Objective To survey avian influenza A viruses(AIVs) in the environment and explore the reasons for the surge in human H7 N9 cases.Methods A total of 1,045 samples were collected from routine surveillance on poultry-re...Objective To survey avian influenza A viruses(AIVs) in the environment and explore the reasons for the surge in human H7 N9 cases.Methods A total of 1,045 samples were collected from routine surveillance on poultry-related environments and 307 samples from human H7 N9 cases-exposed environments in Henan from 2016 to2017. The nucleic acids of influenza A(Flu A), H5, H7, and H9 subtypes were detected by real-time polymerase chain reaction.Results A total of 27 H7 N9 cases were confirmed in Henan from 2016 to 2017, 24 had a history of live poultry exposure, and 15 had H7 N9 virus detected in the related live poultry markets(LPMs). About 96%(264/275) Flu A positive-environmental samples were from LPMs. H9 was the main AIV subtype(10.05%) from routine surveillance sites with only 1 H7-positive sample, whereas 21.17% samples were H7-positive in H7 N9 cases-exposed environments. Samples from H7 N9 cases-exposed LPMs(47.56%)had much higher AIVs positive rates than those from routine surveillance sites(12.34%). The H7+H9 combination of mixed infection was 78.18%(43/55) of H7-positive samples and 41.34%(43/104) of H9-positive samples.Conclusion The contamination status of AIVs in poultry-related environments is closely associated with the incidence of human infection caused by AIVs. Therefore, systematic surveillance of AIVs in LPMs in China is essential for the detection of novel reassortant viruses and their potential for interspecies transmission.展开更多
Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of e...Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.展开更多
In order to reveal variation and revolution of NP genes of human avian H_5N_1 influenza virus strains,the NP gene of a human avian H_5N_1 influenza virus strain in Guangdong was sequenced and the global NP genes of st...In order to reveal variation and revolution of NP genes of human avian H_5N_1 influenza virus strains,the NP gene of a human avian H_5N_1 influenza virus strain in Guangdong was sequenced and the global NP genes of strains were retrieved.The sequences were analyzed by DNAStar 5.0,and the evolu- tionary speed was studied with reference to the epidemiological data.It was found that NP genes of 45 strains during 1997-2006 were homologically classified into three groups:strains in 1997-1998,strains in 2004-2005 and strains from 2003 to 2006.There were 35 substitutions in NPs in all strains accounting for a ratio of 7.03%(35/498).An additional glycoprotein domain(NGT_(430-432))was found in NP genes in the strains of 2003-2006,the mutation of N_(370)S in GD-01-06 resulted in occurrence of one more glyco- protein domain(NES_(368-370)).In the synonymous variation,K_s values in NP were 2.03×10^(-5)-2.55×10^(-5) Nt/d and K_a values in NP were 1.58×10(-6)-3.10×10^(-6) Nt/d.There didn′t exist obviously selective pres- sure.An additional glycoprotein domain in every strain of 2003-2006 and one more in strain GD-01-06 might change the antigenicity of human avian H_6N_1 influenza virus.The variation on human avian H_5N_1 influenza strains occurred frequently in the natural world,which would result in high probability of hu- man-human transmission along with the natural evolution of the virus.展开更多
Background Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A （H10N8） virus which can infect humans and cau...Background Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A （H10N8） virus which can infect humans and cause severe diseases. Methods Collecting clinical data of three cases of human infection with a novel reassortment avian influenza A （H10N8） virus in Nanchang, Jiangxi Province, China. Results Three cases of human infection with a new reassortment avian influenza A（H10N8） virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome （ARDS） and intractable respiratory failure. Conclusion This novel reassortment avian influenza A （H10N8） virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.展开更多
In this paper,a reaction-diffusion system is proposed to investigate avian-human influenza.Two free boundaries are introduced to describe the spreading frontiers of the avian influenza.The basic reproduction numbers r...In this paper,a reaction-diffusion system is proposed to investigate avian-human influenza.Two free boundaries are introduced to describe the spreading frontiers of the avian influenza.The basic reproduction numbers rF0(t)and RF0(t)are defined for the bird with the avian influenza and for the human with the mutant avian influenza of the free boundary problem,respectively.Properties of these two time-dependent basic reproduction numbers are obtained.Sufficient conditions both for spreading and for vanishing of the avian influenza are given.It is shown that if rF0(0)<1 and the initial number of the infected birds is small,the avian influenza vanishes in the bird world.Furthermore,if rF0(0)<1 and RF0(0)<1,the avian influenza vanishes in the bird and human worlds.In the case that rF0(0)<1 and RF0(0)>1,spreading of the mutant avian influenza in the human world is possible.It is also shown that if rF0(t0)>1 for any t0>0,the avian influenza spreads in the bird world.展开更多
Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecyst...Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient.We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets(LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry(chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.展开更多
Highly pathogenic influenza A (H5N1) virus causes a widespread poultry deaths worldwide. The first human H5N1 infected case was reported in Hong Kong Special Administrative Region of China in 1997. Since then, the vir...Highly pathogenic influenza A (H5N1) virus causes a widespread poultry deaths worldwide. The first human H5N1 infected case was reported in Hong Kong Special Administrative Region of China in 1997. Since then, the virus re-emerged in 2003 and continues to infect people worldwide. Currently, over 400 human infections have been reported in more than 15 countries and mortality rate is greater than 60%. H5N1 viruses still pose a potential pandemic threat in the future because of the continuing global spread and evolution. Here, we summarize the epidemiological, clinical and virological characteristics of human H5N1 infection in China monitored and identified by our national surveillance systems.展开更多
To the Editor: Since avian influenza A(H7N9) was first identified in Shanghai, China, in March 2013, there have been a total of five epidemics. These have amounted to 1564 laboratory-confirmed cases up to September 20...To the Editor: Since avian influenza A(H7N9) was first identified in Shanghai, China, in March 2013, there have been a total of five epidemics. These have amounted to 1564 laboratory-confirmed cases up to September 2017, with a fatality rate of about 40%.[1] In the fifth wave, 4.09% of cases (31/758) were infected with the highly pathogenic avian influenza (HPAI) A(H7N9). This indicated that the pathotype of the A(H7N9) had switched from low pathogenic avian influenza (LPAI) to HPAI.展开更多
基金supported by Henan Department of Science and Technology Project [182102310235]Henan Medical Science and Technology Research Project [201702269]Henan Natural Science Foundation [182300410384]
文摘Objective To survey avian influenza A viruses(AIVs) in the environment and explore the reasons for the surge in human H7 N9 cases.Methods A total of 1,045 samples were collected from routine surveillance on poultry-related environments and 307 samples from human H7 N9 cases-exposed environments in Henan from 2016 to2017. The nucleic acids of influenza A(Flu A), H5, H7, and H9 subtypes were detected by real-time polymerase chain reaction.Results A total of 27 H7 N9 cases were confirmed in Henan from 2016 to 2017, 24 had a history of live poultry exposure, and 15 had H7 N9 virus detected in the related live poultry markets(LPMs). About 96%(264/275) Flu A positive-environmental samples were from LPMs. H9 was the main AIV subtype(10.05%) from routine surveillance sites with only 1 H7-positive sample, whereas 21.17% samples were H7-positive in H7 N9 cases-exposed environments. Samples from H7 N9 cases-exposed LPMs(47.56%)had much higher AIVs positive rates than those from routine surveillance sites(12.34%). The H7+H9 combination of mixed infection was 78.18%(43/55) of H7-positive samples and 41.34%(43/104) of H9-positive samples.Conclusion The contamination status of AIVs in poultry-related environments is closely associated with the incidence of human infection caused by AIVs. Therefore, systematic surveillance of AIVs in LPMs in China is essential for the detection of novel reassortant viruses and their potential for interspecies transmission.
基金supported by the General Program of the National Natural Science Foundation of China[No.31570162]the National Key Research Program[No.2016YFC1200200].
文摘Objective To recover broad-neutralizing monoclonal antibodies(Bn Abs)from avian influenza A(H5N1)virus infection cases and investigate their genetic and functional features.Methods We screened the Abs repertoires of expanded B cells circulating in the peripheral blood of H5N1 patients.The genetic basis,biological functions,and epitopes of the obtained Bn Abs were assessed and modeled.Results Two Bn Abs,2-12 D5,and 3-37 G7.1,were respectively obtained from two human H5N1 cases on days 12 and 21 after disease onset.Both Abs demonstrated cross-neutralizing and Ab-dependent cellular cytotoxicity(ADCC)activity.Albeit derived from distinct Ab lineages,i.e.,V^H1-69-D2-15-JH^4(2-12D5)and V^H1-2-D3-9-JH^5(3-32 G7.1),the Bn Abs were directed toward CR6261-like epitopes in the HA stem,and HA2 I45 in the hydrophobic pocket was the critical residue for their binding.Signature motifs for binding with the HA stem,namely,IFY in VH1-69-encoded Abs and LXYFXW in D3-9-encoded Abs,were also observed in 2-12D5 and 3-32 G7.1,respectively.Conclusions Cross-reactive B cells of different germline origins could be activated and re-circulated by avian influenza virus.The HA stem epitopes targeted by the Bn Abs,and the two Ab-encoding genes usage implied the VH1-69 and D3-9 are the ideal candidates triggered by influenza virus for vaccine development.
文摘In order to reveal variation and revolution of NP genes of human avian H_5N_1 influenza virus strains,the NP gene of a human avian H_5N_1 influenza virus strain in Guangdong was sequenced and the global NP genes of strains were retrieved.The sequences were analyzed by DNAStar 5.0,and the evolu- tionary speed was studied with reference to the epidemiological data.It was found that NP genes of 45 strains during 1997-2006 were homologically classified into three groups:strains in 1997-1998,strains in 2004-2005 and strains from 2003 to 2006.There were 35 substitutions in NPs in all strains accounting for a ratio of 7.03%(35/498).An additional glycoprotein domain(NGT_(430-432))was found in NP genes in the strains of 2003-2006,the mutation of N_(370)S in GD-01-06 resulted in occurrence of one more glyco- protein domain(NES_(368-370)).In the synonymous variation,K_s values in NP were 2.03×10^(-5)-2.55×10^(-5) Nt/d and K_a values in NP were 1.58×10(-6)-3.10×10^(-6) Nt/d.There didn′t exist obviously selective pres- sure.An additional glycoprotein domain in every strain of 2003-2006 and one more in strain GD-01-06 might change the antigenicity of human avian H_6N_1 influenza virus.The variation on human avian H_5N_1 influenza strains occurred frequently in the natural world,which would result in high probability of hu- man-human transmission along with the natural evolution of the virus.
文摘Background Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A （H10N8） virus which can infect humans and cause severe diseases. Methods Collecting clinical data of three cases of human infection with a novel reassortment avian influenza A （H10N8） virus in Nanchang, Jiangxi Province, China. Results Three cases of human infection with a new reassortment avian influenza A（H10N8） virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome （ARDS） and intractable respiratory failure. Conclusion This novel reassortment avian influenza A （H10N8） virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.
基金supported by National Natural Science Foundation of China(Grant No.11071209)Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,Science and Technology(Grant No.2010-0025700)Natural Science Foundation of the Higher Education Institutions of Jiangsu Province(Grant No.12KJD110008)
文摘In this paper,a reaction-diffusion system is proposed to investigate avian-human influenza.Two free boundaries are introduced to describe the spreading frontiers of the avian influenza.The basic reproduction numbers rF0(t)and RF0(t)are defined for the bird with the avian influenza and for the human with the mutant avian influenza of the free boundary problem,respectively.Properties of these two time-dependent basic reproduction numbers are obtained.Sufficient conditions both for spreading and for vanishing of the avian influenza are given.It is shown that if rF0(0)<1 and the initial number of the infected birds is small,the avian influenza vanishes in the bird world.Furthermore,if rF0(0)<1 and RF0(0)<1,the avian influenza vanishes in the bird and human worlds.In the case that rF0(0)<1 and RF0(0)>1,spreading of the mutant avian influenza in the human world is possible.It is also shown that if rF0(t0)>1 for any t0>0,the avian influenza spreads in the bird world.
基金supported by National Science and Technology Major Project of China (2015ZX09101044)Science & Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention of Jiangsu Province, China (BE2015714 & BE2017749)Key Medical Discipline of Jiangsu Science & Technology Project of China (epidemiology,ZDXKA2016008)
文摘Human infections with influenza H7 subtypes, such as H7N9, have raised concerns worldwide. Here, we report a human infection with a novel influenza A(H7N4) virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICU. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient.We obtained the medical records and collected serial respiratory and blood specimens from her. We collected throat, cloacal and/or feces samples of poultry and wild birds from the patient's backyard, neighborhood, local live poultry markets(LPMs) and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird samples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry(chickens and ducks) by sequencing, which is distinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.
基金Chinese Nature Science Foundation Key Project (Grant No. 30599433)Chinese Basic Science Research Program (973)Key Project (Grant No. 2005CB523006)
文摘Highly pathogenic influenza A (H5N1) virus causes a widespread poultry deaths worldwide. The first human H5N1 infected case was reported in Hong Kong Special Administrative Region of China in 1997. Since then, the virus re-emerged in 2003 and continues to infect people worldwide. Currently, over 400 human infections have been reported in more than 15 countries and mortality rate is greater than 60%. H5N1 viruses still pose a potential pandemic threat in the future because of the continuing global spread and evolution. Here, we summarize the epidemiological, clinical and virological characteristics of human H5N1 infection in China monitored and identified by our national surveillance systems.
文摘To the Editor: Since avian influenza A(H7N9) was first identified in Shanghai, China, in March 2013, there have been a total of five epidemics. These have amounted to 1564 laboratory-confirmed cases up to September 2017, with a fatality rate of about 40%.[1] In the fifth wave, 4.09% of cases (31/758) were infected with the highly pathogenic avian influenza (HPAI) A(H7N9). This indicated that the pathotype of the A(H7N9) had switched from low pathogenic avian influenza (LPAI) to HPAI.
