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Objective@#To understand characteristics of demographic, seasonal and spatial distribution of H5N1 cases in major countries of Asia (Indonesia, Cambodia, Vietnam, China) and Africa (Egypt).@*Methods@#Through searching public data resource and published papers, we collected cases information in five countries from May 1st, 1997 to November 6th, 2017, including general characteristics, diagnosis, onset and exposure history, etc. Different characteristics of survived and death cases in different countries were described and χ2 test was used to compare the differences among death cases and odds ratio (OR) and 95%CI value was used to compare death risk in different countries.@*Results@#A total of 856 cases were reported in five countries with Egypt had the most cases (44.3%). The highest number of cases were reported in 2015 (18.3%). 53% cases were reported from January to March, and 96.1% of cases had the history of poultry exposure. 64.2% (43 cases) cases in China had live poultry market exposure, but the sick/dead poultry exposure was the major exposure for cases in other four countries. 452 death cases were reported in five countries, and the fatality rate was 52.8%. With Egypt as the reference group, the highest death risk was seen in Indonesia (OR (95%CI): 11.52 (7.46-17.77)), followed by Cambodia (OR (95%CI): 4.27(2.37-7.69)) and China (OR (95%CI): 2.87 (1.73-4.74)). The age distribution of death cases among 5 countries was statistically significant, and the highest fatality rate was in 15-54 years group in Egypt (83.6%, 102 cases), while in Cambodia the highest fatality rate was in 0-14 years group (76.9%, 30 cases). The highest number of deaths were reported in 2006, and 48.3% were reported from January to March. There was difference in exposure routes among 5 countries (χ2=43.85, P=0.001), 63.2% (24 cases) of the death cases in China had live poultry market exposure. 92.9% (79 cases), 83.3% (40 cases) and 100.0% (38 cases) death cases in Indonesia, Vietnam and Camodia had sick/dead poultry exposure, respectively;and 81.6% (31 cases) of the death cases in Egypt had backyard poultry exposure.@*Conclusion@#The geographical distribution, seasonal age, gender, exposure matter and outcome of H5N1 cases in five countries were different.
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A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice. In this study, we generated PR8-derived H5N1 recombinant viruses harboring hemagglutinin (attenuated) and neuraminidase genes of a clade 2.3.2.1c H5N1 HPAIV (K10-483), as well as the 01310 or 0028 PB2 genes, and investigated their replication and immunogenicity. Compared with a control virus harboring six internal PR8 genes (rK10-483), the recombinant viruses possessing the 01310 and 0028 PB2 genes showed significantly higher replication efficiency in ECEs and higher antibody titers in chickens. In contrast to rK10-483, none of the viruses replicated in BALB/c mice, and all showed low titers in Madin-Darby canine kidney cells. Additionally, the recombinant viruses did not induce a neutralization antibody but elicited decreased protective immune responses against K10-483 in mice. Thus, the highly replicative and mammalian nonpathogenic recombinant H5N1 strains might be promising vaccine candidates against HPAI in poultry.
Subject(s)
Animals , Mice , Chickens , Efficiency , Eggs , Hemagglutinins , Influenza in Birds , Influenza Vaccines , Kidney , Neuraminidase , Ovum , Poultry , Reverse Genetics , Seasons , Vaccines , VirulenceABSTRACT
Objective To analyze domestic and foreign papers on H5N1 virus research using literature metrology and visualized knowledge mapping.Methods Pajek, Bibexcel,and VoSviewer software were used based on Web of Knowledge platform.Results Study on H5N1 virus has been a research focus wide since 2005 and a series of institutions and investi-gators have appeared, with US being the leader in this area and followed by China.The most popular topics of studies on H5N1 included its virology, epidemiology, basic research, anti-virus drugs and vaccines.Conclusion Studies on H5N1 have received more attention, which suggests that more efforts have to be made in China in terms of communication and co-operation with key institutions and famous researchers so as to achieve more success in key areas.
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Objective To construct a eukaryotic vector which contains avian H5N1 influenza virus hemagglutinin (HA) antigen and the cholera toxin B subunit (CTB) and to investigate its expression in COS7 cells,and the ability to induce specific immune responses in vivo in different periods.Methods After cloned by polymerase chain reaction (PCR),CTB and HA genes were digested with BamH Ⅰ and connected into CTB-HA gene with T4 ligase.The connected gene was referred to as CH.After double digestion,CH gene was inserted into a eukaryotic recombinant plasmid pCI-neo.The pCI-CH plasmid was then transfected into COS7 cells.Western blot was used to detect the expression of HA antigen.After New Zealand white rabbits were immunized,the titer of HA antigen-specific antibody in serum and its specificity with other strains such as H1N1,H9N1,H3N2 and influenza B virus were determined by indirect enzyme-linked immunosorbent assay.Results The pCI-CH vector (DNA vaccine) was successfully constructed,which could be efficiently expressed in COS7 cells and induce specific antibodies against pCI-CH in rabbits.Cross reactions indicated that DNA vaccine pCI-CH specific antisera could not only react with H5N1 strain (P/N＞2.1),but also H1N1,H9N1 and H3N2 strains,but did not cross react with influenza B virus.Conclusion The newly constructed avian H5N1 influenza virus nucleic acid vaccine has good immunogenicity.
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Objective To analyze the clinical features,epidemiologic information and outcome in confirmed cases of human infection with a highly pathogenic influenza A(H5N1).Methods The clinical features and epidemiologic findings in 2 confirmed cases of avian influenza A(H5N1)in Anhui province,in November 2005.Clinical data on vital signs,physical findings,laboratory tests and roentgenology were obtained by means of retrospective review of the hospital records.Epidemiologic data were collected through interviews of the patients and their relatives.Results In both cases,the diagnosis of influenza A(H5N1)was confirmed by means of viral culture and real-time polymerase chain reaction with specific primers for H5 and N1 in samples obtained from tracheal aspiration.All patients were previously healthy young women and resided in village.They had a clear history of di- rect contact with sick/dead poultry and prepared dead chickens at home for eating(removed feathers, washed,cut)hut no report of confirmed HSN1 animals in the village.The time between exposure and onset of illness were 5 days,no one else in family sick.The time between the onset of illness and hos- pitalization were 5 days and 6 days,respectively.Two patients have initial symptoms of high fever (typically a temperature more than 38℃).The prominent clinical features were those of influenza syndrome,including fever,cough,and shortness of breath.Upper respiratory tract symptoms were absent.The platelet counts were decreased.In both patients,there were marked abnormalities on chest radiography,radiographic changes include bilateral and unilateral lobular consolidations with air bronchograms,and had dramatic worsening of findings.Two patients developed acute respiratory dis- tress syndrome(ARDS)complicated multiple organ dysfunction syndrome(MODS)and died of pro- gressive respiratory failure.Conclusions Exposure to dead poultry within a week before the onset of illness was associated with Influenza A(H5N1)infection in humans,but no definitive evidence of hu man-to-human transmission has been found yet.Influenza A(HSNI)infection,characterized by fe- ver,an influenza-like illness with lower respiratory tract symptoms,carries a high risk of death.
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The outbreak of high-pathogenicity avian influenza viruses causing severe illness and death has severely disrupted poultry production and trade and posed a significant threat to public health.In recent thirty years,the virus has been endemic in Southeast Asia,China,Europe and Africa.Although the virus shows little ability of transmission between humans,a process of genetic reassortment could occur in a human co-infected with avian influenza A virus and a human strain of influenza A virus.So H5N1 represents a potential source of the next pandemic influenza.Direct avian-human H5N1 virus transmission is the predominant means of human infection,through direct contact with infected birds and virus-contaminated fomites or with fertilizer containing poultry feces.After several rounds of infection the viruses acquire the mutations required for crossing species barrier and infect a range of mammalian species including humans.Currently,vaccination is still the key strategy to prevent severe illness and death from pandemic influenza.Antiviral drugs such as NA inhibitors play an important role in antiviral treatment.The features of avian influenza virus and its mechanism of transmission in animals and humans are herewith reviewed,and the pathopoiesis of the virus,the current status of vaccine development and antiviral treatment are also discussed.