黄热病现情分析与卫生检疫工作的研究进展

黄热病（Yellow Fever,YF）病毒是一种黄热病毒属虫媒病毒。经媒蚊传播,在非洲和南美洲热带地区呈地方性流行。据世界卫生组织（WHO）估计,全球年发病人数20万例,死亡3万例。其中90％以上发生在非洲,严重威胁人类的健康。随着全球经济的不断发展,国际间人群交往的频繁,黄热病疫情进入非黄热病流行区的风险日益增加。因此,我国对及时预防、控制该病通过国境口岸传入的警惕性不容忽视。     

西尼罗热研究进展

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

1例黄热病疫苗引发的嗜内脏损害反应患者的营养治疗

黄热病是由黄热病毒引起的发热性疾病，由蚊子或蜱类为媒介传播，主要在南美洲和非洲流行，病死率高达20％以上。黄热病疫苗是一种减毒活疫苗，存在疫苗毒株毒性恢复的潜在危险，近年来美国和澳大利亚等国都有接种疫苗发生严重不良反应的报道。[第一段]     

黄热病疫苗接种所致不良反应及防控措施

目的探讨黄热病疫苗接种所致严重不良反应、引起不良反应的危险因子、危险人群及结合工作实际提出防控措施。方法通过对研究全球黄热病流行概况及其对人类的严重威胁、黄热病疫苗及接种所引起的严重不良反应、接种禁忌症、危险人群等,深入探讨目前黄热病疫苗接种现状和急需改进的措施。结果结合新《国际卫生条例》草案提出国境口岸应具备的预防、应对和处理黄热病疫苗接种所致突发事件的能力。结论国家应严格规范黄热病疫苗的生产,国际旅行保健中心应加强对黄热病疫苗使用的管理,卫生检疫部门应做好疫苗所致不良反应事件的预防和疫苗使用后的监测工作。     

黄热病疫苗接种后不良反应事件及其监测

黄热病毒通过蚊虫叮咬传播,在南美洲热带地区和非洲撒哈拉以南地区自然疫源地的灵长类动物体内长期存在。黄热病不定期暴发人间流行,15%的黄热病毒感染者的临床表现重,病死率达20%~50%,无特效治疗药物,疫苗接种是目前预防人类罹患黄热病的有效措施之一。17D黄热病减毒活疫苗已在全球用于预防黄热病多年,其安全性和有效性已被广泛证实,但接种后不良反应事件仍时有报道,某些人群接种17D黄热病减毒活疫苗后相关的神经系统疾病和内脏疾病等严重不良反应的发生率显著升高。对黄热病疫苗接种后不良反应进行合理的监测,将有助于黄热病疫苗在黄热病防控中发挥更大作用。     

西尼罗病毒E蛋白的结构和应用进展

西尼罗病毒是一种单股正链RNA病毒,属于黄病毒属黄病毒科,主要通过库蚊传播,能引起西尼罗热及神经侵袭性疾病如脑炎、脑膜炎等。近年来,该病毒在多个国家和地区间广泛流行,给发病国家带来了极大的危害。目前对于西尼罗病毒尚未有可用于人类的疫苗上市,也没有特定的抗病毒药物可用,因此加强病毒监测、研发新的疫苗及掌握实验室诊断方法变得尤为重要。本文主要通过对西尼罗病毒E蛋白的结构、疫苗及检测方法的最新进展加以探讨,为研发西尼罗病毒疫苗及诊断试剂盒提供理论依据。     

1例黄热病致死病例的报告

黄热病(Yellow fever,YF)是一种由蚊子传播的病毒性疾病,对前往非洲撒哈拉地区或是南美热带丛林的欧美旅行者构成死亡威胁。目前对于黄热病缺少特效治疗药物,导致部分严重的黄热病病例的死亡率达到20％左右,但是这种严重的疾病可以通过接种疫苗来有效地预防。本文是关于1例未接受预防接种的旅行者,在巴西亚马逊流域的马瑙斯地区度过6d假期回美国后,死于黄热病的病例     

南阳市健康人群脊髓灰质炎带毒情况调查

<正> 脊髓灰质炎是由脊髓灰质炎病毒引起的一种急性肠道传染病。该病传播广泛,危害严重,遍及全球。自脊髓灰质炎疫苗(下称疫苗)问世以来,WHO 已将该病列为重点控制疾病之一。南阳市自1965年开始使用疫     

西尼罗病毒病

1西尼罗病毒病的流行概况、危害 西尼罗病毒（West Nile Virus WNV）于1937年在非洲的乌干达首次被发现，从西尼罗地区的一位发热的成年妇女血液中分离到，因此得名西尼罗病毒。西尼罗病毒属于黄病毒科黄病毒属。黄病毒科成员还有登革热病病毒、日本脑炎病毒以及黄热病病毒等70余种，多属于虫媒病毒。西尼罗病毒广泛分布于非洲、中东和西亚，主要引起西尼罗河热（West Nile Fever），该病毒属黄病毒科的乙型脑炎病毒血清群，可引起人类及马、鸟类等动物发病。     

丙型病毒性肝炎及其检测研究进展

丙型肝炎属黄病毒科丙型肝炎病毒属[1],其基本结构与人类黄病毒如黄热病病毒、登革热病毒和乙型脑炎病毒相似,由结构蛋白和非结构蛋白组成。丙型肝炎病毒的基因分为6个型和100多个亚型,基     

Construction and biological properties of yellow fever 17D/dengue type 1 recombinant virus

Dengue virus, a mosquito-borne flavivirus, is one of the most formidable public health threats in tropical and subtropical regions. As yet, there is no licensed vaccine to protect against the disease. A chimeric yellow fever (YF) 17D/dengue (DEN) type 1 virus was constructed by replacing the pre-membrane and envelope genes of YF 17D virus with those from DEN 1 VeMir95 virus, a Venezuelan isolate. The chimeric YF 17D/DEN 1 VeMir95 virus was regenerated from full-length infectious clones stably propagated in Escherichia coli by transfection of Vero cells with in vitro transcribed RNA. The chimeric virus proliferated efficiently in Vero cells ( approximately 6.6 log(10) plaque-forming units/ml). The chimeric virus was not neurovirulent to 3-week-old Swiss Webster mice inoculated by the intracerebral route, in contrast to the YF 17DD vaccine strain that was lethal for 90% of the mice. The YF 17D/DEN 1 virus at Passage 6 was more attenuated for rhesus monkeys than the YF 17DD commercial vaccine after intracerebral inoculation according to the standard neurovirulence test. This virus is a potential candidate to be included in a tetravalent DEN vaccine formulation. The availability of the cloned cDNA allows further structure/function studies on the viral envelope.     

Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice

Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed. In this study, using the Japanese encephalitis live vaccine strain SA14-14–2 as a backbone, a novel chimeric virus was constructed by replacing the pre-membrane (prM) and envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a reduced growth rate and a much smaller plaque morphology than did either parental virus. Furthermore, the chimera was much less neurovirulent than was YF17D and protected mice that were challenged with a lethal dose of the YF virus. These results suggest that this chimera has potential as a novel attenuated YF vaccine.     

Risk assessment of yellow fever urbanization in Rio de Janeiro, Brazil

Yellow fever (YF), an arthropod-borne viral disease, occurs in regions of tropical America and Africa. Sylvatic YF is endemic in the north and west of Brazil. Urban YF, on the other hand, has not been reported in the country since 1942. However, the widespread presence of the YF urban vector in Brazil has lead to concern about the potential re-emergence of YF in urban centres. Here, we assess the risk of YF emergence in the city of Rio de Janeiro, Brazil, by estimating the probability of infected individuals arriving from YF-endemic areas, and the probability of infective individuals triggering an epidemic. We found that the risk of urban YF emergence may reach values as high as 29% during the epizootic periods but the precision of the estimate is low.     

Vaccination antiamarile : mise au point à propos des effets indésirables rares et graves

Over 500 million people live in yellow fever (YF) endemic areas and more than 3 million travel to endemic countries every year. Prevention against YF, caused by the YF virus, an arbovirus, can only be efficiently obtained by active immunization. The vaccine is well tolerated and severe adverse events are very rare. Exceptionally, YF vaccination may result in serious adverse events, such as viscerotropic and neurotropic diseases, sometimes with a fatal outcome. These rare serious adverse advents are reviewed with their potential risk factors, such as advanced age or history of thymus disease. The benefit/risk ratio remains in favour of vaccination, although the decision to offer yellow fever vaccination, especially to persons 60 years of age or older, should be evaluated according to the planned trip. Additional research investigations should be made on the host immune response since this response is considered to be at the origin of these severe adverse events.     

17D yellow fever vaccines: new insights. A report of a workshop held during the World Congress on medicine and health in the tropics, Marseille, France, Monday 12 September 2005

Yellow fever (YF) is a major health problem in endemic regions of Africa and South America. It also poses a serious health risk to travellers to areas with endemic disease. Currently, there is no effective drug treatment for YF; however, 17D YF vaccines have demonstrated high rates of effectiveness and good safety profiles. This workshop was organized to review key data and issues about YF disease and currently available 17D YF vaccines. Starting with an overview of the current disease epidemiology in Africa and South America and a review of the safety data of 17D YF vaccines, data were then presented demonstrating the genetic stability of multiple production lots of a 17D YF vaccine, the immunological responses of healthy subjects post-vaccination and the long-term immunogenicity of 17D YF vaccines. Finally, the findings of the molecular characterization of 17D YF virus sub-strains recovered from rare, fatal cases of post-vaccination serious adverse events were presented. There was unanimous agreement that current 17D YF vaccines have a highly favourable benefit-risk profile when used in persons at risk of exposure to the YF virus, and that appropriate use of 17D YF vaccines will minimize the occurrence of serious adverse events post-vaccination.     

Indirect fluorescent antibody test for the diagnosis of yellow fever

The indirect fluorescent antibody (FA) test was evaluated for the serodiagnosis of yellow fever (YF) cases and for detection of antibodies after 17D YF vaccination. Results were compared with those of standard serological tests, reactions with heterologous flaviviral antigens were determined, and both IgM and IgG antibodies were measured. Spot slides of infected Vero cells were used as antigen substrate. In cases of primary YF infection, the FA test for IgG antibodies provided clear diagnostic results. Indirect FA tests with anti-IgG were more sensitive than the complement-fixation (CF) test and showed specificity comparable to the CF and neutralization (N) tests. Cases of YF infection superimposed upon pre-existing heterologous flaviviral immunity developed broadly-crossreactive IgG antibodies. IgM antibodies were highly specific in cases of both primary infection and superinfection but were not consistently present. Most individuals without previous flaviviral exposure who received 17D vaccine failed to develop detectable antibodies by the indirect FA test; of those with pre-existing immunity, 79% developed IgG antibodies. The indirect FA test provides a simple, rapid diagnostic procedure which should be especially useful in on-site epidemiological investigations of YF outbreaks.     

Neurologic Disease after Yellow Fever Vaccination,São Paulo,Brazil, 2017–2018

Yellow fever (YF) vaccine can cause neurologic complications. We examined YF vaccine–associated neurologic disease reported from 3 tertiary referral centers in São Paulo, Brazil, during 2017–2018 and compared the performance of criteria established by the Yellow Fever Vaccine Working Group/Centers for Disease Control and Prevention and the Brighton Collaboration. Among 50 patients who met inclusion criteria, 32 had meningoencephalitis (14 with reactive YF IgM in cerebrospinal fluid), 2 died, and 1 may have transmitted infection to an infant through breast milk. Of 7 cases of autoimmune neurologic disease after YF vaccination, 2 were acute disseminated encephalomyelitis, 2 myelitis, and 3 Guillain-Barré syndrome. Neurologic disease can follow fractional vaccine doses, and novel potential vaccine-associated syndromes include autoimmune encephalitis, opsoclonus-myoclonus-ataxia syndrome, optic neuritis, and ataxia. Although the Brighton Collaboration criteria lack direct vaccine causal assessment, they are more inclusive than the Centers for Disease Control and Prevention criteria.     

Differences between coverage of yellow fever vaccine and the first dose of measles-containing vaccine: A desk review of global data sources

IntroductionThe strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies.MethodsWe conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful.ResultsIn America, there were meaningful differences (7–45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4–27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006–2016.ConclusionIn countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However, these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.     

Advanced age a risk factor for illness temporally associated with yellow fever vaccination.

In 1998, the Centers for Disease Control and Prevention was notified of severe illnesses and one death, temporally associated with yellow fever (YF) vaccination, in two elderly U.S. residents. Because the cases were unusual and adverse events following YF vaccination had not been studied, we estimated age-related reporting rates for systemic illness following YF vaccination. We found that the rate of reported adverse events among elderly vaccinees was higher than among vaccinees 25 to 44 years of age. We also found two additional deaths among elderly YF vaccinees. These data signal a potential problem but are not sufficient to reliably estimate incidence rates or to understand potential underlying mechanisms; therefore, enhanced surveillance is needed. YF remains an important cause of severe illness and death, and travel to disease-endemic regions is increasing. For elderly travelers, the risk for severe illness and death due to YF infection should be balanced against the risk for systemic illness due to YF vaccine.     

Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE)

Although the theoretical concern of genetic recombination has been raised related to the use of live attenuated flavivirus vaccines [Seligman, Gould, Lancet 2004;363:2073-5], it has little foundation [e.g., Monath TP, Kanesa-Thasan N, Guirakhoo F, Pugachev K, Almond J, Lang J, et al. Vaccine 2005;23:2956-8]. To investigate biological effects of recombination between a chimeric yellow fever (YF) 17D/Japanese encephalitis (JE) vaccine virus (ChimeriVax-JE) and a wild-type flavivirus Kunjin (KUN-cDNA), the prM-E envelope protein genes were swapped between the two viruses, resulting in new YF 17D/KUN(prM-E) and KUN/JE(prM-E) chimeras. The prM-E genes are easily exchangeable between flavivirues, and thus the exchange was expected to yield the most replication-competent chimeras, while other rationally designed recombinants would be more likely to be crippled or non-viable. The new chimeras proved highly attenuated in comparison with the KUN-cDNA parent, as judged by plaque size and growth kinetics in cell culture, low viremia in hamsters, and reduced neurovirulence/neuroinvasiveness in mice. These data provide strong experimental evidence that the potential of recombinants, should they ever emerge, to cause disease or spread (compete in nature with wild-type flaviviruses) would be indeed extremely low.