The hamster as an animal model for eastern equine encephalitis--and its use in studies of virus entrance into the brain

Eastern equine encephalitis virus (EEEV) produces the most severe human arboviral diseases in the United States, with mortality rates of 30%-70%. Vasculitis associated with microhemorrhages in the brain dominates the pathological picture in fatal human eastern equine encephalitis, and neuronal cell death is detectable during the late stage of the disease. We describe use of the golden hamster to study EEEV-induced acute vasculitis and encephalitis. In hamsters, EEEV replicates in visceral organs, produces viremia, and penetrates the brain. The pathological manifestations and antigen distribution in the brain of a hamster are similar to those described in human cases of EEEV.     

Arboviral infections in the United States.

Arboviruses are important considerations in the differential diagnosis of encephalitis and other acute infections. Alterations in the environment and in human behaviors contribute to changing patterns of arboviral transmission. These trends, the periodic epidemic resurgence of arboviral diseases such as St. Louis encephalitis, and the discovery of new arboviruses present a continued challenge to infectious disease clinicians.     

Antibody response to Culex tarsalis salivary gland antigens among sentinel chickens in California

The arboviral surveillance program in California depends in part on sentinel chickens to detect western equine encephalomyelitis virus, St. Louis encephalitis virus, and West Nile virus activity. From 2000 through 2002, 1,578 serum specimens from 34 sentinel flocks in northern and southern California were tested for antibodies to Culex tarsalis salivary gland antigens. Sentinel chickens that were seropositive for mosquito salivary gland antigens were more likely to seroconvert to St. Louis encephalitis virus than those seronegative for salivary gland antigens. Flocks with mosquito traps located < 50 feet away had a reduced antibody response to mosquito salivary gland antigens. The use of sentinel chickens and mosquito traps for arboviral surveillance should be standardized to ensure that surveillance data from different sites are comparable and that flocks have comparable opportunities for mosquito exposure. Sentinel chickens should be accessible to potential mosquito vectors to maximize their sensitivity for detecting arboviral activity.     

Sylvatic transmission of arboviruses among Bornean orangutans.

Wild populations of nonhuman primates live in regions of sylvatic arbovirus transmission. To assess the status of arbovirus transmission in Bornean forests and the susceptibility of wild orangutans to arboviral infection, blood samples of wild orangutans, semi-captive orangutans, and humans were examined. Samples were tested by plaque reduction neutralization test for antibodies to viruses representing three families (Flaviviridae, Alphaviridae, and Bunyaviridae), including dengue-2, Japanese encephalitis, Zika, Langat, Tembusu, Sindbis, Chikungunya, and Batai viruses. Both wild and semi-captive orangutan groups as well as local human populations showed serologic evidence of arbovirus infection. The presence of neutralizing antibodies among wild orangutans strongly suggests the existence of sylvatic cycles for dengue, Japanese encephalitis, and sindbis viruses in North Borneo. The present study demonstrates that orangutans are susceptible to arboviralinfections in the wild, although the impact of arboviral infections on this endangered ape remain unknown.     

Rapid diagnosis of viral infections in the central nervous system

Rapid diagnosis of viral infections in the central nervous system has become increasingly important. Antiviral treatment, prevention of spread of disease and differentiation from infections caused by agents sensitive to antibiotics may be the important consequences of a virus specific diagnosis gained early in the disease. The diagnosis can be obtained by detection of virus or viral antigen in the human specimen: herpes simplex virus by electron microscopy, immunofluorescence or immunosorbent assays in brain biopsies; rabies virus by immunofluorescence in corneal cells or skin and mucous membranes. The presence of measles or influenza antigens in nasopharyngeal secretions, shown by immunofluorescence or enzyme immunoassays, may diagnose an encephalitis caused by either of these viruses. Where suitable material is not available the detection of virus-specific IgM in a single serum specimen may be used for diagnosis. Mumps specific IgM activity is detected by enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence techniques; tick-borne encephalitis (TBE) specific IgM by immunosorbent assays or by reduction of hemagglutination-inhibition (HI) titer by 2-mercaptoethanol treatment of serum. Reports have been given on the detection of IgM activity by ELISA also in other arboviral infections such as Japanese and LaCrosse encephalitis. The demonstration of an intrathecal production of virus-specific immunoglobulins may reveal the type of virus causing the infection in the central nervous system.     

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神经系统副肿瘤综合征如边缘叶脑炎和许多特异性抗体有关。这些抗体极易识别肿瘤组织和神经组织,均有表达的抗原。细胞内抗原包括Hu、Yo、Ma2、CRMP5蛋白和神经元突触囊泡、谷氨酸脱羧酶(GAD)等。抗细胞内抗原抗体相关脑炎的主要临床表现为边缘叶脑炎、小脑性共济失调和癫痫等。大多数的患者预后不良。     

Pre-West Nile virus outbreak: perceptions and practices to prevent mosquito bites and viral encephalitis in the United States

Mosquitoes can transmit over 100 of the viruses that can cause encephalitis, meningitis, and hemorrhagic disease in humans (Chin 2000; Gubler 1996; Monath 1989). While much is known about the ecology, epidemiology, and clinical manifestations of the arboviral encephalitides (Campbell et al. 2002; Centers for Disease Control and Prevention 1997; Gubler 1998; Hayes 1989; Hubálek and Halouzka 1999), little empirical research exists regarding the U.S. population's knowledge of mosquitoes and arboviral encephalitis, particularly prior to the U.S. outbreak of West Nile virus (WNV) in 1999. A nationally representative 55-item survey instrument was successfully administered to 1,500 adults in the United States and an additional 250 adults in six states in the Northeast (Connecticut, Delaware, New Jersey, New York, Pennsylvania, and Rhode Island) regarding mosquitoes and mosquito-borne viral encephalitis. A summary outcome measure for mosquito bite prevention was created. Analyses revealed that the following were statistically significant predictors of behaviors taken to prevent mosquito bites: being concerned about being bitten by mosquitoes, perceived effectiveness of staying indoors in late afternoon and early evening was protective, perceived effectiveness that mosquito repellent is not harmful to health, owning dogs and/or cats as pets, being married, and being > or = 18-44 years old. Being concerned about being bitten by mosquitoes was the most robust predictor of behavioral action to prevent mosquito bites (OR = 7.3; 95% CI = 4.3, 12.2). Observed misperceptions and inadequate knowledge regarding insect repellents suggest increased promotion of the safety and efficacy of DEET-containing insect repellents is warranted.     

Influence of hosts on the ecology of arboviral transmission: potential mechanisms influencing dengue, Murray Valley encephalitis, and Ross River virus in Australia

Ecological interactions are fundamental to the transmission of infectious disease. Arboviruses are particularly elegant examples, where rich arrays of mechanisms influence transmission between vectors and hosts. Research on host contributions to the ecology of arboviral diseases has been undertaken within multiple subdisciplines, but significant gaps in knowledge remain and multidisciplinary approaches are needed. Through our multidisciplinary review of the literature we have identified five broad areas where hosts may influence the ecology of arboviral transmission: host immunity; cross-protective immunity and antibody-dependent enhancement; host abundance; host diversity; and pathogen spillover and dispersal. Herein we discuss the known and theoretical roles of hosts within these topics and then apply this knowledge to three epidemiologically important mosquito-borne arboviruses that occur in Australia: dengue virus (DENV), Murray Valley encephalitis virus (MVEV), and Ross River virus (RRV). We argue that the underlying mechanisms by which hosts influence arboviral activity are numerous and attempts to delineate these mechanisms further are needed. Investigations that focus on hosts of vector-borne diseases are likely to be rewarding, particularly where the ecology of vectors is relatively well understood. From an applied perspective, enhanced knowledge of host influences upon vector-borne disease transmission is likely to enable better management of disease burden. Finally, we suggest a framework that may be useful to identify and determine host contributions to the ecology of arboviruses.     

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.     

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.     

West Nile Virus Neuroinvasive Disease

West Nile virus (WNV), first recognized in North America in 1999, was responsible for the largest arboviral epidemic of human encephalitis in history and continues to be the most frequent cause of epidemic meningoencephalitis in North America. WNV neuroinvasive disease (WNND) occurs in fewer than 1% of infected individuals, with presentations including aseptic meningitis, encephalitis, and poliomyelitis. Between 1999 and 2009, over 12,000 cases of WNND were reported in the United States, with the peak annual incidence occurring in epidemics of 2002 and 2003. In this review, we first summarize the epidemiology of WNV over the past decade and the salient clinical features of WNND, including a discussion of laboratory and radiographic findings, risk factors, morbidity, and mortality. In addition, we review recent progress in our understanding of virus and host determinants of the pathogenesis of WNND, as well as the prospects for the development of specific therapeutic targets.     

Dengue fever with neurologic expression. Three cases in adults]

Dengue fever, unlike most other arboviral diseases, does not usually cause encephalitis. However, neurologic symptoms with poor prognosis have been regularly reported, mostly in Asian children affected by the severe dengue hemorrhagic fever/dengue shock syndrome, and attributed to a non specific, anoxic or metabolic encephalopathy. Recently, first isolations of dengue viruses from CSF or brain tissue, have renewed this concept. We report 3 dengue fever cases with neurologic manifestations and favorable outcome. Occurrence in adult age, during classic (benign) dengue fever (2 cases), and neurologic sequellae (1 case) were the three outstanding features. We point out the proteiform expression of these neurologic changes and their low incidence rate (< 3% in our series of adult dengue fever). Although their pathogenesis is poorly understood, different mechanisms are suggested: encephalopathy (case n. 1), acute specific encephalitis (questionable in case n(o) 2), or post-infective encephalitis (case n(o) 3).     

中国青海省Tahyna病毒的分离鉴定及其人畜感染

Tahyna病毒(Tahyna virus, TAHV)2007年在位于青藏高原的青海省格尔木市分离到,后续研究证实青海省新分离TAHV是引起当地发热性疾病的新病原,TAHV感染成为我国除乙脑、登革之外的第三种蚊虫传播病毒性疾病。本文从生物学特征、自然循环、人畜动物流行病学、临床致病特点等方面对青海省TAHV相关研究结果等进行系统综述。     

Vector competence of New Zealand mosquitoes for selected arboviruses

New Zealand (NZ) historically has been free of arboviral activity with the exception of Whataroa virus (Togaviridae: Alphavirus), which is established in bird populations and is transmitted by local mosquitoes. This naive situation is threatened by global warming, invasive mosquitoes, and tourism. To determine the threat of selected medically important arboviruses to NZ, vector competence assays were conducted using field collected endemic and introduced mosquito species. Four alphaviruses (Togaviridae): Barmah Forest virus, Chikungunya virus, Ross River virus, and Sindbis virus, and five flaviviruses (Flaviviridae): Dengue virus 2, Japanese encephalitis virus, Murray Valley encephalitis virus, West Nile virus, and Yellow fever virus were evaluated. Results indicate some NZ mosquito species are highly competent vectors of selected arboviruses, particularly alphaviruses, and may pose a threat were one of these arboviruses introduced at a time when the vector was prevalent and the climatic conditions favorable for virus transmission.     

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.     

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。     

Laboratory investigation of human deaths from vampire bat rabies in Peru.

In the spring of 1996, multiple cases of an acute febrile illness resulting in several deaths in remote locations in Peru were reported to the Centers for Disease Control and Prevention (CDC). The clinical syndromes for these cases included dysphagia and encephalitis. Because bat bites were a common occurrence in the affected areas, the initial clinical diagnosis was rabies. However, rabies was discounted primarily because of reported patient recovery. Samples of brain tissue from two of the fatal cases were received at CDC for laboratory confirmation of the rabies diagnosis. An extensive array of tests on the formalin-fixed tissues confirmed the presence of both rabies viral antigen and nucleic acid. The virus was shown to be most closely related to a vampire bat rabies isolate. These results indicate the importance of maintaining rabies in the differential diagnosis of acute febrile encephalitis, particularly in areas where exposure to vampire bats may occur.     

Enhancement of fluorescent antibody staining of viral antigens in formalin-fixed tissues by trypsin digestion.

The staining of viral antigens present in formalin-fixed, paraffin-embedded tissues by fluorescent antibodies is markedly enhanced by trypsin digestion. When the trypsin digestion method was used to detect viral antigens present in hamster brain following experimental infection with measles virus, the results were comparable to those obtained with acetone-fixed, freshly frozen tissues that had been sectioned with a cryostat. Measles antigens were readily identified in brain cells from a patient with subacute sclerosing panencephalitis and in lung and liver tissue from a patient with acute giant cell pneumonia, following preparation of the tissues for routine histologic examination. Viral antigens were detected in brain tissue that had been taken from patients with herpes simplex encephalitis and stored in paraffin for up to 15 years. Cells containing antigen could be precisely identified without loss of histologic detail by restaining the same tissue sections with hematoxylin and eosin.     

检测狂犬病毒的胶体金免疫层析法的建立及应用

目的 建立一种简易快速、适用于野外的胶体金免疫层析法(GICA)用于检测动物脑或唾液中的狂犬病街毒抗原。方法采用柠檬酸三钠还原法制备胶体金颗粒，标记抗狂犬病毒单抗。制成免疫层析测试条。样品中的狂犬病毒抗原与测试条上金标记抗体结合后沿着硝酸纤维素膜移动，与膜上的固相抗体结合形成肉眼可见的红色线条。结果 GICA测试条只与狂犬病毒抗原有特异性反应，与乙型脑炎病毒、正常小鼠脑组织等无交叉反应。GICA与EIA比较检测了48份可疑狂犬病犬唾液样品，两法的符合率为88．2％。结论 GICA检测样品中的狂犬病毒抗原特异性强、灵敏度高、简便快速、无需仪器设备，对基层单位开展初步鉴定狂犬病毒样品工作而言。不失为一种有效的方法。