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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (3) : 333-344     DOI: 10.1007/s11684-013-0275-1
RESEARCH ARTICLE |
The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report
Enfu Chen1, Fenjuan Wang2, Huakun Lv1, Yanjun Zhang1, Hua Ding3, Shelan Liu1, Jian Cai1, Li Xie3, Xiaoping Xu4, Chengliang Chai1, Haiyan Mao1, Jimin Sun1, Junfen Lin1, Zhao Yu1, Lianhong Li1, Zhiping Chen1(), Shichang Xia1()
1. Department of Infectious Diseases, Zhejiang Center for Disease Control and Prevention, Hangzhou 310051, China; 2. Department of Infectious Diseases, Xiaoshan District Center for Disease Control and Prevention, Hangzhou 311201, China; 3. Department of Infectious Diseases, Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China; 4. Department of Infectious Diseases, Jiande Center for Disease Control and Prevention, Hangzhou 311600, China
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Abstract  

This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the low-pathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.

Keywords avian influenza A (H7N9) virus      epidemiology      contacts      person-to-person transmission     
Corresponding Authors: Chen Zhiping,Email:zhpchen@cdc.zj.cn; Xia Shichang,Email:shchxia@cdc.zj.cn   
Issue Date: 05 September 2013
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0275-1     OR     http://academic.hep.com.cn/fmd/EN/Y2013/V7/I3/333
CharacteristicsFirst confirmed influenza A (H7N9) fatality in Zhejiang
Date of specimen collectionAge (year)39
SexMale
OccupationCook
Underlying conditionsChronic hepatitis B
Epidemiologic informationArea of originJiangsu
Exposure in chicken market in past 7 daysYes
Date of specimen collectionMarch 24, 2013
Date of laboratory confirmation of virusApril 1, 2013
Number of contacts125
Contacts with symptoms2 (1 nurse and 1 doctor)
Number of contact samples46 swabs and 98 serum samples (all negative)
Clinical informationDate of illness onsetMarch 7, 2013
Date of admissionMarch 18, 2013 for the first time and March 20, 2013 for the second time
Admission to ICUMarch 25, 2013
Viral isolationA/Zhejiang/1/2013 (H7N9)
Complications
Septic shockNo
Respiratory failureYes
ARDSYes
Acute renal damageYes
EncephalopathyNo
MOFYes
DICYes
Secondary infectionsNo
Oxygen therapyNIPPV+ mechanical ventilation
Extracorporeal membrane oxygenationNo
Continuous renal-replacement therapyYes
Antibiotic therapyPiperacillin sodium and tazobactam sodium moxifloxacin hydrochloride, imipenem, and cilastatin sodium
Antiviral agent ( oseltamivir)No
Glucocorticoid therapyYes
Intravenous immune globulin therapyYes
Length of stay in hospital7 days
Date of deathMarch 27, 2013
Tab.1  Demographic, epidemiologic, and virology, clinical Characteristics of the first confirmed influenza A (H7N9) case in Zhejiang
Fig.1  Blood cell counts of the first avian influenza A (H7N9) fatality. WBC, white blood cell; LY, lymphocyte; NE, neutrophil; RBC, red blood corpuscle; MO, mononuclear cell.
Fig.2  Coagulation index of the first confirmed avian influenza A (H7N9) fatality. APTT, activated partial thromboplastin time; DD2, D-dimer; PT, prothrombin time; TT, thrombin time, PLC, platelet.
Fig.3  Arterial blood gas analysis of the first confirmed avian influenza A (H7N9) fatality. PaO, arterial oxygen tension; PaCO, carbon dioxide tension; SaO (%), arterial oxyhemoglobin saturation; , ion.
Index Reference valueDate of test
2013-3-202013-3-222013-3-24(4∶58 am)2013-3-24(13∶25 pm)2013-3-25(10∶00 am)2013-3-25(15∶38 pm)2013-3-26
AST (U/L)0-38199204156257244281319
ALT (U/L)0-4013498126124
LDH (U/L)135-225495608108810181140
CK (U/L)35-200253310153963542524
CK-MB (U/L)0-252530425337
Na+ (mmol/L)135-145139139146147146148140
K+ (mmol/L)3.5-5.54.004.405.635.475.504.884.80
CRP (mg/L)0-474.9092.2058.3049.80
TB (μmol/L)5.1-22.243.8041.453.3064.20
DB (μmol/L)0.5-8.33732.643.8049.10
Tab.2  Clinical biochemistry findings of the first confirmed death case infected with avian influenza A (H7N9) virus in Zhejiang Province, China, 2013
Fig.4  Chest CT scan images of the first confirmed avian influenza A (H7N9) fatality. 2013-3-20-A: Chest CT scan showed exudation in the dorsal segment of the lower lobe of the right lung; a bronchial air sign was also observed along with patchy consolidation. 2013-3-20-B: Chest CT scan showed large patchy exudation in the basal segment of lower lobe of the right lung.
Fig.5  Timeline of drug administration and dosage for the first confirmed avian influenza A (H7N9) fatality.
Fig.6  Phylogenetic tree of NA gene of the first confirmed avian influenza A (H7N9) fatality. : An isolate from th0065 first confirmed H7N9 case in Zhejiang; : isolates from the confirmed H7N9 patients from Anhui and Shanghai China; : isolates from human H7 cases; : influenza vaccine strains in 2012.
Fig.7  Phylogenetic tree of NA gene of the first confirmed avian influenza A (H7N9) fatality. : An isolate from the first confirmed H7N9 case in Zhejiang; : isolates from the confirmed H7N9 patients from Anhui and Shanghai China; : isolates from human H7 cases .
Fig.8  MP gene phylogenetic tree of the first confirmed avian influenza A(H7N9) fatality. : An isolate from the first confirmed H7N9 case in Zhejiang; : isolates from the confirmed H7N9 patients in Anhui and Shanghai, China.
SegmentsActive SitesPositionA/Zhejiang /1/2013A/Shanghai/1/2013A/Shanghai/2/2013A/Anhui/1/2013
(H7N9)(H7N9)H7N9)(H7N9)
HARBS135-138ATSAATSSATSAATSA
190-198EQTKLYGSGEQTKLYGSGEQTKLYGSGEQTKLYGSG
221-228PQVNGISGPQVNGLSGPQVNGLQSGPQVNGQSG
Cleavage site325-336PEIPKGRGLFGAPEIPKGRGLFGAPEIPKGRGLFGAPEIPKGRGLFGA
Glycosylation sites30NGTKNGTKNGTKNGTK
46NATENATENATENATE
249NDTVNDTVNDTVNDTV
421NWTRNWTRNWTRNWTR
493NNTYNNTYNNTYNNTY
NASingle substitution26IIMI
Single substitution40GSGG
Stalk69-73del del del del
Antiviral resistance (oseltamivir) H275Y275HHHH
Antiviral resistance (oseltamivir) R294K294RKRR
M1Virulence sites (N30D)30DDDD
Virulence sites (T215A)215AAAA
M2Antiviral resistance (amantadine) S31N31NNNN
Tab.3  HA, NA, and MP gene active sites analysis of the H7N9 confirmed cases from Zhejiang, Anhui, and Shanghai in China, 2013
Fig.9  The MDCK cells exhibited the characteristic cytopathic effect (CPE) when inoculated with the patient’s swabs. The CPE presented as cell swelling and becoming rounded, with increased intercellular spaces; the cells ruptured within 24 h after infection (×100). (A) Control; (B) CPE; Yellow arrow, CPE site.
1 Uyeki TM, Cox NJ. Global concerns regarding novel influenza A (H7N9) virus infections. N Engl J Med 2013; 368(20): 1862–1864
doi: 10.1056/NEJMp1304661 pmid:23577629
2 Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 2013; 368(20): 1888–1897
doi: 10.1056/NEJMoa1304459 pmid:23577628
3 Who. http://www.who.int/influenza/human_animal_interface/update_20130405/en/index.html.
4 USA. CDC . http://www.cdc.gov/flu/avianflu/h7n9-virus.htm.
5 Who. http://www.who.int/influenza/human_animal_interface/influenza_h7n9/06_ReportWebH7N9Number.pdf.
6 National Health and Family Planning Commission (NHFPC). http://www.moh.gov.cn/mohyzs/s3586/201304/826ca1fb686f41ab9e8938ecdfa46a70.shtml.
7 National Health and Family Planning Commission (NHFPC). http://www.moh.gov.cn/mohjbyfkzj/s3578/201304/c1ab8ea6b2bf447dbfda724cc0afbb6e.shtml.
8 Pasick J, Pedersen J, Hernandez MS. Avian influenza in North America, 2009-2011. Avian Dis 2012; 56(4 Suppl): 845–848
doi: 10.1637/10206-041512-Reg.1 pmid:23402102
9 Hirst M, Astell CR, Griffith M, Coughlin SM, Moksa M, Zeng T, Smailus DE, Holt RA, Jones S, Marra MA, Petric M, Krajden M, Lawrence D, Mak A, Chow R, Skowronski DM, Tweed SA, Goh S, Brunham RC, Robinson J, Bowes V, Sojonky K, Byrne SK, Li Y, Kobasa D, Booth T, Paetzel M. Novel avian influenza H7N3 strain outbreak, British Columbia. Emerg Infect Dis 2004; 10(12): 2192–2195
doi: 10.3201/eid1012.040743 pmid:15663859
10 Nguyen-Van-Tam JS, Nair P, Acheson P, Baker A, Barker M, Bracebridge S, Croft J, Ellis J, Gelletlie R, Gent N, Ibbotson S, Joseph C, Mahgoub H, Monk P, Reghitt TW, Sundkvist T, Sellwood C, Simpson J, Smith J, Watson JM, Zambon M, Lightfoot N; Incident Response Team. Outbreak of low pathogenicity H7N3 avian influenza in UK, including associated case of human conjunctivitis. Euro Surveill 2006; 11(5): E060504.2
pmid:16816456
11 Arzey GG, Kirkland PD, Arzey KE, Frost M, Maywood P, Conaty S, Hurt AC, Deng YM, Iannello P, Barr I, Dwyer DE, Ratnamohan M, McPhie K, Selleck P. Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis 2012; 18(5): 814–816
doi: 10.3201/eid1805.111852 pmid:22516302
12 Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum GJ, Koch G, Bosman A, Koopmans M, Osterhaus AD. Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 2004; 101(5): 1356–1361
doi: 10.1073/pnas.0308352100 pmid:14745020
13 Li Q, Zhou L, Zhou M, Chen Z, Li F, Wu H, Xiang N, Chen E, Tang F, Wang D, Meng L, Hong Z, Tu W, Cao Y, Li L, Ding F, Liu B, Wang M, Xie R, Gao R, Li X, Bai T, Zou S, He J, Hu J, Xu Y, Chai C, Wang S, Gao Y, Jin L, Zhang Y, Luo H, Yu H, Gao L, Pang X, Liu G, Shu Y, Yang W, Uyeki TM, Wang Y, Wu F, Feng Z. Preliminary report: epidemiology of the avian influenza A (H7N9) outbreak in China. N Engl J Med 2013Apr24. [Epub ahead of print]
doi: 10.1056/NEJMoa1304617 pmid:10.1056/NEJMoa1304617PMID:23614499" target="blank">
doi: 10.1056/NEJMoa1304617PMID:23614499
14 Tweed SA, Skowronski DM, David ST, Larder A, Petric M, Lees W, Li Y, Katz J, Krajden M, Tellier R, Halpert C, Hirst M, Astell C, Lawrence D, Mak A. Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis 2004; 10(12): 2196–2199
doi: 10.3201/eid1012.040961 pmid:15663860
15 Robert M, Holle Rv, Setiawaty V, Pangesti KN, Sedyaningsih ER. Seroprevalence of avian influenza A/H5N1 among poultry farmers in rural Indonesia, 2007. Southeast Asian J Trop Med Public Health 2010; 41(5): 1095–1103
pmid:21073030
16 Wang H, Feng Z, Shu Y, Yu H, Zhou L, Zu R, Huai Y, Dong J, Bao C, Wen L, Wang H, Yang P, Zhao W, Dong L, Zhou M, Liao Q, Yang H, Wang M, Lu X, Shi Z, Wang W, Gu L, Zhu F, Li Q, Yin W, Yang W, Li D, Uyeki TM, Wang Y. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet 2008; 371(9622): 1427–1434
doi: 10.1016/S0140-6736(08)60493-6 pmid:18400288
17 Mounts AW, Kwong H, Izurieta HS, Ho Y, Au T, Lee M, Buxton Bridges C, Williams SW, Mak KH, Katz JM, Thompson WW, Cox NJ, Fukuda K. Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997. J Infect Dis 1999; 180(2): 505–508
doi: 10.1086/314903 pmid:10395870
18 Yu H, Feng Z, Zhang X, Xiang N, Huai Y, Zhou L, Li Z, Xu C, Luo H, He J, Guan X, Yuan Z, Li Y, Xu L, Hong R, Liu X, Zhou X, Yin W, Zhang S, Shu Y, Wang M, Wang Y, Lee CK, Uyeki TM, Yang W; Avian Influenza H5N1 study Group.Human influenza A (H5N1) cases, urban areas of People’s Republic of China, 2005-2006. Emerg Infect Dis 2007; 13(7): 1061–1064
doi: 10.3201/eid1307.061557 pmid:18214180
19 Liu SL, Zhang ZR, Wang C, Dong Y, Cui LB, Yang XH, Sun Z, Wang J, Chen J, Huang RJ, Miao F, Ruan B, Xie L, He HX, Deng J. 2009 pandemic characteristics and controlling experiences of influenza H1N1 virus 1 year after the inception in Hangzhou, China. J Med Virol 2010; 82(12): 1985–1995
doi: 10.1002/jmv.21964 pmid:20981784
20 World Health Organization. Cumulative number of confirmed human cases for avian influenza A (H5N1) reported to WHO, 2003-2013. http://www.who.int/influenza/human_animal_interface/EN_GIP_20130312Cumulativ eNumberH5N1cases.pdf (Accessed on April6, 2013)
21 Ito T, Kawaoka Y. Host-range barrier of influenza A viruses. Vet Microbiol 2000; 74(1-2): 71–75
doi: 10.1016/S0378-1135(00)00167-X pmid:10799779
22 Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 2000; 69(1): 531–569
doi: 10.1146/annurev.biochem.69.1.531 pmid:10966468
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