流感病毒脑病

最近30年来,冬季流行的流感病毒没有较大变异。但2003年,亚洲发生了高致病性禽流感,致使家禽大量死亡,在越冬的候鸟中,也有感染这种H5N1病毒。在泰国、越南、柬埔寨等亚洲国家已有10多人感染了H5N1病毒,且致死率在50%以上。在此背景下,流感病毒感染性疾病和相关疫苗临床应用的研究备受瞩目。本文选译自《日本医师会杂志》2006年134卷第10期“インフルエンザウイルス感染症と阌連するワクチンの臨床”专辑,选文11篇,对流感病毒的预测、诊断、治疗及各种相关疾病进行详细阐述,内容较新,有很高的参考价值。

2016年朝阳区动物诊疗机构犬狂犬病和A型流感的流行病学调查报告

本文对动物诊疗机构中因不同的原因前来就诊的宠物进行采样调查,针对狂犬病和A-型流感病毒病开展检测活动,动物诊疗机构共计采样84份,应用V8实时快速荧光PCR检测设备,开展病原学检测,未发现有携带以上两个病毒的宠物犬。

一例疑似鸭低致病禽流感与沙门氏杆菌病混感的诊治

禽流感是由A型禽流感病毒引起的一种以禽类为主要侵害对象的人禽共患传染病。根据禽流感病毒的致病性和毒力的不同,将禽流感分为高致病性禽流感（H5、H7）、低致病性禽流感（H9）和无致病性禽流感三种。低致病性禽流感（H9）又叫致病性禽流感或非高致病性禽流感或温和型禽流感,它是指某些致病性低的禽流感病毒毒株感染家禽引起的低发病率、低死亡率和低临床症状的疾病。鸭低致病性禽流感（H9）一年四季均可发生，但主要多发于冬春气候变化大的季节。

Effect of Curcumin on Influenza Virus HIN1 and H3N2 in Vitro

Objective：To investigate the inhibitory effect of curcumin on influenza virus HIN1 and H3N2 in vitro, Methods：The directly killing role of cureumin extract in vitro to influenza virus type A subtype H1N1 and H3N2 was evaluated by the canine kidney cells （MDCK）, Results：The largest non toxic concentration of curcumin extract was 12, 5g/L and the effective inhibitory concentration to H1N1 and H3N2 was 6, 25G/1 AND 1,56g/L respectively, Conclusion： Curcumin extract have directly killing effect on H1N1 and H3N2 infections.

Preparation and Preliminary Identification of Fluorescein Labeled Monoclonal Antibody against Canine Distemper Virus

[Objective] The aim of the present study was to develop a direct immunofluorescence method for the diagnosis of canine distemper （CD） with FITC-conjugated monoclonal antibodies （FITC-McAb）.[ Metbod] The McAb against CDV, designated as CE3, was purified with protein G and labeled with FITC through agitation method. After purification and identification, the optimal working concentration of FITC-labeled CE3 was determined. Then 61 clinical samples of suspected canine distemper were detected by direct immunofluorescence assay. [ Result] The absorption test, blocking test and specificity test showed that the labeled antibody had high specificity and sensitivity, but didn＇t have cross reaction with canine parvovirus （CPV）, canine parainfluenza virus （CPIV）, canine adenovirus （CAV） and rabies virus （RV）. The optimal working concentration was 1：80. The positive rate of clinical suspected samples was 48%. [ Conclusion] The direct immunofluorescence assay developed in this study was rapid, specific and convenient, and had great significance for the early diagnosis of canine distemper.

An Overview of the Highly Pathogenic H5N1 Influenza Virus

Since the first human case of H5N1 avian influenza virus infection was reported in 1997, this highly pathogenic virus has infected hundreds of people around the world and resulted in many deaths. The ability of H5N1 to cross species boundaries, and the presence of polymorphisms that enhance virulence, present challenges to developing clear strategies to prevent the pandemic spread of this highly pathogenic avian influenza (HPAI) virus. This review summarizes the current understanding of, and recent research on, the avian influenza H5N1 virus, including transmission, virulence, pathogenesis, clinical characteristics, treatment and prevention.

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.

Subtyping Animal Influenza Virus with General Multiplex RT-PCR and Liquichip High Throughput (GMPLex)

This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses. Primers and probes were designed to amplify NS and M genes of influenza A viruses HA gene of ill, H3, H5, HT, H9 subtypes, and NA gene of the N1 and N2 subtypes. Universal super primers were introduced to establish a multiplex RT-PCR （GM RT-PCR）. It included three stages of RT-PCR amplification, and then the RT-PCR products were further tested by LiquiChip probe, combined to give an influenza virus （IV） rapid high throughput subtyping test, designated as GMPLex. The IV GMPLex rapid high throughput subtyping test presents the following features： high throughput, able to determine the subtypes of 9 target genes in H1, H3, H5, H7, H9, N1, and N2 subtypes of the influenza A virus at one time; rapid, completing the influenza subtyping within 6 hours; high specificity, ensured the specificity of the different subtypes by using two nested degenerate primers and one probe, no cross reaction occurring between the subtypes, no non-specific reactions with other pathogens and high sensitivity. When used separately to detect the product of single GM RT-PCR for single H5 or N1 gene, the GMPLex test showed a sensitivity of 10-5（= 280ELDs0） forboth tests and the Luminex qualitative ratio results were 3.08 and 3.12, respectively. When used to detect the product of GM RT-PCR for H5N1 strain at the same time, both showed a sensitivity of 10-4（=2800 ELD50）. The GMPLex rapid high throughput subtyping test can satisfy the needs of influenza rapid testing.

H5N1 influenza viruses： outbreaks and biological properties

All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1 subtype emerged in Hong Kong that transmitted to humans, resulting in the first documented cases of human death by avian influenza virus infection. A new outbreak started in July 2003 in poultry in Vietnam, Indonesia, and Thailand, and highly pathogenic avian H5N1 influenza viruses have since spread throughout Asia and into Europe and Africa. These viruses continue to infect humans with a high mortality rate and cause worldwide concern of a looming pandemic. Moreover, H5N1 virus outbreaks have had devastating effects on the poultry industries throughout Asia. Since H5N1 virus outbreaks appear to originate from Southern China, we here examine H5N1 influenza viruses in China, with an emphasis on their biological properties.

Screening of a High Growth Influenza B Virus Strain in Vero Cells

Due to the insufficient supply of embryonated chicken eggs,the preparation of large quantities of inactivated influenza vaccines will require an alternative virus culture system after the emergence or reemergence of a pandemic influenza virus.The Vero cell is one of the ideal options since it was used for producing many kinds of human vaccines.However,most of the influenza viruses can not grow well in Vero cells.To develop a new influenza vaccine with Vero cells as a substrate,the virus needs to adapt to this cell substrate to maintain high growth characteristics.By serial passages in Vero cells,the B/Yunnan/2/2005va(B)strain was successfully adapted to Vero cells,with the hemagglutination titer(HAT)of the virus reaching 1:512.The high growth characteristic of this strain is stable up to 21 passages.The strain was identified by hemagglutination inhibition (HAI)test and sequencing respectively;the HA1 gene sequence of the virus was cloned and analyzed.The screening and establishment of high growth B virus provides an important tool for influenza vaccine production in Vero cells.

Genetic Characteristics of 2009 Pandemic H1N1 Influenza A Viruses Isolated from China's Mainland

A total of 100 H1N1 flu real-time-PCR positive throat swabs collected from fever patients in Zhejiang, Hubei and Guangdong between June and November 2009, were provided by local CDC laboratories. After MDCK cell culture, 57 Influenza A Pandemic （H1N1） viruses were isolated and submitted for whole genome sequencing. A total of 39 HA sequences, 52 NA sequences, 36 PB2 sequences, 31 PB1 sequences, 40 PA sequences, 48 NP sequences, 51 MP sequences and 36 NS sequences were obtained, including 20 whole genome sequences. Sequence comparison revealed they shared a high degree of homology （96%-99%） with known epidemic strains （A/Califomia/04/2009（H1N1）. Phylogenetic analysis showed that although the sequences were highly conserved, they clustered into a small number of groups with only a few distinct strains. Site analysis revealed three substitutions at loop 220 （221-228） of the HA receptor binding site in the 39 HA sequences： A/Hubei/86/2009 PKVRDQEG→PKVRDQEA, A/Zhejiang/08/2009 PKVRDQEG→PKVRDQER, A/Hubei/75/2009 PKVRDQEG→PKVRDQGG, the A/Hubei/75/2009 was isolated from an acute case, while the other two were from patients with mild symptoms. Other key sites such as 119, 274, 292 and 294 amino acids of NA protein,627 of PB2 protein were conserved. Meanwhile, all the M2 protein sequences possessed the Ser32Asn mutation, suggesting that these viruses were resistant to adamantanes. Comparison of these sequences with other H1N1 viruses collected from the NCBI database provides insight into H1N1 transmission and circulation patterns.

The HIV epidemic in China: history, response, and challenge

The first case of AIDS was reported in 1985 in China, but by the early 21st century, the government estimated that there were 840,000 citizens living with HIV/AIDS. The number is increasing rapidly. The major risk groups are injection drug users (IDUSs; 43%) and former plasma donors (27%), but rates among heterosexual groups are rising rapidly. Sentinel surveillance was initiated in 1986, and now includes IDUs, men-who-have-sex-with-men, sexually transmitted disease clinic attendees, antenatal women, long-distance truck drivers, and sex workers. Although the government was slow to respond to the epidemic in the late 20th century, it has made a vigorous response in the early 21st century. Components of that response include implementation and evaluation of harm reduction programs for IDUs, education to increase knowledge and reduce stigma, treatment and social support for rural and poor HIV/AIDS patients, widespread testing, and increased funding for HIV/AIDS programs. International agencies have been generous in their support of the government initiatives. To successfully combat the epidemic, China needs to develop and train the necessary infra- structure to implement its intervention programs, particularly in the rural areas, to vigorously combat stigma and discrimination, support research especially in the universities and research institutions other than the China Centers for Disease Control, develop a system for efficient exchange of research and program information, and update legislation to reflect the current situation.

Molecular Characterization of Avian-like H1N1 Swine Influenza A Viruses Isolated in Eastern China, 2011

Currently, three predominant subtypes of influenza virus are prevalent in pig populations worldwide： H1N1, H3N2, and H1N2. European avian-Hke H1N1 viruses, which were initially detected in European pig populations in 1979, have been circulating in pigs in eastern China since 2007. In this study, six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China. Based on whole genome sequencing, molecular characteristics of two isolates were determined. Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations, especially similar to those found in China. Four potential glycosylation sites were observed at positions 13, 26, 198, 277 in the HA1 proteins of the two isolates. Due to the presence of a stop codon at codon 12, the isolates contained truncated PB1-F2 proteins. In this study, the isolates contained 591Q, 627E and 701N in the polymerase subunit PB2, which had been shown to be determinants of virulence and host adaptation. The isolates also had a D rather than E at position 92 of the NS1, a marker of mammalian adaptation. Both isolates contained the GPKV motif at the PDZ ligand domain of the 3＇ end of the NS1, a characteristic marker of the European avian-like swine viruses since about 1999, which is distinct from those of avian, human and classical swine viruses. The M2 proteins of the isolates have the mutation （S31N）, a characteristic marker of the European avian-like swine viruses since about 1987, which may confer resistance to amantadine and rimantadine antivirals. Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs, and raise more concerns about the occurrence of cross-species transmission events.

Prevalence of hepatitis C virus infection and its related risk factors in drug abuser prisoners in Hamedan-Iran

AIM:Recent studies in Iran has shown that prevalence of hepatitis C virus (HCV) infection among Iranian prisoners is high, in spite of low HCV seroprevalence in general population. METHODS: This study was carried out in the central prison of Hamedan - Iran, in year 2002. Inmates were interviewed using a standard questionnaire including demographic, imprisonment history and HCV-related risk behaviors items. Thereafter, the sera drawn from the participants were tested for anti-HIV and anti-HCV antibodies. RESULTS: A total number of 427 drug abuser inmates participated in our study. Three hundred and ninety-seven (93%) were men and 30 (7%) were women. Total number of IV drug abusers (IDA) and non-IV drug abusers (NIDA) was 149 (34.9%) and 278 (65.1%), respectively. The overall rate of antibody positivity among inmates was 0.9% for HIV and 30% for HCV. Of all IDAs, 31.5% and of NIDAs, 29.1% had serological evidence of HCV infection. CONCLUSION: The seroprevalence of HCV infection among drug abuser prisoners in comparison with the general population in Iran, is very high (30% vs in italics 0.2%). Our results indicate the importance of policies to prevent transmission of HCV infection during and following incarceration.

Epidemiology of Hepatitis B and Associated Liver Diseases in China

Hepatitis B virus (HBV) infection has long been a critical public health challenge in China. National surveys revealed a prevalence of approximate 10% for chronic HBV infection in general population. HBV has been the leading cause of chronic hepatitis, cirrhosis, and liver cancers in Chinese population and a common pathogen of acute viral hepatitis. Meanwhile, the epidemic provided important opportunities to research the natural history, public health impact, and therapeutic and preventive interventions for HBV in China. In this review, we summarized the selected key epidemiological studies since 1970s regarding HBV infection and its associated liver diseases in China, and provided considerations for future research, prevention and treatment of HBV.

Antiviral Activity of the Effective Monomers from Folium Isatidis Against Influenza Virus in Vivo

In order to evaluate the anti-influenza virus activity of the effective monomer from Folium Isatidis (FI) in vivo,we established mice model with viral pneumonia and divided them into 3 different dose groups,then observed their lung indexes,pulmonary pathological changes,pulmonary virus hemagglitination titers,living time and death rates.The results showed that the monomer could reduce the pulmonary index from 2.64 to 1.93,1.63 and 1.40 (P<0.01) and decrease the hemagglitination titer from 1.15 to 0.84,0.70 and 0.59 (P<0.01).In addition,different groups of FI could significantly lessen the mortality rate from 100% to 30%,25% and 15%,and prolong the living time from 5.1d to 6.5d,8.4d and 8.9d respectively(P<0.01).The high dose (75 mg/kg/d) has the similar effect with 100 mg/kg/d dose of virazole(P>0.05),and more effective than 200 mg/kg/d dose of antiviral liquor (P<0.05).

MSM and HIV/AIDS in China

This article profiles current status of spread and control of HIV/AIDS in China. China has a significant population of MSM (men who have sex with men) and they have been becoming very much alive in many ways since 1990s due to recent social changes. Some surveys indicate that great many of MSM are engaged in high-risk behaviors. In addition, majority of MSM have also experienced sexual encounters with women sometimes in their lives, which possibly con- tribute to spread of HIV to women. Some reports documented that HIV is becoming rampant among MSM since more than 1% of them are now infected. Political, cultural and custom elements could hinder intervention activities against HIV spread among MSM. Fortunately, many cities in China have seen that MSM were in cooperation with responsible institutions carrying out certain intervention measures. The general situation is promising. The authors forecast that the fast HIV spread among MSM of China could possibly be halted within several years when the authorities become more sensible to this issue, health service institutions offer unswerving efforts toward the MSM community and those who involve in MSM undertakes necessary responsibilities.

Immunogenicity and protective efficacy of recombinant M2e.Hsp70c(Hsp70_(359–610)) fusion protein against influenza virus infection in mice

New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.

Analysis of Oseltamivir Resistance Substitutions in Influenza Virus Glycoprotein Neuraminidase using a Lentivirus-Based Surrogate Assay System

Influenza A virus poses a great threat to global health, and oseltamivir (trade marked as Tamiflu), which targets influenza surface glycoprotein neuraminidase (NA), is used clinically as a major anti-influenza treatment. However, certain substitutions in NA can render an influenza virus resistant to this drug. In this study, using a lentiviral pseudotyping system, which alleviates the safety concerns of studying highly pathogenic influenza viruses such as avian influenza H5N1, that utilizes influenza surface glycoproteins (hemagglutinin or HA, and NA) and an HIV-core combined with a luciferase reporter gene as a surrogate assay, we first assessed the functionality of NA by measuring pseudovirion release in the absence or presence of oseltamivir. We demonstrated that oseltamivir displays a dose-dependent inhibition on NA activity. In contrast, a mutant NA (H274Y) is more resistant to oseltamivir treatment. In addition, the effects of several previously reported substitution NA mutants were examined as well. Our results demonstrate that this lentivirus-based pseudotyping system provides a quick, safe, and effective way to assess resistance to neuraminidase inhibitors. And we believe that as new mutations appear in influenza isolates, their impact on the effectiveness of current and future anti-NA can be quickly and reliably evaluated by this assay.