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Sample records for japanese encephalitis vaccines

  1. Protection against Japanese encephalitis by inactivated vaccines.

    PubMed

    Hoke, C H; Nisalak, A; Sangawhipa, N; Jatanasen, S; Laorakapongse, T; Innis, B L; Kotchasenee, S; Gingrich, J B; Latendresse, J; Fukai, K

    1988-09-01

    Encephalitis caused by Japanese encephalitis virus occurs in annual epidemics throughout Asia, making it the principal cause of epidemic viral encephalitis in the world. No currently available vaccine has demonstrated efficacy in preventing this disease in a controlled trial. We performed a placebo-controlled, blinded, randomized trial in a northern Thai province, with two doses of monovalent (Nakayama strain) or bivalent (Nakayama plus Beijing strains) inactivated, purified Japanese encephalitis vaccine made from whole virus derived from mouse brain. We examined the effect of these vaccines on the incidence and severity of Japanese encephalitis and dengue hemorrhagic fever, a disease caused by a closely related flavivirus. Between November 1984 and March 1985, 65,224 children received two doses of monovalent Japanese encephalitis vaccine (n = 21,628), bivalent Japanese encephalitis vaccine (n = 22,080), or tetanus toxoid placebo (n = 21,516), with only minor side effects. The cumulative attack rate for encephalitis due to Japanese encephalitis virus was 51 per 100,000 in the placebo group and 5 per 100,000 in each vaccine group. The efficacy in both vaccine groups combined was 91 percent (95 percent confidence interval, 70 to 97 percent). Attack rates for dengue hemorrhagic fever declined, but not significantly. The severity of cases of dengue was also reduced. We conclude that two doses of inactivated Japanese encephalitis vaccine, either monovalent or bivalent, protect against encephalitis due to Japanese encephalitis virus and may have a limited beneficial effect on the severity of dengue hemorrhagic fever.

  2. New Japanese encephalitis vaccines: alternatives to production in mouse brain.

    PubMed

    Halstead, Scott B; Thomas, Stephen J

    2011-03-01

    Japanese encephalitis virus (JEV), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito Culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of Asia. Resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. For the past several decades, killed viral vaccines prepared in tissue culture or mouse brain have been used effectively to immunize travelers and residents of enzootic countries. Cost, efficacy and safety concerns led to the development of a live-attenuated virus vaccine (SA14-14-2) and more recently, to the licensure in the USA, Europe, Canada, and Australia of a purified inactivated, tissue culture-based Japanese encephalitis vaccine (IXIARO(®), referred to as IC51; Intercell AG, Vienna, Austria). In addition, a live-attenuated yellow fever-Japanese encephalitis chimeric vaccine (IMOJEV™, referred to as Japanese encephalitis-CV; Sanofi Pasteur, Lyon, France) was recently licensed in Australia and is under review in Thailand. A broad portfolio of safe and effective Japanese encephalitis vaccines has become available to meet the needs of at-risk populations; when appropriately delivered, these new vaccines should greatly diminish the burden of disease.

  3. Japanese Encephalitis Vaccines: WHO position paper, February 2015--Recommendations.

    PubMed

    2016-01-12

    This article presents the World Health Organization's (WHO) recommendations on the use of Japanese Encephalitis (JE) vaccines excerpted from the WHO position paper on Japanese Encephalitis vaccines recently published in the Weekly Epidemiological Record [1]. This updated position paper on JE vaccines replaces the 2006 position paper on this subject [2]; it focuses on new information concerning the availability, safety, immunogenicity and effectiveness of JE vaccines and the duration of protection they confer. Recent data on global prevalence and burden of disease caused by JE and cost-effectiveness considerations regarding JE vaccination are also summarized. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its October 2014 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html.

  4. Japanese encephalitis

    PubMed Central

    Yun, Sang-Im; Lee, Young-Min

    2014-01-01

    Japanese encephalitis (JE) is an infectious disease of the central nervous system caused by Japanese encephalitis virus (JEV), a zoonotic mosquito-borne flavivirus. JEV is prevalent in much of Asia and the Western Pacific, with over 4 billion people living at risk of infection. In the absence of antiviral intervention, vaccination is the only strategy to develop long-term sustainable protection against JEV infection. Over the past half-century, a mouse brain-derived inactivated vaccine has been used internationally for active immunization. To date, however, JEV is still a clinically important, emerging, and re-emerging human pathogen of global significance. In recent years, production of the mouse brain-derived vaccine has been discontinued, but 3 new cell culture-derived vaccines are available in various parts of the world. Here we review current aspects of JEV biology, summarize the 4 types of JEV vaccine, and discuss the potential of an infectious JEV cDNA technology for future vaccine development. PMID:24161909

  5. Inactivated genotype 1 Japanese encephalitis vaccine for swine

    PubMed Central

    2014-01-01

    Purpose Japanese encephalitis is a reproductive disorder caused by Japanese encephalitis virus (JEV) in swine. Recent genotype (G) shift phenomenon (G3 to G1) in the Asia-wide has posed a challenge for proper prevention by the current vaccine strain. Thus, new kinds of JEV G1 vaccines with enhanced immunogenicity have been required for pigs. Materials and Methods Recombinant porcine granulocyte monocyte-colony stimulating factor (reporGM-CSF) protein was expressed in Spodoptera frugiperda (Sf-9) cells using baculovirus expression system. Two kinds of trials with inactivated JEV vaccines containing IMS1313 adjuvant (Seppic, France) were prepared with or without reporGM-CSF protein. Safety and immunogenicity of the pigs inoculated with the JEV vaccines via intramuscular route was evaluated for 28 days after inoculation. Results Mice, guinea pigs, and fattening pigs inoculated with the inactivated vaccine showed no signs for 14 and 21 days. Both hemagglutination inhibition and plaque reduction neutralizing antibody titers were significantly higher in pigs immunized with the vaccine containing reporGM-CSF protein after boosting. However, on the side of vaccine efficacy, most mice (87%) immunized with the inactivated JEV vaccine survived after virulent JEV challenge. Whereas the group with the vaccine containing reporGM-CSF protein showed lower protective effects than the vaccine alone for the biological activity of the GM-CSF depending on species specific. Conclusion Our data indicate that animals inoculated with the JEV vaccines was safe and pigs inoculated with inactivated JEV vaccine containing reporGM-CSF protein showed higher humoral immune responses than that of inactivated JEV vaccine without reporGM-CSF protein. PMID:25003095

  6. Japanese Encephalitis: Frequently Asked Questions

    MedlinePlus

    ... of Page How long does the Japanese encephalitis vaccination last? The duration of protection is unknown. For ... What are the side effects of Japanese encephalitis vaccination? Pain and tenderness are the most commonly reported ...

  7. Allergic reactions to Japanese encephalitis vaccine.

    PubMed

    Plesner, Anne-Marie

    2003-11-01

    The JEV widely is used in Asian countries each year and is an important vaccine for travelers to the East from other parts of the world. JE virus is a zoonotic disease with natural reservoirs and cannot be eliminated. Although a declining incidence of JE has been observed in Asia because of reduced transmission by agricultural approaches and vaccination, the most important control measure now, and in the future, is vaccination of humans against JE. The inactivated vaccine, produced from infected mouse-brain-derived tissue, is the only commercially available vaccine. There are several concerns with the use of this vaccine. It is expensive, requires two or three doses to achieve protective efficacy, and, in practice, requires further booster doses to maintain immunity. The apparent increase in allergic reactions in the first part of the 1990s has set focus on the safety of the JEV. A cheap, live attenuated SA 14-14-2 vaccine is used almost exclusively in China and parts of Korea, but there have been no trials of SA 14-14-2 vaccine outside JE endemic countries. The vaccine seems to be highly efficient, and few adverse events have been observed; however, PHK cells are used for the production of this vaccine, and these cells are not approved by the WHO. A satisfactory cell substrate is needed. A committee under the WHO has proposed that for the live JEV, there should be validity of the assays for retrovirus when applied to PHK cell substrate and validity of the mouse assays for neurovirulence. Further information should be reviewed on the long-term follow-up of recipients of the vaccine. Several new types of vaccines have reached the phase of clinical trials; however, studies remain to be completed. Until a new vaccine is available, the priority of surveillance of adverse events and the continuous reporting of such events to the users of the vaccines must be of importance. This fact is highlighted by the possibility of the varying frequency of adverse events with

  8. Japanese encephalitis.

    PubMed

    Morita, K; Nabeshima, T; Buerano, C C

    2015-08-01

    Japanese encephalitis (JE) is an inflammation of the central nervous system in humans and animals, specifically horses and cattle. The disease, which can sometimes be fatal, is caused by the flavivirus Japanese encephalitis virus (JEV), of which there are five genotypes (genotypes 1, 2, 3, 4 and 5). The transmission cycle of the virus involves pigs and wild birds as virus amplifiers and mosquitoes as vectors for transferring the virus between amplifying hosts and to dead- end hosts, i.e. humans, horses and cattle. In horses and cattle the disease is usually asymptomatic, but when clinical signs do occur they include fever, decreased appetite, frothing at the mouth, rigidity of the legs and recumbency, and neurological signs, such as convulsive fits, circling, marked depression and disordered consciousness. In pigs, it can cause abortion and stillbirths. At present, the virus is detected in a wide area covering eastern and southern Asia, Indonesia, northern Australia, Papua New Guinea and Pakistan. JEV RNA has also been detected in Italy, first in dead birds in 1997 and 2000 and then in mosquitoes in 2010. Genotype shift, i.e. a change of genotype from genotype 3 to genotype 1, has occurred in some countries, namely Japan, South Korea, Chinese Taipei and Vietnam. Laboratory methods are available for confirming the causative agent of the disease. There are control measures to prevent or minimise infection and, among them, vaccination is one of the most important and one which should be adopted in endemic and epidemic areas. PMID:26601447

  9. Development of a vaccine to prevent Japanese encephalitis: a brief review

    PubMed Central

    Wiwanitkit, Viroj

    2009-01-01

    Japanese encephalitis (ICD 10: A83.0) is an important specific viral encephalitis caused by the Japanese encephalitis virus, a virus of the Flavivirus group. Millions of people, especially those in endemic areas of developing countries in Asia, are at high risk from this infection. Therefore proper management to deal with this virus is essential. There is no specific treatment for Japanese encephalitis virus. Supportive and symptomatic treatments are usually used, which emphasize the importance of prevention in this specific neurological disorder. Vector control or vaccination can be used to prevent the disease. Because the existing Japanese encephalitis vaccine poses some undesirable problems, a new vaccine is needed. The process of developing a new vaccine is briefly discussed. PMID:20360904

  10. Studies on Japanese B Encephalitis Virus Vaccines from Tissue Culture

    PubMed Central

    Singh, Balwant; Hammon, W. McD.

    1971-01-01

    A study was carried out to evaluate the reliability of and to determine the mechanism involved in an antigen extinction mouse intraperitoneal (ip) challenge test for potency of a cell culture vaccine for Japanese B encephalitis, a modification of a test originated by Sabin for a mouse brain vaccine. Some comparisons were made with the official Japanese test using an intracerebral (ic) challenge after a more prolonged immunization procedure. The Japanese method of using a lyophilized reference vaccine with each test was also employed. It was found that the ip and the ic test appeared to show similar relative differences between lots. The ip test was more quickly and readily performed, gave reasonably consistent results on repetition, and, when used with a suitable reference vaccine, gave promise of being an entirely suitable and reliable test. Immunization by the intramuscular route rather than by the regular ip route appeared to offer no advantage and was less consistent in responses shown. Neutralizing antibody responses of the mice in the standard procedure were very quick to appear, about 4 days after the first dose of vaccine and had a peak titer about the seventh day, the time of challenge. This titer fell quickly unless challenge occurred. The antibody was heat stable, but it was readily inactivated by 2-mercaptoethanol (2-ME). Not until the 11th or 15th day did a small amount of immunoglobulin G appear. Challenge on day 7 significantly increased titers, but this antibody was also mostly inactivated by 2-ME. Interferon did not appear to play any significant role in the protection shown by the mice. PMID:4325023

  11. Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

    PubMed Central

    Li, Xing; Ma, Shu-Juan; Liu, Xie; Jiang, Li-Na; Zhou, Jun-Hua; Xiong, Yi-Quan; Ding, Hong; Chen, Qing

    2015-01-01

    A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research. PMID:25668666

  12. Immunogenicity and safety of currently available Japanese encephalitis vaccines: a systematic review.

    PubMed

    Li, Xing; Ma, Shu-Juan; Liu, Xie; Jiang, Li-Na; Zhou, Jun-Hua; Xiong, Yi-Quan; Ding, Hong; Chen, Qing

    2014-01-01

    A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research. PMID:25668666

  13. A collaborative study of an alternative in vitro potency assay for the Japanese encephalitis vaccine.

    PubMed

    Kim, Byung-Chul; Kim, Do-Keun; Kim, Hyung-Jin; Hong, Seung-Hwa; Kim, Yeonhee; Lim, Jong-Mi; Hong, JiYoung; Kim, Cheol-Hee; Park, Yong-Keun; Kim, Jaeok

    2016-09-01

    The use of inactivated Japanese encephalitis (JE) vaccines has been ongoing in East Asia for 40 years. A mouse immunogenicity assay followed by a Plaque Reduction Neutralization (PRN) Test (PRNTest) is currently recommended for each lot release of the vaccine by many national authorities. We developed an alternative in vitro ELISA to determine the E antigen content of the Japanese encephalitis virus to observe the 3Rs strategy. A collaborative study for replacing the in vivo potency assay for the Japanese encephalitis vaccine with the in vitro ELISA assay was confirmed comparability between these two methods. The study demonstrated that an in vitro assay could perform faster and was more convenient than the established in vivo PRNTest. Moreover, this assay had better precision and reproducibility compared with the conventional in vivo assay. Additionally, the content of antigen determined using the in vitro ELISA correlated well with the potency of the in vivo assay. Furthermore, this method allowed discrimination between individual lots. Thus, we propose a progressive switch from the in vivo assay to the in vitro ELISA for JE vaccine quality control. PMID:27497622

  14. Use of Japanese Encephalitis Vaccine in US Travel Medicine Practices in Global TravEpiNet

    PubMed Central

    Deshpande, Bhushan R.; Rao, Sowmya R.; Jentes, Emily S.; Hills, Susan L.; Fischer, Marc; Gershman, Mark D.; Brunette, Gary W.; Ryan, Edward T.; LaRocque, Regina C.

    2014-01-01

    Few data regarding the use of Japanese encephalitis (JE) vaccine in clinical practice are available. We identified 711 travelers at higher risk and 7,578 travelers at lower risk for JE who were seen at US Global TravEpiNet sites from September of 2009 to August of 2012. Higher-risk travelers were younger than lower-risk travelers (median age = 29 years versus 40 years, P < 0.001). Over 70% of higher-risk travelers neither received JE vaccine during the clinic visit nor had been previously vaccinated. In the majority of these instances, clinicians determined that the JE vaccine was not indicated for the higher-risk traveler, which contradicts current recommendations of the Advisory Committee on Immunization Practices. Better understanding is needed of the clinical decision-making regarding JE vaccine in US travel medicine practices. PMID:25070999

  15. Short report: absence of protective neutralizng antibodies to West Nile virus in subjects following vaccination with Japanese encephalitis or dengue vaccines.

    PubMed

    Kanesa-Thasan, N; Putnak, J R; Mangiafico, J A; Saluzzo, J E; Ludwig, G V

    2002-02-01

    Protection of individuals against West Nile (WN) encephalitis is an emerging concern in the United States and Europe. We investigated whether immunization with licensed inactivated Japanese encephalitis (JE) vaccine or experimental live attenuated dengue vaccines resulted in induction of cross-neutralizing antibodies against WN virus. Protective neutralizing antibody titers to WN virus were not detected in any volunteer despite successful immunization to related flaviviruses. Vaccination against JE or dengue is unlikely to prevent WN virus infection but may still protect against disease.

  16. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice

    PubMed Central

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-01

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention. PMID:26818736

  17. Cross-protection induced by Japanese encephalitis vaccines against different genotypes of Dengue viruses in mice.

    PubMed

    Li, Jieqiong; Gao, Na; Fan, Dongying; Chen, Hui; Sheng, Ziyang; Fu, Shihong; Liang, Guodong; An, Jing

    2016-01-01

    Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses that cause very high global disease burdens. Although cross-reactivity and cross-protection within flaviviruses have been demonstrated, the effect of JEV vaccination on susceptibility to DENV infection has not been well elucidated. In this study, we found that vaccination with the JEV inactivated vaccine (INV) and live attenuated vaccine (LAV) could induce cross-immune responses and cross-protection against DENV1-4 in mice. Despite the theoretical risk of immune enhancement, no increased mortality was observed in our mouse model. Additionally, low but consistently detectable cross-neutralizing antibodies against DENV2 and DENV3 were also observed in the sera of JEV vaccine-immunized human donors. The results suggested that both JEV-LAV and JEV-INV could elicit strong cross-immunity and protection against DENVs, indicating that inoculation with JEV vaccines may influence the distribution of DENVs in co-circulated areas and that the cross-protection induced by JEV vaccines against DENVs might provide important information in terms of DENV prevention. PMID:26818736

  18. Japanese viral encephalitis

    PubMed Central

    Tiroumourougane, S; Raghava, P; Srinivasan, S

    2002-01-01

    One of the leading causes of acute encephalopathy in children in the tropics is Japanese encephalitis (JE). Transmitted by the culex mosquito, this neurotropic virus predominately affects the thalamus, anterior horns of the spinal cord, cerebral cortex, and cerebellum. It mainly affects children <15 years and is mostly asymptomatic. The occasional symptomatic child typically presents with a neurological syndrome characterised by altered sensorium, seizures, and features of intracranial hypertension. Aetiological diagnosis is based on virus isolation or demonstration of virus specific antigen or antibodies in the cerebrospinal fluid/blood. Though no antiviral drug is available against JE, effective supportive management can improve the outcome. Control of JE involves efficient vector control and appropriate use of vaccines. PMID:11930023

  19. IC-51, an injectable vaccine for the prevention of Japanese encephalitis virus infection.

    PubMed

    Jones, Taff

    2009-02-01

    The mosquito-borne Japanese encephalitis (JE) virus is the major etiological agent of viral encephalitis in children living in South-East Asia, causing comas, seizures and Parkinson's disease-like movement disorders. Travelers and military personnel visiting the region are also highly susceptible to the disease. As the population in South-East Asia increases, more land is irrigated to produce rice paddies (the ideal breeding habitat for mosquitoes), and pig breeding (a zoonotic host for mosquitoes) becomes more widespread. Given the exponential growth in tourism to the region and the globalization of business and commerce, an enhanced requirement for mass vaccination exists. In the West, the current licensed vaccine against JE, JE-VAX, has been highly effective; however, the use of mouse brain-derived virus has been linked to cases of acute disseminated encephalomyelitis. Intercell AG, under license from VaccGen International LLC, is developing IC-51, a formalin-inactivated vaccine derived from cell culture-based attenuated virus that has been adapted to grow in Vero cells (African green monkey kidney cells). In extensive clinical trials performed to date, IC-51 was safe, with mild to moderate adverse events reported. In terms of immunogenicity, IC-51 was highly effective, demonstrating rapid seroconversion rates and long-term maintenance of geometric mean titers that exceeded the protective titer. The results suggests that IC-51 is fully compliant with the stringent regulatory requirements set by the WHO, has an acceptable safety profile and is non-inferior to JE-VAX.

  20. Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis.

    PubMed

    Lai, Ching-Juh; Monath, Thomas P

    2003-01-01

    Many arthropod-borne flaviviruses are important human pathogens responsible for diverse illnesses, including YF, JE, TBE, and dengue. Live, attenuated vaccines have afforded the most effective and economical means of prevention and control, as illustrated by YF 17D and JE SA14-14-2 vaccines. Recent advances in recombinant DNA technology have made it possible to explore a novel approach for developing live attenuated flavivirus vaccines against other flaviviruses. Full-length cDNA clones allow construction of infectious virus bearing attenuating mutations or deletions incorporated in the viral genome. It is also possible to create chimeric flaviviruses in which the structural protein genes for the target antigens of a flavivirus are replaced by the corresponding genes of another flavivirus. By combining these molecular techniques, the DNA sequences of DEN4 strain 814669, DEN2 PDK-53 candidate vaccine and YF 17D vaccine have been used as the genetic backbone to construct chimeric flaviviruses with the required attenuation phenotype and expression of the target antigens. Encouraging results from preclinical and clinical studies have shown that several chimeric flavivirus vaccines have the safety profile and satisfactory immunogenicity and protective efficacy to warrant further evaluation in humans. The chimeric flavivirus strategy has led to the rapid development of novel live-attenuated vaccines against dengue, TBE, JE, and West Nile viruses. PMID:14714441

  1. Safety of Japanese encephalitis live attenuated vaccination in post-marketing surveillance in Guangdong, China, 2005-2012.

    PubMed

    Liu, Yu; Lin, Hualiang; Zhu, Qi; Wu, Chenggang; Zhao, Zhanjie; Zheng, Huizhen

    2014-03-26

    We reviewed the adverse events following immunization of live attenuated Japanese encephalitis vaccine in Guangdong Province, China. During the period of 2005-2012, 23 million doses of live attenuated Japanese encephalitis vaccine were used and 1426 adverse events were reported (61.24 per million doses); of which, 570 (40%) were classified as allergic reactions (24.48 per million doses), 31 (2%) were neurologic events (1.33 per million doses), and 36 (2.5%) were diagnosed as serious adverse events (1.55 per million doses). This study suggests that the JEV-L has a reasonable safety profile, most adverse events are relatively mild, with relatively rare neurologic events being observed. PMID:24503272

  2. Points to consider in the development of a surrogate for efficacy of novel Japanese encephalitis virus vaccines.

    PubMed

    Markoff, L

    2000-05-26

    Although an effective killed virus vaccine to prevent illness due to Japanese encephalitis virus (JEV) infection exists, many authorities recognize that a safe, effective live JEV vaccine is desirable in order to reduce the cost and the number of doses of vaccine required per immunization. A large-scale clinical efficacy trail for such a vaccine would be both unethical and impractical. Therefore, a surrogate for the efficacy of JE vaccines should be established. Detection of virus-neutralizing antibodies in sera of vaccinees could constitute such a surrogate for efficacy. Field studies of vaccinees in endemic areas and studies done in mice already exist to support this concept. Also, titers of virus-neutralizing antibodies are already accepted as a surrogate for the efficacy of yellow fever virus vaccines and for the efficacy of other viral vaccines as well. In developing a correlation between N antibody titers and protection from JEV infection, standard procedures must be validated and adopted for both measuring N antibodies and for testing in animals. A novel live virus vaccine could be tested in the mouse and/or the monkey model of JEV infection to establish a correlation between virus-neutralizing antibodies elicited by the vaccines and protection from encephalitis. In addition, sera of subjects receiving the novel live JEV vaccine in early clinical trials could be passively transferred to mice or monkeys in order to establish the protective immunogenicity of the vaccine in humans. A monkey model for JEV infection was recently established by scientists at WRAIR in the US. From this group, pools of JEV of known infectivity for Rhesus macaques may be obtained for testing of immunity elicited by live JE vaccine virus. PMID:10821970

  3. West Nile virus infection and serologic response among persons previously vaccinated against yellow fever and Japanese encephalitis viruses.

    PubMed

    Johnson, B W; Kosoy, O; Martin, D A; Noga, A J; Russell, B J; Johnson, A A; Petersen, L R

    2005-01-01

    It is hypothesized that previous heterologous flaviviral exposure may modulate clinical illness among persons infected with West Nile virus (WNV). Little is known about the serological response in such persons. In summer 2003, a WNV outbreak occurred in Colorado, the location of the Centers for Disease Control and Prevention, Division of Vector-Borne Infectious Diseases (DVBID). DVBID employees, most previously vaccinated with yellow fever virus (YFV) or Japanese encephalitis virus (JEV) vaccines, were studied to determine whether previous vaccination affected symptom development among those subsequently infected with WNV during the outbreak, as well as their serological response. Serum samples collected in December 2003 and previously banked samples were tested using the plaque reduction neutralization test (PRNT) against WNV, Saint Louis encephalitis virus, dengue- 4 virus, JEV, and YFV. Specimens shown to have WNV antibody by PRNT were tested by IgM and IgG enzymelinked immunosorbent assays (ELISAs). Ten (9%) of 113 serosurvey participants had WNV neutralizing antibody titers in December 2003. PRNT titers from previous specimens showed that one of the ten had seroconverted to WNV before 2003. Of the remaining nine participants, seven reported illness in the summer of 2003, two of which were unvaccinated and five previously vaccinated. In the December 2003 specimens, five persons previously unvaccinated or vaccinated only against YFV had a fourfold or greater neutralizing titer with WNV than with other flaviviruses, whereas no persons previously vaccinated against JEV or JEV and YFV showed a similar difference in neutralizing titers. Eight of nine persons infected in 2003 had negative or indeterminate WNV MAC-ELISA results in the December 2003 sample; the ninth person was vaccinated against YFV one month previously, and was also YFV positive by MAC-ELISA. We conclude that previous flaviviral vaccination does not markedly affect the development of WNV fever and

  4. Comparing the immunogenicity and safety of 3 Japanese encephalitis vaccines in Asia-Pacific area: A systematic review and meta-analysis.

    PubMed

    Wang, Shi-Yuan; Cheng, Xiao-Hua; Li, Jing-Xin; Li, Xi-Yan; Zhu, Feng-Cai; Liu, Pei

    2015-01-01

    Japanese encephalitis virus (JEV), a leading cause of Japanese encephalitis (JE) in children and adults, is a major public health problem in Asian countries. This study reports a meta-analysis of the immunogenicity and safety of vaccines used to protect infants or children from JE. Three types of JE vaccine were examined, namely, Japanese encephalitis live-attenuated vaccine (JEV-L), Japanese encephalitis inactivated vaccine (Vero cell) (JEV-I(Vero)), and Japanese encephalitis inactivated vaccine (primary hamster kidney cell) (JEV-I(PHK)). These vaccines are used to induce fundamental immunity against JE; however, few studies have compared their immunogenicity and safety in infants and young children less than 2 years of age. Data were obtained by searching 5 databases: Web of Science, PubMed, China National Knowledge Infrastructure, the China Wanfang database, and the Cochrane database. Fifteen articles were identified and scored using the Jadad score for inclusion in the meta-analysis. Random effect models were used to calculate the pooled seroconversion rate and adverse reaction rate when tests for heterogeneity were significant. The results showed that the pooled seroconversion rate for JEV-I(PHK) (62.23%) was lower than that for JEV-I(Vero) (86.49%) and JEV-L (83.52%), and that the pooled adverse reaction rate for JEV-L (18.09%) was higher than that for JEV-I(PHK) (10.08%) and JEV-I(Vero) (12.49%). The pooled relative risk was then calculated to compare the seroconversion and adverse reaction rates. The results showed that JEV-I(Vero) and JEV-L were more suitable than JEV-I(PHK) for inducing fundamental immunity to JE in infants and children less than 2 years of age.

  5. Partially Neutralizing Potency against Emerging Genotype I Virus among Children Received Formalin-Inactivated Japanese Encephalitis Virus Vaccine

    PubMed Central

    Fan, Yi-Chin; Chen, Jo-Mei; Chiu, Hsien-Chung; Chen, Yi-Ying; Lin, Jen-Wei; Shih, Chen-Chang; Chen, Chih-Ming; Chang, Chao-Chin; Chang, Gwong-Jen J.; Chiou, Shyan-Song

    2012-01-01

    Background Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII) JEV vaccine. Methodology/Principal Findings To evaluate the influence of genotype replacement on the post-vaccination viral neutralizing ability by GIII and GI viruses, the small panel of vaccinated-children serum specimens was assembled, and the reciprocal 50% plaque-reduction neutralizing antibody titers (PRNT50) were measured against Nakayama vaccine strain, CJN GIII human brain isolate and TC2009-1 GI mosquito isolate. The seropositivity rate (PRNT50≥1∶10) and geometric mean titers (GMT) against the TC2009-1 virus were the lowest among the three viruses. The protective threshold against the CJN and TC2009-1 viruses could only be achieved when the GMT against Nakayama virus was ≥1∶20 or ≥1∶80, respectively. Using undiluted vaccinees' sera, the enhancement of JEV infection in K562 cells was observed in some low or non-neutralizing serum specimens. Conclusions/Significance Our preliminary study has shown that neutralizing antibodies, elicited by the mouse brain-derived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus, but more detailed studies are needed to address the potential impact on the future vaccine policy. PMID:23029592

  6. Safety and immunogenicity of a delta inulin-adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals.

    PubMed

    Bielefeldt-Ohmann, Helle; Prow, Natalie A; Wang, Wenqi; Tan, Cindy S E; Coyle, Mitchell; Douma, Alysha; Hobson-Peters, Jody; Kidd, Lisa; Hall, Roy A; Petrovsky, Nikolai

    2014-12-17

    In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74-152 days old, received two injections of JE-ADVAX™. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAX™ was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAX™ at 36-83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAX™ booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAX™ appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.

  7. Correlation of protection against Japanese encephalitis virus and JE vaccine (IXIARO(®)) induced neutralizing antibody titers.

    PubMed

    Van Gessel, Yvonne; Klade, Christoph S; Putnak, Robert; Formica, Alessandra; Krasaesub, Somporn; Spruth, Martin; Cena, Bruno; Tungtaeng, Anchalee; Gettayacamin, Montip; Dewasthaly, Shailesh

    2011-08-11

    Immune sera from volunteers vaccinated in a blinded Phase 3 clinical trial with JE-VAX(®) and a new Japanese encephalitis virus (JEV) vaccine (IC51 or IXIARO), were tested for the ability to protect mice against lethal JEV challenge. Sera from IXIARO vaccinated subjects were pooled into four batches based on neutralizing antibody measured by plaque reduction neutralization test (PRNT(50) titer): high (∼200), medium (∼40-50), low (∼20) and negative (<10). Pooled sera from JE-VAX(®) vaccinated subjects (PRNT(50) titer∼55) and pooled JEV antibody negative pre-vaccination sera were used as controls. Groups of ten 6- to 7-week-old female ICR mice were injected intraperitoneally with 0.5 ml of each serum pool diluted 1:2 or 1:10, challenged approximately 18 h later with a lethal dose of either JEV strain SA14 (genotype III) or strain KE-093 (genotype I) and observed for 21 days. All mice in the non-immune serum groups developed clinical signs consistent with JEV infection or died, whereas high titer sera from both IXIARO and JE-VAX(®) sera protected 90-100% of the animals. Statistical tests showed similar protection against both JEV strains SA14 and KE-093 and protection correlated with the anti-JEV antibody titer of IXIARO sera as measured by PRNT(50). Ex vivo neutralizing antibody titers showed that almost all mice with a titer of 10 or greater were fully protected. In a separate study, analysis of geometric mean titers (GMTs) of the groups of mice vaccinated with different doses of IXIARO and challenged with JEV SA14 provided additional evidence that titers≥10 were protective.

  8. Bivalent vaccine platform based on Japanese encephalitis virus (JEV) elicits neutralizing antibodies against JEV and hepatitis C virus

    PubMed Central

    Saga, Ryohei; Fujimoto, Akira; Watanabe, Noriyuki; Matsuda, Mami; Hasegawa, Makoto; Watashi, Koichi; Aizaki, Hideki; Nakamura, Noriko; Tajima, Shigeru; Takasaki, Tomohiko; Konishi, Eiji; Kato, Takanobu; Kohara, Michinori; Takeyama, Haruko; Wakita, Takaji; Suzuki, Ryosuke

    2016-01-01

    Directly acting antivirals recently have become available for the treatment of hepatitis C virus (HCV) infection, but there is no prophylactic vaccine for HCV. In the present study, we took advantage of the properties of Japanese encephalitis virus (JEV) to develop antigens for use in a HCV vaccine. Notably, the surface-exposed JEV envelope protein is tolerant of inserted foreign epitopes, permitting display of novel antigens. We identified 3 positions that permitted insertion of the HCV E2 neutralization epitope recognized by HCV1 antibody. JEV subviral particles (SVP) containing HCV-neutralization epitope (SVP-E2) were purified from culture supernatant by gel chromatography. Sera from mice immunized with SVP-E2 inhibited infection by JEV and by trans-complemented HCV particles (HCVtcp) derived from multi-genotypic viruses, whereas sera from mice immunized with synthetic E2 peptides did not show any neutralizing activity. Furthermore, sera from mice immunized with SVP-E2 neutralized HCVtcp with N415K escape mutation in E2. As with the SVP-E2 epitope-displaying particles, JEV SVPs with HCV E1 epitope also elicited neutralizing antibodies against HCV. Thus, this novel platform harboring foreign epitopes on the surface of the particle may facilitate the development of a bivalent vaccine against JEV and other pathogens. PMID:27345289

  9. Japanese encephalitis in the USSR*

    PubMed Central

    Graščenkov, N. I.

    1964-01-01

    The author sketches the history of Japanese encephalitis in the USSR, where it has been thoroughly studied since it first occurred in 1938. After a brief outline of its epidemiology, he describes the pathogenesis, the signs and symptoms, and the pathophysiological mechanisms that make this form of encephalitis so dangerous. He also discusses the diagnosis and the methods of treatment and prevention practised in the USSR. PMID:14153405

  10. Dynamics of Japanese Encephalitis Virus Transmission among Pigs in Northwest Bangladesh and the Potential Impact of Pig Vaccination

    PubMed Central

    Khan, Salah Uddin; Salje, Henrik; Hannan, A.; Islam, Md. Atiqul; Bhuyan, A. A. Mamun; Islam, Md. Ariful; Rahman, M. Ziaur; Nahar, Nazmun; Hossain, M. Jahangir; Luby, Stephen P.; Gurley, Emily S.

    2014-01-01

    Background Japanese encephalitis (JE) virus infection can cause severe disease in humans, resulting in death or permanent neurologic deficits among survivors. Studies indicate that the incidence of JE is high in northwestern Bangladesh. Pigs are amplifying hosts for JE virus (JEV) and a potentially important source of virus in the environment. The objectives of this study were to describe the transmission dynamics of JEV among pigs in northwestern Bangladesh and estimate the potential impact of vaccination to reduce incidence among pigs. Methodology/Principal Findings We conducted a comprehensive census of pigs in three JE endemic districts and tested a sample of them for evidence of previous JEV infection. We built a compartmental model to describe JEV transmission dynamics in this region and to estimate the potential impact of pig vaccination. We identified 11,364 pigs in the study area. Previous JEV infection was identified in 30% of pigs with no spatial differences in the proportion of pigs that were seropositive across the study area. We estimated that JEV infects 20% of susceptible pigs each year and the basic reproductive number among pigs was 1.2. The model suggest that vaccinating 50% of pigs each year resulted in an estimated 82% reduction in annual incidence in pigs. Conclusions/Significance The widespread distribution of historic JEV infection in pigs suggests they may play an important role in virus transmission in this area. Future studies are required to understand the contribution of pig infections to JE risk in humans and the potential impact of pig vaccination on human disease. PMID:25255286

  11. Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

    PubMed Central

    Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

    2014-01-01

    The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

  12. WHO working group on the quality, safety and efficacy of japanese encephalitis vaccines (live attenuated) for human use, Bangkok, Thailand, 21-23 February 2012.

    PubMed

    Trent, Dennis W; Minor, Philip; Jivapaisarnpong, Teeranart; Shin, Jinho

    2013-11-01

    Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.

  13. The Involvement of Microglial Cells in Japanese Encephalitis Infections

    PubMed Central

    Thongtan, Thananya; Thepparit, Chutima; Smith, Duncan R.

    2012-01-01

    Despite the availability of effective vaccines, Japanese encephalitis virus (JEV) infections remain a leading cause of encephalitis in many Asian countries. The virus is transmitted to humans by Culex mosquitoes, and, while the majority of human infections are asymptomatic, up to 30% of JE cases admitted to hospital die and 50% of the survivors suffer from neurological sequelae. Microglia are brain-resident macrophages that play key roles in both the innate and adaptive immune responses in the CNS and are thus of importance in determining the pathology of encephalitis as a result of JEV infection. PMID:22919405

  14. A cohort event monitoring to determine the adverse events following administration of mouse brain derived, inactivated Japanese Encephalitis vaccine in an endemic district in Sri Lanka.

    PubMed

    De Alwis, K N L S K; Abeysinghe, M R N; Wickramesinghe, A R; Wijesinghe, P R

    2014-02-12

    Introduction of human immunization reduced Japanese Encephalitis (JE) cases dramatically in Sri Lanka. However, the increased reporting of adverse events following immunization (AEFI) affected vaccine acceptance by the community. Against this background, we describe the incidence of overall AEFI and incidence and profile of AEFI, thought to be causally related to the mouse-brain derived JE vaccine. A follow-up of 9798 vaccine recipients was performed for a period of two weeks post-vaccination. Parents self-recorded observed signs and symptoms. The self-records were collected by trained supervisors. All monitored children who manifested symptom/s were investigated in details by medical officers experienced in AEFI investigations within two weeks after ending the follow-up period. Using the results of the investigation, the causality assessment was performed. The estimated cumulative incidence rate of overall AEFI was 8.6 children per 100 immunizations. The same for observed AEFI consistent with causal association to the inactivated JE vaccine was 4.3 children (95% CI-3.9-4.7%) per 100 immunizations. The most frequent AEFI was fever (81%). The frequency of high fever (>102 °F) was 26%. Other major AEFI were body ache (22%) vomiting (21%), urticaria (19%), pruritus (5%), and headache (5%). Though 83% of children with AEFI thought to be causally related to the vaccine sought medical care, only 6.6% required hospitalizations. The incidence rate of AEFI in the cohort event monitoring was several-fold higher than that reported through the national AEFI surveillance system. The incidence rate of allergic manifestations among Sri-Lankan children approached what was reported for non-endemic settings and was higher than in other JE endemic populations elsewhere. Contrary to the belief of medical practitioners and the general public, incidence of seizures was low and vaccine related other neurological manifestations were absent.

  15. Epidemiology of Japanese encephalitis: past, present, and future prospects.

    PubMed

    Wang, Huanyu; Liang, Guodong

    2015-01-01

    Japanese encephalitis (JE) is one of severe viral encephalitis that affects individuals in Asia, western Pacific countries, and northern Australia. Although 67,900 JE cases have been estimated among 24 JE epidemic countries annually, only 10,426 have been reported in 2011. With the establishment of JE surveillance and vaccine use in some countries, the JE incidence rate has decreased; however, serious outbreaks still occur. Understanding JE epidemics and identifying the circulating JE virus genotypes will improve JE prevention and control. This review summarizes the current epidemiology data in these countries.

  16. Epidemiology of Japanese encephalitis: past, present, and future prospects

    PubMed Central

    Wang, Huanyu; Liang, Guodong

    2015-01-01

    Japanese encephalitis (JE) is one of severe viral encephalitis that affects individuals in Asia, western Pacific countries, and northern Australia. Although 67,900 JE cases have been estimated among 24 JE epidemic countries annually, only 10,426 have been reported in 2011. With the establishment of JE surveillance and vaccine use in some countries, the JE incidence rate has decreased; however, serious outbreaks still occur. Understanding JE epidemics and identifying the circulating JE virus genotypes will improve JE prevention and control. This review summarizes the current epidemiology data in these countries. PMID:25848290

  17. Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III.

    PubMed

    Fan, Yi-Chin; Chiu, Hsien-Chung; Chen, Li-Kuang; Chang, Gwong-Jen J; Chiou, Shyan-Song

    2015-10-01

    Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H2O2, but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H2O2, which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines. PMID:26495991

  18. Formalin Inactivation of Japanese Encephalitis Virus Vaccine Alters the Antigenicity and Immunogenicity of a Neutralization Epitope in Envelope Protein Domain III

    PubMed Central

    Fan, Yi-Chin; Chiu, Hsien-Chung; Chen, Li-Kuang; Chang, Gwong-Jen J.; Chiou, Shyan-Song

    2015-01-01

    Formalin-inactivated Japanese encephalitis virus (JEV) vaccines are widely available, but the effects of formalin inactivation on the antigenic structure of JEV and the profile of antibodies elicited after vaccination are not well understood. We used a panel of monoclonal antibodies (MAbs) to map the antigenic structure of live JEV virus, untreated control virus (UCV), formalin-inactivated commercial vaccine (FICV), and formalin-inactivated virus (FIV). The binding activity of T16 MAb against Nakayama-derived FICV and several strains of FIV was significantly lower compared to live virus and UCV. T16 MAb, a weakly neutralizing JEV serocomplex antibody, was found to inhibit JEV infection at the post-attachment step. The T16 epitope was mapped to amino acids 329, 331, and 389 within domain III (EDIII) of the envelope (E) glycoprotein. When we explored the effect of formalin inactivation on the immunogenicity of JEV, we found that Nakayama-derived FICV, FIV, and UCV all exhibited similar immunogenicity in a mouse model, inducing anti-JEV and anti-EDII 101/106/107 epitope-specific antibodies. However, the EDIII 329/331/389 epitope-specific IgG antibody and neutralizing antibody titers were significantly lower for FICV-immunized and FIV-immunized mouse serum than for UCV-immunized. Formalin inactivation seems to alter the antigenic structure of the E protein, which may reduce the potency of commercially available JEV vaccines. Virus inactivation by H2O2, but not by UV or by short-duration and higher temperature formalin treatment, is able to maintain the antigenic structure of the JEV E protein. Thus, an alternative inactivation method, such as H2O2, which is able to maintain the integrity of the E protein may be essential to improving the potency of inactivated JEV vaccines. PMID:26495991

  19. Behavioural disturbances following Japanese B encephalitis.

    PubMed

    Monnet, François P

    2003-10-01

    Clinically, Japanese B encephalitis (JBE) is often overlooked as its occurrence in Western countries is rare. However, its neurological, cognitive and psychiatric sequelae constitute a major public health problem in the Far East where JBE is endemic. European and American subjects may however experience the JBE when returning from a Far East journey. In such cases, misdiagnosis is frequent because of the unawareness of psychiatrists and physicians. The present review, therefore, documents the behavioural and cognitive sequelae of JBE. This reactivates the debate concerning the vaccination against the virus all the more that the literature enlightens the importance of the vaccination for those who undertake frequent and extensive tourist excursions to the Orient but still discusses it for occasional travellers. Following is a case-report of a young western European post-graduate student who has contracted JBE by experiencing an acute febrile delirium during an unusual short stay in South East Asia. Pyramidal syndrome, Parkinsonism and amnesia were the prominent acute deficits. Whereas these faded in great part during convalescence, emotional and behavioural instability associated with affective involvement, obsessive-compulsive symptoms and cognitive impairments appeared. A partial recovery was however obtained with neuroleptics, lithium and following electro-convulsive therapy. Organic personality syndrome was persistent and thereafter constituted the main sequelae syndrome. Hypersomnia and several enuretic episodes persisted. PMID:14611920

  20. An inactivated cell culture Japanese encephalitis vaccine (JE-ADVAX) formulated with delta inulin adjuvant provides robust heterologous protection against West Nile encephalitis via cross-protective memory B cells and neutralizing antibody.

    PubMed

    Petrovsky, Nikolai; Larena, Maximilian; Siddharthan, Venkatraman; Prow, Natalie A; Hall, Roy A; Lobigs, Mario; Morrey, John

    2013-09-01

    West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. Given the availability of approved human JE vaccines, this study asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE virus antigen formulated with Advax delta inulin adjuvant, could provide heterologous protection against WNV infection in wild-type and β2-microglobulin-deficient (β2m(-/-)) murine models. Mice immunized twice or even once with JE-ADVAX were protected against lethal WNV challenge even when mice had low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly, β2m(-/-) mice immunized with JE-ADVAX were protected against lethal WNV challenge in the absence of CD8(+) T cells and prechallenge WNV antibody titers. Protection against WNV could be adoptively transferred to naive mice by memory B cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum cross-neutralizing antibody titers, JE-ADVAX induced a memory B-cell population able to provide heterologous protection against WNV challenge. Heterologous protection was reduced when JE vaccine antigen was administered alone without Advax, confirming the importance of the adjuvant to induction of cross-protective immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide an alternative approach for control of a major human WNV epidemic.

  1. Induction of protective immunity in animals vaccinated with recombinant vaccinia viruses that express PreM and E glycoproteins of Japanese encephalitis virus.

    PubMed Central

    Yasuda, A; Kimura-Kuroda, J; Ogimoto, M; Miyamoto, M; Sata, T; Sato, T; Takamura, C; Kurata, T; Kojima, A; Yasui, K

    1990-01-01

    A cDNA clone representing the genome of structural proteins of Japanese encephalitis virus (JEV) was inserted into the thymidine kinase gene of vaccinia virus strains LC16mO and WR under the control of a strong early-late promoter for the vaccinia virus 7.5-kilodalton polypeptide. Indirect immunofluorescence and fluorescence-activated flow cytometric analysis revealed that the recombinant vaccinia viruses expressed JEV E protein on the membrane surface, as well as in the cytoplasm, of recombinant-infected cells. In addition, the E protein expressed from the JEV recombinants reacted to nine different characteristic monoclonal antibodies, some of which have hemagglutination-inhibiting and JEV-neutralizing activities. Radioimmunoprecipitation analysis demonstrated that two major proteins expressed in recombinant-infected cells were processed and glycosylated as the authentic PreM and E glycoproteins of JEV. Inoculation of rabbits with the infectious recombinant vaccinia virus resulted in rapid production of antiserum specific for the PreM and E glycoproteins of JEV. This antiserum had both hemagglutination-inhibiting and virus-neutralizing activities against JEV. Furthermore, mice vaccinated with the recombinant also produced JEV-neutralizing antibodies and were resistant to challenge with JEV. Images PMID:2159544

  2. Knowledge Obtained from an Elderly Case of Japanese Encephalitis.

    PubMed

    Itoh, Kyoko; Iwamoto, Kazuhide; Satoh, Yu; Fujita, Tomoaki; Takahashi, Kenta; Katano, Harutaka; Hasegawa, Hideki; Takasaki, Tomohiko; Tando, So; Fushiki, Shinji

    2016-01-01

    The nationwide introduction of a Japanese encephalitis (JE) vaccine has contributed to a reduction in the annual infection rate of JE in Japan. However, the current neutralizing antibody prevalence ratio in Japan is approximately 20% in children 3-4 years of age and in people in their forties and fifties. We herein report a man with JE who was definitively diagnosed by multi-virus real-time polymerase chain reaction employing biopsied brain tissue and serological examinations. JE should be kept in mind when a patient has severe encephalitis of unknown etiology. In order to protect the susceptible population from JE, vaccination is recommended, especially for children and middle-aged people. PMID:27580555

  3. Transdermal immunization with low-pressure-gene-gun mediated chitosan-based DNA vaccines against Japanese encephalitis virus.

    PubMed

    Huang, Han-Ning; Li, Tsung-Lin; Chan, Yi-Lin; Chen, Chien-Lung; Wu, Chang-Jer

    2009-10-01

    DNA vaccine is a milestone in contemporary vaccine development. It has considerably offset many shortcomings in conventional vaccines. Although DNA vaccines applied through 'traditional' high-pressure gene guns generally elicit high titers of protective immunity, such a practice however requires enormous investment in daunting instruments that often discourage vaccines due to an inevitable pain-eliciting effect. In this study, we exploited a less expensive yet low-pressure-gene-gun that can alleviate such phobia of pain. DNA vaccines were prepared by using the associative feature of cationic chitosan and anionic DNAs. The optimized N/P ratio is 3. The formulized complex sizes to nano-scale. The vaccine complexes were tested in C3H/HeN mice. The expression of GFP reporter gene was observable and traceable in epidermis and spleen over 3 days. The expressions of GFP and the activation of dendritic cells (DCs) were evident and co-localized in hair follicles and epidermis. C3H/HeN mice immunized with the developed chitosan-JEV DNA vaccines can elicit desired JEV specific antibodies, whereby the mice maintained high survival rates against 50xLD(50) JEV challenge. The low-pressure-gene-gun mediated chitosan-based JEV DNA vaccines have proven to be convenient and efficacious, thereby with high capacity in deployment for future prophylaxis against JEV outbreaks.

  4. Japanese encephalitis in two children--United States, 2010.

    PubMed

    2011-03-11

    Japanese encephalitis virus (JEV) is the leading cause of vaccine-preventable encephalitis in Asia and the western Pacific. JEV is maintained in an enzootic cycle involving mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. The virus is transmitted to humans primarily by Culex mosquitoes, which breed in flooded rice fields and pools of stagnant water and most often feed outdoors during the evening and night. JEV transmission occurs mainly in rural agricultural areas, but occasional human cases occur in urban areas. Japanese encephalitis (JE) in persons who have traveled or lived overseas is diagnosed infrequently in the United States, with only four cases identified from 1992 (when a JE vaccine was first licensed in the United States) to 2008. This report describes the only cases diagnosed in the United States and reported to CDC since then. The first was a fatal case in a U.S. child who had visited relatives in the Philippines. The other occurred in a refugee who became ill while traveling from Thailand to the United States and whose diagnosis was complicated by concurrent neurocysticercosis. JE should be considered in the differential diagnosis for any patient with an acute neurologic infection who recently has been in a JE-endemic country. Travelers to JE-endemic countries should be advised of the risk for JE and the importance of personal protective measures to prevent mosquito bites. JE vaccine should be considered for travelers who might be at greater risk based on the season, location, and duration of their visit and their planned activities. PMID:21389931

  5. Japanese encephalitis in two children--United States, 2010.

    PubMed

    2011-03-11

    Japanese encephalitis virus (JEV) is the leading cause of vaccine-preventable encephalitis in Asia and the western Pacific. JEV is maintained in an enzootic cycle involving mosquitoes and amplifying vertebrate hosts, mainly pigs and wading birds. The virus is transmitted to humans primarily by Culex mosquitoes, which breed in flooded rice fields and pools of stagnant water and most often feed outdoors during the evening and night. JEV transmission occurs mainly in rural agricultural areas, but occasional human cases occur in urban areas. Japanese encephalitis (JE) in persons who have traveled or lived overseas is diagnosed infrequently in the United States, with only four cases identified from 1992 (when a JE vaccine was first licensed in the United States) to 2008. This report describes the only cases diagnosed in the United States and reported to CDC since then. The first was a fatal case in a U.S. child who had visited relatives in the Philippines. The other occurred in a refugee who became ill while traveling from Thailand to the United States and whose diagnosis was complicated by concurrent neurocysticercosis. JE should be considered in the differential diagnosis for any patient with an acute neurologic infection who recently has been in a JE-endemic country. Travelers to JE-endemic countries should be advised of the risk for JE and the importance of personal protective measures to prevent mosquito bites. JE vaccine should be considered for travelers who might be at greater risk based on the season, location, and duration of their visit and their planned activities.

  6. Radiological and neurophysiological changes in Japanese encephalitis.

    PubMed Central

    Misra, U K; Kalita, J; Jain, S K; Mathur, A

    1994-01-01

    Six patients with Japanese encephalitis, four males and two females whose age ranged between 2 and 47 years, were subjected to neurophysiological and radiological studies. An EEG in five of the patients showed diffuse delta wave activity and one had an alpha coma. Delta activity seems to be due to thalamic involvement, which was seen on CT of two and MRI of all the patients. The thalamic lesions were characteristically bilateral and were haemorragic in five. Changes on MRI included abnormalities of the brainstem in three and the basal ganglia and spinal cord in one patient each. Lower motor neuron signs were present in three patients but abnormal MRI signals in the spinal cord were present in only one out of three patients in whom spinal MRI was carried out. Central motor conduction time in the upper limb was prolonged in three patients (five sides) and in the lower limbs in one (both sides), which was consistent with involvement of the cerebral cortex, thalamus, brainstem, and spinal cord. Changes in MRI and EEG in the acute stage may provide early diagnostic clues in patients with Japanese encephalitis. Images PMID:7798977

  7. Monoclonal Antibodies Against NS2B of Japanese Encephalitis Virus.

    PubMed

    Dong, Qian; Xu, Qiuping; Ruan, Xindi; Huang, Shaomei; Cao, Shengbo

    2015-04-01

    Japanese encephalitis (JE) is one of the most important viral encephalitis, caused by the Japanese encephalitis virus (JEV). The function of non-structural protein 2B (NS2B) mostly remains unclear. In our study, NS2B of Japanese encephalitis virus (JEV) was expressed in Escherichia coli and purified by dialysis. After fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from NS2B protein immunized mice, three clones of monoclonal antibodies (MAbs), named 1B9, 3E12, and 4E6, were generated. The specificity and sensitivity of MAbs were demonstrated by ELISA, indirect immunofluorescence assay, and Western blot. These MAbs will be useful in further exploration of the functions of NS2B and the pathogenesis of Japanese encephalitis virus. PMID:25897607

  8. The smallpox vaccine and postvaccinal encephalitis.

    PubMed

    Roos, Karen L; Eckerman, Nancy L

    2002-03-01

    Smallpox is one of the deadliest infectious diseases in history. The discovery by Edward Jenner that inoculation with a droplet of pus from a cow with cowpox protected a person from smallpox resulted in the successful vaccination of millions of people. There were, however, complications associated with smallpox vaccination; the most serious complication was postvaccinal encephalitis, which was reported to occur with an incidence of 1 in 110,000 vaccinations and a case-fatality rate of 50%. Before we become complacent with the idea that we will respond to a bioterrorism attack with a mass immunization program for smallpox, it is important to be reminded of the risk and clinical manifestations of postvaccinal encephalitis and the efficacy of antivaccinia gamma-globulin in preventing this complication. The first case of postvaccinal encephalitis as a complication of the Jennerian cowpox inoculation was observed in 1905. A century later, there is no effective therapy. PMID:12170398

  9. [Japanese encephalitis: a fast-changing viral disease].

    PubMed

    Rodhain, F

    2010-08-01

    The following aspects are dealt with in this article: 1) current geographical distribution of Japanese encephalitis; 2) clinical patterns of Japanese encephalitis; 3) vertebrate hosts of Japanese encephalitis virus; 4) vectors of JE virus; 5) epidemiological locations (endemic area, endemoepidemic area, epidemic area); 6) unknown epidemiological aspects; 7) JE virus serotypes; 8) evolution of the disease and recent epidemiological changes; 9) phylogenetic origin of the JE virus; 10) ecological changes in the past, factors in the emergence of the disease; and 11) the future: Can we predict how the situation will evolve?

  10. Estimating the Burden of Japanese Encephalitis Virus and Other Encephalitides in Countries of the Mekong Region

    PubMed Central

    Tarantola, Arnaud; Goutard, Flavie; Newton, Paul; de Lamballerie, Xavier; Lortholary, Olivier; Cappelle, Julien; Buchy, Philippe

    2014-01-01

    Diverse aetiologies of viral and bacterial encephalitis are widely recognized as significant yet neglected public health issues in the Mekong region. A robust analysis of the corresponding health burden is lacking. We retrieved 75 articles on encephalitis in the region published in English or in French from 1965 through 2011. Review of available data demonstrated that they are sparse and often derived from hospital-based studies with significant recruitment bias. Almost half (35 of 75) of articles were on Japanese encephalitis virus (JEV) alone or associated with dengue. In the Western Pacific region the WHO reported 30,000–50,000 annual JEV cases (15,000 deaths) between 1966 and 1996 and 4,633 cases (200 deaths) in 2008, a decline likely related to the introduction of JEV vaccination in China, Vietnam, or Thailand since the 1980s. Data on dengue, scrub typhus and rabies encephalitis, among other aetiologies, are also reviewed and discussed. Countries of the Mekong region are undergoing profound demographic, economic and ecological change. As the epidemiological aspects of Japanese encephalitis (JE) are transformed by vaccination in some countries, highly integrated expert collaborative research and objective data are needed to identify and prioritize the human health, animal health and economic burden due to JE and other pathogens associated with encephalitides. PMID:24498443

  11. Development of an in vitro antigen-detection test as an alternative method to the in vivo plaque reduction neutralization test for the quality control of Japanese encephalitis virus vaccine.

    PubMed

    Kim, Do Keun; Kim, Hye-Youn; Kim, Joo-Young; Ye, Michael B; Park, Kee-Bum; Han, Euiri; Kim, Jaeok; Ja Ban, Sang; Hong, Seung Hwa; Park, Yong Keun; Nam, Jae-Hwan

    2012-07-01

    Japanese encephalitis virus (JEV) causes diseases that attack the human central nervous system. Traditionally, the quality control for JEV vaccines, in which the plaque reduction neutralization (PRN) titer is measured by the national control laboratories before the vaccine batches are marketed, has required laboratory animal testing. However, classical animal tests have inherent problems, including the very fact that animals are used, ethical issues, and the possibility of error. In this study, JEV antigen was measured in an in vitro assay to assess the feasibility of replacing in vivo assays that measure the PRN titers of JEV vaccines. We constructed a double-sandwich enzyme-linked immunosorbent assay (DS-ELISA) that could detect JEV envelope (E). Initially, monoclonal antibodies (mAbs) directed against the JEV E protein were generated and characterized. We isolated 18 mAbs against JEV E protein, and most were the IgG1 or IgG2a isotype. The mAbs (5F15 and 7D71) were selected as the most suitable mAb pair to detect JEV E protein. DS-ELISA with this pair detected as little as approximately 3 μg/mL JEV E protein and demonstrated a relationship between the amount of JEV E protein and the PRN titer. From these results, we surmise that this DS-ELISA may be useful, not only in terms of measuring the amount of JEV E protein, but also as a substitute for the PRN test for JEV vaccine evaluation.

  12. [Construction of a full-length cDNA clone of a live attenuated vaccine strain against Japanese encephalitis virus and preliminary study of expressing exogenous gene].

    PubMed

    Hu, Bing; Yang, Shuang; Fang, Zhi-zheng

    2014-11-01

    This study aimed to construct full-length cDNA clones of the Japanese encephalitis virus (JEV). SA14-14-2 strain and discuss the feasibility of constructing chimeric viruses for exogenous gene expression based on the JEV genetic skeleton. Long-fragment RT-PCR techniques were applied to amplify JEV cD-NAs, and two amplified fragments with corresponding restriction endonuclease sites at both ends were cloned into the pACYC184 vector sequentially. Using standard molecular techniques, the enhanced green fluorescent protein (EGFP) gene was inserted into the 3' non-coding region of JEV as a reporter gene. After in vitro transcription and transfection procedures, wild-type JEV and chimeric JEV that expressed the EGFP as the reporter gene were successfully rescued. The recovered viruses were characterized by RT-PCR, plaque assays, and direct fluorescence microscopy. After six serial passage generations, the stability of the recovered viruses were studied in terms of virus growth characteristics and structural gene expression. The results showed that cDNA clones of rJEV and rJEV-EGFP were successfully constructed and rescued in BHK-21 cells after in vitro transcription and transfection. Each generation of the recovered viruses was stable and the chimeric virus rJEV-EGFP could stably express EGFP. The findings of this study indicate that both rJEV and rJEV-EGFP could be constructed and rescued in BHK-21 cells, and the JEV SA14-14-2 strain could be obtained as a viral vector to express foreign genes.

  13. Estimated global incidence of Japanese encephalitis: a systematic review

    PubMed Central

    Campbell, Grant L; Hills, Susan L; Fischer, Marc; Jacobson, Julie A; Hoke, Charles H; Hombach, Joachim M; Marfin, Anthony A; Solomon, Tom; Tsai, Theodore F; Tsu, Vivien D

    2011-01-01

    Abstract Objective To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. Methods Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. Findings A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67 900 JE cases typically occur annually (overall incidence: 1.8 per 100 000), of which only about 10% are reported to the World Health Organization. Approximately 33 900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51 000 (75%) occur in children aged 0–14 years (incidence: 5.4 per 100 000). Approximately 55 000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12 900 (19%) occur in areas with minimal or no JE vaccination programmes. Conclusion Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates. PMID:22084515

  14. Comparative Spatial Dynamics of Japanese Encephalitis and Acute Encephalitis Syndrome in Nepal

    PubMed Central

    Robertson, Colin; Pant, Dhan Kumar; Joshi, Durga Datt; Sharma, Minu; Dahal, Meena; Stephen, Craig

    2013-01-01

    Japanese Encephalitis (JE) is a vector-borne disease of major importance in Asia. Recent increases in cases have spawned the development of more stringent JE surveillance. Due to the difficulty of making a clinical diagnosis, increased tracking of common symptoms associated with JE—generally classified as the umbrella term, acute encephalitis syndrome (AES) has been developed in many countries. In Nepal, there is some debate as to what AES cases are, and how JE risk factors relate to AES risk. Three parts of this analysis included investigating the temporal pattern of cases, examining the age and vaccination status patterns among AES surveillance data, and then focusing on spatial patterns of risk factors. AES and JE cases from 2007–2011 reported at a district level (n = 75) were examined in relation to landscape risk factors. Landscape pattern indices were used to quantify landscape patterns associated with JE risk. The relative spatial distribution of landscape risk factors were compared using geographically weighted regression. Pattern indices describing the amount of irrigated land edge density and the degree of landscape mixing for irrigated areas were positively associated with JE and AES, while fragmented forest measured by the number of forest patches were negatively associated with AES and JE. For both JE and AES, the local GWR models outperformed global models, indicating spatial heterogeneity in risks. Temporally, the patterns of JE and AES risk were almost identical; suggesting the relative higher caseload of AES compared to JE could provide a valuable early-warning signal for JE surveillance and reduce diagnostic testing costs. Overall, the landscape variables associated with a high degree of landscape mixing and small scale irrigated agriculture were positively linked to JE and AES risk, highlighting the importance of integrating land management policies, disease prevention strategies and promoting healthy sustainable livelihoods in both rural

  15. Molecular detection and genotyping of Japanese Encephalitis Virus in mosquitoes during a 2010 outbreak in the Republic of Korea

    USGS Publications Warehouse

    Seo, Hyun-Ji; Kim, Heung Chul; Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hyee; Kyung, Soon-Goo; Park, Jee-Yong; Cho, In-Soo; Yeh, Jung-Yong

    2013-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0-7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984-2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010.

  16. Molecular Detection and Genotyping of Japanese Encephalitis Virus in Mosquitoes during a 2010 Outbreak in the Republic of Korea

    PubMed Central

    Klein, Terry A.; Ramey, Andrew M.; Lee, Ji-Hye; Kyung, Soon-Goo; Park, Jee-Yong; Cho, Yun Sang; Cho, In-Soo; Yeh, Jung-Yong

    2013-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne zoonotic pathogen, is one of the major causes of viral encephalitis. To reduce the impact of Japanese encephalitis among children in the Republic of Korea (ROK), the government established a mandatory vaccination program in 1967. Through the efforts of this program only 0–7 (mean 2.1) cases of Japanese encephalitis were reported annually in the ROK during the period of 1984–2009. However, in 2010 there was an outbreak of 26 confirmed cases of Japanese encephalitis, including 7 deaths. This represented a >12-fold increase in the number of confirmed cases of Japanese encephalitis in the ROK as compared to the mean number reported over the last 26 years and a 3.7-fold increase over the highest annual number of cases during this same period (7 cases). Surveillance of adult mosquitoes was conducted during the 2010 outbreak of Japanese encephalitis in the ROK. A total of 6,328 culicine mosquitoes belonging to 12 species from 5 genera were collected at 6 survey sites from June through October 2010 and assayed by reverse-transcription polymerase chain reaction (RT-PCR) for the presence of JEV. A total of 34/371 pooled samples tested positive for JEV (29/121 Culex tritaeniorhynchus, 4/64 Cx. pipiens, and 1/26 Cx. bitaeniorhynchus) as confirmed by sequencing of the pre-membrane and envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 culicine vectors for Cx. tritaeniorhynchus, Cx. pipiens, and Cx. bitaeniorhynchus were 11.8, 5.6, and 2.8, respectively. Sequences of the JEV pre-membrane and envelope protein coding genes amplified from the culicine mosquitoes by RT-PCR were compared with those of JEV genotypes I-V. Phylogenetic analyses support the detection of a single genotype (I) among samples collected from the ROK in 2010. PMID:23390520

  17. Ecological Niche Modeling to Estimate the Distribution of Japanese Encephalitis Virus in Asia

    PubMed Central

    Miller, Robin H.; Masuoka, Penny; Klein, Terry A.; Kim, Heung-Chul; Somer, Todd; Grieco, John

    2012-01-01

    Background Culex tritaeniorhynchus is the primary vector of Japanese encephalitis virus (JEV), a leading cause of encephalitis in Asia. JEV is transmitted in an enzootic cycle involving large wading birds as the reservoirs and swine as amplifying hosts. The development of a JEV vaccine reduced the number of JE cases in regions with comprehensive childhood vaccination programs, such as in Japan and the Republic of Korea. However, the lack of vaccine programs or insufficient coverage of populations in other endemic countries leaves many people susceptible to JEV. The aim of this study was to predict the distribution of Culex tritaeniorhynchus using ecological niche modeling. Methods/Principal Findings An ecological niche model was constructed using the Maxent program to map the areas with suitable environmental conditions for the Cx. tritaeniorhynchus vector. Program input consisted of environmental data (temperature, elevation, rainfall) and known locations of vector presence resulting from an extensive literature search and records from MosquitoMap. The statistically significant Maxent model of the estimated probability of Cx. tritaeniorhynchus presence showed that the mean temperatures of the wettest quarter had the greatest impact on the model. Further, the majority of human Japanese encephalitis (JE) cases were located in regions with higher estimated probability of Cx. tritaeniorhynchus presence. Conclusions/Significance Our ecological niche model of the estimated probability of Cx. tritaeniorhynchus presence provides a framework for better allocation of vector control resources, particularly in locations where JEV vaccinations are unavailable. Furthermore, this model provides estimates of vector probability that could improve vector surveillance programs and JE control efforts. PMID:22724030

  18. Outbreak of Japanese encephalitis on the island of Saipan, 1990.

    PubMed

    Paul, W S; Moore, P S; Karabatsos, N; Flood, S P; Yamada, S; Jackson, T; Tsai, T F

    1993-05-01

    During October 1990, an outbreak of encephalitis occurred on Saipan. Although no virus was isolated, patients seroconverted to Japanese encephalitis (JE) virus, indicating the first known occurrence of JE on US territory since 1947. Ten cases occurred among a population of 40,000. The prevalence of antibody to JE virus among 234 lifelong Saipan residents surveyed after the outbreak was 4.2%. Age, household crowding, and lack of air conditioning were risk factors for infection. The seroprevalence in pigs, which are important amplifying hosts of JE virus, was 96% (n = 52). None of 288 stored serum specimens from lifelong Saipan residents sampled in 1984 were seropositive. These data suggest that JE virus was recently introduced onto Saipan and that peridomestic factors affected the risk of human infection. Transmission of JE virus probably ended with exhaustion of the supply of susceptible amplifying hosts. Surveillance for human cases and seroconversions in pigs during 1991 revealed no evidence of ongoing JE virus transmission.

  19. Molecular epidemiology of Japanese encephalitis virus in mosquitoes in Taiwan during 2005-2012.

    PubMed

    Su, Chien-Ling; Yang, Cheng-Fen; Teng, Hwa-Jen; Lu, Liang-Chen; Lin, Cheo; Tsai, Kun-Hsien; Chen, Yu-Yu; Chen, Li-Yu; Chang, Shu-Fen; Shu, Pei-Yun

    2014-10-01

    Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. PMID:25275652

  20. Molecular Epidemiology of Japanese Encephalitis Virus in Mosquitoes in Taiwan during 2005–2012

    PubMed Central

    Su, Chien-Ling; Yang, Cheng-Fen; Teng, Hwa-Jen; Lu, Liang-Chen; Lin, Cheo; Tsai, Kun-Hsien; Chen, Yu-Yu; Chen, Li-Yu; Chang, Shu-Fen; Shu, Pei-Yun

    2014-01-01

    Japanese encephalitis (JE) is a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). Pigs and water birds are the main amplifying and maintenance hosts of the virus. In this study, we conducted a JEV survey in mosquitoes captured in pig farms and water bird wetland habitats in Taiwan during 2005 to 2012. A total of 102,633 mosquitoes were collected. Culex tritaeniorhynchus was the most common mosquito species found in the pig farms and wetlands. Among the 26 mosquito species collected, 11 tested positive for JEV by RT-PCR, including Cx. tritaeniorhynchus, Cx. annulus, Anopheles sinensis, Armigeres subalbatus, and Cx. fuscocephala. Among those testing positive, Cx. tritaeniorhynchus was the predominant vector species for the transmission of JEV genotypes I and III in Taiwan. The JEV infection rate was significantly higher in the mosquitoes from the pig farms than those from the wetlands. A phylogenetic analysis of the JEV envelope gene sequences isolated from the captured mosquitoes demonstrated that the predominant JEV genotype has shifted from genotype III to genotype I (GI), providing evidence for transmission cycle maintenance and multiple introductions of the GI strains in Taiwan during 2008 to 2012. This study demonstrates the intense JEV transmission activity in Taiwan, highlights the importance of JE vaccination for controlling the epidemic, and provides valuable information for the assessment of the vaccine's efficacy. PMID:25275652

  1. Seroprevalence of Japanese encephalitis virus infection in captive Japanese macaques (Macaca fuscata).

    PubMed

    Shimoda, Hiroshi; Saito, Akatsuki; Noguchi, Keita; Terada, Yutaka; Kuwata, Ryusei; Akari, Hirofumi; Takasaki, Tomohiko; Maeda, Ken

    2014-07-01

    Japanese encephalitis virus (JEV), which is transmitted by mosquitoes, infects many animal species and causes serious acute encephalitis in humans and horses. In this study, a serosurvey of JEV in Japanese macaques (Macaca fuscata) reared in Aichi Prefecture was conducted using purified JEV as an antigen for ELISA. The results revealed that 146 of 332 monkeys (44 %) were seropositive for JEV. In addition, 35 of 131 monkeys (27 %) born in the facility were seropositive, and the annual infection rate in the facility was estimated as 13 %. Our results provide evidence of the frequent exposure of many Japanese macaques to JEV, suggesting that there is a risk of JEV transmission to humans by mosquitoes.

  2. Cost-effectiveness of routine immunization to control Japanese encephalitis in Shanghai, China.

    PubMed Central

    Ding, Ding; Kilgore, Paul E.; Clemens, John D.; Wei, Liu; Zhi-Yi, Xu

    2003-01-01

    OBJECTIVE: To assess the cost-effectiveness of inactivated and live attenuated Japanese encephalitis (JE) vaccines given to infants and children in Shanghai. METHODS: A decision-analytical model was constructed in order to compare costs and outcomes for three hypothetical cohorts of 100,000 children followed from birth in 1997 to the age of 30 years who received either no JE vaccine, inactivated JE vaccine (P3), or live attenuated JE vaccine (SA 14-14-2). Cumulative incidences of JE from birth to 30 years of age in the pre-immunization era, i.e. before 1968, were used to estimate expected rates of JE in the absence of vaccination. The economic consequences were measured as cost per case, per death, and per disability-adjusted life year (DALY) averted for the two JE immunization programmes. FINDINGS: In comparison with no JE immunization, a programme using the P3 vaccine would prevent 420 JE cases and 105 JE deaths and would save 6456 DALYs per 100,000 persons; the use of the SA 14-14-2 vaccine would prevent 427 cases and 107 deaths and would save 6556 DALYs per 100,000 persons. Both kinds of immunization were cost saving but the SA 14-14-2 vaccine strategy resulted in a saving that was 47% greater (512,456 US dollars) than that obtained with the P3 vaccine strategy (348,246 US dollars). CONCLUSION: Both JE immunization strategies resulted in cost savings in comparison with no JE immunization. This provides a strong economic rationale for vaccinating against JE in Shanghai and suggests that vaccination against JE might be economically justifiable in other parts of China and in certain other developing countries of Asia where the disease is endemic. PMID:12856051

  3. Potential for the emergence of Japanese encephalitis virus in California.

    PubMed

    Nett, R J; Campbell, G L; Reisen, W K

    2009-10-01

    The potential risk for the introduction and establishment of Japanese encephalitis virus (JEV) within California is described based on the literature. JEV is a mosquito-borne arbovirus endemic to Asia that when transmitted to humans can lead to Japanese encephalitis (JE), a disease affecting mostly children with a fatality rate up to 30%. The geographical expansion of JEV in Asia along with the recent introduction and rapid spread of West Nile virus (WNV) across the United States, demonstrates the ability of arboviruses to rapidly extend their distributions. California is at particular risk for the introduction of JEV because it is a large state functioning as a hub for international travel and commerce with Asia, potentially allowing the introduction of mosquitoes infected with JEV. If JEV is introduced into California, the virus might become established due to the significant number of susceptible mosquito vectors and vertebrate hosts. Once introduced, the lack of active surveillance for JEV, the ambiguous clinical presentation of JE, the cross reactivity of serological testing between JEV and other flaviviruses, and the probability that clinicians and laboratories would not consider JE as a possible diagnosis would likely delay recognition. A significant delay in detection of JEV in California would make control and eradication of the virus very difficult and costly. Public health authorities should consider the need for future control efforts if JEV emerges in the United States. PMID:18973447

  4. Recurrence of Japanese Encephalitis Epidemic in Wuhan, China, 2009–2010

    PubMed Central

    Zhu, Zerong; Tian, Junhua; Zhou, Yu; Zhang, Xiaoyong; Zheng, Xin

    2013-01-01

    Background Japanese encephalitis (JE) was once epidemic in most areas of China, including Wuhan, a city located in the central part of China. The incidence of JE dramatically decreased due to nationwide immunization with the live attenuated JE virus (JEV) vaccine, and no JE cases were reported during 2005–2008 in Wuhan. In 2009 and 2010, 31 JE cases reoccurred in this area. In this study, we investigated the causes of JE recurrence. Methods and Findings All JE cases were laboratory-confirmed by detecting the JEV-specific IgM antibody with an IgM-capture enzyme-linked immunosorbent assay (ELISA). All patients were children between 2 months and 9 years of age with a median age of 2 years. Of the 31 cases, 9 had received one or two doses of the JEV vaccine, 11 had not been immunized previously with the JEV vaccine, and 11 had an unclear immunization history. Through reverse transcription polymerase chain reaction (RT-PCR), sequencing, and phylogenetic analysis, two new strains of JEV were isolated from Culex tritaeniorhynchus and identified as genotype 1 JEV, rather than genotype 3, which circulated in this area previously. Conclusions Vaccine failure or missed vaccination may have caused JE recurrence. Local centers for disease control and prevention need to improve immunization coverage, and the efficacy of the JE vaccine needs to be reevaluated in a population at risk for disease. PMID:23326348

  5. Whooping crane titers to eastern equine encephalitis vaccinations

    USGS Publications Warehouse

    Olsen, G.H.; Kolski, E.; Hatfield, J.S.; Docherty, D.E.; Chavez-Ramirez, Felipe

    2005-01-01

    In 1984 an epizootic of eastern equine encephalitis (EEE) virus killed 7 of 39 (18%) whooping cranes in captivity at the Patuxent Wildlife Research Center in Laurel, Maryland, USA. Since that time whooping cranes have been vaccinated with a human EEE vaccine. This vaccine was unavailable for several years, necessitating use of an equine vaccine in the cranes. This study compared the antibody titers measured for three years using the human vaccine with those measured for two years using the equine form. Whooping cranes developed similarly elevated titers in one year using the human vaccine and both years using the equine vaccine. However, in two years where the human vaccine was used, the whooping cranes developed significantly lower titers compared to other years.

  6. Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang, an Eastern Province of China

    PubMed Central

    Yan, Ju-ying; Zhou, Jia-yue; Tang, Xue-wen; He, Han-qing; Xie, Rong-hui; Mao, Hai-yan; Zhang, Yan-jun; Xie, Shu-yun

    2016-01-01

    Background Sporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains. Methodology/Principal Findings A total of 570 serum specimens were sampled from community population aged from 0 to 92 years old in Xianju county of Zhejiang Province in 2013–2014. Microseroneutralization test results were analyzed to estimate the population immunity and to observe antibody dynamics in vaccinated children. E genes of 28 JEV strains isolated in Zhejiang Province were sequenced for phylogenetic tree construction and molecular characteristics analysis with other selected strains. Positive JE neutralizing antibody rates were higher in residents ≥35 years old (81%~98%) and lower in residents <35 years old (0~57%). 7 or 8 years after the 2nd live attenuated vaccine dose, the antibodies against for 4 different strains with microseroneutralization test were decreased by 55%~73% on seropositive rates and by 25%~38% on GMTs respectively. JEV strains isolated in recent years were all grouped into GI, while those isolated in the 1980s belonged to GIII. On important amino acid sites related to antigenicity, there was no divergence between the Zhejiang JE virus strains and the vaccine strain (SA14-14-2). Conclusion/Significances JE

  7. Fulminant encephalitis associated with a vaccine strain of rubella virus.

    PubMed

    Gualberto, Felipe Augusto Souza; de Oliveira, Maria Isabel; Alves, Venancio A F; Kanamura, Cristina T; Rosemberg, Sérgio; Sato, Helena Keico; Arantes, Benedito A F; Curti, Suely Pires; Figueiredo, Cristina Adelaide

    2013-12-01

    Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, with confusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was also detected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

  8. Crystal Structure of the Japanese Encephalitis Virus Envelope Protein

    SciTech Connect

    Luca, Vincent C.; AbiMansour, Jad; Nelson, Christopher A.; Fremont, Daved H.

    2012-03-13

    Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-{angstrom} resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.

  9. A new genotype of Japanese encephalitis virus from Indonesia.

    PubMed

    Chen, W R; Rico-Hesse, R; Tesh, R B

    1992-07-01

    Primer-extension sequencing of the RNA template of polio, dengue, Rift Valley fever, and Japanese encephalitis (JE) viruses has provided new information on their geographic distribution, origin, and evolution. In a previous study of 46 diverse JE virus strains, we demonstrated the existence of three distinct JE genotypes in Asia. We now report the occurrence of a fourth genotype. In the present study, 19 JE virus isolates, representing various geographic regions of Asia and a 50-year time span, were compared with each other and with Murray Valley encephalitis, West Nile, and Kunjin viruses. Twelve of the JE strains from the Indonesian Archipelago and the Philippines had not been previously examined; the remainder were representatives of the three previously identified genotypes. Two hundred forty nucleotides from the pre-M gene region of the virus were used in these comparisons. Using 12% divergence as a cut-off point, the 19 JE strains fell into four distinct genotypic groups; maximum divergence across the comparison region was 21%. The newly recognized fourth genotype was comprised of five Indonesian isolates that were 7% divergent from the rest of the JE viruses.

  10. The pathogenesis of Japanese encephalitis virus in Culex tritaeniorhynchus mosquitoes.

    PubMed

    Leake, C J; Johnson, R T

    1987-01-01

    Culex tritaeniorhynchus were inoculated intrathoracically with mosquito and human strains of Japanese encephalitis virus and maintained at 26 degrees C or 32 degrees C. Virus titration and localization of viral antigen by avidin-biotin immunoperoxidase staining were done at intervals up to 21 days. Marked differences were noted in the tempo of organ involvement at the 2 temperatures; at both there was initial infection of fat body cells followed by selective infection of the central nervous system (CNS), with consistent infection of cells of the compound eye, patchy involvement of cephalic, thoracic and abdominal ganglia and no infection of Johnston's organ. CNS infection was always present 4 days after infection, when salivary gland involvement was first seen at 32 degrees C; at 26 degrees C CNS infection preceded salivary gland infection by 2 weeks. Late involvement of gut cells, pericardial cells and oviducts was also found, with no involvement of muscle.

  11. Early mental and neurological sequelae after Japanese B encephalitis.

    PubMed

    Huy, B V; Tu, H C; Luan, T V; Lindqvist, R

    1994-09-01

    Japanese B encephalitis is a disease with high mortality and many of those surviving suffer from serious sequelae. During the 1992 epidemic in northern Vietnam 50 patients treated at the Institute for Protection of Children's Health in Hanoi were studied concerning the type of sequelae and the development of the symptoms during the first two months of the disease. The age span was 1 to 15 years. 29 of the patients (58%) did not recover fully during the observation period. Fifteen (30%) showed signs of both neurological and mental disturbances. Nine (18%) only had mental symptoms while 5 (20%) suffered from isolated neurological sequelae. EEG was pathological in 9 out of 30 tested cases (30%); 9 of 23 patients (39%) performed subnormal IQ tests. Deep coma, bronchopneumonia with cyanosis, apnea attacks, prolonged fever and coma were all correlated (without statistical significance) to a higher risk for subsequent sequelae.

  12. Japanese Encephalitis in Travelers from Non-Endemic Countries, 1973–2008

    PubMed Central

    Hills, Susan L.; Griggs, Anne C.; Fischer, Marc

    2010-01-01

    Japanese encephalitis (JE) is a severe disease and a risk for travelers who visit JE-endemic countries. We reviewed all published JE cases in travelers from non-endemic areas from 1973 through 2008, and assessed factors related to risk of infection. There were 55 cases that occurred in citizens of 17 countries. Age range of case-patients was 1–91 years (median = 34 years). Ten (18%) persons died and 24 (44%) had mild to severe sequelae. In a detailed risk assessment of 37 case-patients, 24 (65%) had spent ≥ 1 month in JE-endemic areas, and most had factors identified that may have increased infection risk. The estimate of overall JE risk was low, < 1 case/1 million travelers to JE-endemic countries. Nonetheless, for each traveler, a careful assessment of itinerary and activities, a decision on vaccination, and information on mosquito precautions are needed to reduce the risk of this disease. PMID:20439978

  13. Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

    PubMed Central

    Baylis, Matthew; Barker, Christopher M.; Caminade, Cyril; Joshi, Bhoj R.; Pant, Ganesh R.; Rayamajhi, Ajit; Reisen, William K.; Impoinvil, Daniel E.

    2016-01-01

    The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas. PMID:26956778

  14. Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands?

    PubMed

    Baylis, Matthew; Barker, Christopher M; Caminade, Cyril; Joshi, Bhoj R; Pant, Ganesh R; Rayamajhi, Ajit; Reisen, William K; Impoinvil, Daniel E

    2016-04-01

    The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas. PMID:26956778

  15. Primary viraemia responses of herons to experimental infection with Murray Valley encephalitis, Kunjin and Japanese encephalitis viruses.

    PubMed

    Boyle, D B; Dickerman, R W; Marshall, I D

    1983-12-01

    Rufous night herons, Pacific herons, little egrets and intermediate egrets were experimentally infected with Murray Valley encephalitis, Kunjin or Japanese encephalitis viruses. Viraemias of at least one day's duration were detected in all birds except two intermediate egrets inoculated with a very low dose of Kunjin virus and one rufous night heron inoculated with Japanese encephalitis virus. there was usually a viraemia of 3 to 5 days' duration commencing on the first or second day and continuing until day 5 or 6 and rarely until day 7. Maximum titres tended to be higher in young birds, up to 2-5 months of age (10(4)-10(5) mouse LD50/ml), than in older birds more than 8 months of age (10(3)-10(4) mouse LD50/ml). Significant differences in maximum viraemia titres were not observed in the different species or between Murray Valley encephalitis and Kunjin viruses. Japanese encephalitis viraemias were significantly lower, but this was probably due to the high mouse brain passage level of the strain used. The onset of viraemia was earlier in intermediate egrets than in rufous night herons inoculated with similar doses of Murray Valley encephalitis virus, but no difference in the susceptibility to infection was observed. With Kunjin virus there was a significant difference in the susceptibility of intermediate egrets and rufous night herons, with rufous night herons being more susceptible to infection with low doses of virus. This difference in threshold of infection, if it extends to other species with both Kunjin and Murray Valley encephalitis viruses, may, in part, be an explanation for the greater incidence of natural infections observed in rufous night herons compared with other species and orders of water birds.

  16. Comparison of Genotypes I and III in Japanese Encephalitis Virus Reveals Distinct Differences in Their Genetic and Host Diversity

    PubMed Central

    Han, Na; Adams, James; Chen, Ping; Guo, Zhen-yang; Zhong, Xiang-fu; Fang, Wei; Li, Na; Wen, Lei; Tao, Xiao-yan; Yuan, Zhi-ming

    2014-01-01

    ABSTRACT Japanese encephalitis (JE) is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into five genotypes. Recent surveillance data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. To investigate the mechanism behind the genotype shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination, we collected (i) all full-length and partial JEV molecular sequences and (ii) associated genotype and host information comprising a data set of 873 sequences. We then examined differences between the two genotypes at the genetic and epidemiological level by investigating amino acid mutations, positive selection, and host range. We found that although GI is dominant, it has fewer sites predicted to be under positive selection, a narrower host range, and significantly fewer human isolates. For the E protein, the sites under positive selection define a haplotype set for each genotype that shows striking differences in their composition and diversity, with GIII showing significantly more variety than GI. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but is also more restricted in its host range. IMPORTANCE Japanese encephalitis is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been divided into five genotypes based on sequence similarity. Recent data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. Understanding the reasons behind this shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination is important for controlling the spread of the virus and reducing human

  17. Neuropathogenesis of Japanese Encephalitis in a Primate Model

    PubMed Central

    Myint, Khin Saw Aye; Kipar, Anja; Jarman, Richard G.; Gibbons, Robert V.; Perng, Guey Chuen; Flanagan, Brian; Mongkolsirichaikul, Duangrat; Van Gessel, Yvonne; Solomon, Tom

    2014-01-01

    Background Japanese encephalitis (JE) is a major cause of mortality and morbidity for which there is no treatment. In addition to direct viral cytopathology, the inflammatory response is postulated to contribute to the pathogenesis. Our goal was to determine the contribution of bystander effects and inflammatory mediators to neuronal cell death. Methodology/Principal Findings Material from a macaque model was used to characterize the inflammatory response and cytopathic effects of JE virus (JEV). Intranasal JEV infection induced a non-suppurative encephalitis, dominated by perivascular, infiltrates of mostly T cells, alongside endothelial cell activation, vascular damage and blood brain barrier (BBB) leakage; in the adjacent parenchyma there was macrophage infiltration, astrocyte and microglia activation. JEV antigen was mostly in neurons, but there was no correlation between intensity of viral infection and degree of inflammatory response. Apoptotic cell death occurred in both infected and non-infected neurons. Interferon-α, which is a microglial activator, was also expressed by both. Tumour Necrosis Factor-α, inducible nitric oxide synthase and nitrotyrosine were expressed by microglial cells, astrocytes and macrophages. The same cells expressed matrix metalloproteinase (MMP)-2 whilst MMP-9 was expressed by neurons. Conclusions/Significance The results are consistent with JEV inducing neuronal apoptotic death and release of cytokines that initiate microglial activation and release of pro-inflammatory and apoptotic mediators with subsequent apoptotic death of both infected and uninfected neurons. Activation of astrocytes, microglial and endothelial cells likely contributes to inflammatory cell recruitment and BBB breakdown. It appears that neuronal apoptotic death and activation of microglial cells and astrocytes play a crucial role in the pathogenesis of JE. PMID:25102067

  18. Phylogeography of Japanese Encephalitis Virus: Genotype Is Associated with Climate

    PubMed Central

    Schuh, Amy J.; Ward, Melissa J.; Leigh Brown, Andrew J.; Barrett, Alan D. T.

    2013-01-01

    The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate. PMID:24009790

  19. Phylogeography of Japanese encephalitis virus: genotype is associated with climate.

    PubMed

    Schuh, Amy J; Ward, Melissa J; Brown, Andrew J Leigh; Barrett, Alan D T

    2013-01-01

    The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate.

  20. Fatal wild-type varicella-zoster virus encephalitis without a rash in a vaccinated child.

    PubMed

    Ibraheem, Mam; Marin, Mona; Leung, Jessica; Bryce, Clare H; Schmid, D Scott; Zaki, Sherif R; Drew, Clifton; Liu, Lindy; Smelser, Chad

    2013-02-01

    Encephalitis associated with varicella-zoster virus, rare among children in the varicella vaccine era, has generally been associated with a rash. We report fatal wild-type varicella-zoster virus encephalitis without a rash in a child who had received 1 dose of varicella vaccine. Varicella-zoster virus encephalitis should be considered in the differential diagnosis for children presenting with acute neurologic symptoms, even vaccine recipients.

  1. Antioxidants: potential antiviral agents for Japanese encephalitis virus infection.

    PubMed

    Zhang, Yu; Wang, Zehua; Chen, Huan; Chen, Zongtao; Tian, Yanping

    2014-07-01

    Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE. PMID:24780919

  2. Japanese encephalitis on Saipan: a survey of suspected mosquito vectors.

    PubMed

    Mitchell, C J; Savage, H M; Smith, G C; Flood, S P; Castro, L T; Roppul, M

    1993-04-01

    An outbreak of Japanese encephalitis (JE) occurred on Saipan, Commonwealth of Northern Mariana Islands, in October 1990. Adult and larval mosquitoes were collected during September-October 1991 to retrospectively determine the probable mosquito vector(s). Virus was not isolated from 119 mosquito pools composed of 7,250 adult specimens as follows: Aedes vexans nocturnis (14%), Culex tritaeniorhynchus (39%), Cx. sitiens group (11%), Culex (Culex) species (35%), and < 1% each of Ae. albopictus, Ae. oakleyi, Aedes saipanensis, Cx. annulirostris marianae, and Cx. fuscanus. Three additional species were collected only as larvae: Anopheles indefinitus, Ae. neopandani, and Cx. quinquefasciatus. Among the vectors of JE incriminated in other areas, Cx. tritaeniorhynchus was the predominant species in our collections and the principal species feeding on swine. This is the first published record of the occurrence of this species on Saipan. Culex tritaeniorhynchus is abundant and widely distributed on the southern half of Saipan where human JE cases occurred in 1990, and where swine seroconversions were detected. Although the identity of the mosquito vector(s) responsible for the 1990 outbreak cannot be established with certainty, our results suggest that Cx. tritaeniorhychus was probably involved.

  3. THE AUSTRIAN VACCINATION PARADOX: TICK-BORNE ENCEPHALITIS VACCINATION VERSUS INFLUENZA VACCINATION.

    PubMed

    Kunze, Ursula; Kunze, Michael

    2015-09-01

    This paper describes a paradoxical situation in Austria. The vaccination rate against tick-borne encephalitis (TBE) in the general population is 82%, which is the highest worldwide, whereas the vaccination rate against influenza is about 8% and is among the lowest worldwide. A high awareness of TBE among the Austrian population achieved by an annual social marketing programme and the wide use of effective and well-tolerated vaccines have led to a successful containment of that disease. The vaccination coverage increased from 6% in 1980 to 82% in 2013 and exceeds 90% in some high-risk areas. This has led to a steady decline in the number of TBE cases from several hundred cases to 50 to 100 cases per year. The situation in regard to influenza vaccination is the opposite. Although Austria has issued one of the most extensive recommendations for influenza vaccination worldwide, the vaccination rate of the general population is extremely low. The possible reasons for the failure in the implementation of recommendations are ignorance, lack of social marketing and the predominance of a distinct discordance within the health system in general, and the Austrian medical fraternity in particular. PMID:26615654

  4. Improved surveillance of Japanese encephalitis by detection of virus-specific IgM in desiccated blood specimens*

    PubMed Central

    Burke, D. S.; Chatiyanonda, K.; Anandrik, S.; Nakornsri, S.; Nisalak, A.; Hoke, C. H.

    1985-01-01

    An IgM antibody-capture type enzyme-linked immunoassay (MAC ELISA) was compared with the haemagglutination inhibition method (HI) for establishing a laboratory diagnosis of acute Japanese encephalitis (JE) virus infection using specimens of dried blood eluted from filter paper strips. Paired samples from 243 encephalitis patients, which had been obtained by mail through a national surveillance programme in Thailand, were tested. During the peak of the 1983 encephalitis epidemic, 72% of cases were diagnosed as Japanese encephalitis by MAC ELISA, compared with only 38% by HI. During non-epidemic periods, the proportions diagnosed as Japanese encephalitis by MAC ELISA or HI were 26% and 33%, respectively. Detection of IgM anti-JE activity by the antibody-capture immunoassay is superior to the HI method for establishing a diagnosis of acute Japanese encephalitis using dried blood specimens. PMID:3011302

  5. Japanese encephalitis associated acute encephalitis syndrome cases in West Bengal, India: A sero-molecular evaluation in relation to clinico-pathological spectrum.

    PubMed

    Sarkar, Arindam; Datta, Somenath; Pathak, Bani K; Mukhopadhyay, Subhra K; Chatterjee, Shyamalendu

    2015-08-01

    Japanese encephalitis (JE) is a major public health problem in Asia and worldwide and it is responsible mainly for viral acute encephalitis syndrome (AES). The sole etiologic agent of JE is Japanese encephalitis virus (JEV). Although JE/AES cases have been regarded traditionally as a disease of children, a growing number of patients with JE/AES cases are also seen in the adult age group every year in the state of West Bengal, India in spite of vaccination. Therefore, a systematic study was performed to differentiate and characterize the clinico-pathological parameters and viral diversity among the patients of different age groups. Viral diversity was also evaluated from the JE/AES cases, depending on their disease severity. A total of 441 JE/AES cases were included in this study. By MAC-ELISA, 111 samples were found JEV IgM positive and among the IgM negative cases, 26 samples were found RT-PCR positive against JEV infection. Neck rigidity, abnormal behavior, convulsion, protein in CSF, WBC in CSF, and aspartate transaminase in blood differed significantly among the patients of pediatric-adolescent and adult group in both IgM positive and RT-PCR positive cases. Viral diversity was increased significantly in the pediatric-adolescent group compared to adult patients. Interestingly, with the rise in disease severity the viral diversity was found to be increased among the patients, irrespective of their age distribution. Based on clinico-pathological parameters and analysis of viral diversity, it can be concluded that viral diversity which occurs naturally is likely to affect disease severity, especially in the patients of pediatric-adolescent group.

  6. Japanese encephalitis associated acute encephalitis syndrome cases in West Bengal, India: A sero-molecular evaluation in relation to clinico-pathological spectrum.

    PubMed

    Sarkar, Arindam; Datta, Somenath; Pathak, Bani K; Mukhopadhyay, Subhra K; Chatterjee, Shyamalendu

    2015-08-01

    Japanese encephalitis (JE) is a major public health problem in Asia and worldwide and it is responsible mainly for viral acute encephalitis syndrome (AES). The sole etiologic agent of JE is Japanese encephalitis virus (JEV). Although JE/AES cases have been regarded traditionally as a disease of children, a growing number of patients with JE/AES cases are also seen in the adult age group every year in the state of West Bengal, India in spite of vaccination. Therefore, a systematic study was performed to differentiate and characterize the clinico-pathological parameters and viral diversity among the patients of different age groups. Viral diversity was also evaluated from the JE/AES cases, depending on their disease severity. A total of 441 JE/AES cases were included in this study. By MAC-ELISA, 111 samples were found JEV IgM positive and among the IgM negative cases, 26 samples were found RT-PCR positive against JEV infection. Neck rigidity, abnormal behavior, convulsion, protein in CSF, WBC in CSF, and aspartate transaminase in blood differed significantly among the patients of pediatric-adolescent and adult group in both IgM positive and RT-PCR positive cases. Viral diversity was increased significantly in the pediatric-adolescent group compared to adult patients. Interestingly, with the rise in disease severity the viral diversity was found to be increased among the patients, irrespective of their age distribution. Based on clinico-pathological parameters and analysis of viral diversity, it can be concluded that viral diversity which occurs naturally is likely to affect disease severity, especially in the patients of pediatric-adolescent group. PMID:25939919

  7. Comparative epidemiological features of Japanese encephalitis in the Republic of Korea, China (Taiwan) and Japan

    PubMed Central

    Kono, Reisaku; Kim, Kyong Ho

    1969-01-01

    The epidemiology of Japanese encephalitis in the Republic of Korea from 1949 to 1966 is described and comparisons are made with the situations in Japan and China (Taiwan). Some similarities and some differences are noted. Recent epidemics in Korea coincided with those in southern Japan but the annual fluctuations were more distinct in Korea. The disease mainly affected children in Korea and, in contrast to the situation in Japan, persons in the older age-groups were rarely affected. The authors also discuss the geographical pathology of Japanese encephalitis in Korea. PMID:4308334

  8. Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody

    PubMed Central

    Gupta, Nimesh; de Wispelaere, Mélissanne; Lecerf, Maxime; Kalia, Manjula; Scheel, Tobias; Vrati, Sudhanshu; Berek, Claudia; Kaveri, Srinivas V.; Desprès, Philippe; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D.

    2015-01-01

    Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently dominant JEV genotypes. This study opens new therapeutic options for Japanese encephalitis. PMID:26542535

  9. A Clinical Study of Adult Japanese Encephalitis in the Chonnam District, Korea, During Summer of 1982

    PubMed Central

    Bom, Hee Seung; Kang, Hyung Koo; Joh, Nam Joong; Kim, Sei Jong; Yoon, Chong Mann; Cho, Kun Kook; Park, Hong Bae

    1986-01-01

    In the summer of 1982, we experienced a great number of patients with Japanese encephalitis compared with the previous years. We have studied 85 adult cases of Japanese encephalitis which were diagnosed clinically and/or serologically. A difference between improved and expired cases was also investigated. We found that deteriorated mental state, elevated SGOT (AST) level, lower hemagglutination-inhibition(H-I) titer, and a more acute onset of the illness were associated with higher mortality. The mortality rate in our cases was 35.3 percent. PMID:15759371

  10. Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody.

    PubMed

    Gupta, Nimesh; de Wispelaere, Mélissanne; Lecerf, Maxime; Kalia, Manjula; Scheel, Tobias; Vrati, Sudhanshu; Berek, Claudia; Kaveri, Srinivas V; Desprès, Philippe; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D

    2015-01-01

    Geographical expansion and re-emerging new genotypes of the Japanese encephalitis virus (JEV) require the development of novel therapeutic approaches. Here, we studied a non-conventional approach for antibody therapy and show that, upon exposure to heme, a fraction of natural human immunoglobulins acquires high-affinity reactivity with the antigenic domain-III of JEV E glycoprotein. These JEV-reactive antibodies exhibited neutralizing activity against recently dominant JEV genotypes. This study opens new therapeutic options for Japanese encephalitis. PMID:26542535

  11. The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis.

    PubMed

    Jeffries, Claire L; Walker, Thomas

    2015-01-01

    Japanese encephalitis virus (JEV) is a zoonotic pathogen transmitted by the infectious bite of Culex mosquitoes. The virus causes the development of the disease Japanese encephalitis (JE) in a small proportion of those infected, predominantly affecting children in eastern and southern Asia. Annual JE incidence estimates range from 50,000-175,000, with 25%-30% of cases resulting in mortality. It is estimated that 3 billion people live in countries in which JEV is endemic. The virus exists in an enzootic transmission cycle, with mosquitoes transmitting JEV between birds as reservoir hosts and pigs as amplifying hosts. Zoonotic infection occurs as a result of spillover events from the main transmission cycle. The reservoir avian hosts include cattle egrets, pond herons, and other species of water birds belonging to the family Ardeidae. Irrigated rice fields provide an ideal breeding ground for mosquitoes and attract migratory birds, maintaining the transmission of JEV. Although multiple vaccines have been developed for JEV, they are expensive and require multiple doses to maintain efficacy and immunity. As humans are a "dead-end" host for the virus, vaccination of the human population is unlikely to result in eradication. Therefore, vector control of the principal mosquito vector, Culex tritaeniorhynchus, represents a more promising strategy for reducing transmission. Current vector control strategies include intermittent irrigation of rice fields and space spraying of insecticides during outbreaks. However, Cx. Tritaeniorhynchus is subject to heavy exposure to pesticides in rice fields, and as a result, insecticide resistance has developed. In recent years, significant advancements have been made in the potential use of the bacterial endosymbiont Wolbachia for mosquito biocontrol. The successful transinfection of Wolbachia strains from Drosophila flies to Aedes (Stegomyia) mosquitoes has resulted in the generation of "dengue-refractory" mosquito lines. The successful

  12. The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis

    PubMed Central

    Jeffries, Claire L.; Walker, Thomas

    2015-01-01

    Japanese encephalitis virus (JEV) is a zoonotic pathogen transmitted by the infectious bite of Culex mosquitoes. The virus causes the development of the disease Japanese encephalitis (JE) in a small proportion of those infected, predominantly affecting children in eastern and southern Asia. Annual JE incidence estimates range from 50,000–175,000, with 25%–30% of cases resulting in mortality. It is estimated that 3 billion people live in countries in which JEV is endemic. The virus exists in an enzootic transmission cycle, with mosquitoes transmitting JEV between birds as reservoir hosts and pigs as amplifying hosts. Zoonotic infection occurs as a result of spillover events from the main transmission cycle. The reservoir avian hosts include cattle egrets, pond herons, and other species of water birds belonging to the family Ardeidae. Irrigated rice fields provide an ideal breeding ground for mosquitoes and attract migratory birds, maintaining the transmission of JEV. Although multiple vaccines have been developed for JEV, they are expensive and require multiple doses to maintain efficacy and immunity. As humans are a “dead-end” host for the virus, vaccination of the human population is unlikely to result in eradication. Therefore, vector control of the principal mosquito vector, Culex tritaeniorhynchus, represents a more promising strategy for reducing transmission. Current vector control strategies include intermittent irrigation of rice fields and space spraying of insecticides during outbreaks. However, Cx. Tritaeniorhynchus is subject to heavy exposure to pesticides in rice fields, and as a result, insecticide resistance has developed. In recent years, significant advancements have been made in the potential use of the bacterial endosymbiont Wolbachia for mosquito biocontrol. The successful transinfection of Wolbachia strains from Drosophila flies to Aedes (Stegomyia) mosquitoes has resulted in the generation of “dengue-refractory” mosquito lines

  13. The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis.

    PubMed

    Jeffries, Claire L; Walker, Thomas

    2015-01-01

    Japanese encephalitis virus (JEV) is a zoonotic pathogen transmitted by the infectious bite of Culex mosquitoes. The virus causes the development of the disease Japanese encephalitis (JE) in a small proportion of those infected, predominantly affecting children in eastern and southern Asia. Annual JE incidence estimates range from 50,000-175,000, with 25%-30% of cases resulting in mortality. It is estimated that 3 billion people live in countries in which JEV is endemic. The virus exists in an enzootic transmission cycle, with mosquitoes transmitting JEV between birds as reservoir hosts and pigs as amplifying hosts. Zoonotic infection occurs as a result of spillover events from the main transmission cycle. The reservoir avian hosts include cattle egrets, pond herons, and other species of water birds belonging to the family Ardeidae. Irrigated rice fields provide an ideal breeding ground for mosquitoes and attract migratory birds, maintaining the transmission of JEV. Although multiple vaccines have been developed for JEV, they are expensive and require multiple doses to maintain efficacy and immunity. As humans are a "dead-end" host for the virus, vaccination of the human population is unlikely to result in eradication. Therefore, vector control of the principal mosquito vector, Culex tritaeniorhynchus, represents a more promising strategy for reducing transmission. Current vector control strategies include intermittent irrigation of rice fields and space spraying of insecticides during outbreaks. However, Cx. Tritaeniorhynchus is subject to heavy exposure to pesticides in rice fields, and as a result, insecticide resistance has developed. In recent years, significant advancements have been made in the potential use of the bacterial endosymbiont Wolbachia for mosquito biocontrol. The successful transinfection of Wolbachia strains from Drosophila flies to Aedes (Stegomyia) mosquitoes has resulted in the generation of "dengue-refractory" mosquito lines. The successful

  14. Development of a particle agglutination assay system for detecting Japanese encephalitis virus-specific human IgM, using hydroxyapatite-coated nylon beads.

    PubMed

    Yamamoto, Akira; Nakayama, Mikio; Kurosawa, Yae; Sugo, Ken; Karasawa, Hideharu; Ogawa, Tetsuro; Takasaki, Tomohiko; Tashiro, Masato; Kurane, Ichiro

    2002-07-01

    Japanese encephalitis virus-specific IgM is a reliable indicator for serodiagnosis of Japanese encephalitis. A particle agglutination (PA) assay system was developed to detect anti-Japanese encephalitis virus IgM in human serum samples. The newly developed PA assay consisted of hydroxyapatite-coated nylon beads and V-bottom 96-well microplates. Hydroxyapatite-coated nylon beads were coated with Japanese encephalitis virus antigens. Japanese encephalitis virus antigen-coated, hydroxyapatite-coated nylon beads agglutinated in the IgM-captured wells when anti-Japanese encephalitis virus IgM-positive serum samples were used. A button pattern was formed at the bottom of the wells when anti-Japanese encephalitis virus IgM-negative serum samples were used. Thirty anti-Japanese encephalitis virus IgM-positive serum samples from Japanese encephalitis-confirmed cases were tested by the PA assay. All these serum samples were determined to be Japanese encephalitis virus IgM-positive. IgM titers determined by the PA assay corresponded to those determined by enzyme-linked immunosorbent assay. The titers were consistent in two independent PA assays. These results indicate that the newly developed PA assay is a reliable method for detecting anti-Japanese encephalitis virus IgM in human serum samples and that this assay will be a suitable diagnostic system especially in rural areas of Asia.

  15. Monoclonal antibodies against NS4B protein of japanese encephalitis virus.

    PubMed

    Ruan, Xindi; Huang, Shaomei; Shao, Lin; Ye, Jing; Chen, Zheng; Chen, Huanchun; Cao, Shengbo

    2013-12-01

    Japanese encephalitis (JE) is one of the most prevalent global viral encephalitis viruses. The functions of JEV (virus) NS4B protein are still under investigation. In our study, NS4B was expressed in Escherichia coli and purified by dialysis. Two clones of monoclonal antibodies (MAbs 1B1 and 1C3) against NS4B protein were generated and their characterizations were investigated. IFA, Western blot, and ELISA results showed that the MAbs were specific against JEV NS4B protein. The epitope of the MAbs was further identified using pairs of synthesized overlapping peptides. These MAbs may provide valuable tools for further exploration of the functions of NS4B and the pathogenesis of Japanese encephalitis virus. PMID:24328740

  16. Susceptibility of a North American Culex quinquefasciatus to Japanese encephalitis virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Japanese encephalitis virus (JEV) is a flavivirus that is transmitted by Culex (Cx.) tritaeniorhynchus in tropical and subtropical regions of Asia. The endemic transmission cycle involves domestic pigs and avian species that serve as amplification hosts; humans are incidental hosts that cannot devel...

  17. Comparison of the antigenic relationship between Japanese encephalitis virus genotypes 1 and 3

    PubMed Central

    2016-01-01

    Purpose The Japanese encephalitis virus (JEV) genotype circulating in Korea has changed from G3 to G1. Therefore, the purpose of this study was to compare the antigenic relationship between the two genotypes by using antibody tests. Materials and Methods Blood samples from 42 sows and 216 horses were collected, and their seroprevalence was monitored using the hemagglutination inhibition and virus neutralization tests. Antisera against JEV G1 and G3 were isolated and prepared from guinea pigs. The cross-reactivity of these two viruses was then compared using the neutralizing antibody test. Results We found that there was a difference in the seropositive ratios of JEV G1 and G3. However, the difference was dependent on the antibody test used. There was also an observed difference in the antigenicity between the two genotypes, as ascertained using the neutralizing antibody test. Conclusion There is an evident difference in JEV antigenicity between the genotypes G1 and G3. Therefore, we propose monitoring of the seroprevalence of JEV, and reevaluating the antigenicity of the current vaccine by using the relevant tests. PMID:26866021

  18. Standardization of serum neutralization assay of Japanese encephalitis virus (Nakayama NIH strain) on BHK-21 (Cl-13) cell line.

    PubMed

    Singh, S; Sharma, M; Kumar, S; Gowal, D

    2015-09-01

    Potency testing of Japanese encephalitis (JE) vaccine has been a complex process since its inception. To overcome difficulties encountered therein, an alternative assay, serum neutralization test (SNT), using Baby Hamster Kidney 21 cell line, has been standardized. The antibody response generated against JE vaccine was quantified and the assay was found to be sensitive and specific enough with significant accuracy and precision. On analysis of cell count, a cell concentration of 1.5 x 104 was selected as the optimum, since concentrations above and below this resulted in problems of confluent monolayer formation and incomplete monolayer formation. Incubation time has also been standardized for measuring cytopathic effect (CPE). Out of the four different time points selected, 90 min was found to be adequate for 50% reduction in the amount of CPE. The accuracy of SNT assay is explained in terms of fiducial limits at 95% level. Inter- and intra-assay reproducibility testing was also performed. A comparison of potency of JE vaccine by plaque reduction neutralization test (PRNT) and SNT method was conducted and it was found that SNT can be a reliable approach for estimating the potency of JE vaccine. The results of this study throw a light on the utility of SNT assay for the potency estimation of JE vaccine in routine practice.

  19. A systematic review of the literature to identify and quantify host and vector competence and abundance of Japanese Encephalitis Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Japanese Encephalitis virus (JEV) is a mosquito-borne arbovirus that causes endemic and epidemic encephalitis in Eastern and Southeastern Asia. Swine and wading birds serve as reservoirs for the virus, which can be transmitted to humans via mosquitos. Currently, there is no specific treatment availa...

  20. A Lentiviral Vector Expressing Japanese Encephalitis Virus-like Particles Elicits Broad Neutralizing Antibody Response in Pigs

    PubMed Central

    Souque, Philippe; Frenkiel, Marie-Pascale; Paulous, Sylvie; Garcìa-Nicolàs, Obdulio; Summerfield, Artur; Charneau, Pierre; Desprès, Philippe

    2015-01-01

    Background Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in Southeast Asia. Vaccination of domestic pigs has been suggested as a “one health” strategy to reduce viral disease transmission to humans. The efficiency of two lentiviral TRIP/JEV vectors expressing the JEV envelope prM and E glycoproteins at eliciting protective humoral response was assessed in a mouse model and piglets. Methodology/Principal Findings A gene encoding the envelope proteins prM and E from a genotype 3 JEV strain was inserted into a lentiviral TRIP vector. Two lentiviral vectors TRIP/JEV were generated, each expressing the prM signal peptide followed by the prM protein and the E glycoprotein, the latter being expressed either in its native form or lacking its two C-terminal transmembrane domains. In vitro transduction of cells with the TRIP/JEV vector expressing the native prM and E resulted in the efficient secretion of virus-like particles of Japanese encephalitis virus. Immunization of BALB/c mice with TRIP/JEV vectors resulted in the production of IgGs against Japanese encephalitis virus, and the injection of a second dose one month after the prime injection greatly boosted antibody titers. The TRIP/JEV vectors elicited neutralizing antibodies against JEV strains belonging to genotypes 1, 3, and 5. Immunization of piglets with two doses of the lentiviral vector expressing JEV virus-like particles led to high titers of anti-JEV antibodies, that had efficient neutralizing activity regardless of the JEV genotype tested. Conclusions/Significance Immunization of pigs with the lentiviral vector expressing JEV virus-like particles is particularly efficient to prime antigen-specific humoral immunity and trigger neutralizing antibody responses against JEV genotypes 1, 3, and 5. The titers of neutralizing antibodies elicited by the TRIP/JEV vector are sufficient to confer protection in domestic pigs against different genotypes of JEV and this could be of a great

  1. Malathion Resistance Status and Mutations in Acetylcholinesterase Gene (Ace) in Japanese Encephalitis and Filariasis Vectors from Endemic Area in India.

    PubMed

    Misra, Brij Ranjan; Gore, Milind

    2015-05-01

    Japanese encephalitis (JE) and lymphatic filariasis (LF) are endemic in estern part of Uttar Pradesh in India and transmitted by Culex mosquitoes (Diptera: Culicidae). JE vaccination and mass drug administration for JE and LF management is being undertaken respectively. In addition to this, indoor residual spraying and fogging are used for the control of mosquito vectors. Organophosphate resistance in mosquito is dependent on alteration in acetylcholinesterase (Ace) gene. Hence, it is important to evaluate organophosphate resistance in Culex tritaeniorhynchus Giles (JE vector) and Culex quinquefasciatus Say (LF vector). The current study showed the presence of resistant populations and F331W mutation in Cx. tritaeniorhynchus and G119S mutation in Cx. quinquefasciatus insensitive Ace genes. Resistant populations of these two vectors increase the chances of spreading of resistance in the natural population and may cause failure of intervention programs that include organophosphates against these two vectors in future.

  2. The first report on human cases serologically diagnosed as Japanese encephalitis in Indonesia.

    PubMed

    Yoshida, M; Igarashi, A; Suwendra, P; Inada, K; Maha, M S; Kari, K; Suda, H; Antonio, M T; Arhana, B N; Takikawa, Y; Maesawa, S; Yoshida, H; Chiba, M

    1999-12-01

    Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974, human JE cases have never been reported in Indonesia in spite of the prevalence of anti-JE antibodies among human and pig populations as well as abundant JE vector mosquitos. In this report, we describe serological diagnosis of JE cases in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid (CSF) of the patients. In the first series of our investigation (Series 1), we examined serum specimens from 12 patients with clinical diagnosis of viral encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible JE cases. In the next series (Series 2), we examined both serum and CSF from encephalitis patients and gave laboratory diagnosis of JE. One of them was suspected to have concomitant or recent infection with dengue virus, probably type 3. These results strongly indicated that JE has been prevalent in Bali, Indonesia.

  3. Change in Dengue and Japanese Encephalitis Seroprevalence Rates in Sri Lanka

    PubMed Central

    Jeewandara, Chandima; Gomes, Laksiri; Paranavitane, S. A.; Tantirimudalige, Mihiri; Panapitiya, Sumedha Sandaruwan; Jayewardene, Amitha; Fernando, Samitha; Fernando, R. H.; Prathapan, Shamini

    2015-01-01

    Background Sri Lanka has been affected by epidemics of dengue infections for many decades and the incidence and severity of dengue infections have been rising each year. Therefore, we investigated the age stratified seroprevalence of dengue infections in order to facilitate future dengue vaccine strategies. In addition, since the symptomatic dengue infections have increased during the past few decades, we also investigated the possible association with Japanese Encephalitis Virus (JEV) antibody seropositivity with symptomatic dengue in a community cohort in Sri Lanka. Methods 1689 healthy individuals who were attending a primary health care facility were recruited. Dengue and JEV antibody status was determined in all individuals and JEV vaccination status was recorded. Results 1152/1689 (68.2%) individuals were seropositive for dengue and only 133/1152 (11.5%) of them had been hospitalized to due to dengue. A significant and positive correlation was observed for dengue antibody seropositivity and age in children (Spearmans R = 0.84, p = 0.002) and in adults (Spearmans R = 0.96, p = 0.004). We observed a significant rise in the age stratified seroprevalence rates in children over a period of 12 years. For instance, in year 2003 the annual seroconversion rate was 1.5% per annum, which had risen to 3.79% per annum by 2014. We also found that both adults (p<0.001) and in children (p = 0.03) who were hospitalized due to dengue were more likely to be seropositive for JEV antibodies. However, 244 (91.4%) of adults who were seropositive for JEV had not had the JEV vaccine. Conclusions Dengue seroprevalence rates have risen significantly over the last 12 years in Sri Lanka, possibly due to increased transmission. As individuals who were hospitalized due to dengue were more likely to be seropositive for JEV, the possibility of cross-reactive assays and/or of JEV infection on immunity to the DENV and clinical disease severity should be further investigated. PMID:26696417

  4. Vaccines against tick-borne encephalitis: WHO position paper--recommendations.

    PubMed

    Who Publication

    2011-11-01

    This article presents the WHO recommendations on the use of vaccines against tick-borne encephalitis excerpted from the recently published Vaccines against tick-borne encephalitis: WHO position paper. This is the first WHO position paper on the use of tick-borne encephalitis. It was published in the Weekly Epidemiological Record in June 2011. In this paper, footnotes provide a limited number of core references including references to grading tables that assess the quality of scientific evidence for a few key conclusions; a more comprehensive list of references is offered in the Background document on vaccines and vaccination against tick-borne encephalitis available at http://www.who.int/immunization/sage/6_TBE_backgr_18_Mar_net_apr_2011.pdf. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2011 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html.

  5. Experimental evidence that RNA recombination occurs in the Japanese encephalitis virus

    SciTech Connect

    Chuang, C.-K.; Chen, W.-J.

    2009-11-25

    Due to the lack of a proofreading function and error-repairing ability of genomic RNA, accumulated mutations are known to be a force driving viral evolution in the genus Flavivirus, including the Japanese encephalitis (JE) virus. Based on sequencing data, RNA recombination was recently postulated to be another factor associated with genomic variations in these viruses. We herein provide experimental evidence to demonstrate the occurrence of RNA recombination in the JE virus using two local pure clones (T1P1-S1 and CJN-S1) respectively derived from the local strains, T1P1 and CJN. Based on results from a restriction fragment length polymorphism (RFLP) assay on the C/preM junction comprising a fragment of 868 nucleotides (nt 10-877), the recombinant progeny virus was primarily formed in BHK-21 cells that had been co-infected with the two clones used in this study. Nine of 20 recombinant forms of the JE virus had a crossover in the nt 123-323 region. Sequencing data derived from these recombinants revealed that no nucleotide deletion or insertion occurred in this region favoring crossovers, indicating that precisely, not aberrantly, homologous recombination was involved. With site-directed mutagenesis, three stem-loop secondary structures were destabilized and re-stabilized in sequence, leading to changes in the frequency of recombination. This suggests that the conformation, not the free energy, of the secondary structure is important in modulating RNA recombination of the virus. It was concluded that because RNA recombination generates genetic diversity in the JE virus, this must be considered particularly in studies of viral evolution, epidemiology, and possible vaccine safety.

  6. Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product.

    PubMed

    Zaman, K; Naser, Abu Mohd; Power, Maureen; Yaich, Mansour; Zhang, Lei; Ginsburg, Amy Sarah; Luby, Stephen P; Rahman, Mahmudur; Hills, Susan; Bhardwaj, Mukesh; Flores, Jorge

    2014-10-21

    We conducted a four-arm, double-blind, randomized controlled trial among 818 Bangladeshi infants between 10 and 12 months of age to establish equivalence among three lots of live attenuated SA 14-14-2 JE vaccine manufactured by the China National Biotec Group's Chengdu Institute of Biological Products (CDIBP) in a new Good Manufacturing Practice (GMP) facility and to evaluate non-inferiority of the product with a lot of the same vaccine manufactured in CDIBP's original facility. The study took place in two sites in Bangladesh, rural Matlab and Mirpur in urban Dhaka. We collected pre-vaccination (Day 0) and post-vaccination Day 28 (-4 to +14 days) blood samples to assess neutralizing anti-JE virus antibody titers in serum by plaque reduction neutralization tests (PRNT). Seroprotection following vaccination was defined as a PRNT titer ≥1:10 at Day 28 in participants non-immune at baseline. Follow-up for reactogenicity and safety was conducted through home visits at Day 7 and monitoring for serious adverse events through Day 28. Seroprotection rates ranged from 80.2% to 86.3% for all four lots of vaccine. Equivalence of the seroprotection rates between pairs of vaccine lots produced in the new GMP facility was satisfied at the pre-specified 10% margin of the 95% confidence interval (CI) for two of the three pairwise comparisons, but not for the third (-4.3% observed difference with 95% CI of -11.9 to 3.3%). Nevertheless, the aggregate seroprotection rate for all three vaccine lots manufactured in the GMP facility was calculated and found to be within the non-inferiority margin (within 10%) to the vaccine lot produced in the original facility. All four lots of vaccine were safe and well tolerated. These study results should facilitate the use of SA 14-14-2 JE vaccine as a routine component of immunization programs in Asian countries.

  7. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

    PubMed Central

    Yunoki, Mikihiro; Kurosu, Takeshi; Koketsu, Ritsuko Kubota; Takahashi, Kazuo; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2016-01-01

    Japanese encephalitis virus (JEV), West Nile virus (WNV), and dengue virus (DenV) are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. PMID:27462140

  8. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus.

    PubMed

    Yunoki, Mikihiro; Kurosu, Takeshi; Koketsu, Ritsuko Kubota; Takahashi, Kazuo; Okuno, Yoshinobu; Ikuta, Kazuyoshi

    2016-01-01

    Japanese encephalitis virus (JEV), West Nile virus (WNV), and dengue virus (DenV) are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. PMID:27462140

  9. Hospital-based surveillance of Japanese encephalitis at a tertiary hospital in Manila.

    PubMed

    Alera, Ma Theresa P; Velasco, John Mark S; Ypil-Cardenas, Charity Ann; Jarman, Richard G; Nisalak, Ananda N; Thaisomboonsuk, Butsaya; Gibbons, Robert V; Dimaano, Efren M; Yoon, In-Kyu

    2013-09-01

    Japanese encephalitis virus (JEV) is endemic in the Philippines but the incidence and burden of disease are not well established. We conducted a prospective hospital-based study at San Lazaro Hospital, a tertiary level hospital in Manila, from September 2005 to December 2006. Cases were determined using an in-house dengue and Japanese encephalitis (JE) enzyme-linked immunosorbent assay in order to detect the proportion of JE cases among the acute encephalitis syndrome (AES) cases admitted to our hospital. Fifteen patients were found to have AES, of whom 6 (40%) had confirmed JE. Of the JE cases, 4 were females and 2 were males with an age range of 3-14 years. Three of the 6 JE cases occurred during July. The most common signs and symptoms on admission among JE cases were: fever, headache, loss of appetite, neck rigidity and altered sensorium. JE likely comprises a significant proportion of hospitalized AES cases among children from Manila and nearby provinces. Further studies on the nation-wide prevalence and distribution of JE in the Philippines are needed to guide health authorities in disease control and prevention strategies.

  10. Protective immunity to Japanese encephalitis virus associated with anti-NS1 antibodies in a mouse model

    PubMed Central

    2012-01-01

    Background Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described. Results JEV NS1 was expressed in and purified from Drosophila S2 cells in a native glycosylated multimeric form, which induced T-cell and antibody responses in immunized C3H/HeN mice. Mice vaccinated with 1 μg NS1 with or without water-in-oil adjuvant were partially protected against viral challenge and higher protection was observed in mice with higher antibody titers. IgG1 was preferentially elicited by an adjuvanted NS1 protein, whereas a larger load of IFN-γ was produced in splenocytes from mice immunized with aqueous NS1. Mice that passively received anti-NS1 mouse polyclonal immune sera were protected, and this phenomenon was dose-dependent, whereas protection was low or delayed after the passive transfer of anti-NS1 MAbs. Conclusion The purified NS1 subunit induced protective immunity in relation with anti-NS1 IgG1 antibodies. NS1 protein efficiently stimulated Th1-cell proliferation and IFN-γ production. Protection against lethal challenge was elicited by passive transfer of anti-NS1 antisera, suggesting that anti-NS1 antibodies play a substantial role in anti-viral immunity PMID:22828206

  11. Regional Variation in Pig Farmer Awareness and Actions Regarding Japanese Encephalitis in Nepal: Implications for Public Health Education

    PubMed Central

    Dhakal, Santosh; Joshi, Durga Datt; Ale, Anita; Sharma, Minu; Dahal, Meena; Shah, Yogendra; Pant, Dhan Kumar; Stephen, Craig

    2014-01-01

    Japanese encephalitis (JE) is a mosquito-borne zoonotic disease that has pigs as the major amplifying hosts. It is the most important cause of viral encephalitis in people in Nepal and is spreading in its geographic distribution in that country. Pig farming is increasing in Nepal due to reducing cultural biases against pigs and government programs to support pig farming for poverty alleviation. Major strategies for JE prevention and control include education, vector control, and immunization of people and pigs. This study used a survey of 400 pig farmers in 4 areas of Nepal with different JE and pig farming histories to explore regional variations in farmer awareness and actions towards JE, the association of awareness and actions with farm and farmer variables, and the implications of these associations for public health education. Exposure to JE risk factors was common across pig farms and pig farming districts but there were significant district level differences in knowledge and practices related to on-farm JE risk reduction. Social factors such as literacy, gender, and cultural practices were associated with farmer attitudes, knowledge and practices for JE control. JE vaccine uptake was almost non-existent and mosquito control steps were inconsistently applied across all 4 districts. Income was not a determining factor of the differences, but all farmers were very poor. The low uptake of vaccine and lack of infrastructure or financial capacity to house pigs indoors or away from people suggest that farmer personal protection should be a priority target for education in Nepal. This study re-enforces the need to attack root causes of people’s personal disease prevention behaviours and take into account local variation in needs and capacities when designing health or agriculture education programs. PMID:24416402

  12. A tropical menace of co-infection of Japanese encephalitis and neurocysticercosis in two children

    PubMed Central

    Yoganathan, Sangeetha; Sudhakar, Sniya Valsa; Thomas, Maya Mary; Yadav, Vikas Kapildeo

    2016-01-01

    Japanese encephalitis (JE) is a mosquito borne encephalitis caused by Flavivirus. Neurocysticercosis (NCC) is a parasitic disease of the central nervous system caused by Taenia solium. In this report, we describe the clinical profile, imaging findings, and outcome of two children with JE and coexisting NCC. Eleven and thirteen-year-old boys from the same town of Jharkhand state were brought with history of fever, seizures, altered sensorium, and extrapyramidal symptoms. Dystonia, hypomimia, bradykinesia, and dyskinesia were observed. Meige syndrome observed in one of the children is a novel finding. Magnetic resonance imaging of the brain revealed findings suggestive of JE with cysticercal granulomas. There are few reports of coexistence of JE and NCC in children. Both children were treated with ribavirin, and follow-up imaging had shown significant resolution of signal changes. Both the children had shown marked clinical improvement. Ribavirin was found to beneficial in reducing the morbidity in our patients.

  13. A tropical menace of co-infection of Japanese encephalitis and neurocysticercosis in two children.

    PubMed

    Yoganathan, Sangeetha; Sudhakar, Sniya Valsa; Thomas, Maya Mary; Yadav, Vikas Kapildeo

    2016-01-01

    Japanese encephalitis (JE) is a mosquito borne encephalitis caused by Flavivirus. Neurocysticercosis (NCC) is a parasitic disease of the central nervous system caused by Taenia solium. In this report, we describe the clinical profile, imaging findings, and outcome of two children with JE and coexisting NCC. Eleven and thirteen-year-old boys from the same town of Jharkhand state were brought with history of fever, seizures, altered sensorium, and extrapyramidal symptoms. Dystonia, hypomimia, bradykinesia, and dyskinesia were observed. Meige syndrome observed in one of the children is a novel finding. Magnetic resonance imaging of the brain revealed findings suggestive of JE with cysticercal granulomas. There are few reports of coexistence of JE and NCC in children. Both children were treated with ribavirin, and follow-up imaging had shown significant resolution of signal changes. Both the children had shown marked clinical improvement. Ribavirin was found to beneficial in reducing the morbidity in our patients. PMID:27606026

  14. Vector-free transmission and persistence of Japanese encephalitis virus in pigs

    PubMed Central

    Ricklin, Meret E.; García-Nicolás, Obdulio; Brechbühl, Daniel; Python, Sylvie; Zumkehr, Beatrice; Nougairede, Antoine; Charrel, Remi N.; Posthaus, Horst; Oevermann, Anna; Summerfield, Artur

    2016-01-01

    Japanese encephalitis virus (JEV), a main cause of severe viral encephalitis in humans, has a complex ecology, composed of a cycle involving primarily waterbirds and mosquitoes, as well as a cycle involving pigs as amplifying hosts. To date, JEV transmission has been exclusively described as being mosquito-mediated. Here we demonstrate that JEV can be transmitted between pigs in the absence of arthropod vectors. Pigs shed virus in oronasal secretions and are highly susceptible to oronasal infection. Clinical symptoms, virus tropism and central nervous system histological lesions are similar in pigs infected through needle, contact or oronasal inoculation. In all cases, a particularly important site of replication are the tonsils, in which JEV is found to persist for at least 25 days despite the presence of high levels of neutralizing antibodies. Our findings could have a major impact on the ecology of JEV in temperate regions with short mosquito seasons. PMID:26902924

  15. A tropical menace of co-infection of Japanese encephalitis and neurocysticercosis in two children

    PubMed Central

    Yoganathan, Sangeetha; Sudhakar, Sniya Valsa; Thomas, Maya Mary; Yadav, Vikas Kapildeo

    2016-01-01

    Japanese encephalitis (JE) is a mosquito borne encephalitis caused by Flavivirus. Neurocysticercosis (NCC) is a parasitic disease of the central nervous system caused by Taenia solium. In this report, we describe the clinical profile, imaging findings, and outcome of two children with JE and coexisting NCC. Eleven and thirteen-year-old boys from the same town of Jharkhand state were brought with history of fever, seizures, altered sensorium, and extrapyramidal symptoms. Dystonia, hypomimia, bradykinesia, and dyskinesia were observed. Meige syndrome observed in one of the children is a novel finding. Magnetic resonance imaging of the brain revealed findings suggestive of JE with cysticercal granulomas. There are few reports of coexistence of JE and NCC in children. Both children were treated with ribavirin, and follow-up imaging had shown significant resolution of signal changes. Both the children had shown marked clinical improvement. Ribavirin was found to beneficial in reducing the morbidity in our patients. PMID:27606026

  16. Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus.

    PubMed

    Johari, Jefree; Kianmehr, Aynaz; Mustafa, Mohd Rais; Abubakar, Sazaly; Zandi, Keivan

    2012-12-07

    Japanese encephalitis (JE), a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV) replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA) and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC(50) = 14.28 µg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC(50) = 212.1 µg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC(50) = 7.27 µg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC(50) = 3.44 µg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s) of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus.

  17. Infection of Pericytes In Vitro by Japanese Encephalitis Virus Disrupts the Integrity of the Endothelial Barrier

    PubMed Central

    Ou, Yen-Chuan; Li, Jian-Ri; Chang, Cheng-Yi; Pan, Hung-Chuan; Lai, Ching-Yi; Liao, Su-Lan; Raung, Shue-Ling; Chang, Chen-Jung

    2014-01-01

    Though the compromised blood-brain barrier (BBB) is a pathological hallmark of Japanese encephalitis-associated neurological sequelae, the underlying mechanisms and the specific cell types involved are not understood. BBB characteristics are induced and maintained by cross talk between brain microvascular endothelial cells and neighboring elements of the neurovascular unit. In this study, we show a potential mechanism of disruption of endothelial barrier integrity during the course of Japanese encephalitis virus (JEV) infection through the activation of neighboring pericytes. We found that cultured brain pericytes were susceptible to JEV infection but were without signs of remarkable cytotoxicity. JEV-infected pericytes were found to release biologically active molecules which activated ubiquitin proteasome, degraded zonula occludens-1 (ZO-1), and disrupted endothelial barrier integrity in cultured brain microvascular endothelial cells. Infection of pericytes with JEV was found to elicit elevated production of interleukin-6 (IL-6), which contributed to the aforementioned endothelial changes. We further demonstrated that ubiquitin-protein ligase E3 component n-recognin-1 (Ubr 1) was a key upstream regulator which caused proteasomal degradation of ZO-1 downstream of IL-6 signaling. During JEV central nervous system trafficking, endothelial cells rather than pericytes are directly exposed to cell-free viruses in the peripheral bloodstream. Therefore, the results of this study suggest that subsequent to primary infection of endothelial cells, JEV infection of pericytes might contribute to the initiation and/or augmentation of Japanese encephalitis-associated BBB breakdown in concerted action with other unidentified barrier disrupting factors. PMID:24198423

  18. Antiviral Activity of Baicalein and Quercetin against the Japanese Encephalitis Virus

    PubMed Central

    Johari, Jefree; Kianmehr, Aynaz; Mustafa, Mohd Rais; Abubakar, Sazaly; Zandi, Keivan

    2012-01-01

    Japanese encephalitis (JE), a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV) replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA) and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC50 = 14.28 μg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC50 = 212.1 μg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC50 = 7.27 μg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC50 = 3.44 μg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s) of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus. PMID:23222683

  19. Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. IV. Natural infection in sentinel pigs.

    PubMed

    Maeda, O; Takenokuma, K; Karoji, Y; Kuroda, A; Sasaki, O; Karaki, T; Ishii, T

    1978-08-01

    Natural infection with Japanese encephalitis virus in three sentinel pigs held in separate experimental huts was examined daily by virus recovery from blood samples of the pigs and from mosquitoes after incubation for about 7 days from their blood feeding and by HI antibody titration of the blood samples. After a period of low infection rates, below 6%, for about two weeks in engorged Culex tritaeniorhynchus summorosus, high mosquito infections of over 30% from each viremic pig occurred for two to three days. The pigs may be probably have been bitten by many infected but not infective mosquitoes in a period of about 10 days before infection.

  20. Detection of serum antibody to Japanese encephalitis by enzyme-linked immunosorbent assay.

    PubMed

    Wang, S Y

    1989-02-01

    An enzyme-linked immunosorbent assay (ELISA) for the detection of Japanese encephalitis (JE) antibody is described, after 269 human sera were tested by both hemagglutination inhibition (HI) test and ELISA. In ELISA screening, the antigen concentration and the dilution of horseradish peroxidase conjugated goat anti-human Ig were determined by chequerboard titration as 10 micrograms/ml and 1:1000. The color produced by enzyme-substrate reaction was measured on a spectrophotometer. The results showed a good agreement with those obtained from a routine HI test.

  1. Japanese encephalitis virus antibody among normal individuals of Dibrugarh area, upper Assam.

    PubMed

    Mahanta, J; Boruah, U; Sarmabordoloi, J N; Baruah, H C

    1996-09-01

    In a hospital based study in Dibrugarh upper Assam carried out over a period of one year, 250 normal individuals, were screened for antibody to Japanese encephalitis Virus. 44 individuals (17.6%) showed antibody to JE virus. The highest numbers were found in July and August, each 40%, and lowest in January (4%). The ratio of apparent to inapparent infection in this study was found to be 9.1 : 100, which is lower than reported in Assam earlier, but slightly higher than predicted for India as a whole. PMID:8973018

  2. Combined Alphavirus Replicon Particle Vaccine Induces Durable and Cross-Protective Immune Responses against Equine Encephalitis Viruses

    PubMed Central

    Glass, Pamela J.; Bakken, Russell R.; Barth, James F.; Lind, Cathleen M.; da Silva, Luis; Hart, Mary Kate; Rayner, Jonathan; Alterson, Kim; Custer, Max; Dudek, Jeanne; Owens, Gary; Kamrud, Kurt I.; Parker, Michael D.; Smith, Jonathan

    2014-01-01

    ABSTRACT Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. IMPORTANCE Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV). Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the

  3. Seroprevalence of Cysticercus Antibodies in Japanese Encephalitis Patients in Upper Assam, India: A Hospital Based Study

    PubMed Central

    Mazumdar, Himangshu; Saikia, Lahari

    2016-01-01

    Introduction Co-infection of Japanese Encephalitis (JE) and Cysticercosis is attributed mainly to the common epidemiological features between the two diseases. Not much is known about the clinical implications of one infection over the other. Aim The study aimed at establishing whether JE-Cysticercosis co-infection is prevalent in the Upper Assam districts and to explore additional details about such co-infections both clinically and epidemiologically. Materials and Methods The present study was a retrospective cross-sectional hospital based study conducted between July 2013 and June 2014 and included 272 Acute Encephalitis Syndrome (AES) patients. Out of this, 137 JE positive and 135 non-JE Acute encephalitis patients were taken as cases and controls respectively. The diagnosis of JE and Cysticercosis was established by ELISA. Statistical Analysis EpiInfo ver. 7 was used for statistical analysis. Chi-square was used and p-value < 0.05 was considered to be statistically significant. Results The association of Cysticercosis with JE was found to be statistically significant (14.6%, p = 0.0019) in the cases with reference to the controls (3.7%). Moreover, the co-infections were found to be more common in case of adults (19.32%, p = 0.0360); with males having a greater odds (5.25, p = 0.0008) of harbouring the parasite as compared to females. Conclusion The study proves that the association of Cysticercosis and JE holds true in this region. PMID:27437215

  4. Prevalence of Neutralizing Antibodies to Japanese Encephalitis Virus among High-Risk Age Groups in South Korea, 2010.

    PubMed

    Lee, Eun Ju; Cha, Go-Woon; Ju, Young Ran; Han, Myung Guk; Lee, Won-Ja; Jeong, Young Eui

    2016-01-01

    After an extensive vaccination policy, Japanese encephalitis (JE) was nearly eliminated since the mid-1980s in South Korea. Vaccination in children shifted the affected age of JE patients from children to adults. However, an abrupt increase in JE cases occurred in 2010, and this trend has continued. The present study aimed to investigate the prevalence of neutralizing antibodies to the JE virus (JEV) among high-risk age groups (≥40 years) in South Korea. A plaque reduction neutralization test was conducted to evaluate the prevalence of neutralizing antibodies to JEV in 945 subjects within four age groups (30-39, 40-49, 50-59, and 60-69 years) in 10 provinces. Of the 945 enrolled subjects, 927 (98.1%) exhibited antibodies against JEV. No significant differences were found in the prevalence of neutralizing antibodies according to sex, age, or occupation. However, there were significant differences in the plaque reduction rate according to age and occupation; oldest age group had a higher reduction rate, and subjects who were employed in agriculture or forestry also had a higher value than the other occupations. We also found that three provinces (Gangwon, Jeonnam, and Gyeongnam) had a relatively lower plaque reduction rate than the other locations. In addition, enzyme-linked immunosorbent assays were conducted to determine recent viral infections and 12 (1.3%) subjects were found to have been recently infected by the virus [corrected]. In conclusion, the present study clearly indicated that the prevalence of neutralizing antibodies has been maintained at very high levels among adult age groups owing to vaccination or natural infections, or both. In the future, serosurveillance should be conducted periodically using more representative samples to better understand the population-level immunity to JE in South Korea.

  5. The Spatio-temporal Distribution of Japanese Encephalitis Cases in Different Age Groups in Mainland China, 2004 – 2014

    PubMed Central

    Wang, Huanyu; Song, Miao; Li, Minghua; Fu, Shihong; Lv, Zhi; He, Ying; Lei, Wenwen; Wang, Bin; Lu, Xiaoqing; Liang, Guodong

    2016-01-01

    Background Japanese encephalitis (JE) is very prevalent in China, but the incidence of JE among children has been greatly reduced by extensive promotion of vaccinations. The incidence of JE among adults, however, has increased in some parts of China. Methods/Principal Findings Data on JE in mainland China, in terms of incidence, gender, and age, were collected between 2004 and 2014. We conducted spatial and temporal analyses on data from different age groups. Generally, children aged 0–15 years still represent the major population of JE cases in China, despite the gradual decrease in incidence over years. However, the incidence of JE among adults in several provinces is notably higher than the national average, especially during the epidemic waves in 2006, 2009, and 2013. The JE cases in the 0–15-year-old group are distributed mainly in the area south of the Yangtze River, with peak incidence occurring from July to September. In the adult group, especially for those over 40 years old, the JE cases are concentrated mainly in the area north of the Yangtze River. JE incidence in the adult group in September and October is significantly greater compared to the other groups. Further analysis using Local Indicators of Spatial Association (LISA) reveals that the distribution of adult JE cases in the six provinces north of the Yangtze River, between north 30–35° latitude and east 110–130° longitude, is a hotspot for adult JE cases. Conclusions/Significance The rate of JE case increase for adults is much greater than for children and has become a public health issue. Therefore, studies on the necessity and feasibility of vaccinating adults who live in JE-endemic areas, but have never been vaccinated for JE, should become a new focus of JE prevention in the future. PMID:27050414

  6. Review of Climate, Landscape, and Viral Genetics as Drivers of the Japanese Encephalitis Virus Ecology

    PubMed Central

    Le Flohic, Guillaume; Porphyre, Vincent; Gonzalez, Jean-Paul

    2013-01-01

    The Japanese encephalitis virus (JEV), an arthropod-born Flavivirus, is the major cause of viral encephalitis, responsible for 10,000–15,000 deaths each year, yet is a neglected tropical disease. Since the JEV distribution area has been large and continuously extending toward new Asian and Australasian regions, it is considered an emerging and reemerging pathogen. Despite large effective immunization campaigns, Japanese encephalitis remains a disease of global health concern. JEV zoonotic transmission cycles may be either wild or domestic: the first involves wading birds as wild amplifying hosts; the second involves pigs as the main domestic amplifying hosts. Culex mosquito species, especially Cx. tritaeniorhynchus, are the main competent vectors. Although five JEV genotypes circulate, neither clear-cut genotype-phenotype relationship nor clear variations in genotype fitness to hosts or vectors have been identified. Instead, the molecular epidemiology appears highly dependent on vectors, hosts' biology, and on a set of environmental factors. At global scale, climate, land cover, and land use, otherwise strongly dependent on human activities, affect the abundance of JEV vectors, and of wild and domestic hosts. Chiefly, the increase of rice-cultivated surface, intensively used by wading birds, and of pig production in Asia has provided a high availability of resources to mosquito vectors, enhancing the JEV maintenance, amplification, and transmission. At fine scale, the characteristics (density, size, spatial arrangement) of three landscape elements (paddy fields, pig farms, human habitations) facilitate or impede movement of vectors, then determine how the JEV interacts with hosts and vectors and ultimately the infection risk to humans. If the JEV is introduced in a favorable landscape, either by live infected animals or by vectors, then the virus can emerge and become a major threat for human health. Multidisciplinary research is essential to shed light on the

  7. Nonsuppurative Encephalomyelitis in a Calf in Japan and Isolation of Japanese Encephalitis Virus Genotype 1 from the Affected Calf

    PubMed Central

    Katayama, Takashi; Saito, Sachie; Horiuchi, Sanae; Maruta, Tetsuya; Kato, Tomoko; Yanase, Tohru; Yamakawa, Makoto

    2013-01-01

    Japanese encephalitis virus (JEV) was isolated from the cerebrum of a calf which showed severe neurological symptoms in late September 2009, and the JEV isolate was revealed to be of genotype 1. This is the first report describing the isolation of genotype 1 JEV from cattle. PMID:23885004

  8. Tissue tropism and molecular characterization of a Japanese encephalitis virus strain isolated from pigs in southwest China.

    PubMed

    Yuan, Lei; Wu, Rui; Liu, Hanyang; Wen, Xintian; Huang, Xiaobo; Wen, Yiping; Ma, Xiaoping; Yan, Qigui; Huang, Yong; Zhao, Qin; Cao, Sanjie

    2016-04-01

    Since September 2012, an epidemic has been spreading among swine in a pig farm located in Sichuan province, southwest China, which has resulted in abortion, stillbirth, and fetal mummification. The brains of stillborn pigs were collected and a previously unknown Japanese encephalitis virus (JEV), namely SCYA201201, was isolated. According to the results of agarose gel diffusion precipitation, indirect immunofluorescence analysis, neutralization testing, reverse transcription PCR (RT-PCR) amplification, and physical and chemical testing, the virus was conformed to have the characteristics of JEV. The virus titer in BHK-21 cells was 10(8.47)PFU/ml and the median lethal dose (LD50) to 3-week-old and 7-day-old mice was 1.99 log10 and 1.02 log10 PFU/LD50, respectively. The results of tissue tropism for mice showed that the viral load in the brain was significantly higher than other organs, indicating that the isolate was strongly neurotropic. Additionally, the complete genome sequence of the isolate was determined and compared with other JEV strains. Phylogenetic analysis showed that the isolate belongs to genotype I and may be an imported virus. The isolate had 88.4% nucleotide identity with the Chinese vaccine strain SA14-14-2. However, there were 69 amino acid substitutions compared with the strain SA14-14-2. Some substitutions indicated that SCYA201201 was highly neurovirulent and infective, in accordance with the results of animal testing. PMID:26851509

  9. Structure-based discovery of two antiviral inhibitors targeting the NS3 helicase of Japanese encephalitis virus

    PubMed Central

    Fang, Jin’e; Li, Huan; Kong, Dexin; Cao, Shengbo; Peng, Guiqing; Zhou, Rui; Chen, Huanchun; Song, Yunfeng

    2016-01-01

    Japanese encephalitis virus (JEV) is a flavivirus that threatens more than half of the world’s population. Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy, and the death rate caused by JEV can reach as high as 60%. The C-terminus of non-structural protein 3 (NS3) of flavivirus encodes helicase and has been identified as a potential drug target. In this study, high throughput molecular docking was employed to identify candidate JEV NS3 helicase inhibitors in a commercial library containing 250,000 compounds. Forty-one compounds were then tested for their ability to inhibit NS3 activity. Two compounds inhibited unwinding activity strongly but had no effect on the ATPase activity of the protein. Western blots, IFA, and plaque reduction assays demonstrated that both compounds inhibited the virus in cell culture. The EC50s of the two compounds were 25.67 and 23.50 μM, respectively. Using simulated docking, the two compounds were shown to bind and block the NS3 RNA unwinding channel, consistent with the results of the enzyme inhibition tests. The atoms participating in intramolecular interaction were identified to facilitate future compound optimization. PMID:27679979

  10. Encephalitis

    MedlinePlus

    ... reaction to vaccinations Autoimmune disease Bacteria such as Lyme disease , syphilis, and tuberculosis Parasites such as roundworms, cysticercosis , and toxoplasmosis in AIDS patients and other people who have a weakened immune system The effects of cancer

  11. Dynamics of the Emergence and Establishment of a Newly Dominant Genotype of Japanese Encephalitis Virus throughout Asia

    PubMed Central

    Schuh, Amy J.; Ward, Melissa J.; Leigh Brown, Andrew J.

    2014-01-01

    ABSTRACT In recent years, genotype I (GI) of Japanese encephalitis virus (JEV) has displaced genotype III (GIII) as the dominant virus genotype throughout Asia. In this study, the largest collection of GIII and GI envelope gene-derived viral sequences assembled to date was used to reconstruct the spatiotemporal chronology of genotype displacement throughout Asia and to determine the evolutionary and epidemiological dynamics underlying this significant event. GI consists of two clades, GI-a and GI-b, with the latter being associated with displacement of GIII as the dominant JEV genotype throughout Asia in the 1990s. Phylogeographic analysis indicated that GI-a diverged in Thailand or Cambodia and has remained confined to tropical Asia, whereas GI-b diverged in Vietnam and then dispersed northwards to China, where it was subsequently dispersed to Japan, Korea, and Taiwan. Molecular adaptation was detected by more than one method at one site (residue 15), and coevolution was detected at two pairs of sites (residues 89 to 360 and 129 to 141) within the GI E gene protein alignment. Viral multiplication and temperature sensitivity analyses in avian and mosquito cells revealed that the GI-b isolate JE-91 had significantly higher infectivity titers in mosquito cells from 24 to 48 h postinfection than did the GI-a and GIII isolates. If the JE-91 isolate is indeed representative of GI-b, an increased multiplicative ability of GI-b viruses compared to that of GIII viruses early in mosquito infection may have resulted in a shortened extrinsic incubation period that led to an increased number of GI enzootic transmission cycles and the subsequent displacement of GIII. IMPORTANCE Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, represents the most significant etiology of childhood viral neurological infection in Asia. Despite the existence of effective vaccines, JEV is responsible for an estimated 68,000 human cases and a reported 10,000 to 15,000 deaths annually

  12. Nitazoxanide inhibits the replication of Japanese encephalitis virus in cultured cells and in a mouse model

    PubMed Central

    2014-01-01

    Background Japanese encephalitis virus (JEV) has a significant impact on public health. An estimated three billion people in 'at-risk’ regions remain unvaccinated and the number of unvaccinated individuals in certain Asian countries is increasing. Consequently, there is an urgent need for the development of novel therapeutic agents against Japanese encephalitis. Nitazoxanide (NTZ) is a thiazolide anti-infective licensed for the treatment of parasitic gastroenteritis. Recently, NTZ has been demonstrated to have antiviral properties. In this study, the anti-JEV activity of NTZ was evaluated in cultured cells and in a mouse model. Methods JEV-infected cells were treated with NTZ at different concentrations. The replication of JEV in the mock- and NTZ-treated cells was examined by virus titration. NTZ was administered at different time points of JEV infection to determine the stage at which NTZ affected JEV replication. Mice were infected with a lethal dose of JEV and intragastrically administered with NTZ from 1 day post-infection. The protective effect of NTZ on the JEV-infected mice was evaluated. Findings NTZ significantly inhibited the replication of JEV in cultured cells in a dose dependent manner with 50% effective concentration value of 0.12 ± 0.04 μg/ml, a non-toxic concentration in cultured cells (50% cytotoxic concentration = 18.59 ± 0.31 μg/ml). The chemotherapeutic index calculated was 154.92. The viral yields of the NTZ-treated cells were significantly reduced at 12, 24, 36 and 48 h post-infection compared with the mock-treated cells. NTZ was found to exert its anti-JEV effect at the early-mid stage of viral infection. The anti-JEV effect of NTZ was also demonstrated in vivo, where 90% of mice that were treated by daily intragastric administration of 100 mg/kg/day of NTZ were protected from a lethal challenge dose of JEV. Conclusions Both in vitro and in vivo data indicated that NTZ has anti-JEV activity, suggesting the potential

  13. Comprehensive mapping of a novel NS1 epitope conserved in flaviviruses within the Japanese encephalitis virus serocomplex.

    PubMed

    Hua, Rong-Hong; Liu, Li-Ke; Huo, Hong; Li, Ye-Nan; Guo, Li-Ping; Wang, Xiao-Lei; Qin, Cheng-Feng; Bu, Zhi-Gao

    2014-06-24

    Nonstructural protein-1 (NS1) of the Japanese encephalitis virus (JEV) is an immunogenic protein that is a potential candidate for the development of vaccines and diagnostic reagents. NS1 is known to be more specific than the E protein in serological testing of flavivirus infections. However, NS1 exhibits cross-reactivity among flaviviruses even within the same genus and more so within a serocomplex. However, the cross-reactive epitopes on JEV NS1 are poorly characterized. The present study describes the full mapping of a linear B-cell epitope that is common and specific to the JEV serocomplex of Flaviviridae. We generated an NS1-specific monoclonal antibody that cross-reacts with the West Nile virus (WNV) NS1 protein by immunizing mice with recombinant JEV NS1. For epitope mapping, 51 partially overlapping peptides spanning the entire NS1 protein were expressed with a glutathione S-transferase (GST) tag and screened using monoclonal antibodies. Two linear epitope-containing peptides were identified using enzyme-linked immunosorbent assay (ELISA). By sequentially removing amino acid residues from the carboxy and amino terminal of peptides, we successfully identified the smallest unit of the linear epitope required to react with the monoclonal antibody. The linear epitope was located in amino acids residues ²²⁷ETHTLW²³². Furthermore, results of the sequence alignment revealed that the epitope was highly conserved among JEV strains. Notably, the epitope is highly conserved among viruses of the JEV serocomplex. Furthermore, the homologous regions on NS1 proteins from dengue viruses showed no cross-reactivity with the monoclonal antibodies. The epitope was recognized by antisera against the WNV but not against the dengue virus. This novel JEV serocomplex-specific linear B-cell epitope of NS1 would be helpful in the development of new vaccines and diagnostic assays. PMID:24631788

  14. Human T cell responses to Japanese encephalitis virus in health and disease.

    PubMed

    Turtle, Lance; Bali, Tanushka; Buxton, Gemma; Chib, Savita; Chan, Sajesh; Soni, Mohammed; Hussain, Mohammed; Isenman, Heather; Fadnis, Prachi; Venkataswamy, Manjunatha M; Satishkumar, Vishali; Lewthwaite, Penny; Kurioka, Ayako; Krishna, Srinivasa; Shankar, M Veera; Ahmed, Riyaz; Begum, Ashia; Ravi, Vasanthapuram; Desai, Anita; Yoksan, Sutee; Fernandez, Stefan; Willberg, Christian B; Kloverpris, Henrik N; Conlon, Christopher; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2016-06-27

    Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.

  15. An outbreak of Japanese encephalitis after two decades in Odisha, India

    PubMed Central

    Dwibedi, Bhagirathi; Mohapatra, Namita; Rathore, Sushil Kumar; Panda, Maheswar; Pati, Satya Sundar; Sabat, Jyotsnamayee; Thakur, Bandana; Panda, Sailendra; Kar, Shantanu Kumar

    2015-01-01

    Sudden deaths in children due to acute encephalitis syndrome (AES) from a tribal dominated district of Malkangiri in Odisha, India, was reported during September-November, 2012. The investigation was carried out to search for the possible viral aetiology that caused this outbreak. Clinico-epidemiological survey and seromolecular investigation were carried out to confirm the viral aetiology. Two hundred seventy two suspected cases with 24 deaths were observed. The patients presented with low to moderate grade fever (87%), headache (43%), vomiting (27%), cold (18%), cough (17%), body ache (15%), joint pain (15%), rash (15%), abdomen pain (9%), lethargy (5%), altered sensorium (8%), convulsion (2%), diarrhoea (3%), and haematemesis (3%). Laboratory investigation showed Japanese encephalitis virus (JEV) IgM in 13.8 per cent (13/94) in blood samples and JEV RNA in one of two cerebrospinal fluid (CSF) samples. Paddy fields close to the houses, high pig to cattle ratio, high density (33 per man hour density) of Culex vishnui mosquitoes, low socio-economic status and low health awareness in the tribal population were observed. This report confirmed the outbreak of JEV infection in Odisha after two decades. PMID:26905239

  16. Molecular Epidemiology of Japanese Encephalitis Virus in Mosquitoes during an Outbreak in China, 2013

    PubMed Central

    Tao, Zexin; Liu, Guifang; Wang, Min; Wang, Huanyu; Lin, Xiaojuan; Song, Lizhi; Wang, Suting; Wang, Haiyan; Liu, Xiaodong; Cui, Ning; Song, Yanyan; Xu, Aiqiang

    2014-01-01

    Japanese encephalitis virus (JEV) can cause serious encephalitis and Culex mosquitoes are the primary vector. In 2013, a JE outbreak occurred in Shandong Province, China with 407 confirmed cases, including 11 deaths. An investigation on JEV in mosquitoes during the outbreak was conducted. A total of 14,719 mosquitoes were collected at 3 sites. For the 12,695 Culex tritaeniorhynchus mosquitoes, 88/201 pooled samples were positive by RT-PCR for the presence of the pre-membrane or envelope protein coding genes. The maximum likelihood estimates of JEV positive individuals per 1,000 vectors were 12.0, 7.2, and 6.0 in the 3 sites respectively with an overall estimate of 9.1. Phylogenetic analysis on these pre-membrane (n = 72) and envelope (n = 26) sequences with those of reference strains revealed they belonged to genotype I. This study describes the molecular epidemiology of JEV and suggests the high infection rate in mosquitoes is an important factor for the outbreak. PMID:24809635

  17. Human T cell responses to Japanese encephalitis virus in health and disease.

    PubMed

    Turtle, Lance; Bali, Tanushka; Buxton, Gemma; Chib, Savita; Chan, Sajesh; Soni, Mohammed; Hussain, Mohammed; Isenman, Heather; Fadnis, Prachi; Venkataswamy, Manjunatha M; Satishkumar, Vishali; Lewthwaite, Penny; Kurioka, Ayako; Krishna, Srinivasa; Shankar, M Veera; Ahmed, Riyaz; Begum, Ashia; Ravi, Vasanthapuram; Desai, Anita; Yoksan, Sutee; Fernandez, Stefan; Willberg, Christian B; Kloverpris, Henrik N; Conlon, Christopher; Klenerman, Paul; Satchidanandam, Vijaya; Solomon, Tom

    2016-06-27

    Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus. PMID:27242166

  18. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

    PubMed

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

    2014-12-01

    The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses.

  19. Dengue Virus and Japanese Encephalitis Virus Epidemiological Shifts in Nepal: A Case of Opposing Trends

    PubMed Central

    Dumre, Shyam P.; Shakya, Geeta; Na-Bangchang, Kesara; Eursitthichai, Veerachai; Rudi Grams, Hans; Upreti, Senendra R.; Ghimire, Prakash; KC, Khagendra; Nisalak, Ananda; Gibbons, Robert V.; Fernandez, Stefan

    2013-01-01

    We report on the changing epidemiology of two important flaviviruses in Nepal: Japanese encephalitis (JE) and dengue viruses. Morbidity and mortality in Nepal is in the thousands since JE was introduced in 1978. Nepal launched an extensive laboratory-based JE surveillance in 2004. Nepal experienced a remarkable reduction in disease burden after mass immunizations from 2005 to 2010, when 2,040 JE infections and 205 JE-related deaths were confirmed. With its emergence in 2006, dengue has become a significant challenge in the country, highlighted by a sudden outbreak in 2010 that resulted in 359 confirmed dengue infections. Currently, both viruses cocirculate in Nepal. Here, we document the remarkable expansion of dengue in Nepal, which urgently requires national surveillance to refine the burden and make recommendations regarding control and prevention programs. We believe that the use of existing JE surveillance network for integrated dengue surveillance may represent the most appropriate alternative. PMID:23419366

  20. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.

    PubMed

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L; Eugenin, Eliseo Alberto

    2014-12-01

    The flaviviruses dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex spp.), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  1. Occurrence of Japanese encephalitis virus mosquito vectors in relation to urban pig holdings.

    PubMed

    Lindahl, Johanna; Chirico, Jan; Boqvist, Sofia; Thu, Ho Thi Viet; Magnusson, Ulf

    2012-12-01

    Japanese encephalitis virus (JEV) is transmitted to humans from pigs or birds by mosquitoes. In this study, the association between urban pig keeping and mosquito vectors was analyzed. A total of 7, 419 mosquitoes were collected overnight in urban households with and without pigs in Can Tho City, Vietnam. The most prevalent vectors were Culex tritaeniorhynchus (36%), Cx. gelidus (24%), and Cx. quinquefasciatus (15%), which were present in all parts of the city. Pigs were associated with increased numbers of Cx. tritaeniorhynchus. Traps close to pigs had higher numbers of Cx. tritaeniorhynchus and Cx. gelidus than traps close to humans. Increased number of persons in the household was associated with increased numbers of Cx. quinquefasciatus. We demonstrate that JEV vector species are present at urban households with and without pigs, and show that keeping pigs in an urban area increase the number of mosquitoes competent as vectors for JEV.

  2. Clinical outcome and neurological sequelae in serologically confirmed cases of Japanese encephalitis patients in Assam, India.

    PubMed

    Baruah, H C; Biswas, D; Patgiri, D; Mahanta, J

    2002-12-01

    We report the clinical outcome and prognostic factors in 39 cases of childhood Japanese Encephalitis admitted to a tertiary hospital of Upper Assam and followed up for 421 days in the community. The mortality rate was 20.5% in our study. The mean GCS (9.97 +/- 0.91) was higher in surviving cases than the fatal cases (GCS 7.5 +/- 1.78) at admission. The fatal cases died within 4.75 +/- 3.19 days in the hospital. All the patients had low BMI (surviving cases 13.54 +/- 2.3; fatal cases 12.05 +/- 0.12) and were anemic. Cerebrospinal fluid (CSF) was clear in 91.4% cases but pressure and protein content were increased in all cases. About 10% cases had parkinsonian features at the time of discharge. Residual symptoms remained in about one third of cases even after 421 days. PMID:12522277

  3. TRIM52 inhibits Japanese Encephalitis Virus replication by degrading the viral NS2A

    PubMed Central

    Fan, Wenchun; Wu, Mengge; Qian, Suhong; Zhou, Yun; Chen, Huanchun; Li, Xiangmin; Qian, Ping

    2016-01-01

    The members of tripartite-motif containing (TRIM) protein participate in various cellular processes and play an important role in host antiviral function. TRIM proteins exert their antiviral activity either directly by degrading viral proteins through their E3 ligase activity, or indirectly by promoting host innate immunity. This study demonstrated for the first time that TRIM52 is a novel antiviral TRIM protein against Japanese encephalitis virus (JEV) infection. Overexpression of TRIM52 restricted JEV replication in BHK-21 and 293T cells. In addition, JEV nonstructural protein 2A (NS2A) is a protein that interacts with TRIM52. Their interaction degraded NS2A in a proteasome-dependent manner via the E3 ligase activity of TRIM52. Thus, TRIM52 is a novel antiviral TRIM protein, and it exerted antiviral activity against JEV infection by targeting and degrading viral NS2A. PMID:27667714

  4. Flaviviruses, an expanding threat in public health: focus on Dengue, West Nile, and Japanese encephalitis virus

    PubMed Central

    Daep, Carlo Amorin; Muñoz-Jordán, Jorge L.; Eugenin, Eliseo Alberto

    2014-01-01

    The flaviviruses Dengue, West Nile, and Japanese encephalitis represent three major mosquito-borne viruses worldwide. These pathogens impact the lives of millions of individuals and potentially could affect non-endemic areas already colonized by mosquito vectors. Unintentional transport of infected vectors (Aedes and Culex sp), traveling within endemic areas, rapid adaptation of the insects into new geographic locations, climate change, and lack of medical surveillance have greatly contributed to the increase in flaviviral infections worldwide. The mechanisms by which flaviviruses alter the immune and the central nervous system have only recently been examined despite the alarming number of infections, related deaths, and increasing global distribution. In this review, we will discuss the expansion of the geographic areas affected by flaviviruses, the potential threats to previously unaffected countries, the mechanisms of pathogenesis, and the potential therapeutic interventions to limit the devastating consequences of these viruses. PMID:25287260

  5. Monoclonal Antibodies Against NS3 and NS5 Proteins of Japanese Encephalitis Virus

    PubMed Central

    Chen, Zheng; Shao, Lin; Ye, Jing; Li, Yongmao; Huang, Shaomei; Chen, Huanchun

    2012-01-01

    Non-structural proteins NS3 and NS5 of Japanese encephalitis virus (JEV) were expressed in Escherichia coli and purified by dialysis. Two monoclonal antibodies (MAbs) named 1H7 and 2D4 against NS3 protein and three MAbs named 3C4, 3H7, and 3F10 against NS5 protein were generated by fusing mouse myeloma cell line SP2/0 with spleen lymphocytes from NS3 or NS5 protein immunized mice. Then activity of MAbs was characterized by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunofluorescent assays (IFA). Our results demonstrated that all the MAbs showed high specificity and sensitivity in IFA at 1:100 dilution and in Western blot analysis at 1:500 dilution, which indicated that these MAbs against NS3 and NS5 proteins of JEV may be used as valuable tools for analysis of the protein functions and pathogenesis of JEV. PMID:22509919

  6. A chimeric Sindbis-based vaccine protects cynomolgus macaques against a lethal aerosol challenge of eastern equine encephalitis virus

    PubMed Central

    Roy, Chad J.; Adams, A. Paige; Wang, Eryu; Leal, Grace; Seymour, Robert L.; Sivasubramani, Satheesh K.; Mega, William; Frolov, Ilya; Didier, Peter J.; Weaver, Scott C.

    2013-01-01

    Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus that causes sporadic, often fatal disease outbreaks in humans and equids, and is also a biological threat agent. Two chimeric vaccine candidates were constructed using a cDNA clone with a Sindbis virus (SINV) backbone and structural protein genes from either a North (SIN/NAEEEV) or South American (SIN/SAEEEV) strain of EEEV. The vaccine candidates were tested in a nonhuman primate (NHP) model of eastern equine encephalitis (EEE). Cynomolgus macaques were either sham-vaccinated, or vaccinated with a single dose of either SIN/NAEEEV or SIN/SAEEEV. After vaccination, animals were challenged by aerosol with a virulent North American strain of EEEV (NA EEEV). The SIN/NAEEEV vaccine provided significant protection, and most vaccinated animals survived EEEV challenge (82%) with little evidence of disease, whereas most SIN/SAEEEV-vaccinated (83%) and control (100%) animals died. Protected animals exhibited minimal changes in temperature and cardiovascular rhythm, whereas unprotected animals showed profound hyperthermia and changes in heart rate post-exposure. Acute inflammation and neuronal necrosis were consistent with EEEV-induced encephalitis in unprotected animals, whereas no encephalitis-related histopathologic changes were observed in the SIN/NAEEEV-vaccinated animals. These results demonstrate that the chimeric SIN/NAEEEV vaccine candidate protects against an aerosol EEEV exposure. PMID:23333212

  7. Restriction endonuclease analysis of bovine herpesvirus type 1 isolates from calves with fatal encephalitis: comparison with vaccine virus.

    PubMed

    Horiuchi, M; Yamazaki, N; Furuoka, H; Matsui, T; Nakagawa, M; Ishiguro, N; Shinagawa, M

    1995-06-01

    Meningo-encephalitis in feedlot cattle sporadically occurred in the Tokachi area in northern Japan. The calves had been vaccinated intranasally with a mixed live-vaccine (infectious bovine rhinotracheitis virus, bovine viral diarrhea-mucosal disease virus, and parainfluenza 3 virus) for which intramuscular inoculation was indicated. Two additional live vaccines, bovine adenovirus type 7 and bovine respiratory syncytical virus, had been inoculated simultaneously. Eleven isolates of bovine herpesvirus type 1 were plaque-purified from two brains with fatal encephalitis; their viral DNAs were examined by restriction endonuclease analysis (REA) using PstI and HindIII. The REA patterns of the virus clones were almost identical to those of the vaccine strains 758-43, suggesting that the isolates from this outbreak of fatal encephalitis originated in the abnormally administered vaccine. PMID:7548427

  8. Japanese encephalitis virus in culicine mosquitoes (Diptera: culicidae) of the republic of Korea, 2008-2010.

    PubMed

    Kim, Heung Chul; Takhampunya, Ratree; Tippayachai, Bousaraporn; Chong, Sung-Tae; Park, Jee-Yong; Kim, Myung-Soon; Seo, Hyun-Ji; Yeh, Jung-Yong; Lee, Won-Ja; Lee, Dong-Kyu; Klein, Terry A

    2015-02-01

    A total of 150,805 culicine female mosquitoes were captured by Mosquito Magnet, black light, and New Jersey light traps, and at resting collections in the Republic of Korea from 2008 to 2010 as part of the U.S. Forces Korea malaria and Japanese surveillance programs. Mosquitoes were identified and culicine mosquitoes placed in pools of up to 30 mosquitoes each, by species and date of collection, and screened for flaviviruses using a reverse transcription-polymerase chain reaction assay. A total of 98/6,845 (1.4%) pools were positive by reverse transcription-polymerase chain reaction for Japanese encephalitis virus (JEV). A total of 92/2,031 (4.5%) pools of Culex tritaeniorhynchus were positive for JEV and accounted for 93.9% (92/98) of all JEV positive pools. A total of 4/804 (0.5%) and 2/175 (1.1%) pools of C. pipiens and C. bitaeniorhynchus, respectively, were positive for JEV. The JEV maximum likelihood estimations (estimated number of viral RNA positive mosquitoes per 1,000) for C. tritaeniorhynchus, C. bitaeniorhynchus, and C. pipiens were 1.71, 1.02, and 0.36 respectively. JEV is a severe health threat for local populations and of significant concern for nonimmune (unvaccinated) U.S. soldiers, civilians, and family members deployed to the Republic of Korea.

  9. TNF-α promoter polymorphism: a factor contributing to the different immunological and clinical phenotypes in Japanese encephalitis

    PubMed Central

    2012-01-01

    Background More than three billion populations are living under the threat of Japanese encephalitis in South East Asian (SEA) countries including India. The pathogenesis of this disease is not clearly understood and is probably attributed to genomic variations in viral strains as well as the host genetic makeup. The present study is to determine the role of polymorphism of TNF-alpha promoter regions at positions -238G/A, -308G/A, -857C/T and -863C/A in the severity of Japanese encephalitis patients. Methods Total of 142 patients including 66 encephalitis case (IgM/RT-PCR positive), 16 fever cases (IgM positive) without encephalitis and 60 apparently healthy individuals (IgG positive) were included in the study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using site specific restriction enzymes were implemented for polymorphism study of TNF alpha promoter. Results Following the analysis of the digestion patterns of four polymorphic sites of the TNF- alpha promoter region, a significant association was observed between the allele -308A and -863C with the patients of Japanese encephalitis. Conclusions TNF- alpha 308 G/A has been shown to be associated with elevated TNF- alpha transcriptional activity. On the other hand, polymorphism at position -863C/A in the promoter region has been reported to be associated with reduced TNF- alpha promoter activity and lower plasma TNF levels. As per the literature search, this is the first study to identify the role of TNF- alpha promoter in JE infection. Our results show that subjects with - 308A and -863C alleles are more vulnerable to the severe form of JE infection. PMID:22276993

  10. Cross-protection between West Nile and Japanese encephalitis viruses in red-winged blackbirds (Agelaius phoeniceus).

    PubMed

    Nemeth, Nicole M; Bosco-Lauth, Angela M; Bowen, Richard A

    2009-09-01

    Similar to West Nile virus (WNV), Japanese encephalitis virus (JEV) has a history of intercontinental spread, and birds are important for the maintenance and transmission of both of these closely related viruses. We examined viremic and serologic responses of blackbirds (Agelaius phoeniceus), with and without immunity to WNV, following experimental inoculation with two strains of JEV. Japanese encephalitis (JE) viremia was detected in only one of 16 (6.3%) WNV-immune birds, while all 16 nonimmune birds had detectable JE viremia. Two weeks after JEV inoculation, all birds without pre-existing WNV immunity had clearly distinguishable anti-JEV antibodies, while in all birds with pre-existing WNV immunity, antibodies to WNV and JEV were either indistinguishable or the anti-WNV antibody titers were significantly higher. As WNV is endemic throughout much of North America, WNV immunity among birds may dampen transmission while complicating the serologic diagnosis of JEV, should this pathogen be introduced to North America.

  11. Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload.

    PubMed

    Huang, Su-Hua; Lien, Jin-Cherng; Chen, Chao-Jung; Liu, Yu-Ching; Wang, Ching-Ying; Ping, Chia-Fong; Lin, Yu-Fong; Huang, An-Cheng; Lin, Cheng-Wen

    2016-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 μM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 μM, respectively. CW-33 significantly moderated JEV-triggered Ca(2+) overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. PMID:27563890

  12. Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload

    PubMed Central

    Huang, Su-Hua; Lien, Jin-Cherng; Chen, Chao-Jung; Liu, Yu-Ching; Wang, Ching-Ying; Ping, Chia-Fong; Lin, Yu-Fong; Huang, An-Cheng; Lin, Cheng-Wen

    2016-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 μM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 μM, respectively. CW-33 significantly moderated JEV-triggered Ca2+ overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. PMID:27563890

  13. The role of environmental factors in the spatial distribution of Japanese encephalitis in mainland China.

    PubMed

    Wang, Liya; Hu, Wenbiao; Soares Magalhaes, Ricardo J; Bi, Peng; Ding, Fan; Sun, Hailong; Li, Shenlong; Yin, Wenwu; Wei, Lan; Liu, Qiyong; Haque, Ubydul; Sun, Yansong; Huang, Liuyu; Tong, Shilu; Clements, Archie C A; Zhang, Wenyi; Li, Chengyi

    2014-12-01

    Japanese encephalitis (JE) is the most common cause of viral encephalitis and an important public health concern in the Asia-Pacific region, particularly in China where 50% of global cases are notified. To explore the association between environmental factors and human JE cases and identify the high risk areas for JE transmission in China, we used annual notified data on JE cases at the center of administrative township and environmental variables with a pixel resolution of 1 km×1 km from 2005 to 2011 to construct models using ecological niche modeling (ENM) approaches based on maximum entropy. These models were then validated by overlaying reported human JE case localities from 2006 to 2012 onto each prediction map. ENMs had good discriminatory ability with the area under the curve (AUC) of the receiver operating curve (ROC) of 0.82-0.91, and low extrinsic omission rate of 5.44-7.42%. Resulting maps showed JE being presented extensively throughout southwestern and central China, with local spatial variations in probability influenced by minimum temperatures, human population density, mean temperatures, and elevation, with contribution of 17.94%-38.37%, 15.47%-21.82%, 3.86%-21.22%, and 12.05%-16.02%, respectively. Approximately 60% of JE cases occurred in predicted high risk areas, which covered less than 6% of areas in mainland China. Our findings will help inform optimal geographical allocation of the limited resources available for JE prevention and control in China, find hidden high-risk areas, and increase the effectiveness of public health interventions against JE transmission.

  14. Existing antiviral vaccines.

    PubMed

    Ravanfar, Parisa; Satyaprakash, Anita; Creed, Rosella; Mendoza, Natalia

    2009-01-01

    The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever. PMID:19335723

  15. miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells

    PubMed Central

    Li, Wenjuan; Cheng, Peng; Nie, Shangdan; Cui, Wen

    2016-01-01

    Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury. PMID:27703358

  16. Human Vaccines and Immunotherapeutics: News

    PubMed Central

    2013-01-01

    Two studies on optimal timing for measles vaccination Chinese scientists develop bird flu vaccine Influenza vaccination reduces risk of heart attack and stroke Two-dose vaccination program shows positive impact on varicella incidence WHO prequalifies Chinese-produced Japanese encephalitis vaccine Phase 3: RTS,S almost halves malaria cases in young children Herd immunity protects babies against whooping cough New developments in nanoparticle-based vaccination

  17. IRES-Containing VEEV Vaccine Protects Cynomolgus Macaques from IE Venezuelan Equine Encephalitis Virus Aerosol Challenge

    PubMed Central

    Rossi, Shannan L.; Russell-Lodrigue, Kasi E.; Killeen, Stephanie Z.; Wang, Eryu; Leal, Grace; Bergren, Nicholas A.; Vinet-Oliphant, Heather; Weaver, Scott C.; Roy, Chad J.

    2015-01-01

    Venezuelan equine encephalitis virus (VEEV) is an arbovirus endemic to the Americas that is responsible for severe, sometimes fatal, disease in humans and horses. We previously described an IRES-based VEE vaccine candidate based up the IE serotype that offers complete protection against a lethal subtype IE VEEV challenge in mice. Here we demonstrate the IRES-based vaccine’s ability to protect against febrile disease in cynomolgus macaques. Vaccination was well tolerated and elicited robust neutralizing antibody titers noticed as early as day 14. Moreover, complete protection from disease characterized by absence of viremia and characteristic fever following aerosolized IE VEEV challenge was observed in all vaccinees compared to control animals, which developed clinical disease. Together, these results highlight the safety and efficacy of IRES-based VEEV vaccine to protect against an endemic, pathogenic VEEV IE serotype. PMID:26020513

  18. Herpes simplex virus vaccine: protection from stomatitis, ganglionitis, encephalitis and latency.

    PubMed

    Kitces, E N; Payne, W J; Morahan, P S; Tew, J G; Murray, B K

    1978-01-01

    A mouse model system was developed for studying the pathogenesis of oral infection with herpes simplex virus type 1 and the protection offered by prior immunization with a nucleic acid-free vaccine. Of non-immunized mice, 95-100% developed ulcerative lesions 3-5 days following application of virus to abraded oral epithelial surfaces. Infection of the ipsilateral sensory (trigeminal) ganglion and the cerebellum occurred by day 2 and sequentially progressed to the contralateral ganglion by day 4 and to the cerebrum by day 5. Prior immunization of mice with an inactivated virus vaccine, and most importantly, with a vaccine free of nucleic acid, protected mice from subsequent oral virus infection. Protection was demonstrated by: (i) reduction in the incidence and severity of primary oral lesions; (ii) a decrease in the number of mice with acute ganglionic infection or dying of encephalitis; and (iii) a reduction in the incidence of latent trigeminal ganglionic infection.

  19. Serosurveillance for Japanese encephalitis virus in wild birds captured in Korea.

    PubMed

    Yang, Dong-Kun; Oh, Yoon-I; Kim, Hye-Ryoung; Lee, Youn-Jeong; Moon, Oun-Kyong; Yoon, Hachung; Kim, Byounghan; Lee, Kyung-Woo; Song, Jae-Young

    2011-12-01

    Climate change induced by recent global warming may have a significant impact on vector-borne and zoonotic diseases. For example, the distribution of Japanese encephalitis virus (JEV) has expanded into new regions. We surveyed the levels of hemagglutination-inhibition (HI) antibodies against JEV (Family Flaviviridae, genus Flavivirus) in wild birds captured in Korea. Blood samples were collected from 1,316 wild birds including the following migratory birds: Oceanodroma castro (n = 4), Anas formosa (n = 7), Anas penelope (n = 20), Fulica atra (n = 30), Anas acuta (n = 89), Anas crecca (n = 154), Anas platyrhynchos (n = 214), Aix galericulata (n = 310), and Anas poecilorhyncha (n = 488). All were captured in 16 locations in several Korea provinces between April 2007 and December 2009. Out of the 1,316 serum samples tested, 1,141 (86.7%) were positive for JEV. Wild birds captured in 2009 had a higher seroprevalence of ant-JEV antibodies than those captured in 2007. Wild birds with an HI antibody titer of 1 : 1,280 or higher accounted for 21.2% (280/1,316) of the animals tested. These findings indicated that wild birds from the region examined in our study have been exposed to JEV and may pose a high risk for introducing a new JEV genotype into Korea.

  20. Susceptibility of human embryonic stem cell-derived neural cells to Japanese encephalitis virus infection.

    PubMed

    Shen, Shih-Cheng; Shen, Ching-I; Lin, Ho; Chen, Chun-Jung; Chang, Chia-Yu; Chen, Sheng-Mei; Lee, Hsiu-Chin; Lai, Ping-Shan; Su, Hong-Lin

    2014-01-01

    Pluripotent human embryonic stem cells (hESCs) can be efficiently directed to become immature neuroepithelial precursor cells (NPCs) and functional mature neural cells, including neurotransmitter-secreting neurons and glial cells. Investigating the susceptibility of these hESCs-derived neural cells to neurotrophic viruses, such as Japanese encephalitis virus (JEV), provides insight into the viral cell tropism in the infected human brain. We demonstrate that hESC-derived NPCs are highly vulnerable to JEV infection at a low multiplicity of infection (MOI). In addition, glial fibrillary acid protein (GFAP)-expressing glial cells are also susceptible to JEV infection. In contrast, only a few mature neurons were infected at MOI 10 or higher on the third day post-infection. In addition, functional neurotransmitter-secreting neurons are also resistant to JEV infection at high MOI. Moreover, we discover that vimentin intermediate filament, reported as a putative neurovirulent JEV receptor, is highly expressed in NPCs and glial cells, but not mature neurons. These results indicate that the expression of vimentin in neural cells correlates to the cell tropism of JEV. Finally, we further demonstrate that membranous vimentin is necessary for the susceptibility of hESC-derived NPCs to JEV infection.

  1. How environmental conditions impact mosquito ecology and Japanese encephalitis: an eco-epidemiological approach.

    PubMed

    Tian, Huai-Yu; Bi, Peng; Cazelles, Bernard; Zhou, Sen; Huang, Shan-Qian; Yang, Jing; Pei, Yao; Wu, Xiao-Xu; Fu, Shi-Hong; Tong, Shi-Lu; Wang, Huan-Yu; Xu, Bing

    2015-06-01

    Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast Asia and the Western Pacific region, posing a threat to human health. In rural and suburban areas, traditional rice farming and intensive pig breeding provide an ideal environment for both mosquito development and the transmission of JEV among human beings. Combining surveillance data for mosquito vectors, human JE cases, and environmental conditions in Changsha, China, 2004-2009, generalized threshold models were constructed to project the mosquito and JE dynamics. Temperature and rainfall were found to be closely associated with mosquito density at 1, and 4month lag, respectively. The two thresholds, maximum temperature of 22-23°C for mosquito development and minimum temperature of 25-26°C for JEV transmission, play key roles in the ecology of JEV. The model predicts that, in the upper regime, a 1g/m(3) increase in absolute humidity would on average increase human cases by 68-84%. A shift in mosquito species composition in 2007 was observed, and possibly caused by a drought. Effective predictive models could be used in risk management to provide early warnings for potential JE transmission. PMID:25771078

  2. Small noncoding RNA modulates japanese encephalitis virus replication and translation in trans

    PubMed Central

    2011-01-01

    Background Sequence and structural elements in the 3'-untranslated region (UTR) of Japanese encephalitis virus (JEV) are known to regulate translation and replication. We previously reported an abundant accumulation of small subgenomic flaviviral RNA (sfRNA) which is collinear with the highly conserved regions of the 3'-UTR in JEV-infected cells. However, function of the sfRNA in JEV life cycle remains unknown. Results Northern blot and real-time RT-PCR analyses indicated that the sfRNA becomes apparent at the time point at which minus-strand RNA (antigenome) reaches a plateau suggesting a role for sfRNA in the regulation of antigenome synthesis. Transfection of minus-sense sfRNA into JEV-infected cells, in order to counter the effects of plus-sense sfRNA, resulted in higher levels of antigenome suggesting that the presence of the sfRNA inhibits antigenome synthesis. Trans-acting effect of sfRNA on JEV translation was studied using a reporter mRNA containing the luciferase gene fused to partial coding regions of JEV and flanked by the respective JEV UTRs. In vivo and in vitro translation revealed that sfRNA inhibited JEV translation. Conclusions Our results indicate that sfRNA modulates viral translation and replication in trans. PMID:22040380

  3. [Study on Spatial Dispersal and Migration Events of Japanese Encephalitis Virus].

    PubMed

    Gao, Xiaoyan; Zhou, Haiwei; Liu, Hong; Fu, Shihong; Wang, Huanyu; Guo, Zhenyang; Li, Xiaolong; Liang, Guodong

    2015-05-01

    To explore the spatial distribution mechanism of Japanese encephalitis virus (JEV), PhyML v3.0 was used to build phylogenetic tree using JEV sequences in the dataset. PAUP v4.0 and Migrapyhla softz ware were then used to analyze the migration events. The results showed that a total of 95 migration events were observed during the dispersal of JEV throughout Asia. Further analysis revealed that Thailand, and several Chinese provinces (including Shandong, Shanghai, Sichuan and Yunnan), were the main migration sources of JEV. JEV spread from these migration sources as follows: from Thailand to Australia, Cambodia, Tibet and India; from Shanghai to eastern coastal Asian regions and Yunnan; from Shandong to Korea, Zhejiang, Hubei, Shanxi and Liaoning; from Sichuan mainly to inland regions of China, as well as Vietnam and Japan; and from Yunnan to Zhejiang. This study indicated that frequent migration events occurred during the dispersal of JEV in the Asia and Pacific regions, and that Thailand, Shandong, Shanghai, Sichuan and Yunnan were the sources of JEV dispersal.

  4. North American Birds as Potential Amplifying Hosts of Japanese Encephalitis Virus

    PubMed Central

    Nemeth, Nicole; Bosco-Lauth, Angela; Oesterle, Paul; Kohler, Dennis; Bowen, Richard

    2012-01-01

    Japanese encephalitis virus (JEV) is an emerging arbovirus, and inter-continental spread is an impending threat. The virus is maintained in a transmission cycle between mosquito vectors and vertebrate hosts, including birds. We detected variation in interspecies responses among North American birds to infection with strains of two different JEV genotypes (I and III). Several native North American passerine species and ring-billed gulls had the highest average peak viremia titers after inoculation with a Vietnamese (genotype I) JEV strain. Oral JEV shedding was minimal and cloacal shedding was rarely detected. The majority of birds, both viremic (72 of 74; 97.3%) and non-viremic (31 of 37; 83.8%), seroconverted by 14 days post-inoculation and West Nile virus-immune individuals had cross-protection against JEV viremia. Reservoir competence and serologic data for a variety of avian taxa are important for development of JEV surveillance and control strategies and will aid in understanding transmission ecology in the event of JEV expansion to North America. PMID:22927494

  5. Inhibition of aldolase A blocks biogenesis of ATP and attenuates Japanese encephalitis virus production.

    PubMed

    Tien, Chih-Feng; Cheng, Shih-Ching; Ho, Yen-Peng; Chen, Yi-Shiuan; Hsu, Jung-Hsin; Chang, Ruey-Yi

    2014-01-10

    Viral replication depends on host proteins to supply energy and replication accessories for the sufficient production of viral progeny. In this study, we identified fructose-bisphosphate aldolase A as a binding partner of Japanese encephalitis virus (JEV) untranslated regions (UTRs) on the antigenome via RNA affinity capture and mass spectrometry. Direct interaction of aldolase A with JEV RNAs was confirmed by gel mobility shift assay and colocalization with active replication of double-stranded RNA in JEV-infected cells. Infection of JEV caused an increase in aldolase A expression of up to 33%. Knocking down aldolase A reduced viral translation, genome replication, and viral production significantly. Furthermore, JEV infection consumed 50% of cellular ATP, and the ATP level decreased by 70% in the aldolase A-knockdown cells. Overexpression of aldolase A in aldolase A-knockdown cells increased ATP levels significantly. Taken together, these results indicate that JEV replication requires aldolase A and consumes ATP. This is the first report of direct involvement of a host metabolic enzyme, aldolase A protein, in JEV replication.

  6. Japanese encephalitis virus activates autophagy as a viral immune evasion strategy.

    PubMed

    Jin, Rui; Zhu, Wandi; Cao, Shengbo; Chen, Rui; Jin, Hui; Liu, Yang; Wang, Shaobo; Wang, Wei; Xiao, Gengfu

    2013-01-01

    In addition to manipulating cellular homeostasis and survivability, autophagy also plays a crucial role in numerous viral infections. In this study, we discover that Japanese encephalitis virus (JEV) infection results in the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II) protein and GFP-LC3 puncta in vitro and an increase in autophagosomes/autolysosomes in vivo. The fusion between autophagosomes and lysosomes is essential for virus replication. Knockdown of autophagy-related genes reduced JEV replication in vitro, as indicated by viral RNA and protein levels. We also note that JEV infection in autophagy-impaired cells displayed active caspases cleavage and cell death. Moreover, we find that JEV induces higher type I interferon (IFN) activation in cells deficient in autophagy-related genes as the cells exhibited increased phosphorylation and dimerization of interferon regulatory factor 3 (IRF3) and mitochondrial antiviral signaling protein (MAVS) aggregation. Finally, we find that autophagy is indispensable for efficient JEV replication even in an IFN-defective background. Overall, our studies provide the first description of the mechanism of the autophagic innate immune signaling pathway during JEV infection.

  7. Biting behaviour and biting rhythm of potential Japanese encephalitis vectors in Assam.

    PubMed

    Khan, S A; Narain, K; Dutta, P; Handique, R; Srivastava, V K; Mahanta, J

    1997-06-01

    Studies on biting behaviour and biting cycles of medically important mosquitoes were carried out in Madhupur village and Tarajan tea estate of upper Assam. Collections were made off human baits outdoors and indoors and off cattle bait outdoors from August 1991 to July 1992. Human bait collections were performed using the 'stationary direct bait' technique. A total of 9,072 adult host seeking female mosquitoes representing 26 species and 5 genera were collected off baits of which 36.9% were collected off human baits and the rest from cattle. All mosquitoes were primarily zoophilic, although significant numbers were collected biting man outdoors. Biting preferences of important Japanese encephalitis (JE) vectors for man and cattle were studied using outdoor man:outdoor cattle ratio (attraction ratio = AR). Culex quinquefasciatus was attracted towards human baits the most (AR = 8.1:1), followed by Cx. bitaeniorhynchus (AR = 1.6:1) and Mansonia annulifera (AR = 1.3.1). The hourly biting activity of important JE vectors throughout the night on two bait types was also studied using three point moving averages. Hierarchical agglomerative cluster analysis was used to compare and classify mosquitoes on the basis of their similarity in biting rhythms. PMID:9282509

  8. Prevalence of antibodies to Japanese encephalitis virus among pigs in Bali and East Java, Indonesia, 2008.

    PubMed

    Yamanaka, Atsushi; Mulyatno, Kris Cahyo; Susilowati, Helen; Hendrianto, Eryk; Utsumi, Takako; Amin, Mochamad; Lusida, Maria Inge; Soegijanto, Soegeng; Konishi, Eiji

    2010-01-01

    Japanese encephalitis virus (JEV) is a fatal disease in Asia. Pigs are considered to be the effective amplifying host for JEV in the peridomestic environment. Bali Island and Java Island in Indonesia provide a model to assess the effect of pigs on JEV transmission, since the pig density is nearly 100-fold higher in Bali than Java, while the geographic and climatologic environments are equivalent in these areas. We surveyed antibodies to JEV among 123 pigs in Mengwi (Bali) and 96 pigs in Tulungagung (East Java) in 2008 by the hemagglutination-inhibition (HAI) test. Overall prevalences were 49% in Bali and 6% in Java, with a significant difference between them (P < 0.001). Monthly infection rates estimated from age-dependent antibody prevalences were 11% in Bali and 2% in Java. In addition, 2-mercaptoethanol-sensitive antibodies were found only from Bali samples. Further, the average HAI antibody titer obtained from positive samples was significantly higher in Bali (1:52) than Java (1:10; P < 0.001). These results indicated that JEV transmission in nature is more active in Bali than East Java.

  9. Differential Infectivities among Different Japanese Encephalitis Virus Genotypes in Culex quinquefasciatus Mosquitoes

    PubMed Central

    Huang, Yan-Jang S.; Park, So Lee; Higgs, Stephen; Barrett, Alan D. T.; Hsu, Wei-Wen; Harbin, Julie N.; Cohnstaedt, Lee W.; Vanlandingham, Dana L.

    2016-01-01

    During the last 20 years, the epidemiology of Japanese encephalitis virus (JEV) has changed significantly in its endemic regions due to the gradual displacement of the previously dominant genotype III (GIII) with clade b of GI (GI-b). Whilst there is only limited genetic difference distinguishing the two GI clades (GI-a and GI-b), GI-b has shown a significantly wider and more rapid dispersal pattern in several regions in Asia than the GI-a clade, which remains restricted in its geographic distribution since its emergence. Although previously published molecular epidemiological evidence has shown distinct phylodynamic patterns, characterization of the two GI clades has only been limited to in vitro studies. In this study, Culex quinquefasciatus, a known competent JEV mosquito vector species, was orally challenged with three JEV strains each representing GI-a, GI-b, and GIII, respectively. Infection and dissemination were determined based on the detection of infectious viruses in homogenized mosquitoes. Detection of JEV RNA in mosquito saliva at 14 days post infection indicated that Cx. quinquefasciatus can be a competent vector species for both GI and GIII strains. Significantly higher infection rates in mosquitoes exposed to the GI-b and GIII strains than the GI-a strain suggest infectivity in arthropod vectors may lead to the selective advantage of previously and currently dominant genotypes. It could thus play a role in enzootic transmission cycles for the maintenance of JEV if this virus were ever to be introduced into North America. PMID:27706157

  10. How environmental conditions impact mosquito ecology and Japanese encephalitis: an eco-epidemiological approach.

    PubMed

    Tian, Huai-Yu; Bi, Peng; Cazelles, Bernard; Zhou, Sen; Huang, Shan-Qian; Yang, Jing; Pei, Yao; Wu, Xiao-Xu; Fu, Shi-Hong; Tong, Shi-Lu; Wang, Huan-Yu; Xu, Bing

    2015-06-01

    Japanese encephalitis (JE) is one of the major vector-borne diseases in Southeast Asia and the Western Pacific region, posing a threat to human health. In rural and suburban areas, traditional rice farming and intensive pig breeding provide an ideal environment for both mosquito development and the transmission of JEV among human beings. Combining surveillance data for mosquito vectors, human JE cases, and environmental conditions in Changsha, China, 2004-2009, generalized threshold models were constructed to project the mosquito and JE dynamics. Temperature and rainfall were found to be closely associated with mosquito density at 1, and 4month lag, respectively. The two thresholds, maximum temperature of 22-23°C for mosquito development and minimum temperature of 25-26°C for JEV transmission, play key roles in the ecology of JEV. The model predicts that, in the upper regime, a 1g/m(3) increase in absolute humidity would on average increase human cases by 68-84%. A shift in mosquito species composition in 2007 was observed, and possibly caused by a drought. Effective predictive models could be used in risk management to provide early warnings for potential JE transmission.

  11. Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280

    PubMed Central

    Peng, Guiqing; Xu, Jia; Zhou, Rui; Cao, Shengbo; Chen, Huanchun; Song, Yunfeng

    2013-01-01

    Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection. PMID:24348901

  12. Second Generation Inactivated Eastern Equine Encephalitis Virus Vaccine Candidates Protect Mice against a Lethal Aerosol Challenge

    PubMed Central

    Honnold, Shelley P.; Bakken, Russell R.; Fisher, Diana; Lind, Cathleen M.; Cohen, Jeffrey W.; Eccleston, Lori T.; Spurgers, Kevin B.; Maheshwari, Radha K.; Glass, Pamela J.

    2014-01-01

    Currently, there are no FDA-licensed vaccines or therapeutics for eastern equine encephalitis virus (EEEV) for human use. We recently developed several methods to inactivate CVEV1219, a chimeric live-attenuated eastern equine encephalitis virus (EEEV). Dosage and schedule studies were conducted to evaluate the immunogenicity and protective efficacy of three potential second-generation inactivated EEEV (iEEEV) vaccine candidates in mice: formalin-inactivated CVEV1219 (fCVEV1219), INA-inactivated CVEV1219 (iCVEV1219) and gamma-irradiated CVEV1219 (gCVEV1219). Both fCVEV1219 and gCVEV1219 provided partial to complete protection against an aerosol challenge when administered by different routes and schedules at various doses, while iCVEV1219 was unable to provide substantial protection against an aerosol challenge by any route, dose, or schedule tested. When evaluating antibody responses, neutralizing antibody, not virus specific IgG or IgA, was the best correlate of protection. The results of these studies suggest that both fCVEV1219 and gCVEV1219 should be evaluated further and considered for advancement as potential second-generation inactivated vaccine candidates for EEEV. PMID:25116127

  13. Antibody-capture ELISA for detection of immunoglobulin M antibodies in sera from Japanese encephalitis and dengue hemorrhagic fever patients.

    PubMed

    Bundo, K; Igarashi, A

    1985-05-01

    Immunoglobulin M (IgM) antibody titers in paired sera from 19 encephalitis and 44 dengue hemorrhagic fever (DHF) patients in Thailand and 42 Japanese encephalitis (JE) patients in Japan were measured by the antibody capture ELISA and applied to distinguish JE virus infection from dengue virus infection. Titer distribution and the ratio of the titers against JE and dengue antigens led to the following diagnostic criteria. The specimens can be considered as positive with JE when IgM-ELISA titer showed over 200 against JE and 4-fold or more higher than titers against any types of dengue antigens. The specimens can be considered as positive with dengue infection when IgM ELISA titer showed over 200 against one of the 4 types of dengue antigens and 4-fold or more higher than against JE antigen. Based on these criteria, 41 of 42 patients in Japan and 11 of 19 encephalitis patients in Thailand could be diagnosed as having JE virus infection while 2 of 19 encephalitis patients in Thailand and 26 of 44 DHF patients in Thailand could be diagnosed as having dengue virus infections.

  14. Epidemiology of tick-borne encephalitis (TBE) in Europe and its prevention by available vaccines.

    PubMed

    Amicizia, Daniela; Domnich, Alexander; Panatto, Donatella; Lai, Piero Luigi; Cristina, Maria Luisa; Avio, Ulderico; Gasparini, Roberto

    2013-05-01

    Tick-borne Encephalitis (TBE), which is caused by a Flavivirus, is the most common tick-transmitted disease in Central and Eastern Europe and Russia. Today, TBE is endemic in 27 European countries, and has become an international public health problem. The epidemiology of TBE is changing owing to various factors, such as improvements in diagnosis and case reporting, increased recreational activities in areas populated by ticks, and changes in climatic conditions affecting tick habitats. Vaccination remains the most effective protective measure against TBE for people living in risk zones, occupationally exposed subjects and travelers to endemic areas. The vaccines currently in use are FSME-Immun(®), Encepur(®), EnceVir(®) and TBE vaccine Moscow(®). The numerous studies performed on the efficacy and safety of these vaccines have shown a high level of immunogenicity and an excellent safety profile. Several studies have also shown a high level of cross-protection among strains belonging to different subtypes.   In the present paper we attempted to describe the continuously changing epidemiology of TBE in European States and to overview clinical development of available vaccines paying particular attention on cross-protection elicited by the vaccines.

  15. Epidemiology of tick-borne encephalitis (TBE) in Europe and its prevention by available vaccines

    PubMed Central

    Amicizia, Daniela; Domnich, Alexander; Panatto, Donatella; Lai, Piero Luigi; Cristina, Maria Luisa; Avio, Ulderico; Gasparini, Roberto

    2013-01-01

    Tick-borne Encephalitis (TBE), which is caused by a Flavivirus, is the most common tick-transmitted disease in Central and Eastern Europe and Russia. Today, TBE is endemic in 27 European countries, and has become an international public health problem. The epidemiology of TBE is changing owing to various factors, such as improvements in diagnosis and case reporting, increased recreational activities in areas populated by ticks, and changes in climatic conditions affecting tick habitats. Vaccination remains the most effective protective measure against TBE for people living in risk zones, occupationally exposed subjects and travelers to endemic areas. The vaccines currently in use are FSME-Immun®, Encepur®, EnceVir® and TBE vaccine Moscow®. The numerous studies performed on the efficacy and safety of these vaccines have shown a high level of immunogenicity and an excellent safety profile. Several studies have also shown a high level of cross-protection among strains belonging to different subtypes.   In the present paper we attempted to describe the continuously changing epidemiology of TBE in European States and to overview clinical development of available vaccines paying particular attention on cross-protection elicited by the vaccines. PMID:23377671

  16. Antibody response of sandhill and whooping cranes to an eastern equine encephalitis virus vaccine

    USGS Publications Warehouse

    Clark, G.G.; Dein, F.J.; Crabbs, C.L.; Carpenter, J.W.; Watts, D.M.

    1987-01-01

    As a possible strategy to protect whooping cranes (Grus americana) from fatal eastern equine encephalitis (EEE) viral infection, studies were conducted to determine the immune response of this species and sandhill cranes (Grus canadensis) to a formalin-inactivated EEE viral vaccine. Viral-specific neutralizing antibody was elicited in both species after intramuscular (IM) vaccination. Subcutaneous and intravenous routes of vaccination failed to elicit detectable antibody in sandhill cranes. Among the IM vaccinated cranes, the immune response was characterized by nondetectable or low antibody titers that waned rapidly following primary exposure to the vaccine. However, one or more booster doses consistently elicited detectable antibody and/or increased antibody titers in the whooping cranes. In contrast, cranes with pre-existing EEE viral antibody, apparently induced by natural infection, exhibited a rapid increase and sustained high-antibody titers. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to determine the protective efficacy of the antibody.

  17. Use of an inactivated eastern equine encephalitis virus vaccine in cranes

    USGS Publications Warehouse

    Carpenter, J.W.; Dein, F.J.; Clark, G.G.; Watts, D.M.; Crabbs, C.L.

    1986-01-01

    An unprecedented outbreak of fatal eastern equine encephalitis (EEE) virus occurred during the late summer and fall of 1984 in endangered whooping cranes (Grus americana) at the Patuxent Wildlife Research Center, Laurel, Maryland. As part of efforts to prevent future epizootics of EEE. studies were conducted to evaluate the antibody response of cranes following vaccination with a formalin-inactivated EEE virus vaccine. Viral specific neutralizing antibody was elicited in sandhill cranes (Grus canadensis) and whooping cranes following 1M inoculation with the vaccine. Among the 1M-inoculated cranes, peak antibody titers of 1:80 on days 30 to 60 had waned to undetectable levels by days 90 to 120. Although the initial titers were not increased by the first booster dose, the duration of the antibody was extended considerably. Whooping cranes, receiving vaccine 6 months after their first vaccination, developed titers of 1:80 to 1:320 by day 30. At 45 days after the final vaccination, these titers had dropped to 1:10 to 1:160. Cranes with preexisting EEE virus antibody, apparently reflecting natural infection, exhibited an anamnestic response indicated by a rapid increase and sustained high antibody titer. Even though EEE virus vaccine induced neutralizing antibody and produced no adverse side effects, further studies will be required to assess the significance of this response as a strategy for protecting whooping cranes against natural EEE virus infection. The loss of captive whooping cranes to the EEE virus presented a previously unrecognized risk and obstacle to recovery of this species. Not only was, there a setback in the captive breeding and reintroduction program for the whooping crane, but, because of the susceptibility of the species to the EEE virus. establishment of additional crane populations may be more complicated than initially envisioned. However, through continued surveillance, serological monitoring, and vaccination activities, we are confident that

  18. Bagaza virus inhibits Japanese encephalitis & West Nile virus replication in Culex tritaeniorhynchus & Cx. quinquefasciatus mosquitoes

    PubMed Central

    Sudeep, A.B.; Bondre, V.P.; George, R.; Ghodke, Y.S.; Aher, R.V.; Gokhale, M.D.

    2015-01-01

    Background & objectives: Studies have shown that certain flaviviruses influence susceptibility of mosquitoes by inhibiting/enhancing replication of important flaviviruses. Hence, a study was designed to determine whether Bagaza virus (BAGV), a flavivirus isolated from Culex tritaeniorhynchus mosquitoes in India, alters susceptibility of Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes to Japanese encephalitis (JEV) and West Nile viruses (WNV). Methods: JEV and WNV infection in Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes in the presence of BAGV was carried out by intrathoracic (IT) inoculation and oral feeding methods. Mosquitoes were infected with BAGV and WNV/JEV either simultaneously or in a phased manner, in which mosquitoes were infected with BAGV by IT inoculation followed by super-infection with JEV/WNV after eight days post-infection (PI). JEV and WNV yield on 7th and 14th day PI after super-infection was determined by 50 per cent tissue culture infective dose (TCID50) method. Results: In Cx. tritaeniorhynchus mosquitoes, prior infection with BAGV significantly reduced JEV and WNV replication while in Cx. quinquefasciatus, BAGV influence was only seen with WNV. Reduction in virus titre was observed in IT inoculated and oral fed mosquitoes irrespective of the infection mode. JEV replication was also found reduced in Cx. tritaeniorhynchus mosquitoes persistently infected with BAGV at passage four. Interpretation & conclusions: BAGV infection in Cx. tritaeniorhynchus and Cx. quinquefasciatus mosquitoes altered their susceptibility to JEV and WNV producing low virus yield. However, the role of BAGV in inhibiting JEV/WNV replication in field mosquitoes needs further investigations. PMID:26905241

  19. Multiple-Insecticide Resistance and Classic Gene Mutations to Japanese Encephalitis Vector Culex tritaeniorhynchus from China.

    PubMed

    Wu, Zhi-Ming; Chu, Hong-Liang; Wang, Gang; Zhu, Xiao-Juan; Guo, Xiao-Xia; Zhang, Ying-Mei; Xing, Dan; Yan, Ting; Zhao, Ming-Hui; Dong, Yan-De; Li, Chun-Xiao; Zhao, Tong-Yan

    2016-06-01

    Widespread resistance of insect pests to insecticides has been widely reported in China and there is consequently an urgent need to adjust pest management strategies appropriately. This requires detailed information on the extent and causes of resistance. The aim of the present study was to investigate levels of resistance to 5 insecticides among 12 strains of Culex tritaeniorhynchus, a major vector of Japanese encephalitis in China. Resistance to deltamethrin, beta-cypermethrin, permethrin, dichlorvos, and propoxur were measured using larval bioassays. The allelic frequency of knockdown resistance (kdr) and acetylcholinesterase (AChE) mutations were determined in all strains. Larval bioassay results indicated that the field strains collected from different sites were resistant to deltamethrin, beta-cypermethrin, permethrin, dichlorvos, and propoxur, with resistance ratio values ranging from 1.70- to 71.98-fold, 7.83- to 43.07-fold, 3.54- to 40.03-fold, 291.85- to 530.89-fold, and 51.32- to 108.83-fold, respectively. A polymerase chain reaction amplification of specific alleles method for individual was developed to detect genotypes of the AChE gene mutation F455W in Cx. tritaeniorhynchus. The frequency of the AChE gene mutation F455W was 100.00% in all strains, making this mutation of no value as a marker of resistance to organophosphorous and carbamate pesticides in Cx. tritaeniorhynchus in China. The kdr allele was present in all strains at frequencies of 10.00-29.55%. Regression analysis indicated a significant correlation between kdr allele frequencies and levels of resistance to deltamethrin, beta-cypermethrin, and permethrin. These results highlight the need to monitor and map insecticide resistance in Cx. tritaeniorhynchus and to adjust pesticide use to minimize the development of resistance in these mosquitoes.

  20. Multiple-Insecticide Resistance and Classic Gene Mutations to Japanese Encephalitis Vector Culex tritaeniorhynchus from China.

    PubMed

    Wu, Zhi-Ming; Chu, Hong-Liang; Wang, Gang; Zhu, Xiao-Juan; Guo, Xiao-Xia; Zhang, Ying-Mei; Xing, Dan; Yan, Ting; Zhao, Ming-Hui; Dong, Yan-De; Li, Chun-Xiao; Zhao, Tong-Yan

    2016-06-01

    Widespread resistance of insect pests to insecticides has been widely reported in China and there is consequently an urgent need to adjust pest management strategies appropriately. This requires detailed information on the extent and causes of resistance. The aim of the present study was to investigate levels of resistance to 5 insecticides among 12 strains of Culex tritaeniorhynchus, a major vector of Japanese encephalitis in China. Resistance to deltamethrin, beta-cypermethrin, permethrin, dichlorvos, and propoxur were measured using larval bioassays. The allelic frequency of knockdown resistance (kdr) and acetylcholinesterase (AChE) mutations were determined in all strains. Larval bioassay results indicated that the field strains collected from different sites were resistant to deltamethrin, beta-cypermethrin, permethrin, dichlorvos, and propoxur, with resistance ratio values ranging from 1.70- to 71.98-fold, 7.83- to 43.07-fold, 3.54- to 40.03-fold, 291.85- to 530.89-fold, and 51.32- to 108.83-fold, respectively. A polymerase chain reaction amplification of specific alleles method for individual was developed to detect genotypes of the AChE gene mutation F455W in Cx. tritaeniorhynchus. The frequency of the AChE gene mutation F455W was 100.00% in all strains, making this mutation of no value as a marker of resistance to organophosphorous and carbamate pesticides in Cx. tritaeniorhynchus in China. The kdr allele was present in all strains at frequencies of 10.00-29.55%. Regression analysis indicated a significant correlation between kdr allele frequencies and levels of resistance to deltamethrin, beta-cypermethrin, and permethrin. These results highlight the need to monitor and map insecticide resistance in Cx. tritaeniorhynchus and to adjust pesticide use to minimize the development of resistance in these mosquitoes. PMID:27280353

  1. Genetic diversity of Japanese encephalitis virus isolates obtained from the Indonesian archipelago between 1974 and 1987.

    PubMed

    Schuh, Amy J; Guzman, Hilda; Tesh, Robert B; Barrett, Alan D T

    2013-07-01

    Five genotypes (GI-V) of Japanese encephalitis virus (JEV) have been identified, all of which have distinct geographical distributions and epidemiologies. It is thought that JEV originated in the Indonesia-Malaysia region from an ancestral virus. From that ancestral virus GV diverged, followed by GIV, GIII, GII, and GI. Genotype IV appears to be confined to the Indonesia-Malaysia region, as GIV has been isolated in Indonesia from mosquitoes only, while GV has been isolated on three occasions only from a human in Malaysia and mosquitoes in China and South Korea. In contrast, GI-III viruses have been isolated throughout Asia and Australasia from a variety of hosts. Prior to this study only 13 JEV isolates collected from the Indonesian archipelago had been studied genetically. Therefore the sequences of the envelope (E) gene of 24 additional Indonesian JEV isolates, collected throughout the archipelago between 1974 and 1987, were determined and a series of molecular adaptation analyses were performed. Phylogenetic analysis indicated that over a 14-year time span three genotypes of JEV circulated throughout Indonesia, and a statistically significant association between the year of virus collection and genotype was revealed: isolates collected between 1974 and 1980 belonged to GII, isolates collected between 1980 and 1981 belonged to GIV, and isolates collected in 1987 belonged to GIII. Interestingly, three of the GII Indonesian isolates grouped with an isolate that was collected during the JE outbreak that occurred in Australia in 1995, two of the GIII Indonesian isolates were closely related to a Japanese isolate collected 40 years previously, and two Javanese GIV isolates possessed six amino acid substitutions within the E protein when compared to a previously sequenced GIV isolate collected in Flores. Several amino acids within the E protein of the Indonesian isolates were found to be under directional evolution and/or co-evolution. Conceivably, the tropical climate

  2. Genetic diversity of Japanese encephalitis virus isolates obtained from the Indonesian archipelago between 1974 and 1987.

    PubMed

    Schuh, Amy J; Guzman, Hilda; Tesh, Robert B; Barrett, Alan D T

    2013-07-01

    Five genotypes (GI-V) of Japanese encephalitis virus (JEV) have been identified, all of which have distinct geographical distributions and epidemiologies. It is thought that JEV originated in the Indonesia-Malaysia region from an ancestral virus. From that ancestral virus GV diverged, followed by GIV, GIII, GII, and GI. Genotype IV appears to be confined to the Indonesia-Malaysia region, as GIV has been isolated in Indonesia from mosquitoes only, while GV has been isolated on three occasions only from a human in Malaysia and mosquitoes in China and South Korea. In contrast, GI-III viruses have been isolated throughout Asia and Australasia from a variety of hosts. Prior to this study only 13 JEV isolates collected from the Indonesian archipelago had been studied genetically. Therefore the sequences of the envelope (E) gene of 24 additional Indonesian JEV isolates, collected throughout the archipelago between 1974 and 1987, were determined and a series of molecular adaptation analyses were performed. Phylogenetic analysis indicated that over a 14-year time span three genotypes of JEV circulated throughout Indonesia, and a statistically significant association between the year of virus collection and genotype was revealed: isolates collected between 1974 and 1980 belonged to GII, isolates collected between 1980 and 1981 belonged to GIV, and isolates collected in 1987 belonged to GIII. Interestingly, three of the GII Indonesian isolates grouped with an isolate that was collected during the JE outbreak that occurred in Australia in 1995, two of the GIII Indonesian isolates were closely related to a Japanese isolate collected 40 years previously, and two Javanese GIV isolates possessed six amino acid substitutions within the E protein when compared to a previously sequenced GIV isolate collected in Flores. Several amino acids within the E protein of the Indonesian isolates were found to be under directional evolution and/or co-evolution. Conceivably, the tropical climate

  3. Genetic Diversity of Japanese Encephalitis Virus Isolates Obtained from the Indonesian Archipelago Between 1974 and 1987

    PubMed Central

    Schuh, Amy J.; Guzman, Hilda; Tesh, Robert B.

    2013-01-01

    Abstract Five genotypes (GI–V) of Japanese encephalitis virus (JEV) have been identified, all of which have distinct geographical distributions and epidemiologies. It is thought that JEV originated in the Indonesia-Malaysia region from an ancestral virus. From that ancestral virus GV diverged, followed by GIV, GIII, GII, and GI. Genotype IV appears to be confined to the Indonesia-Malaysia region, as GIV has been isolated in Indonesia from mosquitoes only, while GV has been isolated on three occasions only from a human in Malaysia and mosquitoes in China and South Korea. In contrast, GI–III viruses have been isolated throughout Asia and Australasia from a variety of hosts. Prior to this study only 13 JEV isolates collected from the Indonesian archipelago had been studied genetically. Therefore the sequences of the envelope (E) gene of 24 additional Indonesian JEV isolates, collected throughout the archipelago between 1974 and 1987, were determined and a series of molecular adaptation analyses were performed. Phylogenetic analysis indicated that over a 14-year time span three genotypes of JEV circulated throughout Indonesia, and a statistically significant association between the year of virus collection and genotype was revealed: isolates collected between 1974 and 1980 belonged to GII, isolates collected between 1980 and 1981 belonged to GIV, and isolates collected in 1987 belonged to GIII. Interestingly, three of the GII Indonesian isolates grouped with an isolate that was collected during the JE outbreak that occurred in Australia in 1995, two of the GIII Indonesian isolates were closely related to a Japanese isolate collected 40 years previously, and two Javanese GIV isolates possessed six amino acid substitutions within the E protein when compared to a previously sequenced GIV isolate collected in Flores. Several amino acids within the E protein of the Indonesian isolates were found to be under directional evolution and/or co-evolution. Conceivably, the

  4. A case of aseptic meningitis due to Japanese encephalitis virus in a traveller returning from the Philippines.

    PubMed

    Jeurissen, A; Strauven, T

    2011-06-01

    We here report the case of Japanese encephalitis virus (JEV) meningitis in a previously healthy young women returning from a trip to the Philippines. JEV is a mosquito-borne encephalitic flavivirus pathogen, which is endemic in South East and Eastern Asia. Our patient presented with aseptic meningitis and recovered well under supportive therapy. Although the chance of a traveller getting symptomatic JEV infection is extremely low, clinicians and microbiologist should be aware of patients contracting this emerging infectious disease, especially in the light of the increasing international travel.

  5. Pre-cut Filter Paper for Detecting Anti-Japanese Encephalitis Virus IgM from Dried Cerebrospinal Fluid Spots

    PubMed Central

    Bharucha, Tehmina; Chanthongthip, Anisone; Phuangpanom, Soumphou; Phonemixay, Ooyanong; Sengvilaipaseuth, Onanong; Vongsouvath, Manivanh; Lee, Sue; Newton, Paul N.; Dubot-Pérès, Audrey

    2016-01-01

    Background The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the

  6. [Japanese guidelines for the management of herpes simplex encephalitis; comparison with those from the International Management Herpes Forum].

    PubMed

    Shoji, Hiroshi

    2006-11-01

    Herpes simplex encephalitis (HSE) is still recognized as a severe sporadic encephalitis, although the mortality and morbidity rates have been decreased to 10% and 30%, respectively. This disease is diagnosed using clinical symptoms, CSF, EEG, CT, MRI, and virologic tests such as polymerase chain reaction (PCR) or enzyme immunosorbent assay (EIA). Early diagnosis and treatment are essential for HSE. However, the early symptoms of this disease are various, and the laboratory diagnostic criteria are unclear to the non-specialist. In 2005, Japanese guidelines for the management of HSE have been issued via two sets of Workshops at the Japanese Neuroinfectious Disease Congress. The diagnostic and therapeutic criteria were discussed in comparison with those from the International Management Herpes Forum (IMHF) in 2004. For a definitive diagnosis, CSF PCR for herpes simplex virus (HSV) is recommended, and the detection rate has been reported to be 60 to 80% within the 7th day of the illness. In the IMHF, the PCR method has also been the primary method for early diagnosis and for monitoring the therapy. Further, quantitative real-time PCR has become available for measuring the effectiveness of aciclovir therapy. To measure HSV antibody levels, complement antibody (CF), neutralizing antibody (NT), or enzyme-linked immunosorbent assay (ELISA or EIA) are available. Significant elevation of EIA IgG or intrathecal HSV antibody production should be shown, although these antibody responses often appear two weeks after the onset of HSE. Regarding anti-herpesvirus drugs, in both Japanese and IMHF guidelines aciclovir is consistent with the first choice, and it is recommended that its administration would be started as soon as HSE is suspected on the basis of clinical pictures, CT * MRI, EEG, or CSF findings. However, antiviral therapy may be discontinued if a negative CSF HSV PCR is obtained at > 72 hours after onset. A recent Japanese study shows the efficacy of a combination

  7. Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE Detect™ and DEN Detect™ MAC-ELISA Kits

    PubMed Central

    Johnson, Barbara W.; Goodman, Christin H.; Jee, Youngmee; Featherstone, David A.

    2016-01-01

    Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JE Detect™ MAC-ELISA (JE Detect), a differential testing algorithm was developed in which samples tested by JE Detect with positive results were subsequently tested by the DEN Detect™ MAC-ELISA (DEN Detect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JE Detect and DEN Detect and were classified as JE− (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JE Detect and DEN Detect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID:26856911

  8. Cross-protection between West Nile and Japanese encephalitis viruses in red-winged blackbirds (Agelaius phoeniceus).

    PubMed

    Nemeth, Nicole M; Bosco-Lauth, Angela M; Bowen, Richard A

    2009-09-01

    Similar to West Nile virus (WNV), Japanese encephalitis virus (JEV) has a history of intercontinental spread, and birds are important for the maintenance and transmission of both of these closely related viruses. We examined viremic and serologic responses of blackbirds (Agelaius phoeniceus), with and without immunity to WNV, following experimental inoculation with two strains of JEV. Japanese encephalitis (JE) viremia was detected in only one of 16 (6.3%) WNV-immune birds, while all 16 nonimmune birds had detectable JE viremia. Two weeks after JEV inoculation, all birds without pre-existing WNV immunity had clearly distinguishable anti-JEV antibodies, while in all birds with pre-existing WNV immunity, antibodies to WNV and JEV were either indistinguishable or the anti-WNV antibody titers were significantly higher. As WNV is endemic throughout much of North America, WNV immunity among birds may dampen transmission while complicating the serologic diagnosis of JEV, should this pathogen be introduced to North America. PMID:19848083

  9. Limited potential for mosquito transmission of genetically engineered, live-attenuated western equine encephalitis virus vaccine candidates.

    PubMed

    Turell, Michael J; O'Guinn, Monica L; Parker, Michael D

    2003-02-01

    Specific mutations associated with attenuation of Venezuelan equine encephalitis (VEE) virus in rodent models were identified during efforts to develop an improved VEE vaccine. Analogous mutations were produced in full-length cDNA clones of the Cba 87 strain of western equine encephalitis (WEE) virus by site-directed mutagenesis in an attempt to develop an improved WEE vaccine. Isogenic viral strains with these mutations were recovered after transfection of baby hamster kidney cells with infectious RNA. We evaluated two of these strains (WE2102 and WE2130) for their ability to replicate in and be transmitted by Culex tarsalis, the principal natural vector of WEE virus in the United States. Each of the vaccine candidates contained a deletion of the PE2 furin cleavage site and a secondary mutation in the E1 or E2 glycoprotein. Both of these potential candidates replicated in mosquitoes significantly less efficiently than did either wild-type WEE (Cba 87) virus or the parental clone (WE2000). Likewise, after intrathoracic inoculation, mosquitoes transmitted the vaccine candidate strains significantly less efficiently than they transmitted either the wild-type or the parental clone. One-day-old chickens vaccinated with either of the two vaccine candidates did not become viremic when challenged with virulent WEE virus two weeks later. Mutations that result in less efficient replication in or transmission by mosquitoes should enhance vaccine safety and reduce the possibility of accidental introduction of the vaccine strain to unintentional hosts.

  10. Detection and differentiation of Japanese encephalitis virus genotype I and genotype III by reverse transcription loop-mediated isothermal amplification combined with restriction fragment length polymorphism.

    PubMed

    Zhang, Liang; Cao, Sanjie; Wu, Rui; Zhu, Shuquan; Liu, Hanyang; Yuan, Lei; Shi, Shuangyan; Zhang, Dan; Huang, Xiaobo; Wen, Xintian; Wen, Yiping; Yan, Qigui; Huang, Yong; Ma, Xiaoping

    2015-04-01

    Japanese encephalitis (JE), which is a mosquito-borne arboviral infection, is the leading cause of viral encephalitis in Asian countries. The causative agent of JE is Japanese encephalitis virus (JEV), in which the predominant genotype has changed from genotype III (G III) to genotype I (G I). However, a method for the rapid differentiation between JEV G I and G III remains unavailable. This study aimed to establish a rapid JEV genotyping method using reverse transcription loop-mediated isothermal amplification (RT-LAMP). An Spe I site, which was located in the target sequence (C gene) of JEV G III strains but not in JEV G I strains, was selected as the RT-LAMP target. After testing 64 specimens, results showed that RT-LAMP can detect and differentiate JEV G I and G III specifically. Thus, a novel RT-LAMP system for the rapid detection and differentiation of JEV G I and G III was developed successfully.

  11. [Clinico-immunological study of the effectiveness of vaccination against tick-borne encephalitis in the Maritime Territory].

    PubMed

    Leonova, G N; Krugliak, S P; Stepanova, N M; Gorelikov, V N

    1987-01-01

    Analysis of the severity of the clinical course of tick-borne encephalitis (TBE) in the Maritime Territory, 1966-1983, showed a decline in the incidence of the disease by 20% in the group of subjects vaccinated against TBE, whereas the severity of the disease showed no statistically significant difference from that among nonvaccinated subjects. The causes of the poor protective effect of the liquid tissue culture vaccine produced by the Research Institute of Vaccines and Sera, Ministry of Health of the USSR, Tomsk, were demonstrated alongside with the advantages of the lyophilized concentrated vaccine manufactured by the Institute for Poliomyelitis and Viral Encephalitides of the USSR Academy of Medical Sciences, which should be used for prophylactic vaccinations of subjects working in forests who comprised 29% of the vaccines. In this way, TBE incidence in the region could be reduced considerably.

  12. A diagnostic algorithm to serologically differentiate West Nile virus from Japanese encephalitis virus infections and its validation in field surveillance of poultry and horses.

    PubMed

    Yeh, Jung-Yong; Lee, Ji-Hye; Park, Jee-Yong; Seo, Hyun-Ji; Moon, Jin-San; Cho, In-Soo; Kim, Hee-Pah; Yang, Young-Jin; Ahn, Kei-Myung; Kyung, Soon-Goo; Choi, In-Soo; Lee, Joong-Bok

    2012-05-01

    The detection of West Nile virus (WNV) in areas endemic for Japanese encephalitis virus (JEV) is complicated by the extensive serological cross-reactivity between the two viruses. A testing algorithm was developed and employed for the detection of anti-WNV antibody in areas endemic for JEV. Using this differentiation algorithm, a serological survey of poultry (2004 through 2009) and horses (2007 through 2009) was performed. Among 2681 poultry sera, 125 samples were interpreted as being positive for antibodies against JEV, and 14 were suspected to be positive for antibodies against undetermined flaviviruses other than WNV and JEV. Of the 2601 horse sera tested, a total of 1914 (73.6%) were positive to the initial screening test. Of these positive sera, 132 sera (5.1%) had been collected from horses that had been imported from the United States, where WNV is endemic. These horses had WNV vaccination records, and no significant pattern of increasing titer was observed in paired sera tests. Of the remaining 1782 positive sera 1468 sera (56.4%) were also found to contain anti-JEV antibodies, and were interpreted to be JEV-specific antibodies by the differentiation algorithm developed in this study. The remaining 314 horses (12.1%) for which a fourfold difference in neutralizing antibody titer could not be demonstrated, were determined to contain an antibody against an unknown (unidentified or undetermined) flavivirus. No evidence of WNV infections were found during the period of this study.

  13. The Willingness to Pay for Vaccination against Tick-Borne Encephalitis and Implications for Public Health Policy: Evidence from Sweden.

    PubMed

    Slunge, Daniel

    2015-01-01

    The increasing incidence of tick-borne encephalitis (TBE) in Sweden and several other European countries has sparked a discussion about the need for a public vaccination strategy. However, TBE vaccination coverage is incomplete and there is little knowledge about the factors influencing vaccination behavior. Based on a survey of 1,500 randomly selected respondents in Sweden, we estimate vaccination coverage in areas with different TBE risk levels and analyze the role of vaccine price and other factors influencing the demand for vaccination. First, we find that the average rate of TBE vaccination in Sweden is 33% in TBE risk areas and 18% elsewhere. Income, age and risk-related factors such as incidence of TBE in the area of residence, frequency of visits to areas with TBE risk, and experience with tick bites are positively associated with demand for TBE vaccine. Next, using contingent valuation methodology, we estimate the willingness to pay for TBE vaccination among the unvaccinated respondents and the effect of a possible subsidy. Among the unvaccinated respondents in TBE risk areas, we estimate the mean willingness to pay for the recommended three doses of TBE vaccine to be 465 SEK (approximately 46 euros or 40% of the current market price). We project that a subsidy making TBE vaccines free of charge could increase the vaccination rate in TBE risk areas to around 78%, with a larger effect on low-income households, whose current vaccination rate is only 15% in risk areas. However, price is not the only factor affecting demand. We find significant effects on vaccination behavior associated with trust in vaccine recommendations, perceptions about tick bite-related health risks and knowledge about ticks and tick-borne diseases. Hence, increasing knowledge and trust, as well as ease of access to vaccinations, can also be important measures for public health agencies that want to increase the vaccination rate. PMID:26641491

  14. The Willingness to Pay for Vaccination against Tick-Borne Encephalitis and Implications for Public Health Policy: Evidence from Sweden

    PubMed Central

    Slunge, Daniel

    2015-01-01

    The increasing incidence of tick-borne encephalitis (TBE) in Sweden and several other European countries has sparked a discussion about the need for a public vaccination strategy. However, TBE vaccination coverage is incomplete and there is little knowledge about the factors influencing vaccination behavior. Based on a survey of 1,500 randomly selected respondents in Sweden, we estimate vaccination coverage in areas with different TBE risk levels and analyze the role of vaccine price and other factors influencing the demand for vaccination. First, we find that the average rate of TBE vaccination in Sweden is 33% in TBE risk areas and 18% elsewhere. Income, age and risk-related factors such as incidence of TBE in the area of residence, frequency of visits to areas with TBE risk, and experience with tick bites are positively associated with demand for TBE vaccine. Next, using contingent valuation methodology, we estimate the willingness to pay for TBE vaccination among the unvaccinated respondents and the effect of a possible subsidy. Among the unvaccinated respondents in TBE risk areas, we estimate the mean willingness to pay for the recommended three doses of TBE vaccine to be 465 SEK (approximately 46 euros or 40% of the current market price). We project that a subsidy making TBE vaccines free of charge could increase the vaccination rate in TBE risk areas to around 78%, with a larger effect on low-income households, whose current vaccination rate is only 15% in risk areas. However, price is not the only factor affecting demand. We find significant effects on vaccination behavior associated with trust in vaccine recommendations, perceptions about tick bite-related health risks and knowledge about ticks and tick-borne diseases. Hence, increasing knowledge and trust, as well as ease of access to vaccinations, can also be important measures for public health agencies that want to increase the vaccination rate. PMID:26641491

  15. Highly permissive infection of microglial cells by Japanese encephalitis virus: a possible role as a viral reservoir.

    PubMed

    Thongtan, Thananya; Cheepsunthorn, Poonlarp; Chaiworakul, Voravasa; Rattanarungsan, Chutima; Wikan, Nitwara; Smith, Duncan R

    2010-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne Flavivirus, is a major cause of acute encephalitis, and neurons have been proposed to be the principle JEV target cells in the central nervous system. However, clinically, infection with JEV leads to increased levels of cytokines and chemokines in the serum and cerebrospinal fluid (CSF) the levels of which correlate with the mortality rate of patients. This research aimed to study the role of microglial cells in JEV infection. Mouse microglial cells (BV-2) supported the replication of JEV with extracellular production of virus by 10h post-infection, and virus titer reached a maximum (2.55x10(10)pfu/ml) by day 3 post-infection. While apoptosis was induced in response to virus infection, no alteration in nitric oxide production was observed. Microglial cells remained productively infected with JEV for up to 16 weeks without significant morphological alterations, and the released virions were infectious to mouse neuroblastoma (NA) cells. The high virus production and long persistence of JEV in microglial cells suggests that these cells may serve as viral reservoirs for the infection of neurons in the CNS.

  16. Histone deacetylase inhibition by Japanese encephalitis virus in monocyte/macrophages: a novel viral immune evasion strategy.

    PubMed

    Adhya, Dwaipayan; Dutta, Kallol; Kundu, Kiran; Basu, Anirban

    2013-10-01

    Japanese encephalitis virus (JEV) is a common cause of encephalitis in humans who are dead-end hosts producing negligible viremia. The virus reaches the brain and causes massive inflammation. Our study seeks to understand the virus-host interaction using the murine monocyte/macrophage cell line RAW264.7, an antigen presenting cell involved in eliciting an innate immune response. We have discovered several interesting phenomena occurring in JEV-infected RAW264.7 cells which diverge from established observations. JEV remains inside RAW264.7 and appears to have little negative effect on cell viability. Expression studies of major histocompatibility complexes (MHC) and co-stimulatory molecules show inhibition of antigen presentation. There is enhanced immune suppression creating an anti-viral milieu. Expression of pro-inflammatory cytokines and chemokines is suppressed along with increased expression of anti-inflammatory molecules. Histone deacetylases (HDACs) have known inflammatory properties. In our study, through modulation of HDACs JEV seems to induce a crucial anti-inflammatory and anti-viral role in host macrophages.

  17. Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand.

    PubMed

    Nakgoi, Khajornpong; Nitatpattana, Narong; Wajjwalku, Worawidh; Pongsopawijit, Pornsawan; Kaewchot, Supakarn; Yoksan, Sutee; Siripolwat, Voravit; Souris, Marc; Gonzalez, Jean-Paul

    2014-01-01

    The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand.

  18. Antibodies to H5 subtype avian influenza virus and Japanese encephalitis virus in northern pintails (Anas acuta) sampled in Japan

    USGS Publications Warehouse

    Ramey, Andy M.; Spackman, Erica; Yeh, Jung-Yong; Fujita, Go; Konishi, Kan; Reed, John A.; Wilcox, Benjamin R.; Brown, Justin D.; Stallknecht, David E.

    2013-01-01

    Blood samples from 105 northern pintails (Anas acuta) captured on Hokkaido, Japan were tested for antibodies to avian influenza virus (AIV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) to assess possible involvement of this species in the spread of economically important and potentially zoonotic pathogens. Antibodies to AIV were detected in 64 of 105 samples (61%). Of the 64 positives, 95% and 81% inhibited agglutination of two different H5 AIV antigens (H5N1 and H5N9), respectively. Antibodies to JEV and WNV were detected in five (5%) and none of the samples, respectively. Results provide evidence for prior exposure of migrating northern pintails to H5 AIV which couldhave implications for viral shedding and disease occurrence. Results also provide evidence for limited involvement of this species in the transmission and spread of flaviviruses during spring migration.

  19. Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Protects Nonhuman Primates from Intramuscular and Aerosol Challenge with Ebolavirus

    PubMed Central

    Herbert, Andrew S.; Kuehne, Ana I.; Barth, James F.; Ortiz, Ramon A.; Nichols, Donald K.; Zak, Samantha E.; Stonier, Spencer W.; Muhammad, Majidat A.; Bakken, Russell R.; Prugar, Laura I.; Olinger, Gene G.; Groebner, Jennifer L.; Lee, John S.; Pratt, William D.; Custer, Max; Kamrud, Kurt I.; Smith, Jonathan F.; Hart, Mary Kate

    2013-01-01

    There are no vaccines or therapeutics currently approved for the prevention or treatment of ebolavirus infection. Previously, a replicon vaccine based on Venezuelan equine encephalitis virus (VEEV) demonstrated protective efficacy against Marburg virus in nonhuman primates. Here, we report the protective efficacy of Sudan virus (SUDV)- and Ebola virus (EBOV)-specific VEEV replicon particle (VRP) vaccines in nonhuman primates. VRP vaccines were developed to express the glycoprotein (GP) of either SUDV or EBOV. A single intramuscular vaccination of cynomolgus macaques with VRP expressing SUDV GP provided complete protection against intramuscular challenge with SUDV. Vaccination against SUDV and subsequent survival of SUDV challenge did not fully protect cynomolgus macaques against intramuscular EBOV back-challenge. However, a single simultaneous intramuscular vaccination with VRP expressing SUDV GP combined with VRP expressing EBOV GP did provide complete protection against intramuscular challenge with either SUDV or EBOV in cynomolgus macaques. Finally, intramuscular vaccination with VRP expressing SUDV GP completely protected cynomolgus macaques when challenged with aerosolized SUDV, although complete protection against aerosol challenge required two vaccinations with this vaccine. PMID:23408633

  20. Pathogenic and Genotypic Characterization of a Japanese Encephalitis Virus Isolate Associated with Reproductive Failure in an Indian Pig Herd

    PubMed Central

    Desingu, P. A.; Ray, Pradeep K.; Patel, B. H. M.; Singh, R.; Singh, R. K.; Saikumar, G

    2016-01-01

    Background India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. Methodology/Principal Findings This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. Conclusions/Significance Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of

  1. Sampling Design Influences the Observed Dominance of Culex tritaeniorhynchus: Considerations for Future Studies of Japanese Encephalitis Virus Transmission.

    PubMed

    Lord, Jennifer S; Al-Amin, Hasan Mohammad; Chakma, Sumit; Alam, Mohammad Shafiul; Gurley, Emily S; Pulliam, Juliet R C

    2016-01-01

    Mosquito sampling during Japanese encephalitis virus (JEV)-associated studies, particularly in India, has usually been conducted via aspirators or light traps to catch mosquitoes around cattle, which are dead-end hosts for JEV. High numbers of Culex tritaeniorhynchus, relative to other species, have often been caught during these studies. Less frequently, studies have involved sampling outdoor resting mosquitoes. We aimed to compare the relative abundance of mosquito species between these two previously used mosquito sampling methods. From September to December 2013 entomological surveys were undertaken in eight villages in a Japanese encephalitis (JE) endemic area of Bangladesh. Light traps were used to collect active mosquitoes in households, and resting boxes and a Bina Pani Das hop cage were used near oviposition sites to collect resting mosquitoes. Numbers of humans and domestic animals present in households where light traps were set were recorded. In five villages Cx. tritaeniorhynchus was more likely to be selected from light trap samples near hosts than resting collection samples near oviposition sites, according to log odds ratio tests. The opposite was true for Cx. pseudovishnui and Armigeres subalbatus, which can also transmit JEV. Culex tritaeniorhynchus constituted 59% of the mosquitoes sampled from households with cattle, 28% from households without cattle and 17% in resting collections. In contrast Cx. pseudovishnui constituted 5.4% of the sample from households with cattle, 16% from households with no cattle and 27% from resting collections, while Ar. subalbatus constituted 0.15%, 0.38%, and 8.4% of these samples respectively. These observations may be due to differences in timing of biting activity, host preference and host-seeking strategy rather than differences in population density. We suggest that future studies aiming to implicate vector species in transmission of JEV should consider focusing catches around hosts able to transmit JEV. PMID

  2. Sampling Design Influences the Observed Dominance of Culex tritaeniorhynchus: Considerations for Future Studies of Japanese Encephalitis Virus Transmission

    PubMed Central

    Lord, Jennifer S.; Al-Amin, Hasan Mohammad; Chakma, Sumit; Alam, Mohammad Shafiul; Gurley, Emily S.; Pulliam, Juliet R. C.

    2016-01-01

    Mosquito sampling during Japanese encephalitis virus (JEV)-associated studies, particularly in India, has usually been conducted via aspirators or light traps to catch mosquitoes around cattle, which are dead-end hosts for JEV. High numbers of Culex tritaeniorhynchus, relative to other species, have often been caught during these studies. Less frequently, studies have involved sampling outdoor resting mosquitoes. We aimed to compare the relative abundance of mosquito species between these two previously used mosquito sampling methods. From September to December 2013 entomological surveys were undertaken in eight villages in a Japanese encephalitis (JE) endemic area of Bangladesh. Light traps were used to collect active mosquitoes in households, and resting boxes and a Bina Pani Das hop cage were used near oviposition sites to collect resting mosquitoes. Numbers of humans and domestic animals present in households where light traps were set were recorded. In five villages Cx. tritaeniorhynchus was more likely to be selected from light trap samples near hosts than resting collection samples near oviposition sites, according to log odds ratio tests. The opposite was true for Cx. pseudovishnui and Armigeres subalbatus, which can also transmit JEV. Culex tritaeniorhynchus constituted 59% of the mosquitoes sampled from households with cattle, 28% from households without cattle and 17% in resting collections. In contrast Cx. pseudovishnui constituted 5.4% of the sample from households with cattle, 16% from households with no cattle and 27% from resting collections, while Ar. subalbatus constituted 0.15%, 0.38%, and 8.4% of these samples respectively. These observations may be due to differences in timing of biting activity, host preference and host-seeking strategy rather than differences in population density. We suggest that future studies aiming to implicate vector species in transmission of JEV should consider focusing catches around hosts able to transmit JEV. PMID

  3. MicroRNA-19b-3p Modulates Japanese Encephalitis Virus-Mediated Inflammation via Targeting RNF11

    PubMed Central

    Ashraf, Usama; Zhu, Bibo; Ye, Jing; Wan, Shengfeng; Nie, Yanru; Chen, Zheng; Cui, Min; Wang, Chong; Duan, Xiaodong; Zhang, Hao; Chen, Huanchun

    2016-01-01

    ABSTRACT Japanese encephalitis virus (JEV) can invade the central nervous system and consequently induce neuroinflammation, which is characterized by profound neuronal cell damage accompanied by astrogliosis and microgliosis. Albeit microRNAs (miRNAs) have emerged as major regulatory noncoding RNAs with profound effects on inflammatory response, it is unknown how astrocytic miRNAs regulate JEV-induced inflammation. Here, we found the involvement of miR-19b-3p in regulating the JEV-induced inflammatory response in vitro and in vivo. The data demonstrated that miR-19b-3p is upregulated in cultured cells and mouse brain tissues during JEV infection. Overexpression of miR-19b-3p led to increased production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and chemokine (C-C motif) ligand 5, after JEV infection, whereas knockdown of miR-19b-3p had completely opposite effects. Mechanistically, miR-19b-3p modulated the JEV-induced inflammatory response via targeting ring finger protein 11, a negative regulator of nuclear factor kappa B signaling. We also found that inhibition of ring finger protein 11 by miR-19b-3p resulted in accumulation of nuclear factor kappa B in the nucleus, which in turn led to higher production of inflammatory cytokines. In vivo silencing of miR-19b-3p by a specific antagomir reinvigorates the expression level of RNF11, which in turn reduces the production of inflammatory cytokines, abrogates gliosis and neuronal cell death, and eventually improves the survival rate in the mouse model. Collectively, our results demonstrate that miR-19b-3p positively regulates the JEV-induced inflammatory response. Thus, miR-19b-3p targeting may constitute a thought-provoking approach to rein in JEV-induced inflammation. IMPORTANCE Japanese encephalitis virus (JEV) is one of the major causes of acute encephalitis in humans worldwide. The pathological features of JEV-induced encephalitis are inflammatory reactions and

  4. A Single Amino Acid Substitution in the NS2A Protein of Japanese Encephalitis Virus Affects Virus Propagation In Vitro but Not In Vivo

    PubMed Central

    Takamatsu, Yuki; Morita, Kouichi

    2015-01-01

    We identified a unique amino acid of NS2A113, phenylalanine, that affects the efficient propagation of two Japanese encephalitis virus strains, JaTH160 and JaOArS982, in neuroblastoma Neuro-2a cells but not in cell lines of extraneural origin. This amino acid did not affect viral loads in the brain or survival curves in mice. These findings suggest that virus propagation in vitro may not reflect the level of virus neuroinvasiveness in vivo. PMID:25787282

  5. Isolation of Japanese encephalitis and Getah viruses from mosquitoes (Diptera: Culicidae) collected near Camp Greaves, Gyonggi Province, Republic of Korea, 2000.

    PubMed

    Turell, Michael J; O'Guinn, Monica L; Wasieloski, Leonard P; Dohm, David J; Lee, Wan-Ja; Cho, Hae-Wol; Kim, Heung-Chol; Burkett, Douglas A; Mores, Christopher N; Coleman, Russell E; Klein, Terry A

    2003-07-01

    As part of an evaluation of the ecology of arthropod-borne diseases in the Republic of Korea (ROK), we examined 8,765 mosquitoes captured in Paju County, Gyonggi Province, ROK, for the presence of viruses. Mosquitoes were captured in propane lantern/human-baited Shannon traps, Mosquito Magnet traps, or American Biophysics Corporation (East Greenwich, RI) miniature light traps with or without supplemental octenol bait and/or dry ice. Mosquitoes were identified to species, placed in pools of up to 40 mosquitoes each, and tested on Vero cells for the presence of virus. A total of 15 virus isolations were made from 293 pools of mosquitoes. Viruses were identified by reverse transcriptase-polymerase chain reaction and sequencing and consisted of 14 isolations of Japanese encephalitis (JE) virus and one isolation of Getah (GET) virus. All JE isolates were from Culex tritaeniorhynchus Giles, and the isolate of GET was from Aedes vexans (Meigen). The minimum field infection rate for JE in Cx. tritaeniorhynchus was 3.3 per 1,000, whereas the GET virus infection rate for Ae. vexans was 0.2 per 1,000. Isolation of JE and GET indicated that both viruses were actively circulating in northern Gyonggi Province, ROK. The lack of human cases of JE among the Korean population probably is because of an effective government-mandated vaccination program. The reason for no cases among >10,000 United States military and others that reside or train nearby is unknown, but may be related to personnel protection measures (permethrin-impregnated uniforms and use of deet repellent), adult mosquito control, mosquito selection of nonhuman hosts (unpublished data), and the low symptomatic to asymptomatic ratio of disease in adults.

  6. Simultaneous detection of West Nile and Japanese encephalitis virus RNA by duplex TaqMan RT-PCR.

    PubMed

    Barros, Silvia C; Ramos, Fernanda; Zé-Zé, Líbia; Alves, Maria J; Fagulha, Teresa; Duarte, Margarida; Henriques, Margarida; Luís, Tiago; Fevereiro, Miguel

    2013-11-01

    West Nile virus (WNV) and Japanese encephalitis virus (JEV) are important mosquito-borne viruses of the Flaviviridae family, associated with encephalitis, mainly in humans and horses. WNV is also pathogen for many bird species. The incidence of human and animal WNV infections in Europe has risen, mostly in recent years, and JEV was detected in 2011 in mosquitoes collected in Italy and may emerge in Europe in the same way as other flaviviruses had emerged recently (USUTU and Bagaza virus) and should be regarded as a potential threat to public health. Prompt identification and discrimination between WNV and JEV provides critical epidemiological data for prevalence studies and public and animal health management policies. Here we describe a quantitative one-step duplex TaqMan RT-PCR, targeting non-structural protein 2A gene (NS2A-qRT-PCR), based on only one primer pair and two probes for differential diagnosis of WNV and JEV. Also this assay enables the detection of both WNV lineages (WNV-1 and WNV-2). To access the specificity of NS2A-qRT-PCR a panel of different arboviruses were used. The assay was shown to be specific for both WNV lineages (WNV-1 and WNV-2), WNV related Kunjin virus and JEV, since no cross-reactions were observed with other tested arboviruses. Sensitivity of the assay was determined using serial dilutions of in vitro-transcribed RNA from WNV and JEV. The duplex NS2A-qRT-PCR assay was shown to be very sensitive, being able to detect 10 copies of WNV and JEV RNA. This assay is a suitable tool for the diagnosis of WNV and JEV, and provides a valuable addition to the methods currently available for routine diagnosis of these zoonoses and for surveillance studies.

  7. Seasonal abundance & role of predominant Japanese encephalitis vectors Culex tritaeniorhynchus & Cx. gelidus Theobald in Cuddalore district, Tamil Nadu

    PubMed Central

    Ramesh, D.; Muniaraj, M.; Samuel, P. Philip; Thenmozhi, V.; Venkatesh, A.; Nagaraj, J.; Tyagi, B.K.

    2015-01-01

    Background & objectives: Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. The first major JE outbreak occurred in 1978 and since 1981 several outbreaks had been reported in the Cuddalore district (erstwhile South Arcot), Tamil Nadu, India. Entomological monitoring was carried out during January 2010 - March 2013, to determine the seasonal abundance and transmission dynamics of the vectors of JE virus, with emphasis on the role of Culex tritaeniorhynchus and Cx. gelidus. Methods: Mosquito collections were carried out fortnightly during dusk hours in three villages viz. Soundara Solapuram, Pennadam, Erappavur of Cuddalore district. Mosquitoes were collected during dusk for a period of one hour in and around the cattle sheds using oral aspirator and torch light. The collected mosquitoes were later identified and pooled to detect JE virus (JEV) infection by enzyme linked immunosorbent assay (ELISA). Results: A total of 46,343 mosquitoes comprising of 25 species and six genera were collected. Species composition included viz, Cx. tritaeniorhynchus (46.26%), Cx. gelidus (43.12%) and other species (10.62%). A total of 17,678 specimens (403 pools) of Cx. gelidus and 14,358 specimens (309 pools) of Cx. tritaeniorhynchus were tested, of which 12 pools of Cx. gelidus and 14 pools of Cx. tritaeniorhynchus were positive for JE virus antigen. The climatic factors were negatively correlated with minimum infection rate (MIR) for both the species, except mean temperature (P<0.05) for Cx. gelidus. Interpretation & conclusions: High abundance of Cx. tritaeniorhynchus and Cx. gelidus was observed compared to other mosquito species in the study area. Detection of JEV antigen in the two species confirmed the maintenance of virus. Appropriate vector control measures need to be taken to reduce the vector abundance. PMID:26905238

  8. A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal

    PubMed Central

    Rayamajhi, Ajit; Nightingale, Sam; Bhatta, Nisha Keshary; Singh, Rupa; Ledger, Elizabeth; Bista, Krishna Prasad; Lewthwaite, Penny; Mahaseth, Chandeshwar; Turtle, Lance; Robinson, Jaimie Sue; Galbraith, Sareen Elizabeth; Wnek, Malgorzata; Johnson, Barbara Wilmot; Faragher, Brian

    2015-01-01

    Background Japanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG’s anti-inflammatory properties may also be beneficial. Methodology/Principal Findings We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group. Conclusions/Significance A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study. Trial Registration ClinicalTrials.gov NCT01856205 PMID:25886645

  9. Japanese encephalitis virus nonstructural protein NS5 interacts with mitochondrial trifunctional protein and impairs fatty acid β-oxidation.

    PubMed

    Kao, Yu-Ting; Chang, Bi-Lan; Liang, Jian-Jong; Tsai, Hang-Jen; Lee, Yi-Ling; Lin, Ren-Jye; Lin, Yi-Ling

    2015-03-01

    Infection with Japanese encephalitis virus (JEV) can induce the expression of pro-inflammatory cytokines and cause acute encephalitis in humans. β-oxidation breaks down fatty acids for ATP production in mitochondria, and impaired β-oxidation can induce pro-inflammatory cytokine expression. To address the role of fatty-acid β-oxidation in JEV infection, we measured the oxygen consumption rate of mock- and JEV-infected cells cultured with or without long chain fatty acid (LCFA) palmitate. Cells with JEV infection showed impaired LCFA β-oxidation and increased interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) expression. JEV nonstructural protein 5 (NS5) interacted with hydroxyacyl-CoA dehydrogenase α and β subunits, two components of the mitochondrial trifunctional protein (MTP) involved in LCFA β-oxidation, and NS5 proteins were detected in mitochondria and co-localized with MTP. LCFA β-oxidation was impaired and higher cytokines were induced in cells overexpressing NS5 protein as compared with control cells. Deletion and mutation studies showed that the N-terminus of NS5 was involved in the MTP association, and a single point mutation of NS5 residue 19 from methionine to alanine (NS5-M19A) reduced its binding ability with MTP. The recombinant JEV with NS5-M19A mutation (JEV-NS5-M19A) was less able to block LCFA β-oxidation and induced lower levels of IL-6 and TNF-α than wild-type JEV. Moreover, mice challenged with JEV-NS5-M19A showed less neurovirulence and neuroinvasiveness. We identified a novel function of JEV NS5 in viral pathogenesis by impairing LCFA β-oxidation and inducing cytokine expression by association with MTP.

  10. Japanese Encephalitis Virus Nonstructural Protein NS5 Interacts with Mitochondrial Trifunctional Protein and Impairs Fatty Acid β-Oxidation

    PubMed Central

    Kao, Yu-Ting; Chang, Bi-Lan; Liang, Jian-Jong; Tsai, Hang-Jen; Lee, Yi-Ling; Lin, Ren-Jye; Lin, Yi-Ling

    2015-01-01

    Infection with Japanese encephalitis virus (JEV) can induce the expression of pro-inflammatory cytokines and cause acute encephalitis in humans. β-oxidation breaks down fatty acids for ATP production in mitochondria, and impaired β-oxidation can induce pro-inflammatory cytokine expression. To address the role of fatty-acid β-oxidation in JEV infection, we measured the oxygen consumption rate of mock- and JEV-infected cells cultured with or without long chain fatty acid (LCFA) palmitate. Cells with JEV infection showed impaired LCFA β-oxidation and increased interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) expression. JEV nonstructural protein 5 (NS5) interacted with hydroxyacyl-CoA dehydrogenase α and β subunits, two components of the mitochondrial trifunctional protein (MTP) involved in LCFA β-oxidation, and NS5 proteins were detected in mitochondria and co-localized with MTP. LCFA β-oxidation was impaired and higher cytokines were induced in cells overexpressing NS5 protein as compared with control cells. Deletion and mutation studies showed that the N-terminus of NS5 was involved in the MTP association, and a single point mutation of NS5 residue 19 from methionine to alanine (NS5-M19A) reduced its binding ability with MTP. The recombinant JEV with NS5-M19A mutation (JEV-NS5-M19A) was less able to block LCFA β-oxidation and induced lower levels of IL-6 and TNF-α than wild-type JEV. Moreover, mice challenged with JEV-NS5-M19A showed less neurovirulence and neuroinvasiveness. We identified a novel function of JEV NS5 in viral pathogenesis by impairing LCFA β-oxidation and inducing cytokine expression by association with MTP. PMID:25816318

  11. Comparison of the efficacy of CO2-baited and unbaited light traps, gravid traps, backpack aspirators, and sweep net collections for sampling mosquitoes infected with Japanese encephalitis virus.

    PubMed

    Chen, Yu-Chen; Wang, Chih-Yuan; Teng, Hwa-Jen; Chen, Chien-Fu; Chang, Mi-Chun; Lu, Liang-Chen; Lin, Cheo; Jian, Shu-Wan; Wu, Ho-Sheng

    2011-06-01

    Two field studies were conducted to determine the efficacy of mosquito collection methods for species composition, species abundance, and Japanese encephalitis virus infection rates in Taiwan. Traps evaluated included John W. Hock (JH) model UD black light traps, JH model 1012 new standard miniature CDC light traps, JH model 1712 CDC gravid traps, and Taiwan-made Pest-O-Lite light traps. Backpack aspirators and sweep nets were also used to collect the resting population. Culex tritaeniorhynchus in all studies and Mansonia uniformis in the Taipei areas were the two most abundance species collected. Dry ice-baited UD black light traps were effective in regard to species diversity, species abundance, and Japanese encephalitis virus infection rates. The unbaited Pest-O-Lite light traps collected significantly more female mosquitoes than the UD black light traps but performed similarly with regard to species diversity and male mosquito collection. Most mosquitoes collected by Pest-O-Lite light traps were dried and not suitable for virus detection. Dry ice-baited CDC light traps collected significantly fewer mosquitoes than other light traps. Although CO(2) -baited UD black light traps with octenol attracted more mosquitoes, no statistical significance was found compared to CO(2) -baited UD black light traps without octenol. Japanese encephalitis viruses were isolated from half of the positive pools in UD black light traps and CDC light traps.

  12. Evaluation of immune response and protective effect of four vaccines against the tick-borne encephalitis virus.

    PubMed

    Morozova, O V; Bakhvalova, V N; Potapova, O F; Grishechkin, A E; Isaeva, E I; Aldarov, K V; Klinov, D V; Vorovich, M F

    2014-05-23

    Among three main subtypes of the tick-borne encephalitis virus (TBEV), the Siberian subtype is currently dominant in a majority of the endemic regions of Russia. However, inactivated vaccines are based on TBEV strains of the heterologous Far Eastern or the European subtypes isolated 40-77 years ago. To analyze the efficacy of the available vaccines against currently prevailing TBEV isolates of the Siberian subtype, mice were immunized subcutaneously three times (one group per each vaccine). The expression of seven cytokine genes was determined using RT-PCR. Sera were studied using homologous and heterologous ELISA, hemagglutination inhibition (HI) and neutralization tests with TBEV strains of the Far Eastern, Siberian and European subtypes. Cross-protective efficacy of the vaccines was evaluated with the TBEV strain 2689 of Siberian subtype isolated from an ixodid tick from the Novosibirsk, South-Western Siberia, Russia in 2010. The cytokine gene expression profile indicates a predominantly Th2 response due to exogenous antigen presentation. Titers for homologous combinations of vaccine strain and strain in ELISA, HI and neutralization tests exceeded those for heterologous antigen-antibody pairs. Despite antibody detection by means of ELISA, HI and neutralization tests, the mouse protection afforded by the vaccines differed significantly. Complete protection of mice challenged with 100 LD50 virus of the Siberian subtype was induced by the vaccine "Encevir" ("Microgen", Tomsk, Russia). The minimal immunization doze (MID50) of "Encevir" protecting 50% of the mice was less than 0.0016 ml. Partial protective effect of vaccines produced in Moscow, Russia and Austria revealed MID50 within recommended intervals (0.001-0.017 ml). However, the MID50 for the vaccine "Encepur" (Novartis, Germany) 0.04 ml exceeded acceptable limits with total loss of mice immunized with vaccine diluted 32, 100 and 320 fold. These results suggest regular evaluation of TBEV vaccines in regions

  13. Type-I interferon response affects an inoculation dose-independent mortality in mice following Japanese encephalitis virus infection

    PubMed Central

    2014-01-01

    Background The laboratory mouse model is commonly employed to study the pathogenesis of encephalitic flaviviruses such as Japanese encephalitis virus (JEV). However, it is known that some strains of these viruses do not elicit a typical mortality dose response curve from this organism after peripheral infection and the reason for it has not yet been fully understood. It is suggested that induction of more vigorous Type-I IFN (IFN-I) response might control early virus dissemination following increasing infectious challenge doses of the virus. Thus, the objective of this study was to examine this suggested role of IFN-I in the mortality of mice infected with various doses of JEV. Methods Inbred 129 mice and their IFNAR KO (A129) mice were subcutaneously inoculated with 100, 102, 104 or 106 pfu of JaOArS982 strain of JEV. Mice were weighed daily and observed for clinical signs. Virus titers in the brains and spleens of JEV-infected mice were determined by plaque forming assays. The upregulated mRNA levels of genes related to IFN-I response of mice were examined by real-time PCR. Results The mortality rates of 129 mice infected with JaOArS982 did not significantly increase despite the increase in inoculation dose and no significant difference of viral loads was observed between their brains. However, there was clear elevation of the mRNA levels of interferon regulatory factor (IRF)3, IRF7, IRF9, MDA5 and RIG-I at 24 hours post-infection depending on the inoculation dose. In A129 mice, length of survival days and the viral loads of spleen and brain were observed to be inoculation dose-dependent. Conclusions From these results, it is suggested that early IFN-I response elicited by high inoculation doses of JEV provides an anti-viral effect during the early phase of infection. Accordingly, virus replication is counteracted by IFN-I response at each increasing inoculation dose resulting in the interference of impending severe disease course or fatal outcome; hence, this

  14. [Vaccination for international travelers].

    PubMed

    Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

    2016-05-01

    Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination.

  15. [Vaccination for international travelers].

    PubMed

    Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

    2016-05-01

    Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. PMID:26920587

  16. Green synthesis and characterization of silver nanoparticles fabricated using Anisomeles indica: Mosquitocidal potential against malaria, dengue and Japanese encephalitis vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Veerakumar, Kaliyan; Muthukumaran, Udaiyan; Hoti, S L; Benelli, Giovanni

    2016-02-01

    Mosquitoes (Diptera: Culicidae) represent a key threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. In this scenario, eco-friendly control tools against mosquito vectors are a priority. Green synthesis of silver nanoparticles (AgNP) using a cheap, aqueous leaf extract of Anisomeles indica by reduction of Ag(+) ions from silver nitrate solution has been investigated. Bio-reduced AgNP were characterized by UV-visible spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction analysis (XRD). The acute toxicity of A. indica leaf extract and biosynthesized AgNP was evaluated against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. Both the A. indica leaf extract and AgNP showed dose dependent larvicidal effect against all tested mosquito species. Compared to the leaf aqueous extract, biosynthesized AgNP showed higher toxicity against An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus with LC50 values of 31.56, 35.21 and 38.08 μg/mL, respectively. Overall, this study firstly shed light on the mosquitocidal potential of A. indica, a potential bioresource for rapid, cheap and effective AgNP synthesis.

  17. A Preliminary Study to Forecast Japanese Encephalitis Vector Abundance in Paddy Growing Area, with the Aid of Radar Satellite Images.

    PubMed

    Raju, K Hari Kishan; Sabesan, Shanmugavelu; Rajavel, Aladu Ramakrishnan; Subramanian, Swaminathan; Natarajan, Ramalingam; Thenmozhi, Velayutham; Tyagi, Brij Kishore; Jambulingam, Purushothaman

    2016-02-01

    Vector mosquitoes of Japanese encephalitis (JE) breed mostly in rice fields, and human cases occur scattered over extended rural rice-growing areas. From this, one may surmise an ecological connection with the irrigation facilities and paddy cultivation. Furthermore, it has been hypothesized that a particular stage of paddy growth is a premonitory sign that can lead to a markedly increased population of the vector mosquitoes. The present study aimed to forecast the vector abundance by monitoring the paddy growth using remote sensing and geographical information systems. The abundance of the JE vector Culex tritaeniorhynchus peaked when the paddy crop was at its heading stage and dipped when the crop reached the maturing stage. A significant positive correlation was observed between paddy growth and adult density (r = 0.73, p < 0.008). The sigma naught values (σ0) derived from satellite images of paddy fields ranged from -18.3 (during transplantation stage) to approximately -10 (during the noncultivation period). A significant positive correlation was observed between σ0 and paddy growth stages (r = 0.87, p < 0.05) and adult vector density (r = 0.74, p = 0.04). The σ0 value observed during the vegetative and flowering stages of paddy growth ranged from -17.6 to -17.16, at which period the vector density started building up. This could be the spectral signature that denotes the "risk," following which a high vector abundance is expected during heading stage of the paddy.

  18. Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5

    PubMed Central

    Sharma, Nikhil; Kumawat, Kanhaiya L.; Rastogi, Meghana; Basu, Anirban; Singh, Sunit K.

    2016-01-01

    Japanese encephalitis virus (JEV) is a plus strand RNA virus, which infects brain. MicroRNAs are regulatory non-coding RNAs which regulate the expression of various genes in cells. Viruses modulate the expression of various microRNAs to suppress anti-viral signaling and evade the immune response. SOCS (Suppressor of cytokine signalling) family of proteins are negative regulators of anti-viral Jak-STAT pathway. In this study, we demonstrated the regulatory role of SOCS5 in Jak-STAT signaling and its exploitation by JEV through a microRNA mediated mechanism. JEV infection in human brain microglial cells (CHME3) downregulated the expression of miR-432, and upregulated SOCS5 levels. SOCS5 was validated as a target of miR-432 by using 3′UTR clone of SOCS5 in luciferase vector along with miR-432 mimic. The overexpression of miR-432 prior to JEV infection enhanced the phosphorylation of STAT1 resulting into increased ISRE activity and cellular inflammatory response resulting into diminished viral replication. The knockdown of SOCS5 resulted into increased STAT1 phosphorylation and suppressed viral replication. JEV infection mediated downregulation of miR-432 leads to SOCS5 upregulation, which helps the virus to evade cellular anti-viral response. This study demonstrated that JEV utilizes this microRNA mediated strategy to manipulate cellular immune response promoting JEV pathogenesis. PMID:27282499

  19. Japanese Encephalitis Risk and Contextual Risk Factors in Southwest China: A Bayesian Hierarchical Spatial and Spatiotemporal Analysis

    PubMed Central

    Zhao, Xing; Cao, Mingqin; Feng, Hai-Huan; Fan, Heng; Chen, Fei; Feng, Zijian; Li, Xiaosong; Zhou, Xiao-Hua

    2014-01-01

    It is valuable to study the spatiotemporal pattern of Japanese encephalitis (JE) and its association with the contextual risk factors in southwest China, which is the most endemic area in China. Using data from 2004 to 2009, we applied GISmapping and spatial autocorrelation analysis to analyze reported incidence data of JE in 438 counties in southwest China, finding that JE cases were not randomly distributed, and a Bayesian hierarchical spatiotemporal model identified the east part of southwest China as a high risk area. Meanwhile, the Bayesian hierarchical spatial model in 2006 demonstrated a statistically significant association between JE and the agricultural and climatic variables, including the proportion of rural population, the pig-to-human ratio, the monthly precipitation and the monthly mean minimum and maximum temperatures. Particular emphasis was placed on the time-lagged effect for climatic factors. The regression method and the Spearman correlation analysis both identified a two-month lag for the precipitation, while the regression method found a one-month lag for temperature. The results show that the high risk area in the east part of southwest China may be connected to the agricultural and climatic factors. The routine surveillance and the allocation of health resources should be given more attention in this area. Moreover, the meteorological variables might be considered as possible predictors of JE in southwest China. PMID:24739769

  20. A study of motor activity and catecholamine levels in different brain regions following Japanese encephalitis virus infection in rats.

    PubMed

    Misra, Usha Kant; Kumar, Sandeep; Kalita, Jayantee; Ahmad, Ausaf; Khanna, Vinay Kumar; Khan, Mohammad Yahiya; Palit, Gautam

    2009-10-01

    Japanese encephalitis (JE) is associated with a variety of movement disorders including transient form of pakinsonian features, dystonia and miscellaneous movement disorders. The neurotransmitters have important role in movement disorders. However their role in different brain regions in relation to behavioral activities in animal model of JE is not understood. The present study was aimed to investigate the behavioral parameters, the levels of catecholamine in brain regions--thalamus, midbrain, corpus striatum and frontal cortex on 0, 10 and 20 days post inoculation (dpi) with histopathological observations. Twelve day old Wistar strain rats were inoculated intracerebrally with a dose of 3 x 10(6) pfu of JE virus. Spontaneous locomotor activity (SLA) and grip strength were monitored. The levels of catecholamine were estimated using HPLC-ECD and histopathological changes were observed using haematoxylin and eosine staining. A significant decrease in SLA and grip strength was observed in JEV infected rats as compared to controls on 10 and 20 dpi. The levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and serotonin were significantly decreased in all the brain regions studied with respect to controls. We did not find significant recovery in catecholamine levels and locomotor activities up to 20 dpi and any significant correlation between behavioral changes and neurotransmitter levels. However histopathological studies revealed mild reduction in degree of damage on 20 dpi. The present study demonstrates the involvement of different brain regions in altered locomotor activity which may be associated with reduction in catecholamine levels in rat model of JE.

  1. Green synthesis and characterization of silver nanoparticles fabricated using Anisomeles indica: Mosquitocidal potential against malaria, dengue and Japanese encephalitis vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Veerakumar, Kaliyan; Muthukumaran, Udaiyan; Hoti, S L; Benelli, Giovanni

    2016-02-01

    Mosquitoes (Diptera: Culicidae) represent a key threat for millions of people worldwide, since they act as vectors for devastating parasites and pathogens. In this scenario, eco-friendly control tools against mosquito vectors are a priority. Green synthesis of silver nanoparticles (AgNP) using a cheap, aqueous leaf extract of Anisomeles indica by reduction of Ag(+) ions from silver nitrate solution has been investigated. Bio-reduced AgNP were characterized by UV-visible spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX) and X-ray diffraction analysis (XRD). The acute toxicity of A. indica leaf extract and biosynthesized AgNP was evaluated against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. Both the A. indica leaf extract and AgNP showed dose dependent larvicidal effect against all tested mosquito species. Compared to the leaf aqueous extract, biosynthesized AgNP showed higher toxicity against An. subpictus, Ae. albopictus, and Cx. tritaeniorhynchus with LC50 values of 31.56, 35.21 and 38.08 μg/mL, respectively. Overall, this study firstly shed light on the mosquitocidal potential of A. indica, a potential bioresource for rapid, cheap and effective AgNP synthesis. PMID:26708933

  2. Infectious Japanese encephalitis virus RNA can be synthesized from in vitro-ligated cDNA templates.

    PubMed Central

    Sumiyoshi, H; Hoke, C H; Trent, D W

    1992-01-01

    Japanese encephalitis virus (JEV) is a positive-stranded enveloped RNA virus that belongs to the family Flaviviridae. Genomic JEV RNA is approximately 11 kb long and encodes 10 proteins, 3 structural and 7 nonstructural. A full-length cDNA copy of the JEV genome was constructed by in vitro ligation of two cDNA fragments which encode the 5' (nucleotide positions 1 to 5576) and 3' (nucleotide positions 5577 to 10976) halves of the genome. T7 RNA polymerase transcripts of the ligated full-length cDNA template were infectious when transfected into BHK-21 cells. To identify the recombinant virus, a silent mutation was introduced into the clone encoding the 3' half of the genome, which abolished an XbaI site at nucleotide position 9131. Virus recovered by transfection with the transcripts contained this silent mutation, confirming its identity. Recombinant and parent viruses were identical with respect to growth and plaque production in BHK-21 cells, envelope protein expression in C6/36 cells, and neurovirulence and immunogenicity in mice. Repeated attempts to obtain infectious RNA by transcription from full-length JEV genome cDNA templates cloned into plasmid vectors were unsuccessful. Synthesis of infectious JEV RNA from in vitro-ligated JEV cDNA templates will be useful for molecular and genetic studies of flavivirus replication and virulence. Images PMID:1501281

  3. Development of electrochemical immunosensors based on different serum antibody immobilization methods for detection of Japanese encephalitis virus

    NASA Astrophysics Data System (ADS)

    Tran, Quang Huy; Hanh Nguyen, Thi Hong; Mai, Anh Tuan; Thuy Nguyen, Thi; Khue Vu, Quang; Nga Phan, Thi

    2012-03-01

    This paper describes the development of electrochemical immunosensors based on human serum antibodies with different immobilization methods for detection of Japanese encephalitis virus (JEV). Human serum containing anti-JEV antibodies was used to immobilize onto the surface of silanized interdigitated electrodes by four methods: direct adsorption (APTES-serum), covalent binding with a cross linker of glutaraldehyde (APTES-GA-serum), covalent binding with a cross linker of glutaraldehyde combined with anti-human IgG (APTES-GA-anti-HIgG-serum) and covalent binding with a cross linker of glutaraldehyde combined with a bioaffinity of protein A (APTES-GA-PrA-serum). Atomic force microscopy was used to verify surface characteristics of the interdigitated electrodes before and after treatment with serum antibodies. The output signal of the immunosensors was measured by the change of conductivity resulting from the specific binding of JEV antigens and serum antibodies immobilized on the electrodes, with the help of horseradish peroxidase (HRP)-labeled secondary antibody against JEV. The results showed that the APTES-GA-PrA-serum method provided the highest signal of the electrochemical immunosensor for detection of JEV antigens, with the linear range from 25 ng ml‑1 to 1 μg ml‑1, and the limit of detection was about 10 ng ml‑1. This study shows a potential development of novel electrochemical immunosensors applied for virus detection in clinical samples in case of possible outbreaks.

  4. Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity

    PubMed Central

    2011-01-01

    The serum-free medium from Japanese encephalitis virus (JEV) infected Baby Hamster Kidney-21 (BHK-21) cell cultures was analyzed by liquid chromatography tandem mass spectrometry (LC-MS) to identify host proteins that were secreted upon viral infection. Five proteins were identified, including the molecular chaperones Hsp90, GRP78, and Hsp70. The functional role of GRP78 in the JEV life cycle was then investigated. Co-migration of GRP78 with JEV particles in sucrose density gradients was observed and co-localization of viral E protein with GRP78 was detected by immunofluorescence analysis in vivo. Knockdown of GRP78 expression by siRNA did not effect viral RNA replication, but did impair mature viral production. Mature viruses that do not co-fractionate with GPR78 displayed a significant decrease in viral infectivity. Our results support the hypothesis that JEV co-opts host cell GPR78 for use in viral maturation and in subsequent cellular infections. PMID:21418596

  5. Prevalence of antibodies to Japanese encephalitis virus among inhabitants in Java Island, Indonesia, with a small pig population.

    PubMed

    Konishi, Eiji; Sakai, Yohei; Kitai, Yoko; Yamanaka, Atsushi

    2009-05-01

    Japanese encephalitis virus (JEV) is maintained through a transmission cycle between amplifier swine and vector mosquitoes in a peridomestic environment. Thus, studies on natural JEV activities in an environment with a small size of pig population have been limited. Here, we surveyed antibodies against JEV in inhabitants of Jakarta and Surabaya located in Java Island (Indonesia), which has a small swine population. Overall, 2.2% of 1,211 sera collected in Jakarta and 1.8% of 1,751 sera collected in Surabaya had neutralizing antibody titers of >or= 1:160 (90% plaque reduction). All the samples with titers of >or= 1:160 against JEV were also examined for neutralizing antibodies against each of four dengue viruses to confirm that JEV antibody prevalences obtained in the present survey were not attributable to serologic cross-reactivities among flaviviruses distributed in Java. These results indicated that people in Java Island are exposed to natural JEV infections despite a small swine population.

  6. Japanese encephalitis virus upregulates the expression of SOCS3 in mouse brain and Raw264.7 Cells.

    PubMed

    Li, Xiangmin; Zhu, Qiaoyan; Cao, Qishu; Chen, Huanchun; Qian, Ping

    2014-11-01

    Japanese encephalitis virus (JEV) is one of the pathogens that can invade the central nervous system, causing acute infection and inflammation of brain. SOCS3 protein plays a vital role in immune processes and inflammation of the central nervous system. In this study, Raw264.7 cells and suckling mice were infected with JEV, and SOCS3 expression was analyzed by the gene expression profile, semiquantitative RT-PCR, qRT-PCR, immunohistochemistry (IHC) and Western blot. Results indicated that 520 genes were found to be differentially expressed (fold change ≥ 2.0, p < 0.05) in total. The differentially regulated genes were involved in biological processes, such as stimulus response, biological regulation and immune system processes. JEV early infection could induce SOCS3 expression, upregulating both the mRNA and protein levels in Raw264.7 cells in a time-dependent manner. The SOCS3 expression was much lower in Raw264.7 cells infected with inactivated JEV than wild-type JEV. In vivo, SOCS3 protein was also found to upregulate the expression of mRNA and protein in JEV-infected mouse brain. Taken together, our data showed that JEV early infection could induce the upregulation of SOCS3 expression, both in vitro and in vivo, providing the basic theoretical foundation for future research on the invasion mechanism of JEV. PMID:25390684

  7. [Prevention of virus-related neurological diseases by vaccines].

    PubMed

    Takahashi, M

    1997-04-01

    Prevention of virus-related neurological diseases are surveyed. Patients of poliomyelitis has recently been drastically reduced by world-wide administrating live vaccines. In view of rare incidence of paralysis after giving live vaccine, adoption of inactivated vaccine has recently been reconsidered. A live varicella vaccine was developed and has been world-wide used for normal and high-risk children. Incidence of zoster in vaccinated acute leukemic children is several times higher in those who with rash after vaccination as compared with those without rash, and as no or few rash appears after vaccination of normal children, it is expected that vaccination of normal children would lead to reduction of zoster after their aging. Measles encephalitis has rapidly been reduced by world-wide use of live vaccines. Mouse-brain derived vaccine against Japanese encephalitis(JE) has been used in Asian countries. Development of tissue-culture derived JE vaccine is under way. PMID:9103901

  8. TNF-α Acts as an Immunoregulator in the Mouse Brain by Reducing the Incidence of Severe Disease Following Japanese Encephalitis Virus Infection

    PubMed Central

    Hayasaka, Daisuke; Shirai, Kenji; Aoki, Kotaro; Nagata, Noriyo; Simantini, Dash Sima; Kitaura, Kazutaka; Takamatsu, Yuki; Gould, Ernest; Suzuki, Ryuji; Morita, Kouichi

    2013-01-01

    Japanese encephalitis virus (JEV) causes acute central nervous system (CNS) disease in humans, in whom the clinical symptoms vary from febrile illness to meningitis and encephalitis. However, the mechanism of severe encephalitis has not been fully elucidated. In this study, using a mouse model, we investigated the pathogenetic mechanisms that correlate with fatal JEV infection. Following extraneural infection with the JaOArS982 strain of JEV, infected mice exhibited clinical signs ranging from mild to fatal outcome. Comparison of the pathogenetic response between severe and mild cases of JaOArS982-infected mice revealed increased levels of TNF-α in the brains of severe cases. However, unexpectedly, the mortality rate of TNF-α KO mice was significantly increased compared with that of WT mice, indicating that TNF-α plays a protective role against fatal infection. Interestingly, there were no significant differences of viral load in the CNS between WT and TNF-α KO mice. However, exaggerated inflammatory responses were observed in the CNS of TNF-α KO mice. Although these observations were also obtained in IL-10 KO mice, the mortality and enhanced inflammatory responses were more pronounced in TNF-α KO mice. Our findings therefore provide the first evidence that TNF-α has an immunoregulatory effect on pro-inflammatory cytokines in the CNS during JEV infection and consequently protects the animals from fatal disease. Thus, we propose that the increased level of TNF-α in severe cases was the result of severe disease, and secondly that immunopathological effects contribute to severe neuronal degeneration resulting in fatal disease. In future, further elucidation of the immunoregulatory mechanism of TNF-α will be an important priority to enable the development of effective treatment strategies for Japanese encephalitis. PMID:23940775

  9. Multiplication and distribution of type 2 dengue and Japanese encephalitis viruses in Toxorhynchites splendens after intrathoracic inoculation.

    PubMed

    Yamamoto, N; Kimura, T; Ohyama, A

    1987-01-01

    The nonhematophagous mosquito Toxorhynchites (Tx.) splendens was found to be the most susceptible to type 2 dengue (D-2) and Japanese encephalitis (JEV) viruses among three hosts examined by virus titration and replication assays. After inoculation with D-2, the number of viral antigen positive cells in the head, thorax and abdomen increased up to day 15 and D-2 reached the maximum titer of 8.4 log10 PFU/g in the head on day 15. Hemocytes were the earliest cell type that could be detected as D-2 antigen positive on day 2. Multiplication of JEV was faster than that of D-2 in the mosquito. The number of JEV antigen positive cells in each part of the mosquito increased up to day 3, JEV reaching the maximum titer of 8.0 log10 PFU/g in the abdomen on day 3. Hemocytes and fat body cells (FBC) could be detected as JEV antigen positive cells on day 1. The time course of D-2 and JEV infection suggested that intrathoracically inoculated viruses were probably initially phagocytosed by hemocytes and/or FBC, and multiplied primarily in their cytoplasm. The infected hemocytes were then transported by the flow of body fluid and viruses were disseminated to other susceptible organs, such as ganglia, salivary glands, etc. The results obtained indicate that the course of infection of D-2 and JEV in Tx. splendens is similar to that in vector mosquitoes. Tx. splendens is therefore very useful for the study of these viruses.

  10. Fine mapping of a linear epitope on EDIII of Japanese encephalitis virus using a novel neutralizing monoclonal antibody.

    PubMed

    Deng, Wen-Lei; Guan, Chi-Yu; Liu, Ke; Zhang, Xiao-Min; Feng, Xiu-Li; Zhou, Bin; Su, Xiao-Dong; Chen, Pu-Yan

    2014-01-22

    The domain III (EDIII) of the envelope protein of Japanese encephalitis virus (JEV) is proposed to play an essential role in JEV replication and infection; it is involved in binding to host receptors and contains specific epitopes that elicit neutralizing antibodies. However, most previous studies have not provided detailed molecular information about the functional epitopes on JEV EDIII protein. In this study, we described a monoclonal antibody (mAb 2B4) we produced and characterized by IFA, PRNT, ELISA and Western blot analyses. The results showed that mAb 2B4 was specific to JEV EDIII protein and possessed high neutralization activity against JEV in vitro. Furthermore, we found that the motif, (394)HHWH(397), was the minimal unit of the linear epitope recognized by mAb 2B4 through screening a phage-displayed random 12-mer peptide library. Using sequence alignment analysis it was found that this motif was highly conserved among JEV strains and was present in West Nile Virus (WNV). Indeed, ELISA data showed that this epitope could be recognized by both JEV-positive swine serum and WNV-positive swine serum. Notably, this linear epitope was highly hydrophilic and was located within the terminal end of a β-pleated sheet of EDIII. An analysis of the spatial conformation supported the possibility of inducing specific antibodies to this epitope. Taken together, we identified (394)HHWH(397) as an EDIII-specific linear epitope recognized by mAb 2B4, which would be beneficial for studying the pathogenic mechanism of JEV; and mAb 2B4 was also a potential diagnostic and therapeutic reagent. PMID:24184444

  11. Transcriptional regulation of miR-15b by c-Rel and CREB in Japanese encephalitis virus infection

    PubMed Central

    Zhu, Bibo; Ye, Jing; Ashraf, Usama; Li, Yunchuan; Chen, Huanchun; Song, Yunfeng; Cao, Shengbo

    2016-01-01

    MicroRNAs (miRNAs) have been well known to play diverse roles in viral infection at the level of posttranscriptional repression. However, much less is understood about the mechanism by which miRNAs are regulated during viral infection. It is likely that both host and virus contain factors to modulate miRNA expression. Here we report the up-regulation of microRNA-15b (miR-15b) in vitro upon infection with Japanese encephalitis virus (JEV). Analysis of miR-15b precursor, pri-miR-15b and pre-miR-15b, suggest that the regulation occurs transcriptionally. Further, we identified the transcriptional regulatory region of miR-15b that contains consensus binding motif for NF-κB subunit c-Rel and cAMP-response element binding protein (CREB), which are known as transcription factor to regulate gene expression. By promoter fusion and mutational analyses, we demonstrated that c-Rel and CREB bind directly to the promoter elements of miR-15b, which are responsible for miR-15b transcription in response to JEV infection. Finally, we showed that pharmacological inhibition of ERK and NF-κB signaling pathway blocked induction of miR-15b in JEV infection, suggesting important roles of ERK and NF-κB pathway in the regulation of miR-15b gene. Therefore, our observations indicate that induced expression of miR-15b is modulated by c-Rel and CREB in response to JEV infection. PMID:26931521

  12. Serosurvey of West Nile virus and other flaviviruses of the Japanese encephalitis antigenic complex in birds from Andalusia, southern Spain.

    PubMed

    García-Bocanegra, Ignacio; Busquets, Núria; Napp, Sebastián; Alba, Ana; Zorrilla, Irene; Villalba, Rubén; Arenas, Antonio

    2011-08-01

    Flaviviruses of the Japanese encephalitis virus (JEV) antigenic complex, including West Nile virus (WNV), are recognized as emerging and reemerging pathogens. Circulation of flaviviruses has been recently detected in different mosquito and vertebrate species in several European countries. A serosurvey study was carried out to evaluate the circulation of WNV and other flaviviruses of the JEV antigenic complex in different wild bird species in Spain between 2006 and 2009. Seropositiviy against JEV using a competitive enzyme-linked immunosorbent assay was found in common coot, Montagu's Harrier, black kite, black vulture, Bonelli's eagle, Spanish imperial eagle, Egyptian vulture, and Eurasian spoonbill. Seropositivity to JEV antigenic complex viruses was significantly higher in samples collected during autumn compared with animals sampled during summer. Significantly higher seroprevalence was also observed in 2007 compared with 2009, whereas there were no significant differences in seropositivity among taxonomic levels, migratory versus resident behavior, body size (large vs. medium), or habitats (free-ranging vs. captivity). Neutralizing antibodies against WNV were detected in common coot and Spanish imperial eagle using a virus-neutralization test. Oral shedding of WNV was not detected in any of the Spanish imperial eagles, Egyptian vultures, Eurasian Spoonbills, Lammergeiers, and the Black vultures analyzed by means of real-time reverse transcription-polymerase chain reaction. The results indicate that WNV and others flaviviruses of the JEV antigenic group circulated in migratory and resident wild bird species in Spain between 2007 and 2008. Further studies are necessary to determine the precise role that each of these wild bird species, some of them cataloged as "near threatened," "vulnerable," or "endangered," play in the epidemiology of those viruses. PMID:21142954

  13. Seroprevalence of tetanus toxoid antibody and booster vaccination efficacy in Japanese travelers.

    PubMed

    Mizuno, Yasutaka; Yamamoto, Akihiko; Komiya, Takako; Takeshita, Nozomi; Takahashi, Motohide

    2014-01-01

    Tetanus can be prevented by vaccination, which is especially important for overseas travelers. However, despite booster vaccination every 10 years being recommended, most Japanese adults do not receive it in the absence of physical injury or overseas travel. We aimed to investigate the level of protective immunity against tetanus among Japanese travelers, which may provide valuable information for formulating booster vaccination recommendations. 113 Japanese travelers given tetanus toxoid were recruited. The collected samples included paired samples prior to and 3-5 weeks after receiving the booster vaccination. Travelers who did not return and those lacking sample collection at the second visit were excluded. Finally, 96 paired blood samples were collected. History of immunization against tetanus, including DPT and DT vaccines, was determined from interviews or immunization records. The pre-vaccination geometric mean titer for the 96 participants was 1.07 IU/mL; 76% had a protective antitoxin level (>0.1 IU/mL), and 50% had a long-term protective antitoxin level (>1.0 IU/mL). Most participants <40 years old had protective immunity without receiving booster vaccination, whereas only 30.8% of those >50 years of age had protective immunity. Among the 23 participants without protective antitoxin levels (<0.1 IU/mL), booster vaccination was efficient in 100% of those <40 years but in only 28.6% of those >50 years of age. Although the tetanus antitoxin level decreases with age, booster vaccination helped to achieve an adequate protective antitoxin levels in Japanese travelers <40 years of age. Furthermore, the individuals who have never been vaccinated against tetanus especially in those >50 years old need to obtain protective immunity against tetanus according to a basic immunization schedule to prevent tetanus in travelers and residents of Japan.

  14. Study of the effect of the midgut bacterial flora of Culex quinquefasciatus on the susceptibility of mosquitoes to Japanese encephalitis virus.

    PubMed

    Mourya, D T; Gokhale, M D; Pidiyar, V; Barde, P V; Patole, M; Mishra, A C; Shouche, Y

    2002-01-01

    Culex quinquefasciatus mosquitoes were collected from the field and microbial flora was isolated from their midgut. Isolates belonging to 13 different genera were obtained. Four most abundant isolates viz. Pseudomonas sp., Acinetobacterjunii, Staphylococcus epidermis and Aeromonas culicicola were used to study their effect on the susceptibility of mosquitoes to Japanese encephalitis virus (JEV). Incorporation of individual isolates in the mosquito bloodmeal resulted in an increased susceptibility of mosquitoes to the virus. However, only the effects of Pseudomonas sp. and Acinetobacterjunii could be statistically evaluated but they were found insignificant. PMID:12693864

  15. Japanese encephalitis (JE). Part I: clinical profile of 1,282 adult acute cases of four epidemics.

    PubMed

    Sarkari, N B S; Thacker, A K; Barthwal, S P; Mishra, V K; Prapann, Shiv; Srivastava, Deepak; Sarkari, M

    2012-01-01

    Japanese encephalitis (JE) is numerically the most important global cause of encephalitis and so far confirmed to have caused major epidemics in India. Most of the reported studies have been in children. This largest study involving only adults, belonging to four epidemics, is being reported from Gorakhpur. The aim of this study is to detail the acute clinical profile (not viral) outcome and to classify the sequelae at discharge. This prospective study involved 1,282 adult patients initially diagnosed as JE admitted during the epidemics of 1978, 1980, 1988, and 1989, on identical clinical presentation and CSF examination. In the meantime, the diagnosis of JE was confirmed by serological and/or virological studies in only a representative number of samples (649 of 1,282 cases). Eighty-three left against medical advice (LAMA) at various stages, so 1,199 of 1,282 were available for the study. Peak incidence of [1,061 of 1,282 (83%)] of clinically suspected cases was from September 15 to November 2. Serum IgM and IgG were positive in high titers in 50.87% (330 of 649) and IgM positive in CSF in 88.75% (109 of 123) of the cases. JE virus could be isolated from CSF and brain tissue in 5 of 5 and 4 of 5 samples, respectively. Altered sensorium (AS) in (96%), convulsions (86%), and headache (85%) were the main symptoms for hospitalization by the third day of the onset. Other neurological features included hyperkinetic movements in 593 of 1,282 (46%)-choreoathetoid in 490 (83%) and bizarre, ill-defined in 103 (17%). The features of brain stem involvement consisted of opsoclonus (20%), gaze palsies (16%), and pupillary changes (48%) with waxing and waning character. Cerebellar signs were distinctly absent. Dystonia and decerebrate rigidity was observed in 43 and 6%, respectively, paralytic features in 17% and seizures in 30%. Many non-neurological features of prognostic importance included abnormal breathing patterns (ABP) (45%), pulmonary edema (PO) (33%), and upper

  16. A Japanese Encephalitis Virus Genotype 5 Molecular Clone Is Highly Neuropathogenic in a Mouse Model: Impact of the Structural Protein Region on Virulence

    PubMed Central

    de Wispelaere, Mélissanne; Frenkiel, Marie-Pascale

    2015-01-01

    ABSTRACT Japanese encephalitis virus (JEV) strains can be separated into 5 genotypes (g1 to g5) based on sequence similarity. JEV g5 strains have been rarely isolated and are poorly characterized. We report here the full characterization of a g5 virus generated using a cDNA-based technology and its comparison with a widely studied g3 strain. We did not observe any major differences between those viruses when their infectious cycles were studied in various cell lines in vitro. Interestingly, the JEV g5 strain was highly pathogenic when inoculated to BALB/c mice, which are known to be largely resistant to JEV g3 infection. The study of chimeric viruses between JEV g3 and g5 showed that there was a poor viral clearance of viruses that express JEV g5 structural proteins in BALB/c mice blood, which correlated with viral invasion of the central nervous system and encephalitis. In addition, using an in vitro model of the blood-brain barrier, we were able to show that JEV g5 does not have an enhanced capacity for entering the central nervous system, compared to JEV g3. Overall, in addition to providing a first characterization of the understudied JEV g5, our work highlights the importance of sustaining an early viremia in the development of JEV encephalitis. IMPORTANCE Genotype 5 viruses are genetically and serologically distinct from other JEV genotypes and can been associated with human encephalitis, which warrants the need for their characterization. In this study, we characterized the in vitro and in vivo properties of a JEV g5 strain and showed that it was more neuropathogenic in a mouse model than a well-characterized JEV g3 strain. The enhanced virulence of JEV g5 was associated with poor viral clearance but not with enhanced crossing of the blood-brain barrier, thus providing new insights into JEV pathogenesis. PMID:25787283

  17. Human arboviral encephalitis.

    PubMed

    Rust, Robert S

    2012-09-01

    Worldwide, arboviral illnesses constitute the most important international infectious threat to human neurological health and welfare. Before the availability of effective immunizations, approximately 50,000 cases of Japanese encephalitis occurred in the world each year, one-fifth of which cases proved lethal and a much larger number were left with severe neurological handicaps. With global climate change and perhaps other factors, the prevalences of some arboviral illnesses appear to be increasing. Arboviral illnesses, including Japanese encephalitis, tick-borne encephalitis, Yellow fever, and others, are emerging as possible global health care threats because of biological warfare. This chapter will review ecology, pathophysiology, diagnosis, management, and outcome of the forms of arboviral encephalitis that are of greatest importance in North America, together with some of the most important arboviral encephalitides prevalent in other parts of the world.

  18. Human arboviral encephalitis.

    PubMed

    Rust, Robert S

    2012-09-01

    Worldwide, arboviral illnesses constitute the most important international infectious threat to human neurological health and welfare. Before the availability of effective immunizations, approximately 50,000 cases of Japanese encephalitis occurred in the world each year, one-fifth of which cases proved lethal and a much larger number were left with severe neurological handicaps. With global climate change and perhaps other factors, the prevalences of some arboviral illnesses appear to be increasing. Arboviral illnesses, including Japanese encephalitis, tick-borne encephalitis, Yellow fever, and others, are emerging as possible global health care threats because of biological warfare. This chapter will review ecology, pathophysiology, diagnosis, management, and outcome of the forms of arboviral encephalitis that are of greatest importance in North America, together with some of the most important arboviral encephalitides prevalent in other parts of the world. PMID:22889543

  19. U.S. Army, French Drugmaker to Join Forces on Zika Vaccine

    MedlinePlus

    ... potential vaccine. The institute will transfer its inactivated Zika virus technology to Sanofi Pasteur, opening the door to what ... it's working on pre-clinical studies that utilize technology previously and ... vaccines. "Zika, Japanese encephalitis, and dengue belong to the same ...

  20. Immune interference in the setting of same-day administration of two similar inactivated alphavirus vaccines: eastern equine and western equine encephalitis.

    PubMed

    Reisler, Ronald B; Gibbs, Paul H; Danner, Denise K; Boudreau, Ellen F

    2012-11-26

    We compared the effect on primary vaccination plaque-reduction neutralization 80% titers (PRNT80) responses of same-day administration (at different injection sites) of two similar investigational inactivated alphavirus vaccines, eastern equine encephalitis (EEE) vaccine (TSI-GSD 104) and western equine encephalitis (WEE) vaccine (TSI-GSD 210) to separate administration. Overall, primary response rate for EEE vaccine was 524/796 (66%) and overall primary response rate for WEE vaccine was 291/695 (42%). EEE vaccine same-day administration yielded a 59% response rate and a responder geometric mean titer (GMT)=89 while separate administration yielded a response rate of 69% and a responder GMT=119. WEE vaccine same-day administration yielded a 30% response rate and a responder GMT=53 while separate administration yielded a response rate of 54% and a responder GMT=79. EEE response rates for same-day administration (group A) vs. non-same-day administration (group B) were significantly affected by gender. A logistic regression model predicting response to EEE comparing group B to group A for females yielded an OR=4.10 (95% CL 1.97-8.55; p=.0002) and for males yielded an OR=1.25 (95% CL 0.76-2.07; p=.3768). WEE response rates for same-day administration vs. non-same-day administration were independent of gender. A logistic regression model predicting response to WEE comparing group B to group A yielded an OR=2.14 (95% CL 1.22-3.73; p=.0077). We report immune interference occurring with same-day administration of two completely separate formalin inactivated viral vaccines in humans. These findings combined with the findings of others regarding immune interference would argue for a renewed emphasis on studying the immunological mechanisms of induction of inactivated viral vaccine protection.

  1. Travelers' Health: Japanese Encephalitis

    MedlinePlus

    ... Global TravEpiNet Mobile Apps RSS Feeds Chapter 3 Infectious Diseases Related to Travel Recommend on Facebook Tweet Share ... and Prevention National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) Division of Global Migration and Quarantine (DGMQ) ...

  2. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. PMID:27638116

  3. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    PubMed

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  4. A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1' may derive from ribosomal frameshifting

    PubMed Central

    Firth, Andrew E; Atkins, John F

    2009-01-01

    Japanese encephalitis, West Nile, Usutu and Murray Valley encephalitis viruses form a tight subgroup within the larger Flavivirus genus. These viruses utilize a single-polyprotein expression strategy, resulting in ~10 mature proteins. Plotting the conservation at synonymous sites along the polyprotein coding sequence reveals strong conservation peaks at the very 5' end of the coding sequence, and also at the 5' end of the sequence encoding the NS2A protein. Such peaks are generally indicative of functionally important non-coding sequence elements. The second peak corresponds to a predicted stable pseudoknot structure whose biological importance is supported by compensatory mutations that preserve the structure. The pseudoknot is preceded by a conserved slippery heptanucleotide (Y CCU UUU), thus forming a classical stimulatory motif for -1 ribosomal frameshifting. We hypothesize, therefore, that the functional importance of the pseudoknot is to stimulate a portion of ribosomes to shift -1 nt into a short (45 codon), conserved, overlapping open reading frame, termed foo. Since cleavage at the NS1-NS2A boundary is known to require synthesis of NS2A in cis, the resulting transframe fusion protein is predicted to be NS1-NS2AN-term-FOO. We hypothesize that this may explain the origin of the previously identified NS1 'extension' protein in JEV-group flaviviruses, known as NS1'. PMID:19196463

  5. Phylogenetic analysis of Japanese encephalitis virus: envelope gene based analysis reveals a fifth genotype, geographic clustering, and multiple introductions of the virus into the Indian subcontinent.

    PubMed

    Uchil, P D; Satchidanandam, V

    2001-09-01

    We report the analysis of the complete nucleotide sequence for the Indian isolate (P20778; Genbank Accession number AF080251) of Japanese encephalitis virus (JEV). The phylogenetic tree topology obtained using thirteen complete genome sequences of JEV was reproduced with the envelope, NS1, NS3, and NS5 genes and revealed extensive divergence between the two Indian strains included. A more exhaustive analysis of JEV evolution using 107 envelope sequences available for isolates from different geographic locations worldwide revealed five distinct genotypes of JEV, displaying a minimum nucleotide divergence of 7% with high bootstrap support values. The tree also revealed overall clustering of strains based on geographic location, as well as multiple introductions of JEV into the Indian subcontinent. Nonsynonymous nucleotide divergence rates of the envelope gene estimated that the ancestor common to all JEV genotypes arose within the last three hundred years.

  6. Eco-friendly larvicides from Indian plants: Effectiveness of lavandulyl acetate and bicyclogermacrene on malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Benelli, Giovanni

    2016-11-01

    Mosquitoes (Diptera: Culicidae) are a key threat for millions of people and animals worldwide, since they act as vectors for devastating pathogens and parasites, including malaria, dengue, Japanese encephalitis, filiariasis and Zika virus. Mosquito young instars are usually targeted using organophosphates, insect growth regulators and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment and induce resistance in a number of vectors. In this scenario, newer and safer tools have been recently implemented to enhance mosquito control. The concrete potential of screening plant species as sources of metabolites for entomological and parasitological purposes is worthy of attention, as recently elucidated by the Y. Tu's example. Here we investigated the toxicity of Heracleum sprengelianum (Apiaceae) leaf essential oil and its major compounds toward third instar larvae of the malaria vector Anopheles subpictus, the arbovirus vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. GC-MS analysis showed that EO major components were lavandulyl acetate (17.8%) and bicyclogermacrene (12.9%). The EO was toxic to A. subpictus, A. albopictus, and C. tritaeniorhynchus, with LC50 of 33.4, 37.5 and 40.9µg/ml, respectively. Lavandulyl acetate was more toxic to mosquito larvae if compared to bicyclogermacrene. Their LC50 were 4.17 and 10.3µg/ml for A. subpictus, 4.60 and 11.1µg/ml for A. albopictus, 5.11 and 12.5µg/ml for C. tritaeniorhynchus. Notably, the EO and its major compounds were safer to three non-target mosquito predators, Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC50 ranging from 206 to 4219µg/ml. Overall, this study highlights that H. sprengelianum EO is a promising source of eco-friendly larvicides against three important mosquito vectors with moderate toxicity against non-target aquatic

  7. Japanese encephalitis virus infection of mouse cell lines: ability to prime mice for generation of virus specific cytotoxic T lymphocytes and differences in CTL recognisable viral determinants.

    PubMed

    Murali-Krishna, K; Ravi, V; Manjunath, R

    1995-01-01

    Ten different mouse cell lines were examined for Japanese encephalitis virus (JEV) infection in vitro and then tested for their ability to generate virus specific cytotoxic T lymphocytes (CTL). Among all cell lines examined, Neuro 2a (a neuroblastoma) was readily infected with JEV as examined by immunofluorescence and viral replication. Among other cells, P388D1, RAW 264.7 (Macrophage origin), Sp2/0 (B-cell Hybridoma), YAC-1 (T-cell lymphoma), and L929 (Fibroblast) were semipermissive to JEV infection. The cytopathic effects caused by progressive JEV infection varied from cell line to cell line. In the case of YAC-1 cells long-term viral antigen expression was observed without significant alterations in cell viability. Intermediate degrees of cytopathicity are seen in RAW 264.7 and L929 cells while infection of PS, Neuro 2a, P388D1 and Sp2/0 caused major viability losses. All infected cell lines were able to prime adult BALB/c (H-2d) mice for the generation of secondary JEV specific CTL. In contrast to YAC-1, the permissive neuroblastoma cell line Neuro 2a (H-2KkDd) was found to be least efficient in its ability to stimulate anti-viral CTL generation. Cold target competition studies demonstrated that both Neuro 2a and YAC-1 (H-2KkDd) cells expressed similar viral determinants that are recognised by CTL, suggesting that the reason for the lower ability of Neuro 2a to stimulate anti-viral CTL was not due to lack of viral CTL determinants. These findings demonstrate that a variety of mouse cell lines can be infected with Japanese encephalitis virus, and that these infected cells could be utilised to generate virus specific CTL in BALB/c mice.

  8. Eco-friendly larvicides from Indian plants: Effectiveness of lavandulyl acetate and bicyclogermacrene on malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Benelli, Giovanni

    2016-11-01

    Mosquitoes (Diptera: Culicidae) are a key threat for millions of people and animals worldwide, since they act as vectors for devastating pathogens and parasites, including malaria, dengue, Japanese encephalitis, filiariasis and Zika virus. Mosquito young instars are usually targeted using organophosphates, insect growth regulators and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment and induce resistance in a number of vectors. In this scenario, newer and safer tools have been recently implemented to enhance mosquito control. The concrete potential of screening plant species as sources of metabolites for entomological and parasitological purposes is worthy of attention, as recently elucidated by the Y. Tu's example. Here we investigated the toxicity of Heracleum sprengelianum (Apiaceae) leaf essential oil and its major compounds toward third instar larvae of the malaria vector Anopheles subpictus, the arbovirus vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. GC-MS analysis showed that EO major components were lavandulyl acetate (17.8%) and bicyclogermacrene (12.9%). The EO was toxic to A. subpictus, A. albopictus, and C. tritaeniorhynchus, with LC50 of 33.4, 37.5 and 40.9µg/ml, respectively. Lavandulyl acetate was more toxic to mosquito larvae if compared to bicyclogermacrene. Their LC50 were 4.17 and 10.3µg/ml for A. subpictus, 4.60 and 11.1µg/ml for A. albopictus, 5.11 and 12.5µg/ml for C. tritaeniorhynchus. Notably, the EO and its major compounds were safer to three non-target mosquito predators, Anisops bouvieri, Diplonychus indicus and Gambusia affinis, with LC50 ranging from 206 to 4219µg/ml. Overall, this study highlights that H. sprengelianum EO is a promising source of eco-friendly larvicides against three important mosquito vectors with moderate toxicity against non-target aquatic

  9. Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals

    PubMed Central

    Lindblom, Pontus; Wilhelmsson, Peter; Fryland, Linda; Matussek, Andreas; Haglund, Mats; Sjöwall, Johanna; Vene, Sirkka; Nyman, Dag; Forsberg, Pia; Lindgren, Per-Eric

    2014-01-01

    We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy. PMID:24967619

  10. Influenza-Related Mortality Trends in Japanese and American Seniors: Evidence for the Indirect Mortality Benefits of Vaccinating Schoolchildren

    PubMed Central

    Charu, Vivek; Viboud, Cécile; Simonsen, Lone; Sturm-Ramirez, Katharine; Shinjoh, Masayoshi; Chowell, Gerardo; Miller, Mark; Sugaya, Norio

    2011-01-01

    Background The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US. Methods We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978–1994) and after the program was discontinued (1995–2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control. Results We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17–51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400–1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population. Conclusions The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors. PMID:22087226

  11. MicroRNA-33a-5p Modulates Japanese Encephalitis Virus Replication by Targeting Eukaryotic Translation Elongation Factor 1A1

    PubMed Central

    Chen, Zheng; Ye, Jing; Ashraf, Usama; Li, Yunchuan; Wei, Siqi; Wan, Shengfeng; Zohaib, Ali; Song, Yunfeng; Chen, Huanchun

    2016-01-01

    ABSTRACT Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus responsible for acute encephalitis and meningitis in humans. However, the molecular mechanism for JEV pathogenesis is still unclear. MicroRNAs (miRNAs) are small noncoding RNAs that act as gene regulators. They are directly or indirectly involved in many cellular functions owing to their ability to target mRNAs for degradation or translational repression. However, how cellular miRNAs are regulated and their functions during JEV infection are largely unknown. In the present study, we found that JEV infection downregulated the expression of endogenous cellular miR-33a-5p. Notably, artificially transfecting with miR-33a-5p mimics led to a significant decrease in viral replication, suggesting that miR-33a-5p acts as a negative regulator of JEV replication. A dual-luciferase reporter assay identified eukaryotic translation elongation factor 1A1 (EEF1A1) as one of the miR-33a-5p target genes. Our study further demonstrated that EEF1A1 can interact with the JEV proteins NS3 and NS5 in replicase complex. Through this interaction, EEF1A1 can stabilize the components of viral replicase complex and thus facilitates viral replication during JEV infection. Taken together, these results suggest that miR-33a-5p is downregulated during JEV infection, which contributes to viral replication by increasing the intracellular level of EEF1A1, an interaction partner of JEV NS3 and NS5. This study provides a better understanding of the molecular mechanisms of JEV pathogenesis. IMPORTANCE MiRNAs are critical regulators of gene expression that utilize sequence complementarity to bind to and modulate the stability or translation efficiency of target mRNAs. Accumulating data suggest that miRNAs regulate a wide variety of molecular mechanisms in the host cells during viral infections. JEV, a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans worldwide. The roles of cellular mi

  12. [Tick-borne encephalitis (TBE) and TBE-vaccination in Austria: Update 2014].

    PubMed

    Kunze, Ursula; Böhm, Gabriela

    2015-07-01

    TBE is a public health problem well under control in Austria because of a mass vaccination programme. There have been 50-100 registered cases per year for many years, the vaccination rate of the population is currently 85 %. Special attention has to be given to the "older" generation 40 plus as this is the segment of the population where the majority of cases are observed annually. In comparison of the counties, Tyrol and Upper Austria finished first and second after a long time when Styria and Carynthia had observed most of the cases. For TBE applies the same as for Tetanus, namely the principle of disease control or disease elimination: The virus cannot be eliminated and vaccination provides individual protection. The both available TBE vaccines have proven to be very effective with an effectivity of 96-99 %, also when given irregular vaccinations the protection rate is still very high (>90 %). More than 4000 prevented cases between 2000 and 2011 prove this impressively.

  13. [Tick-borne encephalitis (TBE) and TBE-vaccination in Austria: Update 2014].

    PubMed

    Kunze, Ursula; Böhm, Gabriela

    2015-07-01

    TBE is a public health problem well under control in Austria because of a mass vaccination programme. There have been 50-100 registered cases per year for many years, the vaccination rate of the population is currently 85 %. Special attention has to be given to the "older" generation 40 plus as this is the segment of the population where the majority of cases are observed annually. In comparison of the counties, Tyrol and Upper Austria finished first and second after a long time when Styria and Carynthia had observed most of the cases. For TBE applies the same as for Tetanus, namely the principle of disease control or disease elimination: The virus cannot be eliminated and vaccination provides individual protection. The both available TBE vaccines have proven to be very effective with an effectivity of 96-99 %, also when given irregular vaccinations the protection rate is still very high (>90 %). More than 4000 prevented cases between 2000 and 2011 prove this impressively. PMID:26055812

  14. Dengue fever virus and Japanese encephalitis virus synthetic peptides, with motifs to fit HLA class I haplotypes prevalent in human populations in endemic regions, can be used for application to skin Langerhans cells to prime antiviral CD8+ cytotoxic T cells (CTLs)--a novel approach to the protection of humans.

    PubMed

    Becker, Y

    1994-09-01

    Flaviviruses were reported to induce CD8+ cytotoxic T cells in infected individuals, indicating that nonapeptides, proteolytic cleavage products of the viral precursor protein, enter the endoplasmic reticulum in infected cells and interact with HLA class I molecules. The assembled HLA class I molecules are transported to the plasma membrane and prime CD8+ T cells. Current knowledge of the interaction of viral peptides with HLA molecules is reviewed. Based on this review, an idea is presented to use synthetic flavivirus peptides with an amino acid motif to fit with the HLA class I peptide binding group of HLA haplotypes prevalent in a given population in an endemic area. These synthetic viral peptides may be introduced into the human skin using a lotion containing the peptides ("Peplotion") together with substances capable of enhancing the penetration of these peptides into the skin to reach Langerhans cells. The peptide-treated Langerhans cells, professional antigen-presenting cells, may bind the synthetic viral peptides by their HLA class I peptide-binding grooves. Antigens carrying Langerhans cells are able to migrate and induce the cellular immune response in the lymph nodes. This approach to the priming of antiviral CD8+ cytotoxic T cells may provide cellular immune protection from flavivirus infection without inducing the humoral immune response, which can lead to the shock syndrome in Dengue fever patients. To be able to develop anti-Dengue virus synthetic peptides for populations with different HLA class I haplotypes, it is necessary to develop computational studies to design HLA class I Dengue virus synthetic peptides with motifs to fit the HLA haplotypes of the population living in an endemic region for Dengue fever. Experiments to study Dengue virus and Japanese encephalitis peptides vaccines and their effectiveness in protection against Dengue fever and Japanese encephalitis are needed. The development of human antiviral vaccines for application of viral

  15. Distribution and expression in vitro and in vivo of DNA vaccine against lymphocystis disease virus in Japanese flounder ( Paralichthys olivaceus)

    NASA Astrophysics Data System (ADS)

    Zheng, Fengrong; Sun, Xiuqin; Liu, Hongzhan; Wu, Xingan; Zhong, Nan; Wang, Bo; Zhou, Guodong

    2010-01-01

    Lymphocystis disease, caused by the lymphocystis disease virus (LCDV), is a significant worldwide problem in fish industry causing substantial economic losses. In this study, we aimed to develop the DNA vaccine against LCDV, using DNA vaccination technology. We evaluated plasmid pEGFP-N2-LCDV1.3 kb as a DNA vaccine candidate. The plasmid DNA was transiently expressed after liposome transfection into the eukaryotic COS 7 cell line. The distribution and expression of the DNA vaccine (pEGFP-N2-LCDV1.3kb) were also analyzed in tissues of the vaccinated Japanese flounder by PCR, RT-PCR and fluorescent microscopy. Results from PCR analysis indicated that the vaccine-containing plasmids were distributed in injected muscle, the muscle opposite the injection site, the hind intestine, gill, spleen, head, kidney and liver, 6 and 25 days after vaccination. The vaccine plasmids disappeared 100 d post-vaccination. Fluorescent microscopy revealed green fluorescence in the injected muscle, the muscle opposite the injection site, the hind intestine, gill, spleen, head, kidney and liver of fish 48 h post-vaccination, green fluorescence did not appear in the control treated tissue. Green fluorescence became weak at 60 days post-vaccination. RT-PCR analysis indicated that the mcp gene was expressed in all tested tissues of vaccinated fish 6-50 days post-vaccination. These results demonstrate that the antigen encoded by the DNA vaccine is distributed and expressed in all of the tissues analyzed in the vaccinated fish. The antigen would therefore potentially initiate a specific immune response. the plasmid DNA was injected into Japanese flounder ( Paralichthys olivaceus) intramuscularly and antibodies against LCDV were evaluated. The results indicate that the plasmid encoded DNA vaccine could induce an immune response to LCDV and would therefore offer immune protection against LCD. Further studies are required for the development and application of this promising DNA vaccine.

  16. Serological evidence of widespread West Nile virus and Japanese encephalitis virus infection in native domestic ducks (Anas platyrhynchos var domesticus) in Kuttanad region, Kerala, India.

    PubMed

    Kalaiyarasu, Semmannan; Mishra, Niranjan; Khetan, Rohit Kumar; Singh, Vijendra Pal

    2016-10-01

    Birds can act as reservoirs of West Nile virus (WNV) with a key role in its epidemiology. WNV lineage 1 associated fatal cases of human encephalitis in 2011 and acute flaccid paralysis in 2013 were reported in Alappuzha district, Kerala, India. But no information is available on WNV circulation in domestic ducks, which are abundant, cohabit with humans and occupy wetlands and water bodies in the region. To determine the extent of WNV infection, we investigated 209 sera, 250 oral and 350 cloacal swab samples from local Chara and Chemballi domestic ducks (Anas platyrhynchos var domesticus) in the districts of Alappuzha, Kottayam, Kollam and Pathanamthitta collected during January and March 2015. The serum samples were tested for WNV antibodies first by a competition ELISA and then by a micro virus neutralization test (micro-VNT), while oral and cloacal swabs were subjected to WNV real-time RT-PCR. Ninety five ducks showed evidence of flavivirus antibodies by ELISA. End point neutralizing antibody titre against WNV and Japanese encephalitis virus (JEV) revealed WNV specific antibodies in 24 (11.5%) ducks in 3 districts, JEV specific antibodies in 21 (10%) ducks in 2 districts and flavivirus specific antibodies in 19 (9%) ducks. However, no WNV genomic RNA could be detected. The results of this study demonstrate evidence of widespread WNV and JEV infection in domestic ducks in Kuttanad region, Kerala with a higher seroprevalence to WNV than JEV. Additionally, it highlights the utility of domestic ducks as a surveillance tool to detect WNV/JEV circulation in a region. PMID:27638121

  17. Serological evidence of widespread West Nile virus and Japanese encephalitis virus infection in native domestic ducks (Anas platyrhynchos var domesticus) in Kuttanad region, Kerala, India.

    PubMed

    Kalaiyarasu, Semmannan; Mishra, Niranjan; Khetan, Rohit Kumar; Singh, Vijendra Pal

    2016-10-01

    Birds can act as reservoirs of West Nile virus (WNV) with a key role in its epidemiology. WNV lineage 1 associated fatal cases of human encephalitis in 2011 and acute flaccid paralysis in 2013 were reported in Alappuzha district, Kerala, India. But no information is available on WNV circulation in domestic ducks, which are abundant, cohabit with humans and occupy wetlands and water bodies in the region. To determine the extent of WNV infection, we investigated 209 sera, 250 oral and 350 cloacal swab samples from local Chara and Chemballi domestic ducks (Anas platyrhynchos var domesticus) in the districts of Alappuzha, Kottayam, Kollam and Pathanamthitta collected during January and March 2015. The serum samples were tested for WNV antibodies first by a competition ELISA and then by a micro virus neutralization test (micro-VNT), while oral and cloacal swabs were subjected to WNV real-time RT-PCR. Ninety five ducks showed evidence of flavivirus antibodies by ELISA. End point neutralizing antibody titre against WNV and Japanese encephalitis virus (JEV) revealed WNV specific antibodies in 24 (11.5%) ducks in 3 districts, JEV specific antibodies in 21 (10%) ducks in 2 districts and flavivirus specific antibodies in 19 (9%) ducks. However, no WNV genomic RNA could be detected. The results of this study demonstrate evidence of widespread WNV and JEV infection in domestic ducks in Kuttanad region, Kerala with a higher seroprevalence to WNV than JEV. Additionally, it highlights the utility of domestic ducks as a surveillance tool to detect WNV/JEV circulation in a region.

  18. Tick-borne encephalitis.

    PubMed

    Gritsun, T S; Lashkevich, V A; Gould, E A

    2003-01-01

    Tick-borne encephalitis (TBE) is one of the most dangerous human infections occurring in Europe and many parts of Asia. The etiological agent Tick-borne encephalitis virus (TBEV), is a member of the virus genus Flavivirus, of the family Flaviviridae. TBEV is believed to cause at least 11,000 human cases of encephalitis in Russia and about 3000 cases in the rest of Europe annually. Related viruses within the same group, Louping ill virus (LIV), Langat virus (LGTV) and Powassan virus (POWV), also cause human encephalitis but rarely on an epidemic scale. Three other viruses within the same group, Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV) and Alkhurma virus (ALKV), are closely related to the TBEV complex viruses and tend to cause fatal hemorrhagic fevers rather than encephalitis. This review describes the clinical manifestations associated with TBEV infections, the main molecular-biological properties of these viruses, and the different factors that define the incidence and severity of disease. The role of ticks and their local hosts in the emergence of new virus variants with different pathogenic characteristics is also discussed. This review also contains a brief history of vaccination against TBE including trials with live attenuated vaccine and modern tendencies in developing of vaccine virus strains. PMID:12615309

  19. Tick-borne encephalitis.

    PubMed

    Gritsun, T S; Lashkevich, V A; Gould, E A

    2003-01-01

    Tick-borne encephalitis (TBE) is one of the most dangerous human infections occurring in Europe and many parts of Asia. The etiological agent Tick-borne encephalitis virus (TBEV), is a member of the virus genus Flavivirus, of the family Flaviviridae. TBEV is believed to cause at least 11,000 human cases of encephalitis in Russia and about 3000 cases in the rest of Europe annually. Related viruses within the same group, Louping ill virus (LIV), Langat virus (LGTV) and Powassan virus (POWV), also cause human encephalitis but rarely on an epidemic scale. Three other viruses within the same group, Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV) and Alkhurma virus (ALKV), are closely related to the TBEV complex viruses and tend to cause fatal hemorrhagic fevers rather than encephalitis. This review describes the clinical manifestations associated with TBEV infections, the main molecular-biological properties of these viruses, and the different factors that define the incidence and severity of disease. The role of ticks and their local hosts in the emergence of new virus variants with different pathogenic characteristics is also discussed. This review also contains a brief history of vaccination against TBE including trials with live attenuated vaccine and modern tendencies in developing of vaccine virus strains.

  20. One more shot for the road: a review and update of vaccinations for pediatric international travelers.

    PubMed

    Rebaza, Andre; Lee, Paul J

    2015-04-01

    Increasing numbers of children are traveling to developing countries where they are often at a higher risk than adults of acquiring vaccine-preventable diseases. Yet, they are less likely to receive pretravel medical advice and preventive care. This article reviews the current recommendations for pediatric travel immunizations, including specific travel vaccines such as typhoid, yellow fever, Japanese encephalitis virus, and rabies as well as prospective vaccines for significant global diseases like malaria, dengue, chikungunya, and Ebola. PMID:25875985

  1. Vaccine-preventable disease and immunization in the developing world.

    PubMed

    Bart, K J; Lin, K F

    1990-06-01

    Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world. Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid. In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world. New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine. Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates. PMID:2190145

  2. West Nile virus vaccine.

    PubMed

    Monath, T P; Arroyo, J; Miller, C; Guirakhoo, F

    2001-05-01

    Within the past 5 years, West Nile encephalitis has emerged as an important disease of humans and horses in Europe. In 1999, the disease appeared for the first time in the northeastern United States. West Nile virus (a mosquito-borne flavivirus) has flourished in the North American ecosystem and is expected to expand its geographic range. In this review, the rationale for a human and veterinary vaccine is presented and a novel approach for rapid development of a molecularly-defined, live, attenuated vaccine is described. The technology (ChimeriVax) is applicable to the development of vaccines against all flaviviruses, and products against Japanese encephalitis (a close relative of West Nile) and dengue are in or are nearing clinical trials, respectively. ChimeriVax vaccines utilize the safe and effective vaccine against the prototype flavivirus -yellow fever 17D- as a live vector. Infectious clone technology is used to replace the genes encoding the pre-membrane (prM) and envelope (E) protein of yellow fever 17D vaccine with the corresponding genes of the target virus (e.g., West Nile). The resulting chimeric virus contains the antigens responsible for protection against West Nile but retains the replication efficiency of yellow fever 17D. The ChimeriVax technology is well-suited to the rapid development of a West Nile vaccine, and clinical trials could begin as early as mid-2002. Other approaches to vaccine development are briefly reviewed. The aim of this brief review is to describe the features of West Nile encephalitis, a newly introduced infectious disease affecting humans, horses and wildlife in the United States; the rationale for rapid development of vaccines; and approaches to the development of vaccines against the disease.

  3. Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine.

    PubMed

    Liang, Huabin; Lee, Min; Jin, Xia

    2016-01-01

    Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

  4. Advances in flavivirus vaccine development.

    PubMed

    Coller, Beth-Ann G; Clements, David E; Martyak, Timothy; Yelmene, Michele; Thorne, Mike; Parks, D Elliot

    2010-12-01

    Flaviviruses comprise a diverse family of viruses that are cumulatively responsible for hundreds of millions of cases of infection annually. The Flavivirus genus includes both insect-vectored viruses, such as yellow fever and dengue, and non-vectored viruses such as HCV; the viruses have a broad range of disease presentation and geographic distribution. No specific antiviral therapies are currently available for the diseases caused by insect-vectored flaviviruses. Thus, efforts have been focused on the prevention of disease, through either vaccination or vector control, rather than on the treatment of infected individuals. While vector control can occasionally be successful in controlling the spread of flavivirus outbreaks, vaccines appear to be a more cost-effective, sustainable, and environmentally friendly approach. A review of vaccines for the medically important flaviviruses presents the full spectrum of vaccine options and complexity levels, and provides examples of successes and major challenges. The insect-borne flavivirus vaccine field is dynamic, with new and improved vaccines being advanced to replace existing vaccines, and novel vaccine approaches being developed for those targets that currently lack an approved vaccine. Advances in scientific knowledge and in the application of new technologies are helping to overcome some of the key challenges that have stymied the field for decades. New, safe and effective vaccines to protect against yellow fever, Japanese encephalitis, tick-borne encephalitis, West Nile and dengue viruses will likely result. PMID:21154147

  5. Facile fabrication of magnetic gold electrode for magnetic beads-based electrochemical immunoassay: application to the diagnosis of Japanese encephalitis virus.

    PubMed

    Li, Fang; Mei, Li; Li, Yaoming; Zhao, Kaihong; Chen, Huanchun; Wu, Peng; Hu, Yonggang; Cao, Shengbo

    2011-06-15

    A novel magnetic beads-based electrochemical immunoassay strategy has been developed for the detection of Japanese encephalitis virus (JEV). The magnetic gold electrode was fabricated to manipulate magnetic beads for the direct sensing applications. Gold-coated magnetic beads were employed as the platforms for the immobilization and immunoreaction process, and horseradish peroxidase was chosen as an enzymatic tracer. The proteins (e.g., antibodies or immunocomplexes) attached on the surface of magnetic beads were found to induce a significant decline in their electric conductivity. Multiwalled carbon nanotubes were introduced to improve sensitivity of the assay. The envelope (E) protein, a major immunogenic protein of JEV, was utilized to optimize the assay parameters. Under the optimal conditions, the linear response range of E protein was 0.84 to 11,200 ng/mL with a detection limit of 0.56 ng/mL. When applied for detection of JEV, the proposed method generated a linear response range between 2×10(3) and 5×10(5) PFU/mL. The detection limit for JEV was 2.0×10(3) PFU/mL, which was 2 orders of magnitude lower than that of immunochromatographic strip and similar to that obtained from RT-PCR. This method was also successfully applied to detect JEV in clinical specimens.

  6. A scan statistic for binary outcome based on hypergeometric probability model, with an application to detecting spatial clusters of Japanese encephalitis.

    PubMed

    Zhao, Xing; Zhou, Xiao-Hua; Feng, Zijian; Guo, Pengfei; He, Hongyan; Zhang, Tao; Duan, Lei; Li, Xiaosong

    2013-01-01

    As a useful tool for geographical cluster detection of events, the spatial scan statistic is widely applied in many fields and plays an increasingly important role. The classic version of the spatial scan statistic for the binary outcome is developed by Kulldorff, based on the Bernoulli or the Poisson probability model. In this paper, we apply the Hypergeometric probability model to construct the likelihood function under the null hypothesis. Compared with existing methods, the likelihood function under the null hypothesis is an alternative and indirect method to identify the potential cluster, and the test statistic is the extreme value of the likelihood function. Similar with Kulldorff's methods, we adopt Monte Carlo test for the test of significance. Both methods are applied for detecting spatial clusters of Japanese encephalitis in Sichuan province, China, in 2009, and the detected clusters are identical. Through a simulation to independent benchmark data, it is indicated that the test statistic based on the Hypergeometric model outweighs Kulldorff's statistics for clusters of high population density or large size; otherwise Kulldorff's statistics are superior.

  7. The blood-brain barrier in the cerebrum is the initial site for the Japanese encephalitis virus entering the central nervous system.

    PubMed

    Liu, Tsan-Hsiun; Liang, Li-Ching; Wang, Chien-Chih; Liu, Huei-Chung; Chen, Wei-June

    2008-11-01

    Japanese encephalitis (JE) virus is a member of the encephalitic flaviviruses and frequently causes neurological sequelae in a proportion of patients who survive the acute phase of the infection. In the present study, we molecularly identified viral infection in the brain of mice with rigidity of hindlimbs and/or abnormal gait, in which JE virus particles appeared within membrane-bound vacuoles of neurons throughout the central nervous system. Deformation of tight junctions (TJs) shown as dissociation of endothelial cells in capillaries, implying that the integrity of the blood-brain barrier (BBB) has been compromised by JE virus infection. BBB permeability evidently increased in the cerebrum, but not in the cerebellum, of JE virus-infected mice intravenously injected with the tracer of Evans blue dye. This suggests that the permeability of the BBB differentially changed in response to viral infection, leading to the entry of JE virions and/or putatively infected leukocytes from the periphery to the cerebrum as the initial site of infection in the central nervous system (CNS). Theoretically, the virus spread to the cerebellum soon after the cerebrum became infected.

  8. Short-term effects of floods on Japanese encephalitis in Nanchong, China, 2007-2012: A time-stratified case-crossover study.

    PubMed

    Zhang, Feifei; Liu, Zhidong; Zhang, Caixia; Jiang, Baofa

    2016-09-01

    This time-stratified case-crossover study aimed to quantify the impact of floods on daily Japanese encephalitis (JE) cases from 2007 to 2012 in Nanchong city of Sichuan Province, China. Using conditional logistic regression analysis, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) at different lagged days, adjusting for daily average temperature (AT) and daily average relative humidity (ARH). A total of 370 JE cases were notified during the study period, with the median patient age being 4.2years. The seasonal pattern of JE cases clustered in July and August during the study period. Floods were significantly associated with an increased number of JE cases from lag 23 to lag 24, with the strongest lag effect at lag 23 (OR=2.00, 95% CI: 1.14-3.52). Similarly, AT and ARH were positively associated with daily JE cases from lag 0 to lag 8 and from lag 0 to lag 9, respectively. Floods, with AT and ARH, can be used to forecast JE outbreaks in the study area. Based on the results of this study, recommendations include undertaking control measures before the number of cases increases, especially for regions with similar geographic, climatic, and socio-economic conditions as those in the study area. PMID:27241207

  9. Gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of Japanese encephalitis virus

    NASA Astrophysics Data System (ADS)

    Huang, Su-Hua; Yang, Tsuey-Ching; Tsai, Ming-Hong; Tsai, I.-Shou; Lu, Huang-Chih; Chuang, Pei-Hsin; Wan, Lei; Lin, Ying-Ju; Lai, Chih-Ho; Lin, Cheng-Wen

    2008-10-01

    Virus isolation and antibody detection are routinely used for diagnosis of Japanese encephalitis virus (JEV) infection, but the low level of transient viremia in some JE patients makes JEV isolation from clinical and surveillance samples very difficult. We describe the use of gold nanoparticle-based RT-PCR and real-time quantitative RT-PCR assays for detection of JEV from its RNA genome. We tested the effect of gold nanoparticles on four different PCR systems, including conventional PCR, reverse-transcription PCR (RT-PCR), and SYBR green real-time PCR and RT-PCR assays for diagnosis in the acute phase of JEV infection. Gold nanoparticles increased the amplification yield of the PCR product and shortened the PCR time compared to the conventional reaction. In addition, nanogold-based real-time RT-PCR showed a linear relationship between Ct and template amount using ten-fold dilutions of JEV. The nanogold-based RT-PCR and real-time quantitative RT-PCR assays were able to detect low levels (1-10 000 copies) of the JEV RNA genomes extracted from culture medium or whole blood, providing early diagnostic tools for the detection of low-level viremia in the acute-phase infection. The assays described here were simple, sensitive, and rapid approaches for detection and quantitation of JEV in tissue cultured samples as well as clinical samples.

  10. Spatial and Temporal Variation of Japanese encephalitis Disease and Detection of Disease Hotspots: a Case Study of Gorakhpur District, Uttar Pradesh, India

    NASA Astrophysics Data System (ADS)

    Verma, S.; Gupta, R. D.

    2014-11-01

    In recent times, Japanese Encephalitis (JE) has emerged as a serious public health problem. In India, JE outbreaks were recently reported in Uttar Pradesh, Gorakhpur. The present study presents an approach to use GIS for analyzing the reported cases of JE in the Gorakhpur district based on spatial analysis to bring out the spatial and temporal dynamics of the JE epidemic. The study investigates spatiotemporal pattern of the occurrence of disease and detection of the JE hotspot. Spatial patterns of the JE disease can provide an understanding of geographical changes. Geospatial distribution of the JE disease outbreak is being investigated since 2005 in this study. The JE incidence data for the years 2005 to 2010 is used. The data is then geo-coded at block level. Spatial analysis is used to evaluate autocorrelation in JE distribution and to test the cases that are clustered or dispersed in space. The Inverse Distance Weighting interpolation technique is used to predict the pattern of JE incidence distribution prevalent across the study area. Moran's I Index (Moran's I) statistics is used to evaluate autocorrelation in spatial distribution. The Getis-Ord Gi*(d) is used to identify the disease areas. The results represent spatial disease patterns from 2005 to 2010, depicting spatially clustered patterns with significant differences between the blocks. It is observed that the blocks on the built up areas reported higher incidences.

  11. Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells

    PubMed Central

    Kumari, Bharti; Jain, Pratistha; Das, Shaoli; Ghosal, Suman; Hazra, Bibhabasu; Trivedi, Ashish Chandra; Basu, Anirban; Chakrabarti, Jayprokas; Vrati, Sudhanshu; Banerjee, Arup

    2016-01-01

    Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation. PMID:26838068

  12. Hospital-based diagnosis of hemorrhagic fever, encephalitis, and hepatitis in Cambodian children.

    PubMed

    Chhour, Y Meng; Ruble, Gaye; Hong, Rathavuth; Minn, Kyi; Kdan, Yuvatha; Sok, Touch; Nisalak, Ananda; Myint, Khin Saw Aye; Vaughn, David W; Endy, Timothy P

    2002-05-01

    Surveillance was conducted for three clinical syndromes (hemorrhagic fever, encephalitis, and hepatitis) in Cambodian children admitted to the National Pediatric Hospital in Phnom Penh from July 1996 through September 1998. Acute- and convalescent-phase sera, and cerebrospinal fluid, when applicable, underwent diagnostic evaluation for infections with Dengue virus (DENV), Japanese encephalitis virus (JEV), and Hepatitis A, B, C, and E viruses. Of 621 children admitted with hemorrhagic fever, 499 (80%) were confirmed to have either primary or secondary DENV infection. DENV rates were as high as 10.6/100 hospital admissions in September 1998. Of 50 children with clinical encephalitis, 9 (18%) had serologic evidence of JEV infection. Forty-four children had clinical hepatitis, most (55%) due to Hepatitis A virus (HAV). One patient had Hepatitis B virus, and no patients had hepatitis C or E. This study identified a large number of children with vaccine-preventable diseases (JEV and HAV).

  13. Product review on the JE vaccine IXIARO.

    PubMed

    Firbas, Christa; Jilma, Bernd

    2015-01-01

    Japanese encephalitis virus, as the most important vaccine-preventable cause of viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases yearly. In endemic areas, most Japanese encephalitis infections occur in children younger than 10 y and clinical manifestation of this disease is critical, because there is no effective treatment available. As JEV infections are regarded as one of the most serious viral causes of encephalitis and mass immunization programmes are generally recommended for residents in endemic areas, a safe and effective JEV vaccine was needed to protect them as well as others at risk. Due to the safety concerns with the mouse brain derived vaccine, second generation vaccines against JE produced in cell culture like Vero cells were developed. IXIARO® is a purified, inactivated aluminum-adjuvanted JE vaccine, based on the SA14-14-2 virus strain, and is available in North America, Europe, Canada, Switzerland, Singapore, Hong Kong and Israel as well as in Australia & New Zealand (as JESPECT®).The safety, tolerability and immunogenicity profile of IXIARO® is well established through a number of clinical studies comparing IXIARO® with placebo as well as mouse brain derived vaccine. Recent data show that the global incidence of JE remains substantial, especially young children in endemic areas are most susceptible. As vaccination is the most feasible, reliable and cost effective tool for JE control, IXIARO® with confirmed excellent safety profile is highly recommendable, in particular for vaccination of children at risk. The European Commission as well as the FDA approved the extension of indication of IXIARO® to the pediatric segment (2 months of age and older) based on these data.

  14. Product review on the JE vaccine IXIARO

    PubMed Central

    Firbas, Christa; Jilma, Bernd

    2015-01-01

    Japanese encephalitis virus, as the most important vaccine-preventable cause of viral encephalitis in Asia, is estimated to cause over 68,000 clinical cases yearly. In endemic areas, most Japanese encephalitis infections occur in children younger than 10 y and clinical manifestation of this disease is critical, because there is no effective treatment available. As JEV infections are regarded as one of the most serious viral causes of encephalitis and mass immunization programmes are generally recommended for residents in endemic areas, a safe and effective JEV vaccine was needed to protect them as well as others at risk. Due to the safety concerns with the mouse brain derived vaccine, second generation vaccines against JE produced in cell culture like Vero cells were developed. IXIARO® is a purified, inactivated aluminum-adjuvanted JE vaccine, based on the SA14–14–2 virus strain, and is available in North America, Europe, Canada, Switzerland, Singapore, Hong Kong and Israel as well as in Australia & New Zealand (as JESPECT®).The safety, tolerability and immunogenicity profile of IXIARO® is well established through a number of clinical studies comparing IXIARO® with placebo as well as mouse brain derived vaccine. Recent data show that the global incidence of JE remains substantial, especially young children in endemic areas are most susceptible. As vaccination is the most feasible, reliable and cost effective tool for JE control, IXIARO® with confirmed excellent safety profile is highly recommendable, in particular for vaccination of children at risk. The European Commission as well as the FDA approved the extension of indication of IXIARO® to the pediatric segment (2 months of age and older) based on these data. PMID:25621812

  15. Evaluation of European tick-borne encephalitis virus vaccine against recent Siberian and far-eastern subtype strains.

    PubMed

    Hayasaka, D; Goto, A; Yoshii, K; Mizutani, T; Kariwa, H; Takashima, I

    2001-09-14

    To evaluate the efficacy of the European TBE vaccine in east-Siberian and far-eastern regions of Russia, we examined the immune responses of the vaccine against recent TBE virus Siberian (Irkutsk) and far-eastern (Khabarovsk and Vladivostok) isolates. The sera of vaccinated humans showed efficient neutralizing antibody titers (> or =20) against Siberian and far-eastern strains. To evaluate the efficacy of the vaccine in vivo, mice were vaccinated and challenged with lethal doses of the viruses. All vaccinated mice survived each virus challenge. These results suggest that the European vaccine can prevent the TBE virus infection in east-Siberian and far-eastern regions of Russia.

  16. Eugenol, α-pinene and β-caryophyllene from Plectranthus barbatus essential oil as eco-friendly larvicides against malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Hoti, S L; Bhattacharyya, Atanu; Benelli, Giovanni

    2016-02-01

    Mosquito-borne diseases represent a deadly threat for millions of people worldwide. Eco-friendly mosquitocides are a priority. In Ayurvedic medicine, Plectranthus species have been used to treat heart disease, convulsions, spasmodic pain and painful urination. In this research, we evaluated the acute toxicity of essential oil from Plectranthus barbatus and its major constituents, against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. The chemical composition of P. barbatus essential oil was analyzed by gas chromatography-mass spectroscopy. Nineteen components were identified. Major constituents were eugenol (31.12%), α-pinene (19.38%) and β-caryophyllene (18.42%). Acute toxicity against early third-instar larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus was investigated. The essential oil had a significant toxic effect against larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus, with 50% lethal concentration (LC50) values of 84.20, 87.25 and 94.34 μg/ml and 90% lethal concentration (LC90) values of 165.25, 170.56 and 179.58 μg/ml, respectively. Concerning major constituents, eugenol, α-pinene and β-caryophyllene appeared to be most effective against An. subpictus (LC50 = 25.45, 32.09 and 41.66 μg/ml, respectively), followed by Ae. albopictus (LC50 = 28.14, 34.09 and 44.77 μg/ml, respectively) and Cx. tritaeniorhynchus (LC50 = 30.80, 36.75 and 48.17 μg/ml, respectively). Overall, the chance to use metabolites from P. barbatus essential oil against mosquito vectors seems promising, since they are effective at low doses and could be an advantageous alternative to build newer and safer mosquito control tools. PMID:26518773

  17. Integrative effect of defective interfering RNA accumulation and helper virus attenuation is responsible for the persistent infection of Japanese encephalitis virus in BHK-21 cells.

    PubMed

    Park, Soo Young; Choi, Eunmi; Jeong, Yong Seok

    2013-11-01

    Persistence of RNA viruses is often, but not always, associated with the production of defective interfering (DI) particles. To investigate possible roles of DI particles and helper viruses in RNA virus persistence, persistent infection with Japanese encephalitis virus (JEV) was established in baby hamster kidney (BHK-21) cells. At the 6th and 7th serial undiluted passages of JEV on BHK-21 cells, viral persistence was established spontaneously with DI RNA generation. Seven cell clones exhibiting persistent infection were obtained from the initial BHK-21 cell batches exhibiting JEV persistence, and maintained for over 400 days. Most cell clones produced infectious particles (10(1) -10(5)  PFU/ml) continuously, expressed viral proteins, and resisted homologous superinfection. Two helper viruses, chvBS6-3 and chvBS7-1, were isolated from two of the seven cell clones, and characterized to investigate their roles in JEV persistence. While chvBS6-3 was restored to its full cytopathicity in the absence of DI RNA, chvBS7-1 exhibited almost no cytopathicity, regardless of DI RNA co-replication. Attenuation of chvBS7-1 did not appear to be due to inadequate adsorption or genome replication, but due to inefficient egress of the assembled progeny virions, suggesting altered helper virus emergence during JEV persistence in BHK-21 cells. These observations suggest that at least two mechanisms are involved in JEV persistence; a DI RNA-dependent mechanism, where DI RNA co-replication nullifies the helper virus's cytopathicity, or a DI RNA-independent mechanism, where the helper virus is self-attenuated. This study provides a useful in vitro tool for understanding the mechanisms underlying RNA virus persistent infections.

  18. Construction of an infectious molecular clone of Japanese encephalitis virus genotype V and its derivative subgenomic replicon capable of expressing a foreign gene.

    PubMed

    Ishikawa, Tomohiro; Abe, Makoto; Masuda, Michiaki

    2015-01-01

    Japanese encephalitis virus (JEV) genotype V was originally isolated in Malaysia in 1952 and has long been restricted to the area. In 2009, sudden emergence of the genotype V in China and Korea was reported, suggesting expansion of its geographical distribution. Although studies on the genotype V are becoming more important, they have been limited partly due to lack of its infectious molecular clone. In this study, a plasmid carrying cDNA corresponding to the entire genome of JEV Muar strain, which belongs to genotype V, in the downstream of T7 promoter was constructed. Electroporation of viral RNA transcribed by T7 RNA polymerase (T7RNAP) in vitro from the plasmid led to production of progeny viruses both in mammalian and mosquito cells. Also, transfection of the infectious clone plasmid into mammalian cells expressing T7RNAP transiently or stably was demonstrated to generate infectious progenies. When the viral structural protein genes were partially deleted from the full-length cDNA, the subgenomic RNA transcribed in vitro from the modified plasmid was shown to replicate itself in mammalian cells as a replicon. The replicon carrying the firefly luciferase gene in place of the deleted structural protein genes was also shown to efficiently replicate itself and express luciferase in mammalian cells. Compared with the replicon derived from JEV genotype III (Nakayama strain), the genotype V-derived replicon appeared to be more tolerant to introduction of a foreign gene. The infectious clone and the replicons constructed in this study may serve as useful tools for characterizing JEV genotype V.

  19. Eugenol, α-pinene and β-caryophyllene from Plectranthus barbatus essential oil as eco-friendly larvicides against malaria, dengue and Japanese encephalitis mosquito vectors.

    PubMed

    Govindarajan, Marimuthu; Rajeswary, Mohan; Hoti, S L; Bhattacharyya, Atanu; Benelli, Giovanni

    2016-02-01

    Mosquito-borne diseases represent a deadly threat for millions of people worldwide. Eco-friendly mosquitocides are a priority. In Ayurvedic medicine, Plectranthus species have been used to treat heart disease, convulsions, spasmodic pain and painful urination. In this research, we evaluated the acute toxicity of essential oil from Plectranthus barbatus and its major constituents, against larvae of the malaria vector Anopheles subpictus, the dengue vector Aedes albopictus and the Japanese encephalitis vector Culex tritaeniorhynchus. The chemical composition of P. barbatus essential oil was analyzed by gas chromatography-mass spectroscopy. Nineteen components were identified. Major constituents were eugenol (31.12%), α-pinene (19.38%) and β-caryophyllene (18.42%). Acute toxicity against early third-instar larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus was investigated. The essential oil had a significant toxic effect against larvae of An. subpictus, Ae. albopictus and Cx. tritaeniorhynchus, with 50% lethal concentration (LC50) values of 84.20, 87.25 and 94.34 μg/ml and 90% lethal concentration (LC90) values of 165.25, 170.56 and 179.58 μg/ml, respectively. Concerning major constituents, eugenol, α-pinene and β-caryophyllene appeared to be most effective against An. subpictus (LC50 = 25.45, 32.09 and 41.66 μg/ml, respectively), followed by Ae. albopictus (LC50 = 28.14, 34.09 and 44.77 μg/ml, respectively) and Cx. tritaeniorhynchus (LC50 = 30.80, 36.75 and 48.17 μg/ml, respectively). Overall, the chance to use metabolites from P. barbatus essential oil against mosquito vectors seems promising, since they are effective at low doses and could be an advantageous alternative to build newer and safer mosquito control tools.

  20. Nanoformulation of poly(ethylene glycol) polymerized organic insect repellent by PIT emulsification method and its application for Japanese encephalitis vector control.

    PubMed

    Balaji, A P B; Mishra, Prabhakar; Suresh Kumar, R S; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-04-01

    The utilization of increased dosage of insect repellents to overcome mosquito resistance has raised environmental concerns globally. In accord to this, we have formulated an efficacious, water-dispersive, nanometric formulation of a poor water-soluble insect repellent, diethylphenylacetamide (DEPA) by poly(ethylene glycol) (PEG) polymerization followed by PIT emulsification method. The critical micelle concentration of PEG in the spontaneously emulsified conventional DEPA droplets was determined, based on the droplets physical stability. Subjecting them to PIT emulsification yielded monodispersed polymeric nanomicelles of DEPA (Nano DEPA) with hydrodynamic mean diameter of 153.74 nm. The high-resolution scanning and transmission electron microscopic studies revealed the characteristic core-shell structure of micelle. The comparative efficacy of Bulk DEPA and Nano DEPA was evaluated by larvicidal and WHO cone bioassay against the Japanese encephalitis vector Culex tritaeniorhynchus. The median lethal concentrations (48 h) for 3rd instars C. tritaeniorhynchus larvae were found to be 0.416 mg/L for Bulk DEPA and 0.052 mg/L for Nano DEPA, respectively. The median knockdown concentrations (60 min) for the two to three-day-old, sucrose-fed, female adult mosquitoes were 5.372% (v/v) and 3.471% (v/v) for Bulk and Nano DEPA, respectively. Further investigation by histopathological and biochemical studies propound that Nano DEPA exerted better bioefficacy as comparative to its bulk form even at minimal exposure concentrations. Hence, Nano DEPA will serve as an effective alternate in controlling the vector expansion with reduced dosage. PMID:25766922

  1. Antiviral potential of 4-hydroxypanduratin A, secondary metabolite of Fingerroot, Boesenbergia pandurata (Schult.), towards Japanese Encephalitis virus NS2B/NS3 protease.

    PubMed

    Seniya, Chandrabhan; Mishra, Harshal; Yadav, Ajay; Sagar, Nitin; Chaturvedi, Babita; Uchadia, Kuldeep; Wadhwa, Gulshan

    2013-01-01

    4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme's activity to meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK. The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper. Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski's rule of 5 using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds (Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of 51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV infections using NS2B Site 2 as a Drug target.

  2. The C Terminus of the Core β-Ladder Domain in Japanese Encephalitis Virus Nonstructural Protein 1 Is Flexible for Accommodation of Heterologous Epitope Fusion

    PubMed Central

    Yen, Li-Chen; Liao, Jia-Teh; Lee, Hwei-Jen; Chou, Wei-Yuan; Chen, Chun-Wei; Lin, Yi-Ling

    2015-01-01

    ABSTRACT NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication. This mapped flexible region is located in the conserved tip of the core β-ladder domain of the multimeric NS1 structure and is also known to contain certain linear epitopes, readily triggering specific antibody responses from the host. Despite becoming attenuated, recombinant JEV with insertion of a neutralizing epitope derived from enterovirus 71 (EV71) into the C-terminal end of NS1 not only could be normally released from infected cells, but also induced dual protective immunity for the host to counteract lethal challenge with either JEV or EV71 in neonatal mice. These results indicated that the secreted multimeric NS1 of flaviviruses may serve as a natural protein carrier to render epitopes of interest more immunogenic in the C terminus of the core β-ladder domain. IMPORTANCE The positive-sense RNA genomes of mosquito-borne flaviviruses appear to be flexible in terms of accommodating extra insertions of short heterologous antigens into their virus genes. Here, we illustrate that the newly identified C terminus of the core β-ladder domain in NS1 could be readily inserted into entities such as EV71 epitopes, and the resulting NS1-epitope fusion proteins appeared to maintain normal virus replication, secretion ability, and multimeric formation from infected cells. Nonetheless, such an insertion attenuated the recombinant JEV in mice

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

    PubMed

    Ishikawa, Tomohiro; Yamanaka, Atsushi; Konishi, Eiji

    2014-03-10

    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.

  4. Recent advances in flavivirus antiviral drug discovery and vaccine development.

    PubMed

    Ray, Debashish; Shi, Pei-Yong

    2006-01-01

    Many flaviviruses, including yellow fever virus, dengue virus, Japanese encephalitis virus, tick-borne encephalitis virus, and West Nile virus, are globally important human pathogens. Despite an emergence and resurgence of flavivirus-mediated disease, specific therapies are not yet available; however, significant progress has been made toward the prevention and treatment of flavivirus infections. In this article we review recent advances made in the areas of (i) flavivirus vaccine development, and (ii) antiflavivirus drug discovery reported in literature and patents, and highlight strategies used in these investigations. PMID:18221133

  5. Who's failure? encephalitis kills!

    PubMed

    Potharaju, Nagabhushana Rao

    2014-01-01

    Encephalitis continues to be one of the most dreaded diagnoses because a high rate of morbidity and mortality are accepted even before starting the treatment. Most encephalitis cases occur in rural areas due to poor environmental sanitation, high-vector density, shortage of protected water supplies and lack of health education. Vaccination, environmental sanitation, vector control, health education and attention to prompt diagnosis and treatment in rural hospitals are the four essential pillars for reducing case fatality rate (CFR) of encephalitis. Frequently, virulence of the virus, immunological state of the host, unavailability of antiviral drugs and lack of enough tertiary care hospitals (TCH) are not responsible for the high CFR. Basic supportive care is not being practiced meticulously in Primary and Secondary Care Hospitals (PSCH), and their services are not being utilized fully. Main causes of high mortality and morbidity rates are hypoxia and ischemia of brain and other organs precipitated by preventable, controllable or treatable complications due to lack of basic medical and nursing care during transport to the TCH. Undiagnosed Rickettsial infections are suspected to be partly responsible for the high CFR in some areas. Improving rural hospitals and their ambulance services are the most economical way to reduce CFR. "Treatment facilities must be made available at places where cases occur." The best way to reduce CFR of encephalitis in developing and underdeveloped countries is to increase and improve PSCH and sensitize politicians, administrators, medical/nursing professionals and more importantly to impress and convince the public to utilize them. PMID:25116819

  6. Current status and future prospects of yellow fever vaccines.

    PubMed

    Beck, Andrew S; Barrett, Alan D T

    2015-01-01

    Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.

  7. A DNA Vaccine for Venezuelan Equine Encephalitis Virus Delivered by Intramuscular Electroporation Elicits High Levels of Neutralizing Antibodies in Multiple Animal Models and Provides Protective Immunity to Mice and Nonhuman Primates ▿

    PubMed Central

    Dupuy, Lesley C.; Richards, Michelle J.; Ellefsen, Barry; Chau, Lillian; Luxembourg, Alain; Hannaman, Drew; Livingston, Brian D.; Schmaljohn, Connie S.

    2011-01-01

    We evaluated the immunogenicity and protective efficacy of a DNA vaccine expressing codon-optimized envelope glycoprotein genes of Venezuelan equine encephalitis virus (VEEV) when delivered by intramuscular electroporation. Mice vaccinated with the DNA vaccine developed robust VEEV-neutralizing antibody responses that were comparable to those observed after administration of the live-attenuated VEEV vaccine TC-83 and were completely protected from a lethal aerosol VEEV challenge. The DNA vaccine also elicited strong neutralizing antibody responses in rabbits that persisted at high levels for at least 6 months and could be boosted by a single additional electroporation administration of the DNA performed approximately 6 months after the initial vaccinations. Cynomolgus macaques that received the vaccine by intramuscular electroporation developed substantial neutralizing antibody responses and after an aerosol challenge had no detectable serum viremia and had reduced febrile reactions, lymphopenia, and clinical signs of disease compared to those of negative-control macaques. Taken together, our results demonstrate that this DNA vaccine provides a potent means of protecting against VEEV infections and represents an attractive candidate for further development. PMID:21450977

  8. [Which vaccinations for which travel-destination?].

    PubMed

    De Crom, Susan; Veit, Olivia; Hatz, Christoph

    2016-01-01

    Several vaccinations are recommended to protect international travellers, especially to tropical countries, from diseases in other parts of the world. Firstly, the routine schedule of childhood vaccinations and booster shots according to the Swiss immunisation programme should be checked, updated or even completed. Additional vaccinations against hepatitis A and B, typhoid fever, poliomyelitis, rabies or Japanese encephalitis may be recommended. This will depend on a number of factors including the exact destination and route (developing countries, rural areas), planned activities (backpacker, family visit, business trip), duration of travel, season, age of the traveller and current health status including the current medication and previous vaccinations. Some vaccinations, such as yellow fever, may be required for travellers to certain countries and the international certificate of vaccination may even be required when entering a country from another country where yellow fever is endemic. The international certificate of vaccination (or a letter of exemption when appropriate) is considered valid only if it is administered by an approved vaccination centre. Furthermore, the meningococcal vaccination (A, C, W, Y) is required for pilgrims to Saudi Arabia. It is recommended to start the vaccinations four to six weeks before departure to ensure enough time to administer all the necessary doses for an adequate immune response. All commonly used vaccines can be administered on the same day. The basic health insurance does not usually cover travel vaccines. PMID:27268450

  9. [Which vaccinations for which travel-destination?].

    PubMed

    De Crom, Susan; Veit, Olivia; Hatz, Christoph

    2016-01-01

    Several vaccinations are recommended to protect international travellers, especially to tropical countries, from diseases in other parts of the world. Firstly, the routine schedule of childhood vaccinations and booster shots according to the Swiss immunisation programme should be checked, updated or even completed. Additional vaccinations against hepatitis A and B, typhoid fever, poliomyelitis, rabies or Japanese encephalitis may be recommended. This will depend on a number of factors including the exact destination and route (developing countries, rural areas), planned activities (backpacker, family visit, business trip), duration of travel, season, age of the traveller and current health status including the current medication and previous vaccinations. Some vaccinations, such as yellow fever, may be required for travellers to certain countries and the international certificate of vaccination may even be required when entering a country from another country where yellow fever is endemic. The international certificate of vaccination (or a letter of exemption when appropriate) is considered valid only if it is administered by an approved vaccination centre. Furthermore, the meningococcal vaccination (A, C, W, Y) is required for pilgrims to Saudi Arabia. It is recommended to start the vaccinations four to six weeks before departure to ensure enough time to administer all the necessary doses for an adequate immune response. All commonly used vaccines can be administered on the same day. The basic health insurance does not usually cover travel vaccines.

  10. A model international partnership for community-based research on vaccine-preventable diseases: the Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU).

    PubMed

    Gibbons, Robert V; Nisalak, Ananda; Yoon, In-Kyu; Tannitisupawong, Darunee; Rungsimunpaiboon, Kamchai; Vaughn, David W; Endy, Timothy P; Innis, Bruce L; Burke, Donald S; Mammen, Mammen P; Scott, Robert McNair; Thomas, Stephen J; Hoke, Charles H

    2013-09-23

    This paper describes an international collaboration to carry out studies that contributed to the understanding of pathogenesis, diagnosis, treatment, and prevention of several diseases of public health importance for Thailand and the United States. In Kamphaeng Phet Province, Thailand, febrile syndromes, including encephalitis, hepatitis, hemorrhagic fever, and influenza-like illnesses, occurred commonly and were clinically diagnosed, but the etiology was rarely confirmed. Since 1982, the Kamphaeng Phet Provincial Hospital, the Thai Ministry of Public Health, and the US Army Component of the Armed Forces Research Institute of Medical Sciences, along with vaccine manufacturers and universities, have collaborated on studies that evaluated and capitalized on improved diagnostic capabilities for infections caused by Japanese encephalitis, hepatitis A, dengue, and influenza viruses. The collaboration clarified clinical and epidemiological features of these infections and, in large clinical trials, demonstrated that vaccines against Japanese encephalitis and hepatitis A viruses were over 90% efficacious, supporting licensure of both vaccines. With the introduction of Japanese encephalitis vaccines in Thailand's Expanded Program on Immunization, reported encephalitis rates dropped substantially. Similarly, in the US, particularly in the military populations, rates of hepatitis A disease have dropped with the use of hepatitis A vaccine. Studies of the pathogenesis of dengue infections have increased understanding of the role of cellular immunity in responding to these infections, and epidemiological studies have prepared the province for studies of dengue vaccines. Approximately 80 publications resulted from this collaboration. Studies conducted in Kamphaeng Phet provided experience that contributed to clinical trials of hepatitis E and HIV vaccines, conducted elsewhere. To provide a base for continuing studies, The Kamphaeng Phet-AFRIMS Virology Research Unit (KAVRU) was

  11. Vaccinations for Neuroinfectious Disease: A Global Health Priority.

    PubMed

    Leibovitch, Emily C; Jacobson, Steven

    2016-07-01

    Vaccines for neuroinfectious diseases are becoming an ever-increasing global health priority, as neurologic manifestations and sequelae from existing and emerging central nervous system infections account for significant worldwide morbidity and mortality. The prevention of neurotropic infections can be achieved through globally coordinated vaccination campaigns, which have successfully eradicated nonzoonotic agents such as the variola viruses and, hopefully soon, poliovirus. This review discusses vaccines that are currently available or under development for zoonotic flaviviruses and alphaviruses, including Japanese and tick-borne encephalitis, yellow fever, West Nile, dengue, Zika, encephalitic equine viruses, and chikungunya. Also discussed are nonzoonotic agents, including measles and human herpesviruses, as well as select bacterial, fungal, and protozoal pathogens. While therapeutic vaccines will be required to treat a multitude of ongoing infections of the nervous system, the ideal vaccination strategy is pre-exposure vaccination, with the ultimate goals of minimizing disease associated with zoonotic viruses and the total eradication of nonzoonotic agents. PMID:27365085

  12. Immunogenicity against Far Eastern and Siberian subtypes of tick-borne encephalitis (TBE) virus elicited by the currently available vaccines based on the European subtype: systematic review and meta-analysis.

    PubMed

    Domnich, Alexander; Panatto, Donatella; Arbuzova, Eva Klementievna; Signori, Alessio; Avio, Ulderico; Gasparini, Roberto; Amicizia, Daniela

    2014-01-01

    Tick-borne encephalitis (TBE) virus, which is usually divided into European, Far Eastern and Siberian subtypes, is a serious public health problem in several European and Asian countries. Vaccination is the most effective measure to prevent TBE; cross-subtype protection elicited by the TBE vaccines is biologically plausible since all TBE virus subtypes are closely related. This manuscript systematically explores available data on the cross-subtype immunogenicity elicited by the currently available Western vaccines based on the European subtype. Completed immunization course of 3 doses of both Western vaccines determined very high seroconversion/seropositivity rates against both Far Eastern and Siberian subtypes among previously flavivirus-naïve subjects. All but one study found no statistically significant difference in titers of neutralizing antibodies against strains belonging to homologous and heterologous subtypes. Pooled analysis of randomized controlled trials on head-to-head comparison of immunogenicity of Western and Russian TBE vaccines did not reveal differences in seroconversion rates against Far Eastern isolates in either hemagglutination inhibition (risk ratio = 0.98, p = 0.83) or enzyme-linked immunosorbent (risk ratio = 0.95, p = 0.44) assays after 2 vaccine doses. This suggests that, in regions where a heterogeneous TBE virus population circulates, vaccines based on the European subtype may be used alongside vaccines based on the Far Eastern subtype. Studies on the field effectiveness of TBE vaccines and investigation of vaccination failures, especially in countries where different subtypes co-circulate, will further elucidate TBE vaccination-induced cross-subtype protection.

  13. [Autoimmune encephalitis].

    PubMed

    Günther, Albrecht; Schubert, Julia; Brämer, Dirk; Witte, Otto Wilhelm

    2016-08-01

    Autoimmune encephalitis, an inflammatory disease of the brain, is usually attributed to antibody-mediated damage and dysfunction of neuronal structures. A distinction is made between onconeuronal antibodies (directed against intracellular neuronal antigens with resulting paraneoplastic neurological syndromes) and antibodies directed against neuronal cell surface proteins (with resulting synaptic encephalopathies). Anti-NMDA-Receptor-Encephalitis, the most common form of autoimmune encephalopathy, is characterized by a phased course of disease. Early disease phase involves nonspecific prodromes (fatigue, fever, headache) which lead to family doctor or emergency department consultation. Subsequently, neuropsychiatric behavioural problems, seizures, disturbance of memory and finally coma, dysautonomia and respiratory insufficiency often result in major complications (e.g. status epilepticus) necessitating intensive care treatment. The diagnosis is secured by detection of auto-antibodies in serum or cerebrospinal fluid. An intensive search for tumors is also recommended. The treatment of autoimmune encephalitis comprises of immunomodulatory and immunosuppessive strategies. Tumor therapy is the most important treatment of autoimmune encephalitis by onconeuronal antibodies. PMID:27557073

  14. Recent progress in West Nile virus diagnosis and vaccination.

    PubMed

    De Filette, Marina; Ulbert, Sebastian; Diamond, Mike; Sanders, Niek N

    2012-01-01

    West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections.

  15. CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes.

    PubMed

    Kim, Jin Hyoung; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebileg; Hossain, Ferdaus Mohd Altaf; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2-ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2- and CCL2-ablated mice was unlikely to be mediated by innate natural killer and adaptive T-cell responses. Furthermore, CCL2 produced by haematopoietic stem cell-derived leucocytes played a dominant role in CNS accumulation of Ly-6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE.

  16. [Protection against pertussis by Japanese T type acellular pertussis vaccine: household contact study in Kawasaki City].

    PubMed

    Kato, T; Matsuyoshi, S; Goshima, T; Nakajima, N; Yamamoto, H; Arimoto, Y; Kaku, H; Hayashi, F

    1989-09-01

    To evaluate the vaccine efficacy of acellular pertussis vaccine which has been in clinical use in Japan since 1981, a retrospective study was made by a questionnaire from secondary pertussis attack through family contact in 149 children with pertussis diagnosed in the period from January 1981 through May 1988. In this study, Takeda's acellular vaccine which contains a high level of FHA, low level of PT and a small amount of agglutinogen, was evaluated. Secondary pertussis attacks through family contact were found in 17 of 29 siblings (58.6%) not immunized with pertussis vaccine. On the other hand of the siblings immunized with Takeda's acellular vaccine 27 were exposed to pertussis through family contact and a secondary attack was seen in only one of them (3.4%). The present study revealed an efficacy rate of 94.2% for the Takeda's acellular pertussis vaccine. PMID:2509597

  17. Overview of currently available Japanese acellular pertussis vaccines and future problems.

    PubMed

    Kamiya, H; Nii, R

    1988-01-01

    Acellular pertussis diphtheria, tetanus vaccine (APDT) was licensed in 1981 in Japan. This vaccine contains pertussis toxin (PT), filamentous hemagglutinin (FHA) and agglutinogen (AGG) as the main protective antigens. The new APDT vaccine produced by each company differs slightly in composition. There are two representative types of vaccine. One vaccine (B type) contains PT and FHA in a ratio of 1 to 1 and the other one (T type) contains PT and FHA in a ratio of 4 to 1 or 9 to 1 and also contains different amounts of AGG. We have been comparing the effectiveness of these two types of vaccine. The adverse reactions of APDT were local reactions such as redness and swelling, with a few febrile cases. No central nervous system adverse reactions were observed. The antibody protective level of this vaccine is also being investigated. After we changed from conventional vaccine to APDT, the frequency of serious adverse reactions was reduced and the number of pertussis infections also gradually decreased. This vaccine should be used for the children world-wide. PMID:3273618

  18. Tick-borne encephalitis: What travelers should know when visiting an endemic country

    PubMed Central

    Chrdle, Aleš; Chmelík, Václav; Růžek, Daniel

    2016-01-01

    ABSTRACT Tick-borne encephalitis (TBE) is an acute febrile illness with neurological manifestations that is prevalent in forested areas of moderate climate in Europe and Asia. TBE virus is transmitted by ticks and rarely by unpasteurized milk and dairy products. The disease burden is attributed mainly to resulting long-term disability, especially in individuals over 50 y of age. Currently, there is no causative treatment, but a very effective vaccination is available with a good safety profile. The vaccination requires 3 basic doses to be fully effective and regular boosters afterwards. An accelerated vaccination schedule enables a patient to reach reasonably protective titres within 3 to 4 weeks from the first injection. The risk of travel-related TBE is estimated to be less than the risk of acquiring typhoid fever while visiting highly endemic regions in South Asia, but more than the risk of acquiring Japanese encephalitis, meningococcal invasive disease, or rabies. The pre-travel risk assessment of acquiring TBE should consider known risk factors which include 1) the country and regions to be visited; 2) April to November season; 3) altitude less than 1500 m above the sea level; 4) duration of stay; 5) the extent of tick-exposure associated activities including leisure and professional outdoor activities within the endemic area; and 6) age and comorbidities of the traveler. A major challenge, however, is the very low awareness of the risk of contracting TBE in those who travel to industrialized European countries. PMID:27715427

  19. Paradoxical role of antibodies in dengue virus infections: considerations for prophylactic vaccine development.

    PubMed

    Acosta, Eliana G; Bartenschlager, Ralf

    2016-01-01

    Highly effective prophylactic vaccines for flaviviruses including yellow fever virus, tick-borne encephalitis virus and Japanese encephalitis virus are currently in use. However, the development of a dengue virus (DENV) vaccine has been hampered by the requirement of simultaneous protection against four distinct serotypes and the threat that DENV-specific antibodies might either mediate neutralization or, on the contrary, exacerbate disease through the phenomenon of antibody-dependent enhancement (ADE) of infection. Therefore, understanding the cellular, biochemical and molecular basis of antibody-mediated neutralization and ADE are fundamental for the development of a safe DENV vaccine. Here we summarize current structural and mechanistic knowledge underlying these phenomena. We also review recent results demonstrating that the humoral immune response triggered during natural DENV infection is able to generate neutralizing antibodies binding complex quaternary epitopes only present on the surface of intact virions. PMID:26577689

  20. Towards the Conservation of Endangered Avian Species: A Recombinant West Nile Virus Vaccine Results in Increased Humoral and Cellular Immune Responses in Japanese Quail (Coturnix japonica)

    PubMed Central

    Young, Joanne A.; Jefferies, Wilfred

    2013-01-01

    West Nile Virus (WNV) arrived in North America in 1999 and is now endemic. Many families of birds, especially corvids, are highly susceptible to WNV and infection often results in fatality. Avian species susceptible to WNV infection also include endangered species, such as the Greater Sage-Grouse (Centrocercus uropbasianuts) and the Eastern Loggerhead Shrike (Lanius ludovicianus migrans). The virus has been shown to contribute towards the likelihood of their extinction. Although a clear and present threat, there exists no avian WNV vaccine available to combat this lethal menace. As a first step in establishing an avian model for testing candidate WNV vaccines, avian antibody based reagents were assessed for cross-reactivity with Japanese quail (Coturnix japonica) T cell markers CD4 and CD8; the most reactive were found to be the anti-duck CD8 antibody, clone Du-CD8-1, and the anti-chicken/turkey CD4 antibody, clone CT4. These reagents were then used to assess vaccine performance as well as to establish T cell populations in quail, with a novel population of CD4/CD8 double positive T cells being identified in Japanese quail. Concurrently, non-replicating recombinant adenoviruses, expressing either the WNV envelope or NS3 ‘genes’ were constructed and assessed for effectiveness as avian vaccines. Japanese Quail were selected for testing the vaccines, as they provide an avian model that parallels the population diversity of bird species in the wild. Both the level of WNV specific antibodies and the number of T cells in vaccinated birds were increased compared to unvaccinated controls. The results indicate the vaccines to be effective in increasing both humoral and cellular immune responses. These recombinant vaccines therefore may find utility as tools to protect and maintain domestic and wild avian populations. Their implementation may also arrest the progression towards extinction of endangered avian species and reduce the viral reservoir that potentiates

  1. Towards the conservation of endangered avian species: a recombinant West Nile Virus vaccine results in increased humoral and cellular immune responses in Japanese Quail (Coturnix japonica).

    PubMed

    Young, Jay A; Young, Joanne A; Jefferies, Wilfred

    2013-01-01

    West Nile Virus (WNV) arrived in North America in 1999 and is now endemic. Many families of birds, especially corvids, are highly susceptible to WNV and infection often results in fatality. Avian species susceptible to WNV infection also include endangered species, such as the Greater Sage-Grouse (Centrocercus uropbasianuts) and the Eastern Loggerhead Shrike (Lanius ludovicianus migrans). The virus has been shown to contribute towards the likelihood of their extinction. Although a clear and present threat, there exists no avian WNV vaccine available to combat this lethal menace. As a first step in establishing an avian model for testing candidate WNV vaccines, avian antibody based reagents were assessed for cross-reactivity with Japanese quail (Coturnix japonica) T cell markers CD4 and CD8; the most reactive were found to be the anti-duck CD8 antibody, clone Du-CD8-1, and the anti-chicken/turkey CD4 antibody, clone CT4. These reagents were then used to assess vaccine performance as well as to establish T cell populations in quail, with a novel population of CD4/CD8 double positive T cells being identified in Japanese quail. Concurrently, non-replicating recombinant adenoviruses, expressing either the WNV envelope or NS3 'genes' were constructed and assessed for effectiveness as avian vaccines. Japanese Quail were selected for testing the vaccines, as they provide an avian model that parallels the population diversity of bird species in the wild. Both the level of WNV specific antibodies and the number of T cells in vaccinated birds were increased compared to unvaccinated controls. The results indicate the vaccines to be effective in increasing both humoral and cellular immune responses. These recombinant vaccines therefore may find utility as tools to protect and maintain domestic and wild avian populations. Their implementation may also arrest the progression towards extinction of endangered avian species and reduce the viral reservoir that potentiates infection

  2. [West Nile fever/encephalitis].

    PubMed

    Takasaki, Tomohiko

    2007-12-01

    West Nile virus (WNV), a member of the family Flaviviridae (genus Flavivirus), is a mosquito-borne virus first isolated in 1937 in the West Nile district of Uganda. The disease in humans is characterized by a dengue-like illness with fever, and a more severe form is characterized by central nervous system involvement, including encephalitis, meningitis, and myelitis. WN encephalitis was first reported in the Western Hemisphere in the summer of 1999, there was an outbreak in New York City. Epidemic WNV strains in North America are severely pathogenic, however, attenuated WNV strains were found in Texas and Mexico in 2003. The principal vectors of WNV transmission in North America are Culex. pipiens, Cx. Quinquefasciatus, Cx. restuans, Cx salinarius and Cx talsalis. The number of WN fever case has exceeded 27,000 since 1999 in the United States and 4,600 since 2002 in Canada. The first imported case of West Nile fever in Japan was confirmed in September, 2005. The patient had returned to Japan from the United States and developed symptoms the next day. There is currently no WN vaccine for use in humans. An inactivated WNV vaccine for use in horses has been available since 2001. A DNA vaccine, a chimeric live attenuated vaccine, and a recombinant vaccine have also been licensed for use in horses.

  3. 78 FR 52535 - Disease, Disability, and Injury Prevention and Control Special Emphasis Panel (SEP): Initial Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... Japanese Encephalitis Vaccination in Cambodia, Funding Opportunity Announcement (FOA) CK14-001, initial... evaluation of applications received in response to ``Impact of Japanese Encephalitis Vaccination in...

  4. Formalin-inactivated whole virus and recombinant subunit flavivirus vaccines.

    PubMed

    Eckels, Kenneth H; Putnak, Robert

    2003-01-01

    The Flaviviridae is a family of arthropod-borne, enveloped, RNA viruses that contain important human pathogens such as yellow fever (YF), Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), and the dengue (DEN) viruses. Vaccination is the most effective means of disease prevention for these viral infections. A live-attenuated vaccine for YF, and inactivated vaccines for JE and TBE have significantly reduced the incidence of disease for these viruses, while licensed vaccines for DEN and WN are still lacking despite a significant disease burden associated with these infections. This review focuses on inactivated and recombinant subunit vaccines (non-replicating protein vaccines) in various stages of laboratory development and human testing. A purified, inactivated vaccine (PIV) candidate for DEN will soon be evaluated in a phase 1 clinical trial, and a second-generation JE PIV produced using similar technology has advanced to phase 2/3 trials. The inactivated TBE vaccine used successfully in Europe for almost 30 years continues to be improved by additional purification, new stabilizers, an adjuvant, and better immunization schedules. The recent development of an inactivated WN vaccine for domestic animals demonstrates the possibility of producing a similar vaccine for human use. Advances in flavivirus gene expression technology have led to the production of several recombinant subunit antigen vaccine candidates in a variety of expression systems. Some of these vaccines have shown sufficient promise in animal models to be considered as candidates for evaluation in clinical trials. Feasibility of non-replicating flavivirus vaccines has been clearly demonstrated and further development is now warranted. PMID:14714438

  5. Role of vaccine manufacturers in developing countries towards global healthcare by providing quality vaccines at affordable prices.

    PubMed

    Jadhav, S; Gautam, M; Gairola, S

    2014-05-01

    Vaccines represent one of the greatest achievements of science and medicine in the fight against infectious diseases. Vaccination is one of the most cost-effective public health tools to prevent infectious diseases. Significant progress has been made in expanding the coverage of vaccines globally, resulting in the prevention of more than two million deaths annually. In 2010, nearly 200 countries endorsed a shared vision to extend the benefits of vaccines to every person by 2020, known as the Decade of Vaccine Initiative (DoV). Vaccine manufacturers in developing countries, as represented by the Developing Countries Vaccine Manufacturers Network (DCVMN), make a significant contribution to DoV by supplying quality vaccines at affordable prices to the people who need them most. About 70% of the global Expanded Program on Immunization (EPI) vaccine supplies are met by DCVMN. Besides EPI vaccine supplies, DCVMN is also targeting vaccines against rotavirus, Japanese encephalitis, pneumonia, human papillomavirus, meningitis and neglected tropical diseases. This article reviews the roles and contributions of DCVMN in making the vaccines accessible and affordable to all. PMID:24476201

  6. Role of vaccine manufacturers in developing countries towards global healthcare by providing quality vaccines at affordable prices.

    PubMed

    Jadhav, S; Gautam, M; Gairola, S

    2014-05-01

    Vaccines represent one of the greatest achievements of science and medicine in the fight against infectious diseases. Vaccination is one of the most cost-effective public health tools to prevent infectious diseases. Significant progress has been made in expanding the coverage of vaccines globally, resulting in the prevention of more than two million deaths annually. In 2010, nearly 200 countries endorsed a shared vision to extend the benefits of vaccines to every person by 2020, known as the Decade of Vaccine Initiative (DoV). Vaccine manufacturers in developing countries, as represented by the Developing Countries Vaccine Manufacturers Network (DCVMN), make a significant contribution to DoV by supplying quality vaccines at affordable prices to the people who need them most. About 70% of the global Expanded Program on Immunization (EPI) vaccine supplies are met by DCVMN. Besides EPI vaccine supplies, DCVMN is also targeting vaccines against rotavirus, Japanese encephalitis, pneumonia, human papillomavirus, meningitis and neglected tropical diseases. This article reviews the roles and contributions of DCVMN in making the vaccines accessible and affordable to all.

  7. Amebic encephalitis

    PubMed Central

    Mayer, Peter L.; Larkin, Julie A.; Hennessy, Jill M.

    2011-01-01

    Background: Amebic encephalitis (granulomatous amebic encephalitis, GAE) an extremely rare disease occurring in immunocompromised patients. Presentation and early imaging findings are nonspecific. In GAE, enhancement may or may not be seen on imaging studies despite the presence of an aggressive, necrotizing, parasitic infection. Case Description: The patient was a 79-year-old man with ill-defined autoimmune hepatitis. He was on mild immunosuppression with 6-MP and low-dose prednisone. He presented with an acute febrile illness and obtundation. Imaging revealed a nonenhancing mass lesion of the frontal lobe. The patient briefly improved on high-dose steroids, then deteriorated again, with repeat imaging showing enlargement of the edematous brain lesion and herniation. The patient underwent craniotomy for evacuation of a necrotic brain lesion. His condition did not improve. Frozen section revealed only necrosis. Permanent pathology revealed GAE caused by Acanthamoeba. Conclusion: Neurosurgeons should remain aware of this rare disease. Imaging is variable and may not show enhancement or necrosis despite large areas of parasitic infection. PMID:21697972

  8. Dismantling the Taboo against Vaccines in Pregnancy.

    PubMed

    de Martino, Maurizio

    2016-01-01

    Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

  9. Dismantling the Taboo against Vaccines in Pregnancy

    PubMed Central

    de Martino, Maurizio

    2016-01-01

    Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy. PMID:27338346

  10. Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

    PubMed

    Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc

    2015-06-19

    On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

  11. Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

    PubMed

    Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc

    2015-06-19

    On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses. PMID:26086636

  12. Influence of single nucleotide polymorphisms of cytokine genes on anti-HBs antibody production after hepatitis B vaccination in a Japanese young adult population.

    PubMed

    Yukimasa, Nobuyasu; Sato, Shoichi; Oboshi, Wataru; Watanabe, Toru; Uzawa, Ryuichi

    2016-01-01

    Hepatitis B (HB) vaccination is one of the most efficient tools to prevent the transmission of the virus. Considerable variability exists in HB vaccine responses, with 5-10% of healthy Japanese adults demonstrating no response following a standard vaccination. Recently, polymorphisms of immune-regulatory genes, such as cytokine genes, have been reported to influence the immune response to HB vaccine. The aim of this study was to investigate the underlying mechanisms of the genetic association between several cytokine gene polymorphisms and the immune response to HB vaccination in a Japanese population. One hundred and twenty three vaccinated young adults were classified according to the level of antibody-titer (anti-HBs). Single nucleotide polymorphism typing for IFN-γ (+874, 3'-UTR), IL-10 (-591, -819, -1082), and TNF-α (-308, -857), was accomplished using the PCR-RFLP or SSP-PCR method. The TNF-α (-857) CC type and the IL-10 (-1082) AG type were present more frequently in the low titer group than in the high titer group. The TNF-α (-857) CC type was found to be significantly associated with low response of serum anti-HBs. The anti-HBs antibody was not readily produced in the IL-10 (-1082) AG and TNF-α (-857) CC haplotype. Conversely, the antibody was readily produced in the IL-10 (-1082) AA and TNF-α (-857) CC haplotype, and the IL-10 (-1082) AA and TNF-α (-857) CT haplotype, suggesting a high likelihood of the IL-10 (-1082) AG type to be included in the low anti-HBs group, and high anti-HBs antibody production in those with the TNF-α (-857) CT type. These SNPs may produce ethnically-specific differences in the immune response to HB vaccine in the Japanese population. J. Med. Invest. 63: 256-261, August, 2016. PMID:27644568

  13. Developing Countries Vaccine Manufacturers Network: doing good by making high-quality vaccines affordable for all.

    PubMed

    Pagliusi, Sonia; Leite, Luciana C C; Datla, Mahima; Makhoana, Morena; Gao, Yongzhong; Suhardono, Mahendra; Jadhav, Suresh; Harshavardhan, Gutla V J A; Homma, Akira

    2013-04-18

    The Developing Countries Vaccine Manufacturers Network (DCVMN) is a unique model of a public and private international alliance. It assembles governmental and private organizations to work toward a common goal of manufacturing and supplying high-quality vaccines at affordable prices to protect people around the world from known and emerging infectious diseases. Together, this group of manufacturers has decades of experience in manufacturing vaccines, with technologies, know-how, and capacity to produce more than 40 vaccines types. These manufacturers have already contributed more than 30 vaccines in various presentations that have been prequalified by the World Health Organization for use by global immunization programmes. Furthermore, more than 45 vaccines are in the pipeline. Recent areas of focus include vaccines to protect against rotavirus, human papillomavirus (HPV), Japanese encephalitis, meningitis, hepatitis E, poliovirus, influenza, and pertussis, as well as combined pentavalent vaccines for children. The network has a growing number of manufacturers that produce a growing number of products to supply the growing demand for vaccines in developing countries.

  14. Applications of pox virus vectors to vaccination: an update.

    PubMed

    Paoletti, E

    1996-10-15

    Recombinant pox viruses have been generated for vaccination against heterologous pathogens. Amongst these, the following are notable examples. (i) The engineering of the Copenhagen strain of vaccinia virus to express the rabies virus glycoprotein. When applied in baits, this recombinant has been shown to vaccinate the red fox in Europe and raccoons in the United States, stemming the spread of rabies virus infection in the wild. (ii) A fowlpox-based recombinant expressing the Newcastle disease virus fusion and hemagglutinin glycoproteins has been shown to protect commercial broiler chickens for their lifetime when the vaccine was administered at 1 day of age, even in the presence of maternal immunity against either the Newcastle disease virus or the pox vector. (iii) Recombinants of canarypox virus, which is restricted for replication to avian species, have provided protection against rabies virus challenge in cats and dogs, against canine distemper virus, feline leukemia virus, and equine influenza virus disease. In humans, canarypox virus-based recombinants expressing antigens from rabies virus, Japanese encephalitis virus, and HIV have been shown to be safe and immunogenic. (iv) A highly attenuated vaccinia derivative, NYVAC, has been engineered to express antigens from both animal and human pathogens. Safety and immunogenicity of NYVAC-based recombinants expressing the rabies virus glycoprotein, a polyprotein from Japanese encephalitis virus, and seven antigens from Plasmodium falciparum have been demonstrated to be safe and immunogenic in early human vaccine studies. PMID:8876138

  15. Protracted mumps encephalitis with good outcome.

    PubMed

    Kim, Peter; Cappelen-Smith, Cecilia

    2005-11-01

    There is limited published information regarding the outcome of patients with prolonged encephalitis. This report details the case of a patient with an encephalitic illness with a protracted period of coma and a favourable outcome. Extensive investigation revealed seroconversion for mumps infection. A household contact had measles, mumps, rubella (MMR) vaccination 10 days prior to his presentation. PMID:16257214

  16. Protracted mumps encephalitis with good outcome.

    PubMed

    Kim, Peter; Cappelen-Smith, Cecilia

    2005-11-01

    There is limited published information regarding the outcome of patients with prolonged encephalitis. This report details the case of a patient with an encephalitic illness with a protracted period of coma and a favourable outcome. Extensive investigation revealed seroconversion for mumps infection. A household contact had measles, mumps, rubella (MMR) vaccination 10 days prior to his presentation.

  17. The present situation of prophylactic vaccination in Japan for travel abroad.

    PubMed

    Nakano, Takashi

    2008-11-01

    The current situation of vaccination in Japan is reviewed from a viewpoint of overseas travelers. Vaccinations before travel to developing countries, where the risk of infection is high, are recommended for two reasons: "individual protection" and "prevention of communicable disease importation". However, there are problems in Japan; some vaccines available commonly in foreign nations are not approved in Japan and the vaccination schedule is not convenient for travelers. Vaccination is sometimes needed also for travel to Europe and North America. This is because certain vaccinations are required for entering school or studying abroad. In Japan, there is no regulation which recommends vaccination as an entrance requirement. Compared with other nations, Japanese children receive fewer vaccines routinely. On the other hand, there are different features from other industrialized nations, such as routine childhood BCG vaccination and immunization against Japanese encephalitis in Japan. Compared with foreign nations, awareness as regards "travel medicine" is lower in Japan. Recognizing this situation will lead to improvement of vaccination of travelers. PMID:18984478

  18. The present situation of prophylactic vaccination in Japan for travel abroad.

    PubMed

    Nakano, Takashi

    2008-11-01

    The current situation of vaccination in Japan is reviewed from a viewpoint of overseas travelers. Vaccinations before travel to developing countries, where the risk of infection is high, are recommended for two reasons: "individual protection" and "prevention of communicable disease importation". However, there are problems in Japan; some vaccines available commonly in foreign nations are not approved in Japan and the vaccination schedule is not convenient for travelers. Vaccination is sometimes needed also for travel to Europe and North America. This is because certain vaccinations are required for entering school or studying abroad. In Japan, there is no regulation which recommends vaccination as an entrance requirement. Compared with other nations, Japanese children receive fewer vaccines routinely. On the other hand, there are different features from other industrialized nations, such as routine childhood BCG vaccination and immunization against Japanese encephalitis in Japan. Compared with foreign nations, awareness as regards "travel medicine" is lower in Japan. Recognizing this situation will lead to improvement of vaccination of travelers.

  19. Analysis of the temperature sensitivity of Japanese rubella vaccine strain TO-336.vac and its effect on immunogenicity in the guinea pig.

    PubMed

    Okamoto, Kiyoko; Ami, Yasushi; Suzaki, Yuriko; Otsuki, Noriyuki; Sakata, Masafumi; Takeda, Makoto; Mori, Yoshio

    2016-04-01

    The marker of Japanese domestic rubella vaccines is their lack of immunogenicity in guinea pigs. This has long been thought to be related to the temperature sensitivity of the viruses, but supporting evidence has not been described. In this study, we generated infectious clones of TO-336.vac, a Japanese domestic vaccine, TO-336.GMK5, the parental virus of TO-336.vac, and their mutants, and determined the molecular bases of their temperature sensitivity and immunogenicity in guinea pigs. The results revealed that Ser(1159) in the non-structural protein-coding region was responsible for the temperature sensitivity of TO-336.vac dominantly, while the structural protein-coding region affected the temperature sensitivity subordinately. The findings further suggested that the temperature sensitivity of TO-336.vac affected the antibody induction in guinea pigs after subcutaneous inoculation.

  20. Entacapone, a catechol-O-methyltransferase inhibitor, improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson's disease induced by Japanese encephalitis virus.

    PubMed

    Hamaue, Naoya; Ogata, Akihiko; Terado, Mutsuko; Tsuchida, Shirou; Yabe, Ichiro; Sasaki, Hidenao; Hirafuji, Masahiko; Togashi, Hiroko; Aoki, Takashi

    2010-01-14

    Levodopa is the main medication used for the treatment of Parkinson's disease. However, dyskinesia and wearing-off appear after the administration of high-dose levodopa for a long period. To combat the dyskinesia and wearing-off, levodopa is used together with a dopamine (DA) receptor agonist, and the amount of levodopa is decreased. We have reported the monoamine oxidase (MAO)-B inhibitor selegiline to be effective for treating motor dysfunction in Parkinson's disease model rats. We analyzed the improvement in motor functions and catecholamine contents in various brain regions induced by a combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone and a levodopa/dopadecarboxylase inhibitor (DDCI) in Japanese encephalitis virus (JEV) induced Parkinson's disease model rats. Entacapone (10 mg/kg) was administered via a single oral administration with levodopa/DDCI (10 mg/kg). The motor functions of the JEV model rats were significantly worsened, compared with those of the healthy control rats. The motor functions in the Parkinson's disease model rats were significantly recovered to the same levels as the healthy control rats by the combined administration of entacapone and levodopa/DDCI. A significant improvement in motor function was not demonstrated in the case of the administration of levodopa/DDCI alone. The striatal DA concentrations in the model rat brains were significantly increased by using levodopa/DDCI together with entacapone. Motor function was recovered by raising the striatum DA density in the model rats. Thus, COMT inhibitors are useful for decreasing the amount of levodopa administered to Parkinson's disease patients.

  1. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  2. [Pathogenesis of acute encephalitis and acute encephalopathy].

    PubMed

    Shiomi, Masashi

    2011-03-01

    Many aspects of the pathogenesis of acute encephalitis and acute encephalopathy have been clarified in this decade, although many unknown mechanisms remain to be elucidated. According to progress of MRI and neuroimmunological analysis and the observation of clinical findings, many new syndromes were found, which enhanced our understanding of acute encephalitis and acute encephalopathy. The pathogenesis of encephalitis is divided into infection and immune mediated mechanisms. The antibodies to neuronal surface antigens(NSA) such as NMDA receptors, leucin-rich glioma inactivated 1 (LGI1) and aquaporin 4 were demonstrated in specific encephalitis, limbic encephalitis and neuromyelitis optica. Anti-NSA antibody encephalitis should be treated by immunotherapy such as corticosteroid and plasmapheresis. Acute encephalitis with refractory repetitive partial seizures (AERRPS) is a devastating postinfectious disease in children and adults, although the pathogenesis of AERRPS is poorly understood. Influenza associated encephalopathy(IAE) is characterized by it's high incidence in Japanese children between 1 year and 5 years of age, its onset in the first or the second day of illness and its high mortality (15-30%) and morbidity (25-40%). We proposed the classification of IAE with poor prognosis from the neuroradiological findings. Four types of encephalopathy seem to be differentiated from each other, acute necrotizing encephalopathy (ANE) type, hemorrhagic shock and encephalopathy syndrome (HSES) type, acute brain swelling (ABS) type, febrile convulsive status epilepticus (FCSE) type. The notable radiological features are thalamic lesions in ANE, diffuse cerebral cortical cytotoxic edema in HSES, reversible cerebral swelling in ABS which sometimes reaches lethal brain herniation, and in FCSE type, dendritic high signal in subcortical white matter by DWI ("bright tree appearance") appears simultaneously with the later onset of repetitive focal seizure. These four types are

  3. Safety and immunogenicity of an AS01-adjuvanted varicella zoster virus subunit candidate vaccine (HZ/su): a phase-I, open-label study in Japanese adults.

    PubMed

    Lal, Himal; Zahaf, Toufik; Heineman, Thomas C

    2013-07-01

    An adjuvanted recombinant subunit candidate vaccine (HZ/su) containing varicella zoster virus envelope glycoprotein E was developed for the prevention of herpes zoster and its complications. This study evaluated safety and reactogenicity of HZ/su in an ethnic Japanese population. This was a phase I, open-label and single-center study conducted between March and November of 2010 in Australia. Twenty healthy ethnic Japanese subjects, aged 18-30 y and 50-69 y (1:1) were enrolled. Subjects were administered two doses of HZ/su vaccine according to a 0, 2-mo schedule. Local and general solicited symptoms were recorded for 7 d post-vaccination. Unsolicited symptoms were recorded for 30 d post-vaccination. Serious adverse events (SAEs), new onset of autoimmune disease (NOAD), other potential immune mediated disorders and HZ cases were recorded throughout the study period. All 20 subjects were included in the according-to-protocol cohort for safety. A total of 18 subjects were included in the according-to-protocol cohort for immunogenicity: 10 in the 18-30 y age group and 8 in the 50-69 y age group. The most commonly reported local and general solicited symptoms were pain and fatigue in both groups. Back pain (in the 18-30 y age group) and chills (in the 50-69 y age group) were the most frequently reported unsolicited symptoms. There were no reports of death, SAEs, NOADs, other autoimmune mediated inflammatory disorder or suspected HZ cases. This study indicated that the two-dose regimen of HZ/su exhibited a clinically acceptable safety profile in healthy young and older ethnic Japanese adults.

  4. Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

    PubMed Central

    Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

    2011-01-01

    This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

  5. Estimation of nationwide vaccination coverage and comparison of interview and telephone survey methodology for estimating vaccination status.

    PubMed

    Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong; Park, Sue K

    2011-06-01

    This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

  6. Establishment of an Algorithm Using prM/E- and NS1-Specific IgM Antibody-Capture Enzyme-Linked Immunosorbent Assays in Diagnosis of Japanese Encephalitis Virus and West Nile Virus Infections in Humans

    PubMed Central

    Galula, Jedhan U.; Chang, Gwong-Jen J.

    2015-01-01

    The front-line assay for the presumptive serodiagnosis of acute Japanese encephalitis virus (JEV) and West Nile virus (WNV) infections is the premembrane/envelope (prM/E)-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Due to antibody cross-reactivity, MAC-ELISA-positive samples may be confirmed with a time-consuming plaque reduction neutralization test (PRNT). In the present study, we applied a previously developed anti-nonstructural protein 1 (NS1)-specific MAC-ELISA (NS1-MAC-ELISA) on archived acute-phase serum specimens from patients with confirmed JEV and WNV infections and compared the results with prM/E containing virus-like particle-specific MAC-ELISA (VLP-MAC-ELISA). Paired-receiver operating characteristic (ROC) curve analyses revealed no statistical differences in the overall assay performances of the VLP- and NS1-MAC-ELISAs. The two methods had high sensitivities of 100% but slightly lower specificities that ranged between 80% and 100%. When the NS1-MAC-ELISA was used to confirm positive results in the VLP-MAC-ELISA, the specificity of serodiagnosis, especially for JEV infection, was increased to 90% when applied in areas where JEV cocirculates with WNV, or to 100% when applied in areas that were endemic for JEV. The results also showed that using multiple antigens could resolve the cross-reactivity in the assays. Significantly higher positive-to-negative (P/N) values were consistently obtained with the homologous antigens than those with the heterologous antigens. JEV or WNV was reliably identified as the currently infecting flavivirus by a higher ratio of JEV-to-WNV P/N values or vice versa. In summary of the above-described results, the diagnostic algorithm combining the use of multiantigen VLP- and NS1-MAC-ELISAs was developed and can be practically applied to obtain a more specific and reliable result for the serodiagnosis of JEV and WNV infections without the need for PRNT. The developed algorithm should provide great

  7. Profiling of Viral Proteins Expressed from the Genomic RNA of Japanese Encephalitis Virus Using a Panel of 15 Region-Specific Polyclonal Rabbit Antisera: Implications for Viral Gene Expression

    PubMed Central

    Yun, Sang-Im; Yun, Gil-Nam; Byun, Sung-June; Lee, Young-Min

    2015-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is closely related to West Nile (WN), yellow fever (YF), and dengue (DEN) viruses. Its plus-strand genomic RNA carries a single open reading frame encoding a polyprotein that is cleaved into three structural (C, prM/M, and E) and at least seven nonstructural (NS1/NS1', NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins, based on previous work with WNV, YFV, and DENV. Here, we aimed to profile experimentally all the viral proteins found in JEV-infected cells. We generated a collection of 15 JEV-specific polyclonal antisera covering all parts of the viral protein-coding regions, by immunizing rabbits with 14 bacterially expressed glutathione-S-transferase fusion proteins (for all nine viral proteins except NS2B) or with a chemically synthesized oligopeptide (for NS2B). In total lysates of JEV-infected BHK-21 cells, immunoblotting with these antisera revealed: (i) three mature structural proteins (~12-kDa C, ~8-kDa M, and ~53-kDa E), a precursor of M (~24-kDa prM) and three other M-related proteins (~10-14 kDa); (ii) the predicted ~45-kDa NS1 and its frameshift product, ~58-kDa NS1', with no evidence of the predicted ~25-kDa NS2A; (iii) the predicted but hardly detectable ~14-kDa NS2B and an unexpected but predominant ~12-kDa NS2B-related protein; (iv) the predicted ~69-kDa NS3 plus two major cleavage products (~34-kDa NS3N-term and ~35-kDa NS3C-term), together with at least nine minor proteins of ~16-52 kDa; (v) the predicted ~14-kDa NS4A; (vi) two NS4B-related proteins (~27-kDa NS4B and ~25-kDa NS4B'); and (vii) the predicted ~103-kDa NS5 plus at least three other NS5-related proteins (~15 kDa, ~27 kDa, and ~90 kDa). Combining these data with confocal microscopic imaging of the proteins’ intracellular localization, our study is the first to provide a solid foundation for the study of JEV gene expression, which is crucial for elucidating the regulatory mechanisms of JEV genome replication and pathobiology

  8. Efficacy of quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine (GARDASIL) in Japanese women aged 18-26 years.

    PubMed

    Yoshikawa, Hiroyuki; Ebihara, Keiko; Tanaka, Yoshiyuki; Noda, Kiichiro

    2013-04-01

    A randomized double-blind placebo-controlled phase II trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types most frequently associated with cervical cancer (types 16/18) and genital warts (types 6/11) in Japanese women aged 18-26 years. Participants were randomly assigned to either quadrivalent HPV (types 6/11/16/18) L1 virus-like particle vaccine (GARDASIL) (n = 509) or placebo (n = 512). Participants underwent regular gynecological examinations, cervicovaginal sampling for HPV DNA, testing for serum neutralizing antibodies to HPV and Papanicolau testing. The primary end-point was the combined incidence of persistent infection with HPV types 6, 11, 16 or 18 and cervical or external genital disease (i.e. cervical intraepithelial neoplasia, cervical cancer or external genital lesions related to HPV 6, 11, 16 or 18. Primary analyses were done per protocol. Combined incidence of persistent infection or disease with HPV 6, 11, 16 or 18 fell by 87.6% (95% confidence interval [CI], 59.2-97.6; P < 0.001), with HPV 6 or 11 by 73.1% (95% CI, -1.1-97.3; P = 0.0756) and with HPV 16 or 18 by 94.5% (95% CI, 65.2-99.9; P < 0.001) in those assigned vaccine compared with those assigned placebo. The median duration of follow up after month 7 in subjects was 23 months. In addition, the vaccine was well tolerated in Japanese women aged 18-26 years. Quadrivalent HPV vaccine could significantly reduce the acquisition of infection and clinical disease caused by HPV types 6, 11, 16 and 18.

  9. Serological evaluation of an influenza A virus cold-adapted reassortant live vaccine, CR-37 (H1N1), in Japanese adult volunteers.

    PubMed

    Yamane, N; Nakamura, Y; Yuki, M; Odagiri, T; Ishida, N

    1984-04-01

    A cold-adapted influenza A virus, CR-37 (H1N1), derived from genetic reassortment between A/Ann Arbor/6/60 (H2N2) cold-adapted variant virus and A/California/10/78 (H1N1) wild-type virus, was tested in Japanese adult volunteer. The CR-37 live virus preparation induced only low-grade clinical reactions in volunteers for the first 3-4 days after inoculation. Two vaccinees who did not show any antibody changes became febrile (over 38.0 degrees C). Skin tests using the vaccine preparation and uninfected allantoic fluid were performed, and indicated that one of these two vaccines was positive for the CR-37 vaccine preparation. A high proportion of the vaccinees whose sera had a haemagglutination-inhibition (HI) antibody titre against the vaccine strain of less than or equal to 64 before inoculation, seroconverted in both HI and neuraminidase-inhibition (NAI) antibody titrations, and only a few seroconverted in the titration of antibody against type-specific internal antigens. The serological examinations against heterotypic H1N1 variants indicated that the cold-adapted live influenza virus vaccine could induce a broad spectrum of HI antibody reactivity and immunity of long duration.

  10. Protection of Mice from Fatal Measles Encephalitis by Vaccination with Vaccinia Virus Recombinants Encoding Either the Hemagglutinin or the Fusion Protein

    NASA Astrophysics Data System (ADS)

    Drillien, Robert; Spehner, Daniele; Kirn, Andre; Giraudon, Pascale; Buckland, Robin; Wild, Fabian; Lecocq, Jean-Pierre

    1988-02-01

    Vaccinia virus recombinants encoding the hemagglutinin or fusion protein of measles virus have been constructed. Infection of cell cultures with the recombinants led to the synthesis of authentic measles proteins as judged by their electrophoretic mobility, recognition by antibodies, glycosylation, proteolytic cleavage, and presentation on the cell surface. Mice vaccinated with a single dose of the recombinant encoding the hemagglutinin protein developed antibodies capable of both inhibiting hemagglutination activity and neutralizing measles virus, whereas animals vaccinated with the recombinant encoding the fusion protein developed measles neutralizing antibodies. Mice vaccinated with either of the recombinants resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain.

  11. [Immunization against tick-borne encephalitis].

    PubMed

    Krause, Martin; Majer, Sabine

    2016-01-01

    Tick-borne encephalitis (TBE) is a viral infection that may cause irreversible damage to the brain and even result in death. No specific therapy exists. Active immunization is of major importance in controlling the infection. Vaccination is recommended to all adults and children > 6 years who live in endemic areas. Two inactivated vaccines are available in Switzerland. The vaccination schedule includes a basic immunization composed of 3 injections followed by boosting every 10 years. The efficacy of the vaccines has never been investigated in controlled studies, however, from indirect evidence, the vaccines are thought to cause good protection and to be safe. Local reactions at the injections site may occur in one third and mild systemic side effects in one fifth of vaccinees. Anaphylactic reactions and severe central nervous side effects are very rare. PMID:27268448

  12. Acute nonparaneoplastic limbic encephalitis in childhood: a case series in Japan.

    PubMed

    Sakuma, Hiroshi; Sugai, Kenji; Sasaki, Masayuki

    2010-09-01

    Limbic encephalitis not associated with malignancy was investigated in Japanese children, with particular focus on clinical features distinct from adult cases. Clinical, laboratory, and radiographic findings were studied in pediatric nonparaneoplastic limbic encephalitis, based on a literature review and questionnaire-based analyses. Analysis of 14 cases revealed the predominance of seizure occurrence, disturbance in consciousness, and frequent extralimbic signs. The majority manifested antecedent febrile illnesses, suggesting the involvement of infection-induced autoimmunity targeted to neuronal antigens. These clinical observations indicate a child-specific phenotype of limbic encephalitis. Further studies on its immunopathogenesis are needed to determine whether childhood limbic encephalitis is a distinct subcategory. PMID:20691937

  13. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  14. The molecular biology of tick-borne encephalitis virus. Review article.

    PubMed

    Heinz, F X; Mandl, C W

    1993-10-01

    Tick-borne encephalitis (TBE) virus is a member of the flavivirus genus and the family Flaviviridae. Like other flaviviruses such as yellow fever, Japanese encephalitis or the dengue viruses, it is an important human pathogen, endemic in many European countries, Russia and China. The disease can be effectively prevented by vaccination with a formalin-inactivated whole virus vaccine. In recent years major advances have been made in the understanding of the molecular biology of TBE virus, including the complete sequence analysis of the genomic RNA of the European and Far Eastern strains. As shown in these studies, the virion RNA contains a single long open reading frame that codes for the structural proteins at the 5' end and the nonstructural proteins at the 3' end. Co- and posttranslational cleavages by a viral and cellular proteases lead to the formation of individual viral proteins. The mature virion is composed of an isometric capsid surrounded by a lipid envelope with two membrane-associated proteins. One of these, protein E, is of paramount importance for several important viral functions, especially during the entry phase of the viral life cycle. Protein E is also responsible for the induction of a protective immune response. A detailed map of antigenic sites has been established and the structure of an anchor-free form of E is currently being investigated by X-ray diffraction analysis. Understanding the molecular basis of the functions of this protein together with the knowledge of its three-dimensional structure may provide clues for developing specific antiviral agents. Protein E has also been shown to be an important determinant of virulence, with single amino acid substitutions at selected sites leading to attenuation. Engineering of such mutations into cDNA clones to produce new recombinant viruses may open up new avenues for the development of live vaccines. PMID:8267950

  15. The molecular biology of tick-borne encephalitis virus. Review article.

    PubMed

    Heinz, F X; Mandl, C W

    1993-10-01

    Tick-borne encephalitis (TBE) virus is a member of the flavivirus genus and the family Flaviviridae. Like other flaviviruses such as yellow fever, Japanese encephalitis or the dengue viruses, it is an important human pathogen, endemic in many European countries, Russia and China. The disease can be effectively prevented by vaccination with a formalin-inactivated whole virus vaccine. In recent years major advances have been made in the understanding of the molecular biology of TBE virus, including the complete sequence analysis of the genomic RNA of the European and Far Eastern strains. As shown in these studies, the virion RNA contains a single long open reading frame that codes for the structural proteins at the 5' end and the nonstructural proteins at the 3' end. Co- and posttranslational cleavages by a viral and cellular proteases lead to the formation of individual viral proteins. The mature virion is composed of an isometric capsid surrounded by a lipid envelope with two membrane-associated proteins. One of these, protein E, is of paramount importance for several important viral functions, especially during the entry phase of the viral life cycle. Protein E is also responsible for the induction of a protective immune response. A detailed map of antigenic sites has been established and the structure of an anchor-free form of E is currently being investigated by X-ray diffraction analysis. Understanding the molecular basis of the functions of this protein together with the knowledge of its three-dimensional structure may provide clues for developing specific antiviral agents. Protein E has also been shown to be an important determinant of virulence, with single amino acid substitutions at selected sites leading to attenuation. Engineering of such mutations into cDNA clones to produce new recombinant viruses may open up new avenues for the development of live vaccines.

  16. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study

    PubMed Central

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3–4–5 months of age) and booster vaccination (17–19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ≥0.2 μg/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ≥8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ≥100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children. PMID:25830489

  17. Biomarkers in Japanese Encephalitis: A Review

    PubMed Central

    Kant Upadhyay, Ravi

    2013-01-01

    JE is a flavivirus generated dreadful CNS disease which causes high mortality in various pediatric groups. JE disease is currently diagnosed by measuring the level of viral antigens and virus neutralization IgM antibodies in blood serum and CSF by ELISA. However, it is not possible to measure various disease-identifying molecules, structural and molecular changes occurred in tissues, and cells by using such routine methods. However, few important biomarkers such as cerebrospinal fluid, plasma, neuro-imaging, brain mapping, immunotyping, expression of nonstructural viral proteins, systematic mRNA profiling, DNA and protein microarrays, active caspase-3 activity, reactive oxygen species and reactive nitrogen species, levels of stress-associated signaling molecules, and proinflammatory cytokines could be used to confirm the disease at an earlier stage. These biomarkers may also help to diagnose mutant based environment specific alterations in JEV genotypes causing high pathogenesis and have immense future applications in diagnostics. There is an utmost need for the development of new more authentic, appropriate, and reliable physiological, immunological, biochemical, biophysical, molecular, and therapeutic biomarkers to confirm the disease well in time to start the clinical aid to the patients. Hence, the present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of JE disease and its related disorders in the future. PMID:24455705

  18. Preparing patients to travel abroad safely. Part 2: Updating vaccinations.

    PubMed Central

    Thomas, R. E.

    2000-01-01

    OBJECTIVE: To provide, for family physicians without access to a travel clinic, evidence-based recommendations on vaccinating infants and children, adults, pregnant women, and immunocompromised patients traveling to non-Western countries. QUALITY OF EVIDENCE: Searches were undertaken of MEDLINE from 1990 to November 1998 (372 articles); the Cochrane Collaboration Library; publications of the National Action Committee on Immunization and the Committee to Advise on Tropical Medicine and Travel in Canada Communicable Disease Reports; the Canadian Immunization Guide; and Laboratory Centre for Disease Control, United States Centres for Disease Control, and World Health Organization websites. Evidence-based statements, randomized controlled trials, systematic reviews, and meta-analyses were selected. Vaccination recommendations are based on this evidence. MAIN MESSAGE: Physicians should complete vaccination schedules for children whose primary series is incomplete and vaccinate unvaccinated adults. Hepatitis A is widespread, and travelers to areas where it is endemic should be vaccinated. The elderly should be vaccinated against influenza and pneumococcal disease. Pregnant women should receive vaccines appropriate to their trimester. Immunocompromised patients should be vaccinated, but BCG and live vaccines are contraindicated. Travelers to areas where meningitis, typhoid, cholera, Japanese encephalitis, and rabies are endemic should be vaccinated if they are likely to be exposed. Those traveling to areas where tuberculosis is endemic should take precautions and should have skin tests before traveling and 2 to 4 months after return. CONCLUSIONS: Family physicians can administer all necessary vaccinations. They can advise pregnant women and immunocompromised people about the balance of risk of disease and benefits of vaccination. PMID:10752003

  19. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral particles as a non-transmissible bivalent marker vaccine candidate against CSF and JE infections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A trans-complemented CSF- JE chimeric viral replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The E2 gene of CSFV Alfort/187 strain was deleted and the resultant plasmid pA187delE2 was inserted by a fragment containing the region coding for a truncate...

  20. Comparison of immunogenicity of simultaneous and nonsimultaneous vaccination with MMR and JE vaccine among 15-month-old children.

    PubMed

    Tseng, C Y; Hwang, K P; Lin, K H; Chen, H Y; Lu, C C; Chiang, C H

    1999-01-01

    To evaluate the immunogenicity of measles- mumps- rubella (MMR) vaccination with Japanese encephalitis (JE) vaccine nonsimultaneously and simultaneously, 145 babies, aged 15 months were enrolled into two groups. Group A received MMR and JE vaccines nonsimultaneously at an interval of 6 weeks; group B received the vaccinations simultaneously. Antibody titers of MMR and JE were detected before and 8 weeks after vaccination. A total of 118 babies (61 in group A; 57 in group B) completed the study. In group A, mean increments of logarithmic geometric mean titers (GMTs) of MMR and JE were 4.51, 5.93, 4.07 and 1.99; seroresponse rates were 100% (61/61), 77.05% (47/61), 96.72% (59/61) and 59.02% (36/61) respectively. In group B, mean increments of logarithmic GMTs of MMR and JE were 4.35, 5.37, 4.44 and 1.93; seroresponse rates were 98.25% (56/57), 77.19% (44/57), 98.25% (56/57) and 57.89% (33/57) respectively. There were no significant differences between these two groups. These results suggest that simultaneous and nonsimultaneous vaccination with MMR and JE vaccines were similar in immunogenicity.

  1. Viral meningitis and encephalitis.

    PubMed

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date.

  2. CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model.

    PubMed

    Su, Yan; Connolly, Michael; Marketon, Anthony; Heiland, Teri

    2016-01-01

    Allergies caused by Japanese Red Cedar (JRC) pollen affect up to a third of Japanese people, necessitating development of an effective therapeutic. We utilized the lysosomal targeting property of lysosomal-associated membrane protein-1 (LAMP-1) to make DNA vaccines that encode LAMP-1 and the sequences of immunodominant allergen CryJ1 or CryJ2 from the JRC pollen. This novel strategy is designed to skew the CD4 T cell responses to the target allergens towards a nonallergenic Th1 response. CryJ1-LAMP and CryJ2-LAMP were administrated to BALB/c mice and antigen-specific Th1-type IgG2a and Th2-type IgG1 antibodies, as well as IgE antibodies, were assayed longitudinally. We also isolated different T cell populations from immunized mice and adoptively transferred them into naïve mice followed by CryJ1/CryJ2 protein boosts. We demonstrated that CryJ-LAMP immunized mice produce high levels of IFN-γ and anti-CryJ1 or anti-CryJ2 IgG2a antibodies and low levels of IgE antibodies, suggesting that a Th1 response was induced. In addition, we found that CD4(+) T cells are the immunological effectors of DNA vaccination in this allergy model. Together, our results suggest the CryJ-LAMP Vaccine has a potential as an effective therapeutic for JRC induced allergy by skewing Th1/Th2 responses. PMID:27239481

  3. [Meningitis and encephalitis in Poland in 2006].

    PubMed

    Kicman-Gawłowska, Agnieszka; Chrześcijańska, Irena; Stefanoff, Paweł

    2008-01-01

    In Poland, 3 693 cases of neuroinfections were reported in 2006, of which 989 had bacterial aetiology, 1 874--viral aetiology, and 512--other or unknown origin. The etiological agent was determined in 455 (46%) cases of bacterial neuroinfections. Among them Neisseria meningitidis was found in 148 cases, Haemophilus influenzae type B (Hib) in 39 cases and Streptococcus pneumoniae in 119 cases. An increasing trend in meningococcal infections incidence has been observed in 2006, and a substantial decrease of Hib incidence, related to increasing vaccination coverage. Viral neuroinfections incidence in 2006 increased compared to year 2005. Etiological factors of central nervous system aseptic infections were established only in minor proportion of cases--3% of meningitis and 20% of encephalitis. Among confirmed cases, there were 317 cases of tick-borne encephalitis and 31 cases of herpetic encephalitis. Tick borne encephalitis incidence increased in 2006 (0.83), compared to 2004 - 2005. Most of the cases were reported from endemic areas of north-eastern part of the country.

  4. Complete genome characterization of Rocio virus (Flavivirus: Flaviviridae), a Brazilian flavivirus isolated from a fatal case of encephalitis during an epidemic in Sao Paulo state.

    PubMed

    Medeiros, Daniele B A; Nunes, Márcio R T; Vasconcelos, Pedro F C; Chang, Gwong-Jen J; Kuno, Goro

    2007-08-01

    The flaviviruses of major medical importance in South American countries are yellow fever, dengue, Saint Louis encephalitis, West Nile and Rocio viruses. Rocio virus (ROCV) has been responsible for epidemics of severe encephalitis in Brazil with a case-fatality rate of 10 % and development of sequelae in 20 % of the survivors. We have sequenced and characterized the entire genome of ROCV for the first time, by determining the general traits of the open reading frame and the characteristics of viral genes including the potential cleavage sites, conserved or unique motifs, cysteine residues and potential glycosylation sites. The conserved sequences in the 3'-non-coding region were identified, and the predicted secondary structures during cyclization between 5'- and 3'-non-coding regions were studied. Multiple protein and phylogenetic analyses based on antigenically important and phylogenetically informative genes confirmed a close relationship between ROCV and Ilheus virus (ILHV), together constituting a unique and distinct phylogenetic subgroup as well as the genetic relationship of ROCV with several members of the Japanese encephalitis group. Although ROCV is phylogenetically related to ILHV, our study shows that it is still a virus distinct from the latter virus. This is the first flavivirus uniquely indigenous to Brazil that has been sequenced completely and the genome characterized. The data should be useful for further studies at the molecular level, including construction of infectious clone, identification of gene function, improved disease surveillance based on molecular diagnostic tools and vaccine development.

  5. Meningitis and Encephalitis

    MedlinePlus

    ... No. 04-4840 Back to Meningitis and Encephalitis Information Page See a list of all NINDS Disorders Publicaciones en Español Meningitis y Encefalitis Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  6. Animal intelligence as encephalization.

    PubMed

    Jerison, H J

    1985-02-13

    There is no consensus on the nature of animal intelligence despite a century of research, though recent work on cognitive capacities of dolphins and great apes seems to be on one right track. The most precise quantitative analyses have been of relative brain size, or structural encephalization, undertaken to find biological correlates of mind in animals. Encephalization and its evolution are remarkably orderly, and if the idea of intelligence were unknown it would have to be invented to explain encephalization. The scientific question is: what behaviour or dimensions of behaviour evolved when encephalization evolved? The answer: the relatively unusual behaviours that require increased neural information processing capacity, beyond that attributable to differences among species in body size. In this perspective, the different behaviours that depend on augmented processing capacity in different species are evidence of different intelligences (in the plural) that have evolved.

  7. Eastern Equine Encephalitis

    MedlinePlus

    ... Facebook Tweet Share Compartir Image of Culiseta melanura mosquito, photo taken by Jason Williams, reproduced by permission from the Virginia Mosquito Control Association. Eastern equine encephalitis virus (EEEV) is ...

  8. Meningitis and Encephalitis

    MedlinePlus

    ... Funding Information Research Programs Training & Career Awards Enhancing Diversity Find People About NINDS NINDS Meningitis and Encephalitis ... News From NINDS | Find People | Training | Research | Enhancing Diversity Careers@NINDS | FOIA | Accessibility Policy | Contact Us | Privacy ...

  9. [VACCINES].

    PubMed

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs.

  10. Auto-immune encephalitis as differential diagnosis of infectious encephalitis

    PubMed Central

    Armangue, Thaís; Leypoldt, Frank; Dalmau, Josep

    2014-01-01

    Purpose of review To describe the main types of autoimmune encephalitis with special emphasis on those associated with antibodies against neuronal cell surface or synaptic proteins, and the differential diagnosis with infectious encephalitis. Recent findings There is a continuous expansion of the number of cell surface or synaptic proteins that are targets of autoimmunity. The most recently identified include the mGluR5, DPPX, and the GABAAR. In these and previously known autoimmune encephalitis (NMDAR, AMPAR, GABABR, LGI1, CASPR2), the prodromal symptoms or types of presentations often suggest a viral encephalitis. We review here clues that help in the differential diagnosis with infectious encephalitis. Moreover, recent investigations indicate that viral encephalitis (e.g., herpes simplex) can trigger synaptic autoimmunity. In all these disorders immunotherapy is usually effective. Summary Autoimmune encephalitis comprises an expanding group of potentially treatable disorders that should be included in the differential diagnosis of any type of encephalitis. PMID:24792345

  11. Protection against morbillivirus-induced encephalitis by immunization with a rationally designed synthetic peptide vaccine containing B- and T-cell epitopes from the fusion protein of measles virus.

    PubMed Central

    Obeid, O E; Partidos, C D; Howard, C R; Steward, M W

    1995-01-01

    Synthetic peptides representing T- and B-cell epitopes from the fusion (F) protein of measles virus (MV) were tested for their ability to induce a protective immune response against intracerebral challenge with neuroadapted strains of MV and canine distemper virus (CDV) in mice. Of the panel of peptides tested, only a chimeric peptide consisting of two copies of a promiscuous T-cell epitope (representing residues 288 to 302 of MV F protein) synthesized at the amino terminus of a B-cell epitope (representing residues 404 to 414 of MV F protein) was able to induce a protective response against challenge with MV and CDV in inbred mice. The protective response induced by this peptide (TTB) was associated with a significant reduction in mortality, histological absence of acute encephalitis, and greatly reduced titers of virus in the brains of TTB-immune mice following challenge compared with the results for nonimmunized controls. A chimeric peptide comprising one copy of the T-cell epitope and one copy of the B-cell epitope (TB) did not induce a protective response. A comparison of the antibody responses induced by the two chimeras suggested that differences in protective efficacy following immunization may be a result of the higher affinity of the antibody induced by the TTB peptide than that of the antibody induced by the TB peptide. In addition, differences in the immunoglobulin G subclass of the antipeptide antibody responses were observed, and these may play a role in the differences in protection observed. These results indicate that appropriately designed synthetic peptides have potential as vaccines for the induction of cross-reactive protection against morbilliviruses. PMID:7531779

  12. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review.

    PubMed

    Yuan, Jun-Liang; Wang, Shuang-Kun; Guo, Xiao-Juan; Hu, Wen-Li

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM. PMID:27478662

  13. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

    PubMed Central

    Yuan, Jun-liang; Wang, Shuang-kun; Guo, Xiao-juan

    2016-01-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM. PMID:27478662

  14. Specificities of human CD4+ T cell responses to an inactivated flavivirus vaccine and infection: correlation with structure and epitope prediction.

    PubMed

    Schwaiger, Julia; Aberle, Judith H; Stiasny, Karin; Knapp, Bernhard; Schreiner, Wolfgang; Fae, Ingrid; Fischer, Gottfried; Scheinost, Ondrej; Chmelik, Vaclav; Heinz, Franz X

    2014-07-01

    Tick-borne encephalitis (TBE) virus is endemic in large parts of Europe and Central and Eastern Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to the mosquito-borne yellow fever, dengue, Japanese encephalitis, and West Nile viruses, and vaccination with an inactivated whole-virus vaccine can effectively prevent clinical disease. Neutralizing antibodies are directed to the viral envelope protein (E) and an accepted correlate of immunity. However, data on the specificities of CD4(+) T cells that recognize epitopes in the viral structural proteins and thus can provide direct help to the B cells producing E-specific antibodies are lacking. We therefore conducted a study on the CD4(+) T cell response against the virion proteins in vaccinated people in comparison to TBE patients. The data obtained with overlapping peptides in interleukin-2 (IL-2) enzyme-linked immunosorbent spot (ELISpot) assays were analyzed in relation to the three-dimensional structures of the capsid (C) and E proteins as well as to epitope predictions based on major histocompatibility complex (MHC) class II peptide affinities. In the C protein, peptides corresponding to two out of four alpha helices dominated the response in both vaccinees and patients, whereas in the E protein concordance of immunodominance was restricted to peptides of a single domain (domain III). Epitope predictions were much better for C than for E and were especially erroneous for the transmembrane regions. Our data provide evidence for a strong impact of protein structural features that influence peptide processing, contributing to the discrepancies observed between experimentally determined and computer-predicted CD4(+) T cell epitopes. Importance: Tick-borne encephalitis virus is endemic in large parts of Europe and Asia and causes more than 10,000 annual cases of neurological disease in humans. It is closely related to yellow fever, dengue, Japanese encephalitis, and

  15. [Tick-borne encephalitis--an update].

    PubMed

    Stock, Ingo

    2016-05-01

    Tick-borne encephalitis (TBE) is a systemic infectious disease with nonspecific symptoms and/or severe neurological disorders such as meningitis, encephalitis and myelitis. The disease is caused by TBE virus, an enveloped RNA virus belonging to the family of flaviviruses. Three subtypes are currently present in different parts of Europe and Asia. The TBE virus is transmitted to humans primarily by the tick bite of Ixodes species such as I. ricinus, but also by the ingestion of contaminated raw milk and raw milk products. In Germany, more than 75% of all TBE cases occur in Bavaria and Baden-Württemberg (southern Germany). Depending on the region, 1 to 4% of adult I. ricinus ticks in southern Germany are infected with the central European TBE virus variant. Treatment of TBE is symptomatic and supportive, a specific antiviral therapy does not exist. TBE cases acquired in central European countries have usually a good prognosis. Mortality rates above 2% have been documented in cases of tick-borne encephalitis in the elderly. In endemic areas, active immunization with inactivated TBE virus vaccines provides the most secure protection against TBE. In addition, exposure prophylaxis (protection against tick bites) plays a crucial role for TBE prevention.

  16. Tick-borne encephalitis associated with consumption of raw goat milk, Slovenia, 2012.

    PubMed

    Hudopisk, Neda; Korva, Miša; Janet, Evgen; Simetinger, Marjana; Grgič-Vitek, Marta; Gubenšek, Jakob; Natek, Vladimir; Kraigher, Alenka; Strle, Franc; Avšič-Županc, Tatjana

    2013-05-01

    Tick-borne encephalitis (TBE) developed in 3 persons in Slovenia who drank raw milk; a fourth person, who had been vaccinated against TBE, remained healthy. TBE virus RNA was detected in serum and milk of the source goat. Persons in TBE-endemic areas should be encouraged to drink only boiled/pasteurized milk and to be vaccinated.

  17. Infection and transmission of live recombinant Newcastle disease virus vaccines in Rock Pigeons, European House Sparrows, and Japanese Quail

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In China and Mexico, engineered recombinant Newcastle disease virus (rNDV) strains are used as live vaccines for the control of Newcastle disease and as vectors to express the avian influenza virus hemagglutinin (HA) gene to control avian influenza in poultry. In this study, non-target species wer...

  18. The vaccine data link in Nha Trang, Vietnam: a progress report on the implementation of a database to detect adverse events related to vaccinations.

    PubMed

    Ali, Mohammad; Canh, Do Gia; Clemens, John D; Park, Jin-Kyung; von Seidlein, Lorenz; Thiem, Vu Dinh; Tho, Le Huu; Trach, Dang Duc

    2003-04-01

    Real, perceived and unknown adverse events secondary to vaccinations are a source of concern for care providers of children. In the USA large linked databases have provided helpful information regarding the safety of vaccines. Very little prospectively collected data on vaccine safety is available from resource poor countries, but safety concerns may be even more relevant in such settings. Vaccine manufacturers do not have to pass the same rigorous safety standards as vaccine manufacturers in rich countries. Vaccines, which protect against cholera, Japanese encephalitis, rabies or typhoid fever are predominantly used in resource poor, tropical countries and frequently do not undergo vigorous post marketing surveillance. New vaccines specifically suited for resource poor countries are sometimes marketed without the scrutiny of vigilant, independent regulatory authorities. We describe here the design and implementation of a large linked database for a semi-rural province in central Vietnam. The design overcomes several problems inherent in data bases of medical events and vaccinations in developing countries. Assigning a permanent identification (ID) number to each resident avoids the ambiguities of ID numbers based on the address. The distribution and use of medical identification cards with a permanent ID number assists in the unambiguous identification of vaccinees and patients. Medical records of all admissions are coded according to International Classification of Diseases (ICD-10) and transcribed into a computer system. Because these processes are novel the data collected by the study will be validated. Project staff will check records on vaccinations and hospital admissions through household visits at regular intervals. Data describing vaccinations and medical events are linked to the data collected by the project staff in a computer system. Based on the validation of the data we hope to optimize this model. Once we find the model working it is planned export

  19. Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV.

    PubMed

    Lin, Chih-Wei; Chang, Ching-Yun; Chen, Wei-Lin; Lin, Shih-Chang; Liao, Chien-Chun; Chang, Jui-Yuan; Liu, Chia-Chyi; Hu, Alan Yung-Chih; Lu, Tsung-Chun; Chou, Ai-Hsiang; Wu, Suh-Chin; Chong, Pele; Huang, Ming-Hsi

    2013-11-01

    Combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. Here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (H5N1/H1N1), enterovirus 71 (EV71), and/or Japanese encephalitis virus (JEV) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. We demonstrated that the antigenic competition happens between H5N1/H1N1 or H5N1/EV71 inactivated virions when the vaccine combinations either formulated with Alum suspensions or without adjuvant. In the presence of PELC emulsified particles, EV71-specific immune responses before and after incorporating H5N1 virus into EV71 vaccine were detected of no significant difference; in addition, H5N1- and EV71-specific immune responses were found at the same level when H5N1/EV71/JEV consolidating into combination vaccine. Emulsified vaccine formulation was represented as a potential tool that is found to reduce the number of injections required to prevent multiple infectious strains causing the same disease (H5N1/H1N1) and/or that protect against different diseases (H5N1/EV71). Combination vaccines can also include a third component to protect against H5N1/EV71/JEV at the same time.

  20. An evaluation of serious neurological disorders following immunization: a comparison of whole-cell pertussis and acellular pertussis vaccines.

    PubMed

    Geier, David A; Geier, Mark R

    2004-08-01

    Serious neurological disorders reported following whole-cell pertussis in comparison to acellular pertussis vaccines were evaluated. The Vaccine Adverse Events Reporting System (VAERS) was analyzed for Emergency Department (ED) visits, life-threatening reactions, hospitalizations, disabilities, deaths, seizures, infantile spasms, encephalitis/encephalopathy, autism, Sudden Infant Death Syndrome (SIDS) and speech disorders reported with an initial onset of symptoms within 3 days following whole-cell pertussis and acellular pertussis vaccines among those residing in the US from 1997 to 1999. Controls were employed to evaluate potential biases in VAERS. Evaluations as to whether whole-cell and acellular vaccines were administered to populations of similar age and sex were undertaken because these factors might influence the study's results. Statistical increases were observed for all events examined following whole-cell pertussis vaccination in comparison to acellular pertussis vaccination, excepting cerebellar ataxia. Reporting biases were minimal in VAERS, and whole-cell and acellular pertussis vaccines were administered to populations of similar age and sex. Biologic mechanisms for the increased reactogenicity of whole-cell pertussis vaccines may stem from the fact that whole-cell pertussis vaccines contain 3,000 different proteins, whereas DTaP contains two to five proteins. Whole-cell pertussis vaccine contains known neurotoxins including: endotoxin, pertussis toxin and adenylate cyclase. Our results, and conclusions by the US Institute of Medicine, suggest an association between serious neurological disorders and whole-cell pertussis immunization. In light of the presence of a safer and at least equally efficacious acellular pertussis vaccine alternative, the Japanese and US switch to using acellular pertussis vaccine seems well justified. Other countries using whole-cell pertussis-containing vaccines should consider following suite in the near future.

  1. Nipah encephalitis - an update.

    PubMed

    Sherrini, B A; Chong, T T

    2014-08-01

    Between September 1998 to May 1999, Malaysia and Singapore were hit by an outbreak of fatal encephalitis caused by a novel virus from the paramyxovirus family. This virus was subsequently named as Nipah virus, after the Sungei Nipah village in Negeri Sembilan, where the virus was first isolated. The means of transmission was thought to be from bats-topigs and subsequently pigs-to-human. Since 2001, almost yearly outbreak of Nipah encephalitis has been reported from Bangladesh and West Bengal, India. These outbreaks were characterized by direct bats-to-human, and human-to-human spread of infection. Nipah virus shares many similar characteristics to Hendra virus, first isolated in an outbreak of respiratory illness involving horses in Australia in 1994. Because of their homology, a new genus called Henipavirus (Hendra + Nipah) was introduced. Henipavirus infection is a human disease manifesting most often as acute encephalitis (which may be relapsing or late-onset) or pneumonia, with a high mortality rate. Pteropus bats act as reservoir for the virus, which subsequently lead to human spread. Transmission may be from consumption of food contaminated by bats secretion, contact with infected animals, or human-to-human spread. With wide geographical distribution of Pteropus bats, Henipavirus infection has become an important emerging human infection with worldwide implication. PMID:25417957

  2. Japanese; Japanese Songs.

    ERIC Educational Resources Information Center

    Defense Language Inst., Washington, DC.

    This supplementary textbook for students of Japanese presents a collection of 43 songs--folk songs, nursery songs, lullabies, love songs, wedding songs, graduation songs, the national anthem, drinking songs, school songs, and Christmas carols. With the exception of the carols, the musical scores are presented with their Japanese lyrics. The…

  3. Antiviral macrophage responses in flavivirus encephalitis.

    PubMed

    Ashhurst, Thomas Myles; Vreden, Caryn van; Munoz-Erazo, Luis; Niewold, Paula; Watabe, Kanami; Terry, Rachael L; Deffrasnes, Celine; Getts, Daniel R; Cole King, Nicholas Jonathan

    2013-11-01

    Mosquito-borne flaviviruses are a major current and emerging threat, affecting millions of people worldwide. Global climate change, combined with increasing proximity of humans to animals and mosquito vectors by expansion into natural habitats, coupled with the increase in international travel, have resulted in significant spread and concomitant increase in the incidence of infection and severe disease. Although neuroinvasive disease has been well described for some viral infections such as Japanese Encephalitis virus (JEV) and West Nile virus (WNV), others such as dengue virus (DENV) have recently displayed an emerging pattern of neuroinvasive disease, distinct from the previously observed, systemically-induced encephalomyelopathy. In this setting, the immune response is a crucial component of host defence, in preventing viral dissemination and invasion of the central nervous system (CNS). However, subversion of the anti-viral activities of macrophages by flaviviruses can facilitate viral replication and spread, enhancing the intensity of immune responses, leading to severe immune-mediated disease which may be further exacerbated during the subsequent infection with some flaviviruses. Furthermore, in the CNS myeloid cells may be responsible for inducing specific inflammatory changes, which can lead to significant pathological damage during encephalitis. The interaction of virus and cells of the myeloid lineage is complex, and this interaction is likely responsible at least in part, for crucial differences between viral clearance and pathology. Recent studies on the role of myeloid cells in innate immunity and viral control, and the mechanisms of evasion and subversion used by flaviviruses are rapidly advancing our understanding of the immunopathological mechanisms involved in flavivirus encephalitis and will lead to the development of therapeutic strategies previously not considered. PMID:24434318

  4. The impact of new vaccine introduction on immunization and health systems: A review of the published literature

    PubMed Central

    Hyde, Terri B.; Dentz, Holly; Wang, Susan A.; Burchett, Helen E.; Mounier-Jack, Sandra; Mantel, Carsten F.

    2015-01-01

    We conducted a systematic review of the published literature to examine the impact of new vaccine introduction on countries’ immunization and broader health systems. Six publication databases were searched using 104 vaccine and health system-related search terms. The search yielded 15,795 unique articles dating from December 31, 1911 to September 29, 2010. Based on review of the title and abstract, 654 (4%) of these articles were found to be potentially relevant and were referred for full review. After full review, 130 articles were found to be relevant and included in the analysis. These articles represented vaccines introduced to protect against 10 different diseases (hepatitis A, hepatitis B, Haemophilus influenzae type b disease, human papilloma virus infection, influenza, Japanese encephalitis, meningococcal meningitis, Streptococcus pneumoniae disease, rotavirus diarrhea and typhoid), in various formulations and combinations. Most reviewed articles (97 [75%]) reported experiences in high-income countries. New vaccine introduction was most efficient when the vaccine was introduced into an existing delivery platform and when introduced in combination with a vaccine already in the routine childhood immunization schedule (i.e., as a combination vaccine). New vaccine introduction did not impact coverage of vaccines already included in the routine childhood immunization schedule. The need for increased cold chain capacity was frequently reported. New vaccines facilitated the introduction and widespread use of auto-disable syringes into the immunization and the broader health systems. The importance of training and education for health care workers and social mobilization was frequently noted. There was evidence in high-income countries that new vaccine introduction was associated with reduced health-care costs. Future evaluations of new vaccine introductions should include the systematic and objective assessment of the impacts on a country’s immunization system

  5. The impact of new vaccine introduction on immunization and health systems: a review of the published literature.

    PubMed

    Hyde, Terri B; Dentz, Holly; Wang, Susan A; Burchett, Helen E; Mounier-Jack, Sandra; Mantel, Carsten F

    2012-10-01

    We conducted a systematic review of the published literature to examine the impact of new vaccine introduction on countries' immunization and broader health systems. Six publication databases were searched using 104 vaccine and health system-related search terms. The search yielded 15,795 unique articles dating from December 31, 1911 to September 29, 2010. Based on review of the title and abstract, 654 (4%) of these articles were found to be potentially relevant and were referred for full review. After full review, 130 articles were found to be relevant and included in the analysis. These articles represented vaccines introduced to protect against 10 different diseases (hepatitis A, hepatitis B, Haemophilus influenzae type b disease, human papilloma virus infection, influenza, Japanese encephalitis, meningococcal meningitis, Streptococcus pneumoniae disease, rotavirus diarrhea and typhoid), in various formulations and combinations. Most reviewed articles (97 [75%]) reported experiences in high-income countries. New vaccine introduction was most efficient when the vaccine was introduced into an existing delivery platform and when introduced in combination with a vaccine already in the routine childhood immunization schedule (i.e., as a combination vaccine). New vaccine introduction did not impact coverage of vaccines already included in the routine childhood immunization schedule. The need for increased cold chain capacity was frequently reported. New vaccines facilitated the introduction and widespread use of auto-disable syringes into the immunization and the broader health systems. The importance of training and education for health care workers and social mobilization was frequently noted. There was evidence in high-income countries that new vaccine introduction was associated with reduced health-care costs. Future evaluations of new vaccine introductions should include the systematic and objective assessment of the impacts on a country's immunization system and

  6. Enveloped virus-like particles as vaccines against pathogenic arboviruses.

    PubMed

    Pijlman, Gorben P

    2015-05-01

    Arthropod-borne arboviruses form a continuous threat to human and animal health, but few arboviral vaccines are currently available. Advances in expression technology for complex, enveloped virus-like particles (eVLPs) create new opportunities to develop potent vaccines against pathogenic arboviruses. In this short review, I highlight the successes and challenges in eVLP production for members of the three major arbovirus families: Flaviviridae (e.g., dengue, West Nile, Japanese encephalitis); Bunyaviridae (e.g., Rift Valley fever); and Togaviridae (e.g., chikungunya). The results from pre-clinical testing will be discussed as well as specific constraints to the large-scale manufacture and purification of eVLPs, which are complex assemblies of membranes and viral glycoproteins. Insect cells emerge as ideal substrates for correct arboviral glycoprotein folding and posttranslational modification to yield high quality eVLPs. Furthermore, baculovirus expression in insect cell culture is scalable and has a proven safety record in industrial human and veterinary vaccine manufacturing. In conclusion, eVLPs produced in insect cells using modern biotechnology have a realistic potential to be used in novel vaccines against arboviral diseases.

  7. Enveloped virus-like particles as vaccines against pathogenic arboviruses.

    PubMed

    Pijlman, Gorben P

    2015-05-01

    Arthropod-borne arboviruses form a continuous threat to human and animal health, but few arboviral vaccines are currently available. Advances in expression technology for complex, enveloped virus-like particles (eVLPs) create new opportunities to develop potent vaccines against pathogenic arboviruses. In this short review, I highlight the successes and challenges in eVLP production for members of the three major arbovirus families: Flaviviridae (e.g., dengue, West Nile, Japanese encephalitis); Bunyaviridae (e.g., Rift Valley fever); and Togaviridae (e.g., chikungunya). The results from pre-clinical testing will be discussed as well as specific constraints to the large-scale manufacture and purification of eVLPs, which are complex assemblies of membranes and viral glycoproteins. Insect cells emerge as ideal substrates for correct arboviral glycoprotein folding and posttranslational modification to yield high quality eVLPs. Furthermore, baculovirus expression in insect cell culture is scalable and has a proven safety record in industrial human and veterinary vaccine manufacturing. In conclusion, eVLPs produced in insect cells using modern biotechnology have a realistic potential to be used in novel vaccines against arboviral diseases. PMID:25692281

  8. [Herpetic encephalitis: a clinical case].

    PubMed

    Dryhant, L P; Sereda, V H; Kushpiĭ, O V; Tkachenko, V V; Kravchuk, N A; Inhula, N I; Sizina, A V; Sachko, Iu Iu; Andrusenko, A S; Tytenko, Iu I; Babirad, A M

    2012-01-01

    An example of diagnostics and treatment of patient is in-process made with herpetic encephalitis. It is well-proven in researches, that a herpetic encephalitis is 11.5% among sharp encephalitises. Morbidity is sporadic, some researchers specify on an increase its spring. An infection can be passed tiny and pin a way. Seasonal vibrations are not incident to the herpetic encephalitis. Two peaks of morbidity are on 5-30 years and age more senior 50 years. More than in 95% cases the virus of simple herpes of type serves as an exciter of herpetic encephalitis 1. A characteristic triad of herpetic encephalitis is the sharp feverish beginning, development of cramps of dzheksonovskogo type and violation of consciousness, developing usually after a brief respirator infection. Sometimes sudden development of cramps and loss of consciousness is preceded a fever. Example of such development of disease is made an in our work.

  9. Infectious Meningitis and Encephalitis.

    PubMed

    Piquet, Amanda L; Lyons, Jennifer L

    2016-08-01

    The clinician who is evaluating a patient with a suspected central nervous system infection often faces a large differential diagnosis. There are several signs, symptoms, geographical clues, and diagnostic testing, such as cerebrospinal fluid abnormalities and magnetic resonance imaging abnormalities, which can be helpful in identifying the etiological agent. By taking a systematic approach, one can often identify life-threatening, common, and/or treatable etiologies. Here the authors describe some of the pearls and pitfalls in diagnosing and treating acute infectious meningitis and encephalitis. PMID:27643906

  10. Internal Ribosome Entry Site-Based Attenuation of a Flavivirus Candidate Vaccine and Evaluation of the Effect of Beta Interferon Coexpression on Vaccine Properties

    PubMed Central

    Frese, Michael; Lee, Eva; Larena, Maximilian; Lim, Pek Siew; Rao, Sudha; Matthaei, Klaus I.; Khromykh, Alexander; Ramshaw, Ian

    2014-01-01

    ABSTRACT Infectious clone technologies allow the rational design of live attenuated viral vaccines with the possibility of vaccine-driven coexpression of immunomodulatory molecules for additional vaccine safety and efficacy. The latter could lead to novel strategies for vaccine protection against infectious diseases where traditional approaches have failed. Here we show for the flavivirus Murray Valley encephalitis virus (MVEV) that incorporation of the internal ribosome entry site (IRES) of Encephalomyocarditis virus between the capsid and prM genes strongly attenuated virulence and that the resulting bicistronic virus was both genetically stable and potently immunogenic. Furthermore, the novel bicistronic genome organization facilitated the generation of a recombinant virus carrying an beta interferon (IFN-β) gene. Given the importance of IFNs in limiting virus dissemination and in efficient induction of memory B and T cell antiviral immunity, we hypothesized that coexpression of the cytokine with the live vaccine might further increase virulence attenuation without loss of immunogenicity. We found that bicistronic mouse IFN-β coexpressing MVEV yielded high virus and IFN titers in cultured cells that do not respond to the coexpressed IFN. However, in IFN response-sufficient cell cultures and mice, the virus produced a self-limiting infection. Nevertheless, the attenuated virus triggered robust innate and adaptive immune responses evidenced by the induced expression of Mx proteins (used as a sensitive biomarker for measuring the type I IFN response) and the generation of neutralizing antibodies, respectively. IMPORTANCE Flaviviridae Dengue virus Yellow fever virus Japanese encephalitis virus West Nile virus Hepatitis C virus Dengue virus Hepatitis C virus PMID:24307589

  11. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    PubMed

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  12. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    PubMed

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  13. Vaccination for safe travel to India.

    PubMed

    Mehta, Bharti; Jindal, Harashish; Bhatt, Bhumika; Kumar, Vijay; Singh Choudhary, Satvinder

    2014-01-01

    Worldwide more than 900 million international journeys are undertaken every year. India is one of the favorite tourist destinations around the world. International travel exposes travelers to a range of health risks. Traveling to India possess a threat to travelers with waterborne diseases like bacterial diarrhea, hepatitis A and E, and typhoid fever; vector borne diseases like dengue fever, Japanese encephalitis, and malaria; animal contact disease like rabies. Furthermore diseases spreading through behavior aspects cannot be ruled out hence posing a risk for hepatitis B, HIV/AIDS, hepatitis C as well. Hence, before travel the travelers are advised about the risk of disease in the country or countries they plan to visit and the steps to be taken to prevent illness. Vaccination offers the possibility of avoiding a number of infectious diseases that may be countered abroad. There is no single vaccination schedule that fits all travelers. Each schedule must be individualized according to the traveler's previous immunizations, countries to be visited, type and duration of travel, and the amount of time available before departure. PMID:24284411

  14. Vaccination for safe travel to India.

    PubMed

    Mehta, Bharti; Jindal, Harashish; Bhatt, Bhumika; Kumar, Vijay; Singh Choudhary, Satvinder

    2014-01-01

    Worldwide more than 900 million international journeys are undertaken every year. India is one of the favorite tourist destinations around the world. International travel exposes travelers to a range of health risks. Traveling to India possess a threat to travelers with waterborne diseases like bacterial diarrhea, hepatitis A and E, and typhoid fever; vector borne diseases like dengue fever, Japanese encephalitis, and malaria; animal contact disease like rabies. Furthermore diseases spreading through behavior aspects cannot be ruled out hence posing a risk for hepatitis B, HIV/AIDS, hepatitis C as well. Hence, before travel the travelers are advised about the risk of disease in the country or countries they plan to visit and the steps to be taken to prevent illness. Vaccination offers the possibility of avoiding a number of infectious diseases that may be countered abroad. There is no single vaccination schedule that fits all travelers. Each schedule must be individualized according to the traveler's previous immunizations, countries to be visited, type and duration of travel, and the amount of time available before departure.

  15. [Vaccination therapy for Alzheimer's disease].

    PubMed

    Tabira, Takeshi

    2009-11-01

    Since AN-1792 vaccine induced autoimmune encephalitis, several pharmaceutical companies are now concentrated in developing antibody therapy in Alzheimer's disease (AD). Each antibody has own characteristics. Thus, it is unpredictable at present which antibody is the most beneficial until we see the result of clinical trials. If disease modifying antibodies were found, they will be widely used for treatment of AD in near future. As a candidate of such antibodies, we have developed TAPIR-like antibody with much higher affinity to Abeta42 than Abeta40, and it effectively deleted senile plaque amyloid and Abeta oligomers without increasing microhemorrhages. Although passive immunization can avoid autoimmune encephalitis, it is expensive and it is not suitable for prevention. Thus, safe vaccines by active immunization would be better. Vaccines that induce Th2 type immune responses such as oral vaccine or per-nasal vaccine would be promising. PMID:20030228

  16. [Meningitis and encephalitis in Poland in 2008].

    PubMed

    Turczyńska, Aleksandra; Polkowska, Aleksandra

    2010-01-01

    In Poland, 2 475 cases of neuroinfections were reported in 2008, of which 979 had bacterial aetiology, 1 122--viral aetiology, and 374--other or unknown origin. The etiological agent was determined in 555 (56%) cases of bacterial neuroinfections. Among them Neisseria meningitidis was found in 220 cases, Haemophilus influenzae type B (Hib) in 23 cases and Streptococcus pneumoniae in 151 cases. An increasing trend in meningococcal infections incidence has been observed in 2008, and a substantial decrease of Hib incidence, related to increasing vaccination coverage. Viral neuroinfections incidence in 2008 decreased compared to year 2007. Among confirmed cases, there were 202 cases of tick-borne encephalitis. Most of the cases were reported from endemic areas of north-eastern part of the country.

  17. [Meningitis and encephalitis in Poland in 2009].

    PubMed

    Polkowska, Aleksandra

    2011-01-01

    In Poland, 2 517 cases of neuroinfections were reported in 2009, of which 865 had bacterial aetiology, 1 244--viral aetiology, and 408-- other or unknown origin. The etiological agent was determined in 493 (57%) cases of bacterial neuroinfections. Among them Neisseria meningitidis was found in 190 cases, Haemophilus influenzae type B (Hib) in 13 cases and Streptococcus pneumoniae in 163 cases. An increasing trend in pneumococcal infections incidence has been observed since 2005, and a substantial decrease of Hib incidence, related to increasing vaccination coverage. Viral neuroinfections incidence in 2009 increased compared to year 2008. Among confirmed cases, there were 351 cases of tick-borne encephalitis. Most of the cases were reported from endemic areas of north-eastern part of the country.

  18. [Meningitis and encephalitis in Poland in 2007].

    PubMed

    Lankiewicz, Aleksandra; Polkowska, Aleksandra; Chrześcijańska, Irena; Kicman-Gawłowska, Agnieszka; Stefanoff, Paweł

    2009-01-01

    In Poland, 3,361 cases of neuroinfections were reported in 2007, of which 1,078 had bacterial etiology, 1,717--viral aetiology, and 566--other or unknown origin. The etiological agent was determined in 611 (57%) cases of bacterial neuroinfections. Among them N. meningitidis was found in 224 cases, H. influenzae type B (Hib) in 35 cases and S. pneumoniae in 161 cases. An increasing trend in meningococcal infections incidence has been observed in 2007, and a substantial decrease ofHib incidence, related to increasing vaccination coverage. Viral neuroinfections incidence in 2007 increased compared to year 2006. Among confirmed cases, there were 233 cases oftick-borne encephalitis. Most of the cases were reported from endemic areas of north-eastern part of the country.

  19. Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

    PubMed Central

    Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  20. Reading Recovery Following Herpes Encephalitis.

    ERIC Educational Resources Information Center

    Rogers, C. D.; Peters, Phyllis

    1979-01-01

    The article presents the medical, psychological, and reading diagnoses of a 24-year-old man with herpes encephalitis, an acute neurological disease. Test results are reported and the client's response to learning disability remedial techniques are reviewed. (SBH)

  1. The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: development of new live flavivirus vaccines.

    PubMed

    Bonaldo, M C; Caufour, P S; Freire, M S; Galler, R

    2000-01-01

    The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF), dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.

  2. Systematic review of economic evaluations of vaccination programs in mainland China: Are they sufficient to inform decision making?

    PubMed

    Pan, Xiong-Fei; Griffiths, Ulla K; Pennington, Mark; Yu, Hongjie; Jit, Mark

    2015-11-17

    The purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland China. We searched for economic evaluations of vaccination in China published prior to August 3, 2015 in eight English-language and three Chinese-language databases. Each article was appraised against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We found 23 papers evaluating vaccines against hepatitis B (8 articles), Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles), Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1 article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six Chinese-language articles conformed to fewer than half of the 19 criteria items. The main criteria that studies failed to conform to included: inappropriate measurement (20 articles) and valuation (18 articles) of treatment and/or vaccination costs, no discussion about distributional implications (18 articles), missing major health outcomes (14 articles), no discussion about generalizability to other contexts (14 articles), and inadequate sensitivity analysis (13 articles). In addition, ten studies did not include major cost components of vaccination programs, and nine did not report outcomes in terms of life years even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a societal perspective for analysis. All studies concluded that the appraised vaccination programs were cost-effective except for one evaluation of universal 7-valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the five studies on PCV-7 showed poor overall quality, and the number of studies on vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion, major methodological flaws and reporting problems exist in current economic evaluations of vaccination programs in China. Local

  3. Systematic review of economic evaluations of vaccination programs in mainland China: Are they sufficient to inform decision making?

    PubMed

    Pan, Xiong-Fei; Griffiths, Ulla K; Pennington, Mark; Yu, Hongjie; Jit, Mark

    2015-11-17

    The purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland China. We searched for economic evaluations of vaccination in China published prior to August 3, 2015 in eight English-language and three Chinese-language databases. Each article was appraised against the 19-item Consensus on Health Economic Criteria list (CHEC-list). We found 23 papers evaluating vaccines against hepatitis B (8 articles), Streptococcus pneumoniae (5 articles), human papillomavirus (3 articles), Japanese encephalitis (2 articles), rotavirus (2 articles), hepatitis A (1 article), Enterovirus 71 (1 article) and influenza (1 article). Studies conformed to a mean of 12 (range: 6-18) items in the CHEC-list criteria. Five of six Chinese-language articles conformed to fewer than half of the 19 criteria items. The main criteria that studies failed to conform to included: inappropriate measurement (20 articles) and valuation (18 articles) of treatment and/or vaccination costs, no discussion about distributional implications (18 articles), missing major health outcomes (14 articles), no discussion about generalizability to other contexts (14 articles), and inadequate sensitivity analysis (13 articles). In addition, ten studies did not include major cost components of vaccination programs, and nine did not report outcomes in terms of life years even in cases where QALYs or DALYs were calculated. Only 13 studies adopted a societal perspective for analysis. All studies concluded that the appraised vaccination programs were cost-effective except for one evaluation of universal 7-valent pneumococcal conjugate vaccine (PCV-7) in children. However, three of the five studies on PCV-7 showed poor overall quality, and the number of studies on vaccines other than hepatitis B vaccine and PCV-7 was limited. In conclusion, major methodological flaws and reporting problems exist in current economic evaluations of vaccination programs in China. Local

  4. Internal ribosome entry site-based attenuation of a flavivirus candidate vaccine and evaluation of the effect of beta interferon coexpression on vaccine properties.

    PubMed

    Frese, Michael; Lee, Eva; Larena, Maximilian; Lim, Pek Siew; Rao, Sudha; Matthaei, Klaus I; Khromykh, Alexander; Ramshaw, Ian; Lobigs, Mario

    2014-02-01

    Infectious clone technologies allow the rational design of live attenuated viral vaccines with the possibility of vaccine-driven coexpression of immunomodulatory molecules for additional vaccine safety and efficacy. The latter could lead to novel strategies for vaccine protection against infectious diseases where traditional approaches have failed. Here we show for the flavivirus Murray Valley encephalitis virus (MVEV) that incorporation of the internal ribosome entry site (IRES) of Encephalomyocarditis virus between the capsid and prM genes strongly attenuated virulence and that the resulting bicistronic virus was both genetically stable and potently immunogenic. Furthermore, the novel bicistronic genome organization facilitated the generation of a recombinant virus carrying an beta interferon (IFN-β) gene. Given the importance of IFNs in limiting virus dissemination and in efficient induction of memory B and T cell antiviral immunity, we hypothesized that coexpression of the cytokine with the live vaccine might further increase virulence attenuation without loss of immunogenicity. We found that bicistronic mouse IFN-β coexpressing MVEV yielded high virus and IFN titers in cultured cells that do not respond to the coexpressed IFN. However, in IFN response-sufficient cell cultures and mice, the virus produced a self-limiting infection. Nevertheless, the attenuated virus triggered robust innate and adaptive immune responses evidenced by the induced expression of Mx proteins (used as a sensitive biomarker for measuring the type I IFN response) and the generation of neutralizing antibodies, respectively. IMPORTANCE The family Flaviviridae includes a number of important human pathogens, such as Dengue virus, Yellow fever virus, Japanese encephalitis virus, West Nile virus, and Hepatitis C virus. Flaviviruses infect large numbers of individuals on all continents. For example, as many as 100 million people are infected annually with Dengue virus, and 150 million people

  5. An epidemiological study on Japanese autism concerning routine childhood immunization history.

    PubMed

    Takahashi, Hiroshi; Suzumura, Shynsuke; Shirakizawa, Fumiko; Wada, Noriyuki; Tanaka-Taya, Keiko; Arai, Satoru; Okabe, Nobuhiko; Ichikawa, Hironobu; Sato, Taizo

    2003-06-01

    To assess the causal association of autism with measles, mumps, and rubella (MMR) vaccine versus that with monovalent measles, mumps, and rubella immunization, a 1:2 sex-adjusted logistic regression analysis was conducted using data on subjects who were growing up in the Tokyo area between 1988 and 1992. When MMR immunization was used as a reference, monovalent measles immunization (odds ratio [OR] = 5.33, 99% confidence interval [CI]: 1.03-27.74), non-mumps immunization (OR = 8, 99%CI: 1.33-48.2), and non-rubella immunization (OR = 8.57, 99%CI: 1.30-56.4) with development of autistic spectrum disorders (ASD) were significantly increased. These results suggest a decreased risk of developing ASD with MMR compared to monovalent antigens. However, our findings may reflect potential selection bias due to requiring written consent, possible delayed vaccination in suspected autism cases, and small sample size (case = 21). For the case group and the control group, immunization completeness rate of each antigen, regardless of the timing of immunization, was 90.5% versus 100% in measles, 42.9% versus 78.6% in mumps (P < 0.01), 52.3% versus 83.3% in rubella (P < 0.01), 14.3% versus 45.2% in varicella (P < 0.01), 100% versus 90.5% in polio>2, 100% versus 97.6% in Diphtheria (D), pertussis, and tetanus (T)>3, 85.7% versus 66.7% in DT, 95.2% versus 92.9% in BCG, and 52.4% versus 81.0% in Japanese encephalitis>3 (P<0.01). Only two case subjects and four control subjects received their measles, mumps, and rubella immunizations separately, suggesting that few Japanese parents might have had concerns about the safety of MMR vaccine. A nation-wide study would be a practical measure to scientifically judge the safety of MMR and other routine childhood immunizations.

  6. An epidemiological study on Japanese autism concerning routine childhood immunization history.

    PubMed

    Takahashi, Hiroshi; Suzumura, Shynsuke; Shirakizawa, Fumiko; Wada, Noriyuki; Tanaka-Taya, Keiko; Arai, Satoru; Okabe, Nobuhiko; Ichikawa, Hironobu; Sato, Taizo

    2003-06-01

    To assess the causal association of autism with measles, mumps, and rubella (MMR) vaccine versus that with monovalent measles, mumps, and rubella immunization, a 1:2 sex-adjusted logistic regression analysis was conducted using data on subjects who were growing up in the Tokyo area between 1988 and 1992. When MMR immunization was used as a reference, monovalent measles immunization (odds ratio [OR] = 5.33, 99% confidence interval [CI]: 1.03-27.74), non-mumps immunization (OR = 8, 99%CI: 1.33-48.2), and non-rubella immunization (OR = 8.57, 99%CI: 1.30-56.4) with development of autistic spectrum disorders (ASD) were significantly increased. These results suggest a decreased risk of developing ASD with MMR compared to monovalent antigens. However, our findings may reflect potential selection bias due to requiring written consent, possible delayed vaccination in suspected autism cases, and small sample size (case = 21). For the case group and the control group, immunization completeness rate of each antigen, regardless of the timing of immunization, was 90.5% versus 100% in measles, 42.9% versus 78.6% in mumps (P < 0.01), 52.3% versus 83.3% in rubella (P < 0.01), 14.3% versus 45.2% in varicella (P < 0.01), 100% versus 90.5% in polio>2, 100% versus 97.6% in Diphtheria (D), pertussis, and tetanus (T)>3, 85.7% versus 66.7% in DT, 95.2% versus 92.9% in BCG, and 52.4% versus 81.0% in Japanese encephalitis>3 (P<0.01). Only two case subjects and four control subjects received their measles, mumps, and rubella immunizations separately, suggesting that few Japanese parents might have had concerns about the safety of MMR vaccine. A nation-wide study would be a practical measure to scientifically judge the safety of MMR and other routine childhood immunizations. PMID:12944678

  7. Turning Japanese?

    ERIC Educational Resources Information Center

    Huwitz, Nina

    1990-01-01

    Relates observations of the Japanese educational system by a U.S. high school history teacher. Finds the Japanese system impressive but argues that such a centralized and authoritarian system would not work in the United States. Educators should learn from Japanese schools, not copy them. Recommends U.S. educators seek agreement on educational…

  8. Things Japanese.

    ERIC Educational Resources Information Center

    Shigeta, Jessie M.

    Presented in this booklet are brief descriptions of items and activities that are symbolic of Japanese culture. Some of the items and activities described include Japanese musical instruments and records, toys and crafts, traditional clothing and accessories, and food utensils. Several recipes for Japanese dishes are provided. Lists of pertinent…

  9. Japanese language and Japanese science

    NASA Astrophysics Data System (ADS)

    Tanikawa, Kiyotaka

    2003-08-01

    Japanese mathematical scientists including astronomers, physicists, and mathematicians obtain ideas in Japanese, discuss their problems in Japanese, and arrive at conclusions in Japanese, and yet they write their results in foreign languages such as English. This uncomfortable situation has continued for nearly one hundred years and has had serious effects on Japanese science. In this short report, the author discusses and analyses these effects. In order to put Japanese science on a sound basis, the author proposes to increase the number of articles, reviews and textbooks in Japanese, first by translation and second by the voluntary efforts of scientists themselves. As centers devoted to this activity, the author proposes to construct "Airborne Libraries" which are maintained and accumulate in an electronic form the scientific documents written in Japanese.

  10. Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management

    PubMed Central

    Bogovic, Petra; Strle, Franc

    2015-01-01

    Tick-borne encephalitis is an infection of central nervous system caused by tick-borne encephalitis virus transmitted to humans predominantly by tick bites. During the last few decades the incidence of the disease has been increasing and poses a growing health problem in almost all endemic European and Asian countries. Most cases occur during the highest period of tick activity, in Central Europe mainly from April to November. Tick-borne encephalitis is more common in adults than in children. Clinical spectrum of the disease ranges from mild meningitis to severe meningoencephalitis with or without paralysis. Rare clinical manifestations are an abortive form of the disease and a chronic progressive form. A post-encephalitic syndrome, causing long-lasting morbidity that often affects the quality of life develops in up to 50% of patients after acute tick-borne encephalitis. Clinical course and outcome vary by subtype of tick-borne encephalitis virus (the disease caused by the European subtype has milder course and better outcome than the disease caused by Siberian and Far-Easter subtypes), age of patients (increasing age is associated with less favorable outcome), and host genetic factors. Since clinical features and laboratory results of blood and cerebrospinal fluid are nonspecific, the diagnosis must be confirmed by microbiologic findings. The routine laboratory confirmation of the tick-borne encephalitis virus infection is based mainly on the detection of specific IgM and IgG antibodies in serum (and cerebrospinal fluid), usually by enzyme-linked immunosorbent assay. There is no specific antiviral treatment for tick-borne encephalitis. Vaccination can effectively prevent the disease and is indicated for persons living in or visiting tick-borne encephalitis endemic areas. PMID:25984517

  11. Dengue encephalitis in French Guiana.

    PubMed

    Hommel, D; Talarmin, A; Deubel, V; Reynes, J M; Drouet, M T; Sarthou, J L; Hulin, A

    1998-01-01

    Thousands of cases of dengue fever (DF) and several cases of dengue haemorrhagic fever were recorded in French Guiana during the recent outbreak of dengue-2 virus (1991-1992) and in subsequent years. One case with clinical signs typical of classical DF with neurological complications is reported in this study. The neurological features (encephalitis) appeared during the acute phase, 2 days after the onset of fever. Dengue-2 virus was detected in both the cerebrospinal fluid and blood sample. This case was fatal. This first reported case of classical DF with encephalitis in French Guiana is a new demonstration of the potential neurovirulence of dengue viruses.

  12. Efficacy of eastern encephalitis immunization in whooping cranes

    USGS Publications Warehouse

    Olsen, G.H.; Turell, M.J.; Pagac, B.B.

    1997-01-01

    An epizootic of eastern equine encephalitis (EEE) at the Patuxent Wildlife Research Center (PWRC), Laurel, Maryland (USA), in 1989 provided an opportunity to determine if EEE immunization protected whooping cranes (Grus americana). Based on seroconversion of 31 % of sympatric hatch-year sandhill cranes, Grus canadensis, and a previous 35% case fatality rate in whooping cranes, 17 (37%) of the 46 susceptible whooping cranes should have been exposed to virus and six should have died. As there were no deaths in these birds, the EEE vaccination program appeared to be efficacious in this whooping crane population.

  13. Refusal of recommended travel-related vaccines among U.S. international travellers in Global TravEpiNet

    PubMed Central

    Lammert, Sara M.; Rao, Sowmya R.; Jentes, Emily S.; Fairley, Jessica K.; Erskine, Stefanie; Walker, Allison T.; Hagmann, Stefan H.; Sotir, Mark J.; Ryan, Edward T.

    2016-01-01

    Background: International travellers are at risk of travel-related, vaccine-preventable diseases. More data are needed on the proportion of travellers who refuse vaccines during a pre-travel health consultation and their reasons for refusing vaccines. Methods: We analyzed data on travellers seen for a pre-travel health consultation from July 2012 through June 2014 in the Global TravEpiNet (GTEN) consortium. Providers were required to indicate one of three reasons for a traveller refusing a recommended vaccine: (1) cost concerns, (2) safety concerns or (3) not concerned with the illness. We calculated refusal rates among travellers eligible for each vaccine based on CDC recommendations current at the time of travel. We used multivariable logistic regression models to examine the effect of individual variables on the likelihood of accepting all recommended vaccines. Results: Of 24 478 travellers, 23 768 (97%) were eligible for at least one vaccine. Travellers were most frequently eligible for typhoid (N = 20 092), hepatitis A (N = 12 990) and influenza vaccines (N = 10 539). Of 23 768 eligible travellers, 6573 (25%) refused one or more recommended vaccine(s). Of those eligible, more than one-third refused the following vaccines: meningococcal: 2232 (44%) of 5029; rabies: 1155 (44%) of 2650; Japanese encephalitis: 761 (41%) of 1846; and influenza: 3527 (33%) of 10 539. The most common reason for declining vaccines was that the traveller was not concerned about the illness. In multivariable analysis, travellers visiting friends and relatives (VFR) in low or medium human development countries were less likely to accept all recommended vaccines, compared with non-VFR travellers (OR = 0.74 (0.59–0.95)). Conclusions: Travellers who sought pre-travel health care refused recommended vaccines at varying rates. A lack of concern about the associated illness was the most commonly cited reason for all refused vaccines. Our data suggest more effective

  14. A case of dengue hemorrhagic fever in a Japanese child.

    PubMed

    Okuno, Y; Harada, T; Ogawa, M; Okamoto, Y; Maeda, K

    1989-01-01

    A 6-year-old Japanese girl contracted a febrile illness with hemorrhagic manifestations when she traveled in Indonesia. A remarkable decrease in the numbers of platelets and white blood cells was observed in her acute-phase blood specimens. Her father, who accompanied her, showed dengue fever-like symptoms at almost the same time as her illness. It was determined by serological tests that they were infected with dengue virus type 1. Moreover, she showed a secondary antibody response to the flavivirus due to the pre-existing antibody to Japanese encephalitis virus. This is the first confirmed case of dengue hemorrhagic fever (DHF) in Japanese people.

  15. [Autoimmune Associated Encephalitis and Dementia].

    PubMed

    Watanabe, Osamu

    2016-04-01

    Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.

  16. [Autoimmune Associated Encephalitis and Dementia].

    PubMed

    Watanabe, Osamu

    2016-04-01

    Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution. PMID:27056852

  17. [Update on Herpes Simplex Encephalitis].

    PubMed

    Kuroda, Hiroshi

    2015-07-01

    Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K+ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing.

  18. Ebola Virus-Related Encephalitis.

    PubMed

    de Greslan, Thierry; Billhot, Magali; Rousseau, Claire; Mac Nab, Christine; Karkowski, Ludovic; Cournac, Jean-Marie; Bordes, Julien; Gagnon, Nicolas; Dubrous, Philippe; Duron, Sandrine; Moroge, Sophie; Quentin, Benoit; Koulibaly, Fassou; Bompaire, Flavie; Renard, Jean-Luc; Cellarier, Gilles

    2016-10-15

    Ebola patients frequently exhibit behavioral modifications with ideation slowing and aggressiveness, sometimes contrasting with mild severity of Ebola disease. We performed lumbar punctures in 3 patients with this presentation and found Ebola virus in all cerebrospinal fluid samples. This discovery helps to discuss the concept of a specific Ebola virus encephalitis. PMID:27418576

  19. [Update on Herpes Simplex Encephalitis].

    PubMed

    Kuroda, Hiroshi

    2015-07-01

    Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K+ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing. PMID:26160820

  20. Study of infection with an Iranian field-isolated H9N2 avian influenza virus in vaccinated and unvaccinated Japanese quail.

    PubMed

    Ebrahimi, Seyyed Mahmoud; Ziapour, Soudeh; Tebianian, Majid; Dabaghian, Mehran; Mohammadi, Mashallah

    2011-06-01

    In the present study, we examined the mortality rate, egg production, and clinical signs of quail experimentally infected with a field isolate of A/Chicken/Iran/339/02 (H9N2) avian influenza virus obtained from an infected commercial layer farm with severe morbidity and mortality. A total of 120 quail at 14 days old were randomly divided into four groups of vaccinated (B and C) and unvaccinated (A and D) birds. Vaccination was done on days 20 and 32, and viral inoculation of birds in groups C and D was then carried out on day 43. For evaluation of viral transmission, at 24 hr postinoculation additional unvaccinated birds were placed in direct contact with challenged birds. All the birds were evaluated for clinical signs, egg production, antibody production, viral titration in lung homogenates, and viral transmission following inoculation. All unvaccinated-challenged birds were infected and showed clinical signs, whereas the infection rate along with clinical signs of vaccinated-challenged birds reached 30%-40%. Although vaccination induced high antibody titers, reduction in food and water consumption was evident in this vaccinated-challenged group compared with the unchallenged control group. These results could indicate that inactivated vaccine did not fully prevent the infection, although it was capable of protecting birds against clinical signs and significantly decreased viral titers in lungs after intranasal challenge.

  1. Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

    PubMed

    Azumagawa, Kohji; Nomura, Shohei; Shigeri, Yasushi; Jones, Leslie Sargent; Sato, Douglas Kazutoshi; Nakashima, Ichiro; Kashiwagi, Mitsuru; Tanabe, Takuya; Shimakawa, Shuichi; Nakajima, Hideto; Tamai, Hiroshi

    2016-08-01

    The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection.

  2. Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

    PubMed

    Azumagawa, Kohji; Nomura, Shohei; Shigeri, Yasushi; Jones, Leslie Sargent; Sato, Douglas Kazutoshi; Nakashima, Ichiro; Kashiwagi, Mitsuru; Tanabe, Takuya; Shimakawa, Shuichi; Nakajima, Hideto; Tamai, Hiroshi

    2016-08-01

    The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection. PMID:26922251

  3. Dengue haemorrhagic fever and Japanese B encephalitis in Indonesia.

    PubMed

    Nathin, M A; Harun, S R; Sumarmo

    1988-09-01

    Dengue haemorrhagic fever (DHF) was first recognized in Indonesia in the cities of Jakarta and Surabaya in 1968, 15 years after its recognition in the Philippines. During the 1968 outbreak, a total of 58 clinical cases with 24 deaths were reported. The number of reported cases since then has increased sharply, with the highest number of cases recorded in the years 1973 (10,189 cases), 1983 (13,668 cases), and 1985 (13,588 cases). Outbreaks of the disease have spread to involve most of the major urban areas, as well as some of the rural areas. In 1985, the disease had spread to 26 of 27 Provinces and 160 of 300 regencies of municipalities. At present, the disease is endemic in many large cities and small towns. Interestingly, DHF has not been reported in some cities, even though dengue virus transmission rates in those cities are high. The epidemic pattern of DHF for the country as a whole has become irregular. Since 1982, the intensity and spread of DHF has created an increasing public health problem in Indonesia, particularly in Java where 60% of the total population of the country resides. Java contributed about 71% of all cases occurring in the country in 1982, 84% in 1983, and 91% in 1984. The peak monthly incidence of DHF was frequently reported during October through April, months which coincide with the rainy season. The morbidity rate for Indonesia, estimated from reported cases over five years (1981-1985), ranged between 3.39 to 8.65 per 100,000 population. The overall case fatality rate has steadily declined from 41.3% in 1968 to 3% in 1984.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Prospective safety monitoring of Haemophilus influenzae type b and heptavalent pneumococcal conjugate vaccines in Kagoshima, Japan.

    PubMed

    Nishi, Junichiro; Tokuda, Koichi; Imuta, Naoko; Minami, Taketsugu; Kawano, Yoshifumi

    2013-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine (PRP-T) and heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in December 2008 and February 2010, respectively. The concurrent administration of these vaccines is routinely performed worldwide. However, the safety of the simultaneous administration of these vaccines has not been fully evaluated in Japan, because it has rarely been performed thus far. We conducted a 2-year prospective, observational, multicenter study on PRP-T and PCV7 safety from February 2009 through January 2011 in 29 facilities located in Kagoshima Prefecture, Japan. Objective severe adverse events included anaphylactoid reaction, encephalitis/encephalopathy, neurological events, severe focal reactions, systemic eruption/urticaria, fever above 39℃ within 2 days after inoculation, and other complications requiring hospitalization. The incidences of these events for PRP-T and PCV7 administration were 0.68% (76/11,197) and 0.92% (28/3,049), respectively. No deaths or subsequent complications were reported during the course of the study. There was no significant difference in the incidence of severe adverse events between the single and co-administration groups for both vaccines: PRP-T, 0.55% (31/5,662) versus 0.81% (45/5,535; P = 0.11); PCV7, 0.88% (11/1,247) versus 0.94% (17/1,802; P = 0.86). These results suggest that the simultaneous administration of vaccines including PRP-T and/or PCV7 does not increase the incidence of severe adverse events in Japanese children.

  5. Acute Measles Encephalitis in an Immigrant Syrian Child: Case Report and Review of the Literature.

    PubMed

    Al-Qayoudhi, Abdullah; Al-Kindi, Hanan; Meki, Nabil; Al-Maani, Amal

    2016-03-01

    The introduction of measles vaccination programs and broad coverage worldwide has meant this infection a rare encounter for pediatricians. In Oman, with almost 100% measles vaccination coverage for children, this infection disappeared from the list of fever and rash differential diagnoses. Encephalitis is a well-known complication of measles infection and sometimes can be the only manifestation especially in adults. We report a seven-year-old Syrian immigrant who was admitted to the Royal Hospital, Muscat, with acute encephalitis secondary to wild measles infection. Although she had a classical presentation of measle infection, the diagnosis was missed in the private and regional hospital she attended before getting referred to Royal Hospital. She was later identified to be exposed to an outbreak of the infection in an unvaccinated population. Magnetic resonance imaging showed high signal intensity of both basal ganglia suggestive of measles encephalitis. The diagnosis was confirmed by detection of measles virus from her urine and blood, and a throat swab. The isolated measles virus was D8 serotype, which was prevalent in Syria around the same time. The child was treated with steroids and vitamin A. She achieved full recovery despite her severe presentation. A high degree of suspicion for measles infection should be maintained in unvaccinated children with a compatible presentation of the infection or its complications. There might be a role for steroid use in cases of acute measles encephalitis. PMID:27168928

  6. Acute Measles Encephalitis in an Immigrant Syrian Child: Case Report and Review of the Literature

    PubMed Central

    Al-Qayoudhi, Abdullah; Al-Kindi, Hanan; Meki, Nabil; Al-Maani, Amal

    2016-01-01

    The introduction of measles vaccination programs and broad coverage worldwide has meant this infection a rare encounter for pediatricians. In Oman, with almost 100% measles vaccination coverage for children, this infection disappeared from the list of fever and rash differential diagnoses. Encephalitis is a well-known complication of measles infection and sometimes can be the only manifestation especially in adults. We report a seven-year-old Syrian immigrant who was admitted to the Royal Hospital, Muscat, with acute encephalitis secondary to wild measles infection. Although she had a classical presentation of measle infection, the diagnosis was missed in the private and regional hospital she attended before getting referred to Royal Hospital. She was later identified to be exposed to an outbreak of the infection in an unvaccinated population. Magnetic resonance imaging showed high signal intensity of both basal ganglia suggestive of measles encephalitis. The diagnosis was confirmed by detection of measles virus from her urine and blood, and a throat swab. The isolated measles virus was D8 serotype, which was prevalent in Syria around the same time. The child was treated with steroids and vitamin A. She achieved full recovery despite her severe presentation. A high degree of suspicion for measles infection should be maintained in unvaccinated children with a compatible presentation of the infection or its complications. There might be a role for steroid use in cases of acute measles encephalitis. PMID:27168928

  7. [Anti-NMDA-receptor encephalitis].

    PubMed

    Engen, Kristine; Agartz, Ingrid

    2016-06-01

    BACKGROUND In 2007 a clinical disease caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor was described for the first time. Anti-NMDA-receptor encephalitis is a subacute, autoimmune neurological disorder with psychiatric manifestations. The disease is a form of limbic encephalitis and is often paraneoplastic. The condition is also treatable. In this review article we examine the development of the disease, clinical practice, diagnostics and treatment.MATERIAL AND METHOD The article is based on references retrieved from searches in PubMed, and a discretionary selection of articles from the authors' own literature archive.RESULTS The disease most frequently affects young women. It may initially be perceived as a psychiatric condition, as it usually presents in the form of delusions, hallucinations or mania. The diagnosis should be suspected in patients who later develop neurological symptoms such as various movement disorders, epileptic seizures and autonomic instability. Examination of serum or cerebrospinal fluid for NMDA receptor antibodies should be included in the assessment of patients with suspected encephalitis. MRI, EEG and assessment for tumours are important tools in diagnosing the condition and any underlying malignancy.INTERPRETATION If treatment is initiated early, the prognosis is good. Altogether 75 % of patients will fully recover or experience significant improvement. Apart from surgical resection of a possible tumour, the treatment consists of immunotherapy. Because of good possibilities for treatment, it is important that clinicians, particularly those in acute psychiatry, are aware of and alert to this condition. PMID:27325034

  8. Genetic characterization of Bagaza virus (BAGV) isolated in India and evidence of anti-BAGV antibodies in sera collected from encephalitis patients.

    PubMed

    Bondre, Vijay P; Sapkal, Gajanan N; Yergolkar, Prasanna N; Fulmali, Pradip V; Sankararaman, Vasudha; Ayachit, Vijay M; Mishra, Akhilesh C; Gore, Milind M

    2009-11-01

    During investigations into the outbreak of encephalitis in 1996 in the Kerala state in India, an arbovirus was isolated from a Culex tritaeniorhynchus mosquito pool. It was characterized as a Japanese encephalitis and West Nile virus cross-reactive arbovirus by complement fixation test. A plaque reduction-neutralization test was performed using hyperimmune sera raised against the plaque-purified arbovirus isolate. The sera did not show reactivity with Japanese encephalitis virus and were weakly reactive with West Nile virus. Complete open reading frame sequence analysis characterized the arbovirus as Bagaza virus (BAGV), with 94.80 % nucleotide identity with African BAGV strain DakAr B209. Sera collected from the encephalitic patients during the acute phase of illness showed 15 % (8/53) positivity for anti-BAGV neutralizing antibodies. This is the first report of the isolation of BAGV from India. The presence of anti-BAGV neutralizing antibodies suggests that the human population has been exposed to BAGV.

  9. Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

    DOE PAGESBeta

    Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.; Fang, Ying; Wheeler, Sarah S.; Coffey, Lark L.

    2016-01-25

    In this study, collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized publicmore » health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.« less

  10. Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification

    PubMed Central

    Wheeler, Sarah S.; Ball, Cameron S.; Langevin, Stanley A.; Fang, Ying; Coffey, Lark L.; Meagher, Robert J.

    2016-01-01

    Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance. PMID:26807734

  11. Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification.

    PubMed

    Wheeler, Sarah S; Ball, Cameron S; Langevin, Stanley A; Fang, Ying; Coffey, Lark L; Meagher, Robert J

    2016-01-01

    Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3' untranslated region (3'-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.

  12. Surveillance for Western Equine Encephalitis, St. Louis Encephalitis, and West Nile Viruses Using Reverse Transcription Loop-Mediated Isothermal Amplification.

    PubMed

    Wheeler, Sarah S; Ball, Cameron S; Langevin, Stanley A; Fang, Ying; Coffey, Lark L; Meagher, Robert J

    2016-01-01

    Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3' untranslated region (3'-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance. PMID:26807734

  13. Molecular characterization of two Rocio flavivirus strains isolated during the encephalitis epidemic in São Paulo State, Brazil and the development of a one-step RT-PCR assay for diagnosis.

    PubMed

    Coimbra, Terezinha Lisieux Moraes; Santos, Raimundo N; Petrella, Selma; Nagasse-Sugahara, Teresa Keico; Castrignano, Silvana Beres; Santos, Cecília L Simões

    2008-01-01

    Rocio virus (ROCV) was responsible for an explosive encephalitis epidemic in the 1970s affecting about 1,000 residents of 20 coastland counties in São Paulo State, Brazil. ROCV was first isolated in 1975 from the cerebellum of a fatal human case of encephalitis. Clinical manifestations of the illness are similar to those described for St. Louis encephalitis. ROCV shows intense antigenic cross-reactivity with Japanese encephalitis complex (JEC) viruses, particularly with Ilheus (ILHV), St. Louis encephalitis, Murray Valley and West Nile viruses. In this study, we report a specific RT-PCR assay for ROCV diagnosis and the molecular characterization of the SPAn37630 and SPH37623 strains. Partial nucleotide sequences of NS5 and E genes determined from both strains were used in phylogenetic analysis. The results indicated that these strains are closely related to JEC viruses, but forming a distinct subclade together with ILHV, in accordance with results recently reported by Medeiros et al. (2007).

  14. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  15. Autoimmune encephalitis and its relation to infection.

    PubMed

    Venkatesan, Arun; Benavides, David R

    2015-03-01

    Encephalitis, an inflammatory condition of the brain that results in substantial morbidity and mortality, has numerous causes. Over the past decade, it has become increasingly recognized that autoimmune conditions contribute significantly to the spectrum of encephalitis causes. Clinical suspicion and early diagnosis of autoimmune etiologies are of particular importance due to the need for early institution of immune suppressive therapies to improve outcome. Emerging clinical observations suggest that the most commonly recognized cause of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, may in some cases be triggered by herpes virus infection. Other conditions such as Rasmussen's encephalitis (RE) and febrile infection-related epilepsy syndrome (FIRES) have also been posited to be autoimmune conditions triggered by infectious agents. This review focuses on emerging concepts in central nervous system autoimmunity and addresses clinical and mechanistic findings linking autoimmune encephalitis and infections. Particular consideration will be given to anti-NMDA receptor encephalitis and its relation to herpes simplex encephalitis.

  16. Seroprevalence of St. Louis encephalitis virus and West Nile virus (Flavivirus, Flaviviridae) in horses, Uruguay.

    PubMed

    Burgueño, Analía; Spinsanti, Lorena; Díaz, Luis Adrián; Rivarola, María Elisa; Arbiza, Juan; Contigiani, Marta; Delfraro, Adriana

    2013-01-01

    St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) belong to the Japanese encephalitis antigenic complex (Flavivirus genus, Flaviviridae family). They show antigenic close relationships and share many similarities in their ecology. Both are responsible for serious human diseases. The aim of this study was to investigate the presence of neutralizing antibodies to these viruses in horses from Uruguay. To do this, 425 horse sera were collected in 2007 and analyzed by plaque reduction neutralization tests. As a result, 205 sera (48.2%) were found positive for SLEV, with titers ranging between 10 and 80. Two sera remained inconclusive, since they showed low titers to WNV and SLEV (10 and 20), not allowing us to demonstrate activity of WNV in our territory. This is the first report of circulation of SLEV in horses in Uruguay.

  17. Immunologic interference from sequential administration of live attenuated alphavirus vaccines.

    PubMed

    McClain, D J; Pittman, P R; Ramsburg, H H; Nelson, G O; Rossi, C A; Mangiafico, J A; Schmaljohn, A L; Malinoski, F J

    1998-03-01

    Two different human vaccine trials examined interference arising from sequential administration of vaccines against heterologous alphaviruses. The first trial indicated that persons previously vaccinated against Venezuelan equine encephalitis virus (VEEV) exhibited poor neutralizing antibody responses to a live attenuated chikungunya virus (CHIKV) vaccine (46% response rate). The second trial prospectively examined neutralizing antibody responses to live attenuated VEEV vaccine in persons previously inoculated with either CHIKV vaccine or placebo. Following seroconversion to CHIKV, CHIKV vaccine recipients' geometric mean titers (GMTs) to VEEV by 80% plaque-reduction neutralization titration never exceeded 10, compared with a peak GMT of 95 after VEEV vaccination for alphavirus-naive volunteers who initially received placebo (P < .003). ELISA antibody responses demonstrated cross-reactive IgG to VEEV after primary CHIKV immunization and then an anamnestic response upon subsequent VEEV vaccination. These data indicate that preexisting alphavirus immunity in humans interferes with subsequent neutralizing antibody response to a live attenuated, heterologous vaccine.

  18. Recent vaccine technology in industrial animals.

    PubMed

    Kim, Hyunil; Lee, Yoo-Kyoung; Kang, Sang Chul; Han, Beom Ku; Choi, Ki Myung

    2016-01-01

    Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with the PED virus spike gene. Recombinant vaccines can be produced by substitution of the target gene in the VEE vector. Both of these new vaccine technologies made it possible to control the infectious disease efficiently in a relatively short time. PMID:26866019

  19. Recent vaccine technology in industrial animals

    PubMed Central

    2016-01-01

    Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with the PED virus spike gene. Recombinant vaccines can be produced by substitution of the target gene in the VEE vector. Both of these new vaccine technologies made it possible to control the infectious disease efficiently in a relatively short time. PMID:26866019

  20. Viral Etiology of Encephalitis in Children in Southern Vietnam: Results of a One-Year Prospective Descriptive Study

    PubMed Central

    Tan, Le Van; Qui, Phan Tu; Ha, Do Quang; Hue, Nguyen Bach; Bao, Lam Quoi; Cam, Bach Van; Khanh, Truong Huu; Hien, Tran Tinh; Vinh Chau, Nguyen Van; Tram, Tran Tan; Hien, Vo Minh; Nga, Tran Vu Thieu; Schultsz, Constance; Farrar, Jeremy; van Doorn, H. Rogier; de Jong, Menno D.

    2010-01-01

    Background Acute encephalitis is an important and severe disease in children in Vietnam. However, little is known about the etiology while such knowledge is essential for optimal prevention and treatment. To identify viral causes of encephalitis, in 2004 we conducted a one-year descriptive study at Children's Hospital Number One, a referral hospital for children in southern Vietnam including Ho Chi Minh City. Methodology/Principal Findings Children less than 16 years of age presenting with acute encephalitis of presumed viral etiology were enrolled. Diagnostic efforts included viral culture, serology and real time (RT)-PCRs. A confirmed or probable viral causative agent was established in 41% of 194 enrolled patients. The most commonly diagnosed causative agent was Japanese encephalitis virus (n = 50, 26%), followed by enteroviruses (n = 18, 9.3%), dengue virus (n = 9, 4.6%), herpes simplex virus (n = 1), cytomegalovirus (n = 1) and influenza A virus (n = 1). Fifty-seven (29%) children died acutely. Fatal outcome was independently associated with patient age and Glasgow Coma Scale (GCS) on admission. Conclusions/Significance Acute encephalitis in children in southern Vietnam is associated with high mortality. Although the etiology remains unknown in a majority of the patients, the result from the present study may be useful for future design of treatment and prevention strategies of the disease. The recognition of GCS and age as predictive factors may be helpful for clinicians in managing the patient. PMID:21049060

  1. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.

    PubMed

    Yamshchikov, Vladimir; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-01

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use.

  2. Case Definitions, Diagnostic Algorithms, and Priorities in Encephalitis: Consensus Statement of the International Encephalitis Consortium

    PubMed Central

    Venkatesan, A.; Tunkel, A. R.; Bloch, K. C.; Lauring, A. S.; Sejvar, J.; Bitnun, A.; Stahl, J-P.; Mailles, A.; Drebot, M.; Rupprecht, C. E.; Yoder, J.; Cope, J. R.; Wilson, M. R.; Whitley, R. J.; Sullivan, J.; Granerod, J.; Jones, C.; Eastwood, K.; Ward, K. N.; Durrheim, D. N.; Solbrig, M. V.; Guo-Dong, L.; Glaser, C. A.; Sheriff, Heather; Brown, David; Farnon, Eileen; Messenger, Sharon; Paterson, Beverley; Soldatos, Ariane; Roy, Sharon; Visvesvara, Govinda; Beach, Michael; Nasci, Roger; Pertowski, Carol; Schmid, Scott; Rascoe, Lisa; Montgomery, Joel; Tong, Suxiang; Breiman, Robert; Franka, Richard; Keuhnert, Matt; Angulo, Fred; Cherry, James

    2013-01-01

    Background.Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. Methods.In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results.We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions.We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis. PMID:23861361

  3. [Changes in the reproduction of tick-borne encephalitis virus in cell cultures].

    PubMed

    Morozova, O V; Grishechkin, A E; Bakhvalova, V N; Isaeva, E I; Podcherniaeva, R Ia

    2012-01-01

    The currently used tick-borne encephalitis virus vaccines are based on the inactivation of tick-borne encephalitis virus (TBEV) of Far Eastern or West European genetic types from the primary cultures of chick embryo fibroblasts. Since the WHO recommends that vaccines should be designed using continuous cell cultures rather than chick embryos as a substrate, this investigation has compared the infection of continuous monolayer SPEV, Vero E6, and vaccine line Vero (B) cell cultures with TBEV strains of the Siberian and Far Eastern genetic types dominating in the endemic regions of Russia. After cell infection with Far Eastern (Sofyin and 205 strains) or Siberian (Aina, 2530, 2689, and 2703 strains) TBEV genetic types, the viable TBEV titers reached 2.8 Ig CPD50 for Vero (B) cells, 5.5 Ig CPD50 for Vero E6 cells, and up to 9 Ig CPD50 for SPEV cells. The quantitative scores of TBEV E antigen in enzyme immunoassay (EIA) and genome equivalents by reverse-transcription polymerase chain reaction (PCR), followed by real-time PCR, permitted one to estimate as high as 108 virions in 1 ml of culture fluid, which corresponded to those of the microscopic observations of CPD for SPEV cells and substantially exceeded the values for Vero E6 cells, and for Vero (B) cells in particular. The data of TBEV strain titration, EIA, and realtime reverse-transcription PCR suggest that the Russian vaccine Vero (B) cell line defined as meeting the WHO requirements, as well as Vero E6 cells may be used to design tick-borne encephalitis vaccine.

  4. Universal varicella vaccine immunization in Japan.

    PubMed

    Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

    2016-04-01

    In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections.

  5. Emergency Neurologic Life Support: Meningitis and Encephalitis.

    PubMed

    Gaieski, David F; Nathan, Barnett R; O'Brien, Nicole F

    2015-12-01

    Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis, are severe neurological infections that, if not treated promptly and effectively, lead to poor neurological outcome or death. Because treatment is more effective if given early, the topic of meningitis and encephalitis was chosen as an Emergency Neurological Life Support protocol. This protocol provides a practical approach to recognition and urgent treatment of bacterial meningitis and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric treatment is discussed. Though uncommon in its full form, the typical clinical triad of headache, fever, and neck stiffness should alert the clinical practitioner to the possibility of a central nervous system infection. Early attention to the airway and maintaining normotension is crucial in treatment of these patients, as is rapid treatment with anti-infectives and, in some cases, corticosteroids. PMID:26438456

  6. Emergency Neurologic Life Support: Meningitis and Encephalitis.

    PubMed

    Gaieski, David F; Nathan, Barnett R; O'Brien, Nicole F

    2015-12-01

    Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis, are severe neurological infections that, if not treated promptly and effectively, lead to poor neurological outcome or death. Because treatment is more effective if given early, the topic of meningitis and encephalitis was chosen as an Emergency Neurological Life Support protocol. This protocol provides a practical approach to recognition and urgent treatment of bacterial meningitis and encephalitis. Appropriate imaging, spinal fluid analysis, and early empiric treatment is discussed. Though uncommon in its full form, the typical clinical triad of headache, fever, and neck stiffness should alert the clinical practitioner to the possibility of a central nervous system infection. Early attention to the airway and maintaining normotension is crucial in treatment of these patients, as is rapid treatment with anti-infectives and, in some cases, corticosteroids.

  7. [Saint Louis encephalitis: case report].

    PubMed

    Carballo, Carolina; Cabana, Magdalena; Ledezma, Francisca; Pascual, Carolina; Cazes, Claudia; Mistchenko, Alicia; López, Eduardo

    2016-08-01

    Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge.

  8. [Saint Louis encephalitis: case report].

    PubMed

    Carballo, Carolina; Cabana, Magdalena; Ledezma, Francisca; Pascual, Carolina; Cazes, Claudia; Mistchenko, Alicia; López, Eduardo

    2016-08-01

    Saint Louis encephalitis is transmitted by Culex mosquitoes. In Argentina sporadic cases are registered. Symptomatic illness is unusual in children. We present a case of meningoencephalitis caused by an uncommon viral infection. The clinical signs and symptoms are unusual for pediatric patients and the bilateral thalamic compromise showed on magnetic resonance has not been described previously. An 8-year-old girl consulted due to fever, behavior disorders and ataxia. Clonus and neck stiffness were detected at physical exam. Cerebrospinal fluid revealed mononuclear leukocytosis; bilateral ischemic compromise was observed in thalamus by magnetic resonance. Saint Louis virus was confirmed by serology: serum and cerebrospinal fluid IgM were positive during the acute phase of the disease and serum IgG was positive four weeks later. Most of the signs and symptoms of the disease were resolved, however mild behavior disorders were observed as acute sequelae up to 45 days after hospital discharge. PMID:27399031

  9. Encephalitis

    MedlinePlus

    ... include oral and intravenous (IV) medicines to reduce inflammation and treat infection. Patients with breathing difficulties may need artificial respiration. Some people may need physical, speech, and occupational therapy once the illness is under control. NIH: National ...

  10. Encephalitis

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  11. Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation against Japanese cedar pollen allergy.

    PubMed

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

  12. Concentrated protein body product derived from rice endosperm as an oral tolerogen for allergen-specific immunotherapy--a new mucosal vaccine formulation against Japanese cedar pollen allergy.

    PubMed

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation.

  13. Concentrated Protein Body Product Derived from Rice Endosperm as an Oral Tolerogen for Allergen-Specific Immunotherapy—A New Mucosal Vaccine Formulation against Japanese Cedar Pollen Allergy

    PubMed Central

    Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

    2015-01-01

    The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

  14. Present situation and challenges of vaccinations for overseas travelers from Japan.

    PubMed

    Hamada, Atsuo; Fukushima, Shinji

    2015-06-01

    The vaccination rates of Japanese people travelling abroad are still relatively low compared to travelers from Europe and the U.S. The following 3 causes are considered to contribute to the low vaccination rates among Japanese. First point is the lack of attention to the prevention of diseases during overseas travel in Japanese people. Second point is the limited number of healthcare facilities where Japanese overseas travelers can receive vaccinations. Third, many vaccines administered to travelers are still unapproved in Japan. However, there appear to be recent developments in each matter. With these social changes, the vaccination rate should be improved by disseminating recognition of the importance of the travel medicine in Japan. This report summarizes the present situation of vaccination of Japanese overseas travelers and discusses the challenges to improving vaccination rates.

  15. Studying avian encephalization with geometric morphometrics.

    PubMed

    Marugán-Lobón, Jesús; Watanabe, Akinobu; Kawabe, Soichiro

    2016-08-01

    Encephalization is a core concept in comparative neurobiology, aiming to quantify the neurological capacity of organisms. For measuring encephalization, many studies have employed relative brain sizes corrected for expected allometric scaling to body size. Here we highlight the utility of a multivariate geometric morphometric (GM) approach for visualizing and analyzing neuroanatomical shape variation associated with encephalization. GM readily allows the statistical evaluation of covariates, such as size, and many software tools exist for visualizing their effects on shape. Thus far, however, studies using GM have not attempted to translate the meaning of encephalization to shape data. As such, we tested the statistical relationship between size and encephalization quotients (EQs) to brain shape utilizing a broad interspecific sample of avian endocranial data. Although statistically significant, the analyses indicate that allometry accounts for <10% of total neuroanatomical shape variation. Notably, we find that EQs, despite being corrected for allometric scaling based on size, contain size-related neuroanatomical shape changes. In addition, much of what is traditionally considered encephalization comprises clade-specific trends in relative forebrain expansion, particularly driven by landbirds. EQs, therefore, fail to capture 90% of the total neuroanatomical variation after correcting for allometry and shared phylogenetic history. Moving forward, GM techniques provide crucial tools for investigating key drivers of this vast, largely unexplored aspect of avian brain morphology. PMID:27112986

  16. Relevance of Neuroinflammation and Encephalitis in Autism

    PubMed Central

    Kern, Janet K.; Geier, David A.; Sykes, Lisa K.; Geier, Mark R.

    2016-01-01

    In recent years, many studies indicate that children with an autism spectrum disorder (ASD) diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. Encephalitis, which is defined as inflammation of the brain, is medical diagnosis code G04.90 in the International Classification of Disease, 10th revision; however, children with an ASD diagnosis are not generally assessed for a possible medical diagnosis of encephalitis. This is unfortunate because if a child with ASD has neuroinflammation, then treating the underlying brain inflammation could lead to improved outcomes. The purpose of this review of the literature is to examine the evidence of neuroinflammation/encephalitis in those with an ASD diagnosis and to address how a medical diagnosis of encephalitis, when appropriate, could benefit these children by driving more immediate and targeted treatments. PMID:26834565

  17. Anti-NMDA Receptor Encephalitis in a Pregnant Woman

    PubMed Central

    Kim, Jiyoung; Park, Seung Ha; Jung, Yu Ri; Park, Soon Won; Jung, Dae Soo

    2015-01-01

    Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is one of the most common types of autoimmune synaptic encephalitis. Anti-NMDA receptor encephalitis commonly occurs in young women with ovarian teratoma. It has variable clinical manifestations and treatment responses. Sometimes it is misdiagnosed as a psychiatric disorder or viral encephalitis. To the best of our knowledge, anti-NMDA receptor encephalitis is a rare condition in pregnant women. We report a case of anti-NMDA receptor encephalitis in a pregnant woman who presented with abnormal behavior, epileptic seizure, and hypoventilation. PMID:26157673

  18. Japanese Characters in Written Japanese.

    ERIC Educational Resources Information Center

    Buck, James H.

    From the sixth to the eighth century A.D., Japan was the recipient of massive cultural infusions from China. This acceptance of the Chinese pattern included, and to a great extent was based on, the acceptance of the Chinese language. The Chinese writing system was applied to Japanese because there was no other model to follow and in spite of the…

  19. Current status of toxoplasmosis vaccine development.

    PubMed

    Kur, Józef; Holec-Gasior, Lucyna; Hiszczyńska-Sawicka, Elzbieta

    2009-06-01

    Toxoplasmosis, caused by an intracellular protozoan parasite, Toxoplasma gondii, is widespread throughout the world. The disease is of major medical and veterinary importance, being a cause of congenital disease and abortion in humans and domestic animals. In addition, recently it has gained importance owing to toxoplasma encephalitis in AIDS patients. In the last few years, there has been considerable progress towards the development of a vaccine for toxoplasmosis, and a vaccine based on the live-attenuated S48 strain was developed for veterinary uses. However, this vaccine is expensive, causes side effects and has a short shelf life. Furthermore, this vaccine may revert to a pathogenic strain and, therefore, is not suitable for human use. Various experimental studies have shown that it may be possible to develop a vaccine against human toxoplasmosis. Recent progress in knowledge of the protective immune response generated by T. gondii and the current status of development of a vaccine for toxoplasmosis are highlighted.

  20. HPV vaccine

    MedlinePlus

    ... Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; ...

  1. Status of immunodiagnosis and immunocontraceptive vaccines in India.

    PubMed

    Gupta, S K

    2003-01-01

    The article focuses on the Indian initiative of making kits for diagnosis of various infectious and non-infectious diseases as well as reproductive hormones and hormones in various other endocrine disorders. Indigenous diagnostic kits for the detection of various infections such as filariasis, typhoid, amebiasis, Japanese encephalitis, hepatitis, HIV, dengue, leishmaniasis, malaria, rabies, toxoplasmosis, rotavirus, and group A streptococci have been developed. Agreements to transfer the know-how of some of these leads to industries have been signed. The know-how of enzyme-linked immunosorbent assay (ELISA) for detection of hepatitis C has been successfully transferred to industry and is being commercially produced. For detection of HIV-1 and HIV-2, indigenous diagnostic kits based on three different formats, namely ELISA, Western blot and rapid test have been developed and are being commercially produced by Indian industries. The factors influencing the successful transfer of laboratory-scale diagnostic assays from academia to industry and their commercial exploitation have been discussed. Indian scientists have made seminal contributions in exploring the possibility to develop an effective and safe contraceptive vaccine to control the increasing human population of India. Achieving contraception by means of vaccine is a novel approach, which entails generation of a specific antibody response against antigens critically involved in the process of mammalian reproduction. In India, three major programs on contraceptive vaccines based on the beta-subunit of human chorionic gonadotrophin ((beta)hCG) for women, ovine follicle stimulating hormone (oFSH) for men, and riboflavin carrier protein for both males and females have been initiated. The work at the National Institute of Immunology, New Delhi on contraceptive vaccine for women, based on (beta)hCG, has demonstrated, for the first time, that it is feasible to regulate fertility by such an approach. Basic research

  2. Tick-borne encephalitis as a notifiable disease--Status quo and the way forward. Report of the 17th annual meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE).

    PubMed

    Kunze, Ursula

    2015-07-01

    The 17th meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE), a group of neurologists, general practicioners, clinicians, travel physicians, virologists, pediatricians, and epidemiologists, was held under the title "Tick-borne encephalitis as a notifiable disease--status quo and the way forward". The conference agenda was divided into three parts on the first day: "Epidemiology & Risk areas", "Poster Walk: Epidemiological Update in Europe", and "News in TBE Research". On the second day, a World Café Working Session took place where the participants could choose three tables out of six to join for discussion. Key topics on current epidemiological developments and investigations, risk areas, cases, travel and mobility, TBE in children, vaccination rates, and latest news on vaccination were presented and extensively discussed.

  3. Tick-borne encephalitis-still on the map: Report of the 18th annual meeting of the international scientific working group on tick-borne encephalitis (ISW-TBE).

    PubMed

    Kunze, Ursula

    2016-07-01

    The 18th meeting of the International Scientific Working Group on Tick-Borne Encephalitis (ISW-TBE)-a group of neurologists, general practitioners, clinicians, travel physicians, virologists, pediatricians and epidemiologists-was held under the title 'Tick-borne encephalitis-still on the map'. The conference agenda was divided into six sessions: 'National Implementation of EU notifiable disease status', 'Virology', 'Epidemiology and Risk areas & Poster Walk Epidemiological Update', 'Clinic', 'Environmental Factors' and 'New Findings and Diagnosis'. Key topics such as 'TBE as a notifiable disease-results of the third European survey', 'TBE vaccines over the years', 'Overview of flaviviruses', 'TBE virus phylogenetics', 'Current epidemiological developments and investigations', 'Clinical aspects', 'TBE in veterinary medicine', 'Laboratory diagnostic', 'Occupational risk', 'Allergy, obesity, and vaccination' were presented and extensively discussed.

  4. Encephalization of Australian and New Guinean marsupials.

    PubMed

    Ashwell, K W S

    2008-01-01

    Encephalization of Australian marsupials was analyzed using the endocranial volume (ECV) of 52 species of Dasyuromorphia and Notoryctemorphia, 14 species of Peramelemorphia and 116 species of Diprotodontia from Australia and New Guinea and compared with 16 species of Ameridelphian marsupials and 3 species of native and recently introduced Australian eutherian carnivores (dingo, feral cat and feral fox). Linear regression analysis of the relationship between ECV and body weight for marsupials revealed that allometric parameters for these groups are different from those previously derived for samples of (mainly eutherian) mammals, with higher slopes for Dasyuromorphia and Diprotodontia and lower slopes for Ameridelphians and Peramelemorphia. Absolute ECV for small Australian and New Guinea marsupial carnivores (Antechinus and Sminthopsis) were found to be comparable to eutherians of similar body weight, but large marsupial carnivores such as the Tasmanian devil and thylacine had substantially smaller ECVs than eutherian carnivores of similar body weight. Similarly, members of some superfamilies within Diprotodontia (Burramyoidea, Petauroidea, Tarsipedoidea) had ECVs comparable to prosimians, whereas bandicoots, bilbies and many macropods were found to be poorly encephalized. When both encephalization quotient (EQ) and residuals from regression analysis were used to compare relative ECV of extinct/threatened species with common species there were no significant differences for any of the orders of Australian marsupials, suggesting that encephalization is not a major factor in the current extinction crisis for Australian marsupials. Similarly there were no consistent differences in relative ECV between marsupials from New Guinea and associated islands compared to Australia or between arid and non-arid Australian regions for any of the marsupial orders. The results indicate that marsupials are not uniformly poorly encephalized and that small marsupial carnivores and

  5. Rethinking Japanese Language Pedagogy.

    ERIC Educational Resources Information Center

    Larson, Phyllis

    2003-01-01

    Discusses the work of Seiichi Makino, a scholar of Japanese, noting that his work in establishing the Japanese proficiency guidelines helped make it appear that Japanese language teaching was part of mainstream American language teaching. (Author/VWL)

  6. PSYCHOTIC DISORDERS GENERATED BY AUTOIMMUNE ENCEPHALITIS (CLINICAL CASE).

    PubMed

    Craciun, Georgiana; Cucoş, Liliana; Ungureanu, Elena; Pendefunda, L; Petrariu, F D; Nechita, Petronela

    2015-01-01

    Encephalitis is a brain inflammation, which could involve also the meninges. The etiology of encephalitis could be: viral, bacterial, fungal or autoimmune. Anti-NMDAR encephalitis is an immune disorder, easy to diagnose and is a treatable condition. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, to catatonic state and breathing instability. We present a case report of a 20-year old woman, who presented: amnesia, visual hallucination, illusions, seizures after that occurred following autoimmune encephalitis. The exact incidence of anti-NMDAR encephalitis is unknown, but it seems to be more frequent than any other known paraneoplastic encephalitis. The present case is important considering that autoimmune encephalitis is a rare frequency disorder in Romania, with patients presenting resounding psychiatric and neurological manifestations. PMID:26793848

  7. PSYCHOTIC DISORDERS GENERATED BY AUTOIMMUNE ENCEPHALITIS (CLINICAL CASE).

    PubMed

    Craciun, Georgiana; Cucoş, Liliana; Ungureanu, Elena; Pendefunda, L; Petrariu, F D; Nechita, Petronela

    2015-01-01

    Encephalitis is a brain inflammation, which could involve also the meninges. The etiology of encephalitis could be: viral, bacterial, fungal or autoimmune. Anti-NMDAR encephalitis is an immune disorder, easy to diagnose and is a treatable condition. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from psychosis, memory deficits, seizures, to catatonic state and breathing instability. We present a case report of a 20-year old woman, who presented: amnesia, visual hallucination, illusions, seizures after that occurred following autoimmune encephalitis. The exact incidence of anti-NMDAR encephalitis is unknown, but it seems to be more frequent than any other known paraneoplastic encephalitis. The present case is important considering that autoimmune encephalitis is a rare frequency disorder in Romania, with patients presenting resounding psychiatric and neurological manifestations.

  8. Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia.

    PubMed

    Hoyos-López, Richard; Soto, Sandra Uribe; Rúa-Uribe, Guillermo; Gallego-Gómez, Juan Carlos

    2015-09-01

    Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E) protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba). We used reverse transcription-polymerase chain reaction to amplify a fragment of the E-gene to confirm the virus identity and complete E-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba) in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites.

  9. Molecular identification of Saint Louis encephalitis virus genotype IV in Colombia

    PubMed Central

    Hoyos-López, Richard; Soto, Sandra Uribe; Rúa-Uribe, Guillermo; Gallego-Gómez, Juan Carlos

    2015-01-01

    Saint Louis encephalitis virus (SLEV) is a member of the Japanese-encephalitis virus serocomplex of the genus Flavivirus. SLEV is broadly distributed in the Americas and the Caribbean Islands, where it is usually transmitted by mosquitoes of the genus Culex and primarily to birds and mammalian-hosts. Humans are occasionally infected by the virus and are dead-end hosts. SLEV causes encephalitis in temperate regions, while in tropical regions of the Americas, several human cases and a wide biological diversity of SLEV-strains have been reported. The phylogenetic analysis of the envelope (E) protein genes indicated eight-genotypes of SLEV with geographic overlap. The present paper describes the genotyping of two SLEV viruses detected in mosquito-pools collected in northern Colombia (department of Cordoba). We used reverse transcription-polymerase chain reaction to amplify a fragment of theE-gene to confirm the virus identity and completeE-gene sequencing for phylogenetic analysis and genotyping of the two-SLEV viruses found circulating in Córdoba. This is the first report of SLEV genotype IV in Colombia (Córdoba) in mosquitoes from a region of human inhabitation, implicating the risk of human disease due to SLEV infection. Physicians should consider SLEV as a possible aetiology for undiagnosed febrile and neurologic syndromes among their patients who report exposure to mosquito-bites. PMID:26313538

  10. An outbreak of tick-borne encephalitis associated with raw goat milk and cheese consumption, Croatia, 2015.

    PubMed

    Markovinović, Leo; Kosanović Ličina, M L; Tešić, V; Vojvodić, D; Vladušić Lucić, I; Kniewald, T; Vukas, T; Kutleša, M; Krajinović, Lidija Cvetko

    2016-10-01

    The aim of this report is to emphasize the risk of acquiring TBE by the consumption of raw milk and dairy products. In April-May 2015, we registered the first outbreak of tick-borne encephalitis in Croatia in seven members out of ten exposed persons who consumed raw goat milk or cheese from the same supplier. Infection was confirmed by TBEV enzyme-linked immunosorbent assay (ELISA) in all patients. None had been vaccinated nor had observed a tick bite.

  11. A pediatric case of Bickerstaff's brainstem encephalitis.

    PubMed

    Park, Ju Yi; Ko, Kyong Og; Lim, Jae Woo; Cheon, Eun Jung; Yoon, Jung Min; Kim, Hyo Jeong

    2014-12-01

    Bickerstaff's brainstem encephalitis is characterized by ophthalmoplegia, ataxia, and disturbance of consciousness. It is similar to Miller Fisher syndrome, a variant of Guillain-Barre syndrome, in that they share features such as ophthalmoplegia and ataxia. The difference is that patients with Bickerstaff's brainstem encephalitis have impaired consciousness, whereas patients with Miller Fisher syndrome have alert consciousness and areflexia. Here, we report the case of a 3-year-old child who was diagnosed with Bickerstaff's brainstem encephalitis presenting typical clinical features and interesting radiological findings. The patient showed ophthalmoplegia, ataxia, and subsequent stuporous mentality. Brain magnetic resonance imaging revealed high signal intensity in the pons and cerebellum around the 4th ventricle on a T2-weighted image. He was successfully treated with intravenous immunoglobulin. Differentiation of Bickerstaff's brainstem encephalitis and Miller Fisher syndrome is often difficult because they possess many overlapping features. Brain magnetic resonance imaging may be helpful in diagnosing Bickerstaff's brainstem encephalitis, especially when lesions are definitely found. PMID:25653689

  12. The Diagnosis and Treatment of Autoimmune Encephalitis.

    PubMed

    Lancaster, Eric

    2016-01-01

    Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important.

  13. The Diagnosis and Treatment of Autoimmune Encephalitis

    PubMed Central

    2016-01-01

    Autoimmune encephalitis causes subacute deficits of memory and cognition, often followed by suppressed level of consciousness or coma. A careful history and examination may show early clues to particular autoimmune causes, such as neuromyotonia, hyperekplexia, psychosis, dystonia, or the presence of particular tumors. Ancillary testing with MRI and EEG may be helpful for excluding other causes, managing seizures, and, rarely, for identifying characteristic findings. Appropriate autoantibody testing can confirm specific diagnoses, although this is often done in parallel with exclusion of infectious and other causes. Autoimmune encephalitis may be divided into several groups of diseases: those with pathogenic antibodies to cell surface proteins, those with antibodies to intracellular synaptic proteins, T-cell diseases associated with antibodies to intracellular antigens, and those associated with other autoimmune disorders. Many forms of autoimmune encephalitis are paraneoplastic, and each of these conveys a distinct risk profile for various tumors. Tumor screening and, if necessary, treatment is essential to proper management. Most forms of autoimmune encephalitis respond to immune therapies, although powerful immune suppression for weeks or months may be needed in difficult cases. Autoimmune encephalitis may relapse, so follow-up care is important. PMID:26754777

  14. Microbial study of meningitis and encephalitis cases.

    PubMed

    Selim, Heba S; El-Barrawy, Mohamed A; Rakha, Magda E; Yingst, Samuel L; Baskharoun, Magda F

    2007-01-01

    Meningitis and/or encephalitis can pose a serious public health problem especially during outbreaks. A rapid and accurate diagnosis is important for effective earlier treatment. This study aimed to identify the possible microbial causes of meningitis and/or encephalitis cases. CSF and serum samples were collected from 322 patients who had signs and symptoms suggestive of meningitis and/or encephalitis. Out of 250 cases with confirmed clinical diagnosis, 83 (33.2%) were definitely diagnosed as bacterial meningitis and/or encephalitis cases (by using CSF culture, biochemical tests, latex agglutination test, and CSF stain), 17 (6.8%) were definitely diagnosed as having viral causes ( by viral isolation on tissue culture, PCR and ELISA), and one (0.4%) was diagnosed as fungal meningitis case (by India ink stain, culture, and biochemical tests). Also, there was one encephalitis case with positive serum ELISA IgM antibodies against Sandfly scilian virus. N. meningitidis, S. pneumonia and M. tuberculosis were the most frequently detected bacterial agents, while Enteroviruses, herpes simplex viruses and varicella zoster viruses were the most common viral agents encountered. Further studies are needed to assess the role of different microbial agents in CNS infections and their effective methods of diagnosis.

  15. Deaths following vaccination: What does the evidence show?

    PubMed

    Miller, Elaine R; Moro, Pedro L; Cano, Maria; Shimabukuro, Tom T

    2015-06-26

    Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014-2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral

  16. Deaths following vaccination: What does the evidence show?

    PubMed

    Miller, Elaine R; Moro, Pedro L; Cano, Maria; Shimabukuro, Tom T

    2015-06-26

    Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014-2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral

  17. [Fisher Syndrome and Bickerstaff Brainstem Encephalitis].

    PubMed

    Kuwabara, Satoshi

    2015-11-01

    Fisher syndrome has been regarded as a peculiar inflammatory neuropathy with ophthalmoplegia, ataxia, and areflexia, whereas Bickerstaff brainstem encephalitis has been considered a pure central nervous system disease characterized by ophthalmoplegia, ataxia, and consciousness disturbance. Both disorders share common features including preceding infection, albumin-cytological dissociation, and association with Guillain-Barré syndrome. The discovery of anti-GQ1b IgG antibodies further supports the view that the two disorders represent a single disease spectrum. The lesions in Fisher syndrome and Bickerstaff brainstem encephalitis are presumably determined by the expression of ganglioside GQ1b in the human peripheral and central nervous systems. Bickerstaff brainstem encephalitis is likely to represent a variant of Fisher syndrome with central nervous system involvement. PMID:26560952

  18. A Practical Approach to Meningitis and Encephalitis.

    PubMed

    Richie, Megan B; Josephson, S Andrew

    2015-12-01

    Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid examination. In contrast, encephalitis refers to inflammation of the brain parenchyma itself and often results in focal neurologic deficits or seizures. In this article, the authors review the differential diagnosis of meningitis and encephalitis, with an emphasis on infectious etiologies. The recommended practical clinical approach focuses on early high-yield diagnostic testing and empiric antimicrobial administration, given the high morbidity associated with these diseases and the time-sensitive nature of treatment initiation. If the initial workup does not yield a diagnosis, further etiology-specific testing based upon risk factors and clinical characteristics should be pursued. Effective treatment is available for many causes of meningitis and encephalitis, and when possible should address both the primary disease process as well as potential complications.

  19. Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation

    PubMed Central

    Cyril, Asha Caroline; Nair, Sruthi S.; Mathai, Annamma; Kannoth, Sudheeran; Thomas, Sanjeev V.

    2015-01-01

    Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU) of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.'s, criteria for autoimmune encephalitis were identified during the period December 2009–June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females) were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 %) was the most common presenting symptom; status epilepticus occurred in 23 (60.5%) patients during the course of the illness. Fourteen (35.9%) patients were N-methyl-D-aspartate receptor (NMDAR) antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients. PMID:26713011

  20. Alphavirus-based vaccines.

    PubMed

    Lundstrom, Kenneth

    2014-06-01

    Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.

  1. Functional hemispherectomy: radical treatment for Rasmussen's encephalitis.

    PubMed

    Lilly, D J

    2000-04-01

    Rasmussen's encephalitis is a progressive, debilitating disease that usually appears in the pediatric population but also may affect adults. Uncontrolled seizures, cognitive decline, and a progressive hemiparesis accompany this disorder. Treatment options are limited and consist of medical management, which is somewhat experimental and ineffective; the use of either intravenous antiviral agents or steroids; or surgical resection of the affected hemisphere. Patients undergoing hemispherectomy for Rasmussen's encephalitis are complex. Nurses caring for these patients require a high degree of knowledge and specialized skills. Patient outcome is highly affected by the knowledge and skill of the entire team of healthcare professionals needed to manage these patients. PMID:10826294

  2. Rasmussen's encephalitis presenting as focal cortical dysplasia.

    PubMed

    O'Rourke, D J; Bergin, A; Rotenberg, A; Peters, J; Gorman, M; Poduri, A; Cryan, J; Lidov, H; Madsen, J; Harini, C

    2014-01-01

    Rasmussen's encephalitis is a rare syndrome characterized by intractable seizures, often associated with epilepsia partialis continua and symptoms of progressive hemispheric dysfunction. Seizures are usually the hallmark of presentation, but antiepileptic drug treatment fails in most patients and is ineffective against epilepsia partialis continua, which often requires surgical intervention. Co-occurrence of focal cortical dysplasia has only rarely been described and may have implications regarding pathophysiology and management. We describe a rare case of dual pathology of Rasmussen's encephalitis presenting as a focal cortical dysplasia (FCD) and discuss the literature on this topic. PMID:25667877

  3. Rabies encephalitis in a child: a failure of rabies post exposure prophylaxis?

    PubMed

    Tinsa, Faten; Borgi, Aida; Jahouat, Imen; Boussetta, Khadija

    2015-01-01

    Rabies remains a serious public health problem in many developing countries. The diagnosis is easy when a non-immunised patient presents with hydrophobia and hypersalivation after a bite by a known rabid animal but more difficult when a patient presents atypical symptoms after having received rabies postexposure prophylaxis. Rabies postexposure prophylaxis failure is rare. We report a case of a 6-year-old boy who presented febrile seizure with agitation and cerebellar signs, without hydrophobia or hypersalivation, 17 days after a dog bite. Despite four doses of rabies vaccine and immunoglobulin, he died. Diagnostic confirmation of rabies encephalitis was made in post mortem on brain biopsies by fluorescent antibody technique.

  4. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    PubMed

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD.

  5. Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

    PubMed

    Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

    2015-01-01

    Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. PMID:26535889

  6. Induction of neutralizing antibodies to Hendra and Nipah glycoproteins using a Venezuelan equine encephalitis virus in vivo expression system.

    PubMed

    Defang, Gabriel N; Khetawat, Dimple; Broder, Christopher C; Quinnan, Gerald V

    2010-12-16

    The emergence of Hendra Virus (HeV) and Nipah Virus (NiV) which can cause fatal infections in both animals and humans has triggered a search for an effective vaccine. Here, we have explored the potential for generating an effective humoral immune response to these zoonotic pathogens using an alphavirus-based vaccine platform. Groups of mice were immunized with Venezuelan equine encephalitis virus replicon particles (VRPs) encoding the attachment or fusion glycoproteins of either HeV or NiV. We demonstrate the induction of highly potent cross-reactive neutralizing antibodies to both viruses using this approach. Preliminary study suggested early enhancement in the antibody response with use of a modified version of VRP. Overall, these data suggest that the use of an alphavirus-derived vaccine platform might serve as a viable approach for the development of an effective vaccine against the henipaviruses.

  7. Polio Vaccination

    MedlinePlus

    ... inactive polio vaccine OPV=oral polio vaccine Polio Vaccination Pronounced [PO-lee-oh] Recommend on Facebook Tweet ... handling and storage Related Pages Global Vaccines and Immunization Global Polio Also Known As & Abbreviations Polio=poliomyelitis ...

  8. Murray Valley encephalitis in an adult traveller complicated by long-term flaccid paralysis: case report and review of the literature.

    PubMed

    Douglas, Mark W; Stephens, Dianne P; Burrow, James N C; Anstey, Nicholas M; Talbot, Kevin; Currie, Bart J

    2007-03-01

    Murray Valley encephalitis (MVE) virus, a mosquito-borne flavivirus, is the most common cause of viral encephalitis in the tropical 'Top End' of northern Australia. Clinical encephalitis due to MVE virus has a mortality rate of approximately 30%, with a similar proportion of patients being left with significant neurological deficits. We report the case of a 25-year-old man from the UK who acquired MVE while travelling through northern Australia. He required prolonged admission to the Intensive Care Unit and several years later remains partly ventilator-dependent, with flaccid quadriparesis. To our knowledge, this is the first reported case of MVE virus-induced flaccid paralysis in an adult in northern Australia, although it is well described in children. Paralysis was thought to be due to anterior horn cell involvement in the spinal cord and extensive bilateral thalamic destruction, both of which are well recognised complications of infection with MVE virus. Cases of flaccid paralysis with similar pathology have been described following infection with the related flavivirus Japanese encephalitis virus as well as more recently with West Nile virus. Our case highlights the potential severity of flavivirus-induced encephalitis and the importance of avoiding mosquito bites while travelling through endemic areas.

  9. Herpes Simplex Encephalitis: An Uncommon Presentation

    PubMed Central

    Bansal, Sunil; Bhatia, Rohan; Ahmad, Sohaib

    2016-01-01

    Herpes Simplex Virus (HSV) encephalitis is an uncommon illness, with about 2 cases per 250,000 per year. Most are caused by HSV-1, with 10% having HSV-2 as the aetiologic factor. We present a case of Herpes simplex type1encephalitis in a 70 year old male with an uncommon presentation. The patient was a known case of endogenous depression with no medical records and on no treatment for the same, reported with acute changes in mental state for the past five days. He was talking irrelevantly, had hallucinations and was unduly aggressive and violent. He was subjected to a thorough clinical and diagnostic work-up which included cerebrospinal fluid analysis, CT head and MRI brain. MRI brain was suggestive of mild subdural effusion which hinted towards infectious cause of encephalitis. The cerebrospinal fluid viral serology panel detected herpes simplex type 1 virus (HSV1) that was later confirmed by CSF Polymerase Chain Reaction (PCR) technique. Hence, acyclovir was initiated by intravenous route at a dosage of 10mg/kg body weight and continued for two weeks. This case holds significance in view of the fact that organic causes must be excluded in suspected cases of psychiatric illness especially in the absence of fever. Also, CSF-PCR testing plays a pivotal role in diagnosing herpes simplex encephalitis. PMID:27437286

  10. Herpes Simplex Encephalitis: An Uncommon Presentation.

    PubMed

    Kaeley, Nidhi; Bansal, Sunil; Bhatia, Rohan; Ahmad, Sohaib

    2016-05-01

    Herpes Simplex Virus (HSV) encephalitis is an uncommon illness, with about 2 cases per 250,000 per year. Most are caused by HSV-1, with 10% having HSV-2 as the aetiologic factor. We present a case of Herpes simplex type1encephalitis in a 70 year old male with an uncommon presentation. The patient was a known case of endogenous depression with no medical records and on no treatment for the same, reported with acute changes in mental state for the past five days. He was talking irrelevantly, had hallucinations and was unduly aggressive and violent. He was subjected to a thorough clinical and diagnostic work-up which included cerebrospinal fluid analysis, CT head and MRI brain. MRI brain was suggestive of mild subdural effusion which hinted towards infectious cause of encephalitis. The cerebrospinal fluid viral serology panel detected herpes simplex type 1 virus (HSV1) that was later confirmed by CSF Polymerase Chain Reaction (PCR) technique. Hence, acyclovir was initiated by intravenous route at a dosage of 10mg/kg body weight and continued for two weeks. This case holds significance in view of the fact that organic causes must be excluded in suspected cases of psychiatric illness especially in the absence of fever. Also, CSF-PCR testing plays a pivotal role in diagnosing herpes simplex encephalitis. PMID:27437286

  11. [Meningitis and encephalitis in Poland in 2005].

    PubMed

    Stefanoff, Paweł; Rosińska, Magdalena

    2007-01-01

    In Poland, 2 806 cases of neuroinfections were reported in 2005, of which 998 had bacterial aetiology, 1469 viral, and 339 cases had other or unknown origin. Incidence of bacterial neuroin-fections increased in 2003-2005, following a decreasing trend observed during the past decade. Etiological factor was determined in 486 (49%) cases of bacterial neuroinfections. Among them Neisseria meningitidis was found in 135 cases, Haemophilus influenzae in 59 cases and Streptococ-cus pneumoniae in 111 cases. Unlike previously in 2005 serogroup B was no longer the predominant type of N. meningitidis cultured from patients. Both types B and C constituted similar proportions of all strains serotyped in 2005. Viral neuroinfections incidence in 2005 remained on the same level as in 2004. Etiological factor of central nervous system aseptic infections were established only in minor proportion of cases--3% of meningitis and 20% of encephalitis. Among confirmed cases, there were 177 cases of tick-borne encephalitis and 13 cases of herpetic encephalitis. Tick borne encephalitis incidence decreased in 2005 (0.46), compared to 2003-2004. Most of the cases were reported from endemic areas of northeastern part of the country.

  12. Can Herpes Simplex Virus Encephalitis Cause Aphasia?

    ERIC Educational Resources Information Center

    Naude, H.; Pretorius, E.

    2003-01-01

    Aphasia implies the loss or impairment of language caused by brain damage. The key to understanding the nature of aphasic symptoms is the neuro-anatomical site of brain damage, and not the causative agent. However, because "Herpes simplex" virus (HSV) encephalitis infection usually affects the frontal and temporal lobes, subcortical structures and…

  13. Vaccine hesitancy

    PubMed Central

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  14. Tick-borne encephalitis (TBE) trends in epidemiology and current and future management.

    PubMed

    Petri, Eckhardt; Gniel, Dieter; Zent, Olaf

    2010-07-01

    Tick-borne encephalitis (TBE) is considered an international health issue, as the number of risk areas and reported cases across Europe, Russia, and parts of Asia continues to increase. The incidence of TBE has fluctuated considerably from year to year in many countries, but in the past decade the number of TBE cases has significantly increased in the Baltic states, the Czech Republic, and Germany, in addition to occurring in countries previously considered to be free from TBE, such as Denmark (specifically the main island of Zealand), France, and Italy. A number of factors have been suggested to explain the increase in incidence, including climate change, and increased travel and outdoor pursuits, placing people in increased contact with infected ticks. There is no causal treatment available once infected, but TBE can be effectively prevented by vaccination, for which several vaccines are widely available. Three vaccination schedules are available for immunization against TBE, and the recommendations for TBE vaccination vary considerably across the countries in which TBE foci are found. However, plans are in place to raise awareness of TBE and to standardize the vaccination programme across Europe, with the aim of reducing the number of future cases of TBE. PMID:20970726

  15. The impact of eastern equine encephalitis virus on efforts to recover the endangered whooping crane

    USGS Publications Warehouse

    Carpenter, J.W.; Clark, G.G.; Watts, D.M.; Cooper, J.E.

    1989-01-01

    The whooping crane (Grus americana), although never abundant in North America, became endangered primarily because of habitat modification and destruction. To help recovery, a captive propagation and reintroduction program was initiated at the Patuxent Wildlife Research Center (PWRC) in 1966. However, in 1984, 7 of 39 whooping cranes at PWRC died from infection by eastern equine encephalitis (EEE) virus, an arbovirus that infects a wide variety of indigenous bird species, although mortality is generally restricted to introduced birds. Following identification of the aetiological agent, surveillance and control measures were implemented, including serological monitoring of both wild and captive birds for EEE viral antibody and assay of locally-trapped mosquitoes for virus. In addition, an inactivated EEE virus vaccine developed for use in humans was evaluated in captive whooping cranes. Results so far suggest that the vaccine will afford protection to susceptible birds.