infection with the dengue viruses, while Tx. theobaldi was relatively resistant to infection with those viruses. All five mosquito species were equally susceptible to infection with the encephalitis viruses. The intensity of immunofluorescence in head squashes was slightly less in Tx. brevipalpis infected with the dengue viruses as compared to the other three mosquito species susceptible to those viruses. Immunofluorescence was also less in Tx. theobaldi infected with the encephalitis viruses as compared with all the other mosquito species.     

Arbovirus studies in the Guajira region of Venezuela: activities of eastern equine encephalitis and Venezuelan equine encephalitis viruses during an interepizootic period

Repeated outbreaks of Venezuelan equine encephalitis (VEE) in humans and equines in the Guajira region of Venezuela suggested a sylvatic focus of an epizootic subtype of VEE virus. A surveillance system was established, and virus isolations were attempted from 67,760 mosquitoes as well as sentinel hamsters. Sixteen isolates of eastern equine encephalitis (EEE) and a strain of Itaqui virus were recovered from mosquitoes, and 60 isolates of EEE, two of VEE, and two of Itaqui viruses were recovered from tissues of sentinel hamsters. The VEE virus isolates were shown to be closely related antigenically to prototype VEE ID and the EEE virus isolates were shown to be more closely related to the South American than the North American variety of EEE virus. Evidence for the presence of VEE and EEE viruses in small wild vertebrates was obtained from serologic testing. This study showed, for the first time, the enzootic presence of both VEE ID and EEE viruses during a nonepizoodemic period in the Guajira region.     

Antigenic relationships between sylvatic and endemic dengue viruses

Sylvatic dengue viruses (DENVs) are transmitted between non-human primates and arboreal Aedes spp. mosquitoes in Southeast Asia and west Africa. Recent evidence suggests that the risk for re-emergence of sylvatic DENV into the urban endemic/epidemic cycle may be high, which could limit the potential for eradicating the human transmission cycle with vaccines now under development. We assessed the likelihood of sylvatic DENV re-emergence in the face of immunity to current endemic strains or vaccines by evaluating the neutralization capacity of sera from DENV vaccinees and convalescent patients after primary infection with DENV-2 and DENV-3 serotypes. Our data indicate robust homotypic cross-immunity between human sera and sylvatic DENV strains, but limited heterotypic neutralization. Should a licensed vaccine lead to the eradication of the urban transmission cycle in the future, re-emergence of sylvatic strains into the urban cycle would be limited by homotypic immunity mediated by virus-neutralizing antibodies.     

Serological evidence of Japanese encephalitis virus activity in Bihar

Serum samples from 404 pigs originating from eight districts of Bihar were examined for haemagglutination-inhibiting and complement fixing antibodies of Japanese Encephalitis, Dengue-2, West Nile and Chikungunya viruses. Japanese Encephalitis viral infection was found to be widely prevalent compared to other arboviruses tested. RElatively large number of pigs had antibodies to JEV only (i.e. monoconverters). High geometric mean titre to JEV was observed. These observations appear to be of epidemiologic significance to the 1978 epidemic of encephalitis in Bihar. Epidemic of encephalitis was reported in 1978 from several states of India including Bihar. The only evidence of the activity of Japanese Encephalitis in Bihar came from Khan and Banerjee who found neutralizing antibodies in ardeid birds from Asansol - Dhanbad regions. Evidences are presented in this paper on the prevalence of Japanese Encephalitis in eight districts including Dhanbad of Bihar.     

中国云浮口岸蚊媒病毒的首次调查

目的 掌握云浮国境口岸蚊类携带重要蚊媒病毒的现状,探讨提高口岸蚊媒病毒检测有效性的方法,为预防和控制口岸蚊媒传染病的发生提供科学依据。方法 于2011年5月~11月在云浮口岸捕捉活蚊,对蚊标本研磨液提取核酸后应用多重实时荧光RT-PCR技术快速筛查蚊类携带的登革热病毒、日本脑炎(乙脑)病毒、基孔肯雅病毒、西尼罗热病毒和黄热病毒。对实时荧光RT-PCR检测核酸阳性的标本进行PCR扩增和序列分析。结果 在云浮共采集39 254只蚊虫,鉴定后分为460组。经实时荧光RT-PCR检测,14组蚊虫乙脑病毒核酸阳性,其余病毒(登革热病毒、乙脑病毒、基孔肯雅病毒、西尼罗热病毒和黄热病毒)均为阴性。PCR扩增和序列分析显示云浮乙脑病毒属于基因Ⅰ型。所捕获的三带喙库蚊的最小感染率为0.937‰比中华按蚊的0.385‰稍高。结论 本研究首次在云浮口岸进行大规模系统的蚊媒病毒调查,云浮口岸的蚊虫很可能没有携带登革热病毒、基孔肯雅病毒、西尼罗热病毒和黄热病毒,但有少数蚊虫携带乙脑病毒。此次调查检出的基因Ⅰ型乙脑病毒是广东省内的首次报道,为今后蚊媒病毒的媒介监测检测工作提供了有效方法。虽然蚊虫最小感染率的差别没有统计学意义,但是蚊媒病毒病的暴发和流行风险仍然存在。     

Antibody Prevalence of Select Arboviruses in Mute Swans (Cygnus olor) in the Great Lakes Region and Atlantic Coast of the United States

Mute swans (Cygnus olor) are an invasive species in the United States. The dramatic increase in their populations in localized areas has led to various problems, among them competition with native species and attacks on humans by aggressive swans. However, very little is known about the ability of these swans to transmit pathogens to humans, domestic birds, or wildlife or participate in enzootic maintenance. To learn more about select pathogens that mute swans may harbor, a survey was conducted from April of 2011 to August of 2012 in the Great Lakes region and localized areas of the Atlantic coast, which revealed serologic evidence of arbovirus exposure in mute swans. Of 497 mute swans tested, antibodies were detected for eastern equine encephalitis (4.8%), St. Louis encephalitis (1.4%), West Nile (1.2%), and Turlock (0.6%) viruses. Samples were also tested for evidence of antibodies to La Crosse virus, but none were positive.     

An animal model for the tickborne flavivirus--Omsk hemorrhagic fever virus

The tickborne encephalitis (TBE) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include Omsk hemorrhagic fever virus (OHFV), a virus that is genetically related to other TBE serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. The objective of this study was to examine a potential small-animal model for OHFV and to compare the pathology of infection with that of the neurotropic tickborne flavivirus, Powassan virus (POWV). POWV-infected BALB/c mice demonstrated typical arboviral encephalitis, characterized by paresis and paralysis before death, and viral infection of the cerebrum, characterized by inflammation and necrosis. In contrast, lethal OHFV infection did not cause paralysis or significant infection of the cerebrum but showed marked involvement of the cerebellum. Distinct pathological results in the spleens suggest that the immune response in OHFV-infected mice is different from that in POWV-infected mice. This study demonstrates a clear pathological difference between OHFV-infected mice and POWV-infected mice and supports the use of the BALB/c mouse as a disease model for OHFV.     

Emerging tropical diseases in Australia. Part 4. Mosquitoborne diseases

Mosquito-borne diseases continue to be a serious public-health concern in Australia. Endemic alphaviruses (including Ross River and Barmah Forest viruses) account for the majority of the arboviral notifications, while some flaviviruses (Murray Valley encephalitis, Japanese encephalitis and Kunjin viruses) cause occasional outbreaks of encephalitis. Dengue epidemics are increasing in frequency in northern Queensland, with the largest outbreak in 50 years occurring during the 2008-2009 wet season. Of great concern are the threats posed by the importation of exotic arboviruses, such as West Nile, chikungunya and Rift Valley fever viruses, the introduction of exotic vectors, and the potential range expansion of key Australian vectors. Environmental and anthropogenic influences provide additional uncertainty regarding the future impact of mosquito-borne pathogens in Australia. This review discusses the trends, threats and challenges that face the management of mosquito-borne disease in Australia. Topical mosquito-borne pathogens of biosecurity and public-health concern, and the potential impacts of environmental and global trends, are discussed. Finally, a short overview of the public-health response capability in Australia is provided.     

Arboviral Bottlenecks and Challenges to Maintaining Diversity and Fitness during Mosquito Transmission

The term arbovirus denotes viruses that are transmitted by arthropods, such as ticks, mosquitoes, and other biting arthropods. The infection of these vectors produces a certain set of evolutionary pressures on the virus; involving migration from the midgut, where the blood meal containing the virus is processed, to the salivary glands, in order to transmit the virus to the next host. During this process the virus is subject to numerous bottlenecks, stochastic events that significantly reduce the number of viral particles that are able to infect the next stage. This article reviews the latest research on the bottlenecks that occur in arboviruses and the way in which these affect the evolution and fitness of these viruses. In particular we focus on the latest research on three important arboviruses, West Nile virus, Venezuelan equine encephalitis virus and Chikungunya viruses and compare the differing effects of the mosquito bottlenecks on these viruses as well as other evolutionary pressures that affect their evolution and transmission.     

Arbovirus studies in southwestern Venezuela during 1973-1981. II. Isolations and further studies of Venezuelan and eastern equine encephalitis, Una, Itaqui, and Moju viruses

Increasing utilization of arable land in southwestern Venezuela has led to a potential increase in human exposure to arbovirus infections. Since previous studies in the Catatumbo region of this area documented the presence of eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses, an attempt was made to study the transmission and maintenance of these viruses from 1973 to 1981. Isolations of EEE, VEE ID strains, Una, Itaqui , and Moju viruses were repeatedly obtained from mosquitoes, mostly Culex ( Melanoconion ) spp. and sentinel hamsters. The results indicate that these viruses constitute a potential hazard to public health in the area. Further, the strategic location of the Catatumbo region, between enzootic tropical foci of arboviruses, may provide circumstances and conditions for study of both enzootic maintenance and movement of these viruses.