病毒性出血热的研究进展
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摘要
病毒性出血热(viral hemorrhagic fevers,VHFs)是一组由媒介病原微生物引起的以发热和出血为主要临床症状的急性传染病,可引起人类VHFs的病毒包括黄病毒科病毒[如西尼罗河病毒(West Nile Virus,WNV)、日本脑炎病毒(Japanese encephalitis virus,JEV)、蜱传脑炎病毒(tick-borne encephalitis virus,TBEV)、黄热病毒(yellow fever virus,YFV)和登革病毒(Dengue virus,DENV)]、布尼亚病毒科病毒[如汉坦病毒(Hantavirus,HV)、克里米亚-刚果出血热病毒(Crimean-Congo hemorrhagic fever virus,CCHFV)、发热伴血小板减少综合征布尼亚病毒(severe fever with thrombocytopenia syndrome bunyavirus,SFTSV)]、丝状病毒科病毒[如埃博拉病毒(Ebola virus,EBOV)和马尔堡病毒(Marburg virus,MARV)]、沙粒病毒科病毒[如拉沙病毒(Lassa virus,LASV)和Lujo病毒]、披膜病毒科病毒[如基孔肯雅病毒(Chikungunya virus,CHIKV)]。近年新发突发VHFs病例不断增加,且目前尚无有效治疗药物,VHFs严重威胁人类健康。本文就VHFs的病原学、临床特征、快速早期诊断及疫苗研究等方面作一综述。
Viral hemorrhagic fevers(VHFs)are a group of acute infectious diseases with main clinical symptom of fever and hemorrhage,which are caused by vehicle-borne pathogenic microorganisms. The viruses causing VHFs in humans include Flaviviruses[such as West Nile virus(WNV),Japanese encephalitis virus(JEV),tick-borne encephalitis virus(TBEV),yellow fever virus(YFV)and Dengue virus(DENV)],bunyavirus[such as Hantavirus(HV),Crimean-Congo Hemorrhagic fever virus(CCHFV),severe fever with thrombocytopenia syndrome bunyavirus(SFTSV)],filovirus[such Ebola virus(EBOV)and Marburg virus(MARV)]Grit virus[such as Lassa virus(LASV)and Lujo virus]and Togaviridae virus such as Chikungunya virus(CHIKV). In recent years,the outbreaks of new and sudden viral hemorrhagic fever have been increasing,while there is no effective drug. VHFs are serious threats to human health. The pathogenicity,clinical features,rapid early diagnosis and vaccine research of VHFs are reviewed in this paper.
Viral hemorrhagic fevers(VHFs)are a group of acute infectious diseases with main clinical symptom of fever and hemorrhage,which are caused by vehicle-borne pathogenic microorganisms. The viruses causing VHFs in humans include Flaviviruses[such as West Nile virus(WNV),Japanese encephalitis virus(JEV),tick-borne encephalitis virus(TBEV),yellow fever virus(YFV)and Dengue virus(DENV)],bunyavirus[such as Hantavirus(HV),Crimean-Congo Hemorrhagic fever virus(CCHFV),severe fever with thrombocytopenia syndrome bunyavirus(SFTSV)],filovirus[such Ebola virus(EBOV)and Marburg virus(MARV)]Grit virus[such as Lassa virus(LASV)and Lujo virus]and Togaviridae virus such as Chikungunya virus(CHIKV). In recent years,the outbreaks of new and sudden viral hemorrhagic fever have been increasing,while there is no effective drug. VHFs are serious threats to human health. The pathogenicity,clinical features,rapid early diagnosis and vaccine research of VHFs are reviewed in this paper.
引文
[1] FALZARANO D, FELDMANN H. Vaccines for viral hemorrhagic fevers—progress and shortcomings[J]. Curr Opin Virol,2013, 3(3):343-351.
[2] BOS S, GADEA G, DESPRES P. Dengue:a growing threat requiring vaccine development for disease prevention[J]. Pathog Global Health, 2018, 112(6):294-305.
[3] SABCHAREON A,WALLACE D,SIRIVICHAYAKUL C,et al.Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren:a randomi-sed,controlled phase 2b trial[J]. Lancet, 2012, 380(9853):1559.
[4] CAPEDING M R, TRAN N H, HADINEGORO S R, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia:a phase 3,randomised, observer-masked, placebo-controlled trial[J]. Lancet, 2014, 384(9951):1358-1365.
[5] HAMDY R F. Efficacy of a tetravalent Dengue vaccine in children in Latin America[J]. New Engl J Med, 2015, 372(2):113.
[6] KIRKPATRICK B D, WHITEHEAD S S, PIERCE K K, et al.The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model[J]. Sci Translat Med, 2016, 8(330):330ra36.
[7] OSORIO J E, WALLACE D, DAN T S. A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone[J]. Expert Rev Vaccin, 2015,15(4):497-508.
[8] WANG L, ZHOU P, FU X, et al. Yellow fever virus:Increasing impored cases in China[J]. J Infect, 2016,73(4):377-380.
[9] ProMED. Yellow fever-Africa(05):Angola(Huila):International Society for Infectious Diseases. ProMED-mail. 2016.(2016-04-11)[2018-11-01]. http://www.promedmail.org/post/3977685.
[10] LING Y, LU H Z. Research progress of yellow fever and its vaccine[J]. World Clinic Drugs, 2017, 8:6-8.(in Chinese)凌云,卢洪洲.黄热病及其疫苗的研究进展[J].世界临床药物,2017, 8:6-8.
[11] VACCINES C G F S 0 Y F. Duration of post-vaccination immunity against yellow fever in adults[J]. Vaccine, 2014, 32(39):4977-4984.
[12] CAMPIAZEVEDO A C, COSTAPEREIRA C, ANTONELLI L R,et al. Booster dose after 10 years is recommended following17DD-YF primary vaccination[J]. Hum Vaccin,2016,12(2):491-502.
[13] ORGANIZATION P-P A H. Yellow fever:number of confirmed cases and deaths by country in the Americas, 1960-2015[EB/OL].(2017-07-25)[2018-11-09]. http://ais.paho.org/phip/viz/ed_yellowfever.asp. 2016.
[14] NIEDRIG M, LADEMANN M P, LAFRENZ M. Assessment of IgG antibodies against yellow fever virus after vaccination with17D by different assays:neutralization test, haemagglutination inhibition test, immunofluorescence assay and ELISA[J]. Trop Med&Int Health, 1999, 4(12):867-871.
[15] LEE H W, AN C N. Development of vaccine against hemorrhagic fever with renal syndrome[J]. J Bacteriol Virol, 1988,18(2):143-148.
[16] HOOPER J W, MOON J E, PAOLINO K M, et al. A phase 1clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation[J]. Clin Microbiol&Infect, 2014, 20(Suppl 5):110.
[17] LI P Y, YU L, WU X A, et al. Modification of the adenoviral transfer vector enhances expression of the Hantavirus fusion protein GnSO. 7 and induces a strong immune response in C57BL/6 mice[J]. J Virol Mtd, 2012, 179(1):90.
[18] MOSTAFAVI E, POURHOSSEIN B, ESMAEILI S, et al. Seroepidemiology and risk factors of Crimean-Congo hemorrhagic fever among butchers and slaughterhouse workers in southeastern Iran[J]. Int J Infect Dis, 2017, 64.
[19] DOWALL S D, BUTTIGIEG K R, SJD F W, et al. A CrimeanCongo hemorrhagic fever(CCHF)viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease[J]. Hum Vaccin, 2016, 12(2):519-527.
[20] BUTTIGIEG K R, DOWALL S D, FINDLAYWILSON S, et al.A novel vaccine against Crimean-Congo haemorrhagic fever protects 100%of animals against lethal challenge in a mouse model[J]. Plos One, 2014, 9(3):e91516.
[21] HINKULA J, DEVIGNOT S, KERSTROM S, et al. Immunization with DNA plasmids coding for Crimean-Congo hemor-rhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice[J]. J Virol, 2017, 91(10):e02076-e92116.
[22] GARRISON A R, SHOEMAKER C J, GOLDEN J W, et al. A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models[J]. Plos Negl Trop Dis, 2017, 11(9):e0005908.
[23] ZIVCEC M, SAFRONETZ D, SCOTT D P, et al. Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge[J]. Plos Neglected Trap Dis, 2018, 12(7):e0006628.
[24] YU X J, LIANG M F, ZHANG S Y, et al. Fever with thrombocytopenia associated with a novel Bunyavirus in China[J]. N Engl J Med, 2011, 364(16):1523-1532.
[25] SUN J, LU L, WU H, et al. The changing epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2011-2016[J]. Sci Rep, 2017, 7(1):9236.
[26]世界卫生组织:首种埃博拉疫苗通过临床试验[J].上海医药,2017(1):30.
[27] ZHU F C, WURIE A H, HOU L H, et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone:a singlecentre,randomised, double-blind, placebo-controlled, phase 2 trial[J].Lancet, 2016, 389(10069):621-628.
[28]张子龙,杨柳,张宏,等.马尔堡病毒的流行病学及检测方法概述[J].国际病毒学杂志,2017, 24(2):141-144.
[29] SWENSON D, WANG D, M, WARFIELD K, et al. Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections[J]. Clin&Va-ccin Immunol Cvi, 2008, 15(3):460.
[30] JONES S M,FELDMANN H,STROHER U,et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses[J]. Nat Med, 2005, 11(7):786-790.
[31] SAKA M J, GUBIO A B, YENNAN S, et al. Lassa fever epidemic in Nigeria-outbreak investigation, risk factors and empirical analysis from 2012 to 2016[J]. 2017, 3:170.
[32] ZAPATA J C, GOICOCHEA M, NADAI Y, et al. Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate[J].J Virol, 2014, 88(6):3058.
[33] BREDENBEEK P J, MOLENKAMP R, SPAAN W J, et al. A recombinant yellow fever 17D vaccine expressing Lassa virus glycoproteins[J]. Virology, 2006, 345(2):299.
[34] GARBUTT M, LIEBSCHER R, WAHLJENSEN V, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses[J].J Virol, 2004, 78(10):5458-5465.
[35] EDELMAN R, TACKET C O, WASSERMAN S S, et al. Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218[J]. Am J Trop Med&Hyg, 2000, 62(6):681-685.
[36] BRANDLER S, RUFFIE C, COMBREDET C, et al. A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus[J]. Vaccine, 2013, 31(36):3718.
[37] RAMSAUER K, SCHWAMEIS M, FIRBAS C, et al. Immunogenicity,safety,and tolerability of a recombinant measlesvirus-based chikungunya vaccine:a randomised, double-blind,placebo-controlled, active-comparator, first-in-man trial[J].Lancet Infect Dis, 2015, 15(5):519-527.
[38] AKAHATA W, YANG Z Y, ANDERSEN H, et al. A viruslike particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection[J]. Nat Med,2010,16(3):334-338.
[39] CHANG L J,DOWD K A,MENDOZA F H,et al. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults:a phase 1 dose-escalation trial[J]. Lancet, 2014,384(9959):2046-2452.
[40] MUTHUMANI K, LANKARAMAN K M, LADDY D J, et al.Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus[J]. Vaccine, 2008, 26(40):5128-5134.
[41] ERASMUS J H, AUGUSTE A J, KAELBER J T, et al. A chikungunya fever vaccine utilizing an insect-specific virus platform[J]. Nat Med, 2017, 23(2):192.
[42] PLANTE K, WANG E, PARTIDOS C D, et al. Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism[J]. Plos Pathog,2011,7(7):e1002142.
[43] PLANTE K S, ROSSI S L, BERGREN N A, et al. Extended preclinical safety,efficacy and stability testing of a live-attenuated chikungunya vaccine candidate[J]. Plos Neglected Trop Dis, 2015, 9(9):e0004007.
[2] BOS S, GADEA G, DESPRES P. Dengue:a growing threat requiring vaccine development for disease prevention[J]. Pathog Global Health, 2018, 112(6):294-305.
[3] SABCHAREON A,WALLACE D,SIRIVICHAYAKUL C,et al.Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren:a randomi-sed,controlled phase 2b trial[J]. Lancet, 2012, 380(9853):1559.
[4] CAPEDING M R, TRAN N H, HADINEGORO S R, et al. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia:a phase 3,randomised, observer-masked, placebo-controlled trial[J]. Lancet, 2014, 384(9951):1358-1365.
[5] HAMDY R F. Efficacy of a tetravalent Dengue vaccine in children in Latin America[J]. New Engl J Med, 2015, 372(2):113.
[6] KIRKPATRICK B D, WHITEHEAD S S, PIERCE K K, et al.The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model[J]. Sci Translat Med, 2016, 8(330):330ra36.
[7] OSORIO J E, WALLACE D, DAN T S. A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone[J]. Expert Rev Vaccin, 2015,15(4):497-508.
[8] WANG L, ZHOU P, FU X, et al. Yellow fever virus:Increasing impored cases in China[J]. J Infect, 2016,73(4):377-380.
[9] ProMED. Yellow fever-Africa(05):Angola(Huila):International Society for Infectious Diseases. ProMED-mail. 2016.(2016-04-11)[2018-11-01]. http://www.promedmail.org/post/3977685.
[10] LING Y, LU H Z. Research progress of yellow fever and its vaccine[J]. World Clinic Drugs, 2017, 8:6-8.(in Chinese)凌云,卢洪洲.黄热病及其疫苗的研究进展[J].世界临床药物,2017, 8:6-8.
[11] VACCINES C G F S 0 Y F. Duration of post-vaccination immunity against yellow fever in adults[J]. Vaccine, 2014, 32(39):4977-4984.
[12] CAMPIAZEVEDO A C, COSTAPEREIRA C, ANTONELLI L R,et al. Booster dose after 10 years is recommended following17DD-YF primary vaccination[J]. Hum Vaccin,2016,12(2):491-502.
[13] ORGANIZATION P-P A H. Yellow fever:number of confirmed cases and deaths by country in the Americas, 1960-2015[EB/OL].(2017-07-25)[2018-11-09]. http://ais.paho.org/phip/viz/ed_yellowfever.asp. 2016.
[14] NIEDRIG M, LADEMANN M P, LAFRENZ M. Assessment of IgG antibodies against yellow fever virus after vaccination with17D by different assays:neutralization test, haemagglutination inhibition test, immunofluorescence assay and ELISA[J]. Trop Med&Int Health, 1999, 4(12):867-871.
[15] LEE H W, AN C N. Development of vaccine against hemorrhagic fever with renal syndrome[J]. J Bacteriol Virol, 1988,18(2):143-148.
[16] HOOPER J W, MOON J E, PAOLINO K M, et al. A phase 1clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation[J]. Clin Microbiol&Infect, 2014, 20(Suppl 5):110.
[17] LI P Y, YU L, WU X A, et al. Modification of the adenoviral transfer vector enhances expression of the Hantavirus fusion protein GnSO. 7 and induces a strong immune response in C57BL/6 mice[J]. J Virol Mtd, 2012, 179(1):90.
[18] MOSTAFAVI E, POURHOSSEIN B, ESMAEILI S, et al. Seroepidemiology and risk factors of Crimean-Congo hemorrhagic fever among butchers and slaughterhouse workers in southeastern Iran[J]. Int J Infect Dis, 2017, 64.
[19] DOWALL S D, BUTTIGIEG K R, SJD F W, et al. A CrimeanCongo hemorrhagic fever(CCHF)viral vaccine expressing nucleoprotein is immunogenic but fails to confer protection against lethal disease[J]. Hum Vaccin, 2016, 12(2):519-527.
[20] BUTTIGIEG K R, DOWALL S D, FINDLAYWILSON S, et al.A novel vaccine against Crimean-Congo haemorrhagic fever protects 100%of animals against lethal challenge in a mouse model[J]. Plos One, 2014, 9(3):e91516.
[21] HINKULA J, DEVIGNOT S, KERSTROM S, et al. Immunization with DNA plasmids coding for Crimean-Congo hemor-rhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice[J]. J Virol, 2017, 91(10):e02076-e92116.
[22] GARRISON A R, SHOEMAKER C J, GOLDEN J W, et al. A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models[J]. Plos Negl Trop Dis, 2017, 11(9):e0005908.
[23] ZIVCEC M, SAFRONETZ D, SCOTT D P, et al. Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge[J]. Plos Neglected Trap Dis, 2018, 12(7):e0006628.
[24] YU X J, LIANG M F, ZHANG S Y, et al. Fever with thrombocytopenia associated with a novel Bunyavirus in China[J]. N Engl J Med, 2011, 364(16):1523-1532.
[25] SUN J, LU L, WU H, et al. The changing epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2011-2016[J]. Sci Rep, 2017, 7(1):9236.
[26]世界卫生组织:首种埃博拉疫苗通过临床试验[J].上海医药,2017(1):30.
[27] ZHU F C, WURIE A H, HOU L H, et al. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone:a singlecentre,randomised, double-blind, placebo-controlled, phase 2 trial[J].Lancet, 2016, 389(10069):621-628.
[28]张子龙,杨柳,张宏,等.马尔堡病毒的流行病学及检测方法概述[J].国际病毒学杂志,2017, 24(2):141-144.
[29] SWENSON D, WANG D, M, WARFIELD K, et al. Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections[J]. Clin&Va-ccin Immunol Cvi, 2008, 15(3):460.
[30] JONES S M,FELDMANN H,STROHER U,et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses[J]. Nat Med, 2005, 11(7):786-790.
[31] SAKA M J, GUBIO A B, YENNAN S, et al. Lassa fever epidemic in Nigeria-outbreak investigation, risk factors and empirical analysis from 2012 to 2016[J]. 2017, 3:170.
[32] ZAPATA J C, GOICOCHEA M, NADAI Y, et al. Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate[J].J Virol, 2014, 88(6):3058.
[33] BREDENBEEK P J, MOLENKAMP R, SPAAN W J, et al. A recombinant yellow fever 17D vaccine expressing Lassa virus glycoproteins[J]. Virology, 2006, 345(2):299.
[34] GARBUTT M, LIEBSCHER R, WAHLJENSEN V, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses[J].J Virol, 2004, 78(10):5458-5465.
[35] EDELMAN R, TACKET C O, WASSERMAN S S, et al. Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218[J]. Am J Trop Med&Hyg, 2000, 62(6):681-685.
[36] BRANDLER S, RUFFIE C, COMBREDET C, et al. A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus[J]. Vaccine, 2013, 31(36):3718.
[37] RAMSAUER K, SCHWAMEIS M, FIRBAS C, et al. Immunogenicity,safety,and tolerability of a recombinant measlesvirus-based chikungunya vaccine:a randomised, double-blind,placebo-controlled, active-comparator, first-in-man trial[J].Lancet Infect Dis, 2015, 15(5):519-527.
[38] AKAHATA W, YANG Z Y, ANDERSEN H, et al. A viruslike particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection[J]. Nat Med,2010,16(3):334-338.
[39] CHANG L J,DOWD K A,MENDOZA F H,et al. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults:a phase 1 dose-escalation trial[J]. Lancet, 2014,384(9959):2046-2452.
[40] MUTHUMANI K, LANKARAMAN K M, LADDY D J, et al.Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus[J]. Vaccine, 2008, 26(40):5128-5134.
[41] ERASMUS J H, AUGUSTE A J, KAELBER J T, et al. A chikungunya fever vaccine utilizing an insect-specific virus platform[J]. Nat Med, 2017, 23(2):192.
[42] PLANTE K, WANG E, PARTIDOS C D, et al. Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism[J]. Plos Pathog,2011,7(7):e1002142.
[43] PLANTE K S, ROSSI S L, BERGREN N A, et al. Extended preclinical safety,efficacy and stability testing of a live-attenuated chikungunya vaccine candidate[J]. Plos Neglected Trop Dis, 2015, 9(9):e0004007.