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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
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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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,; Xia Shichang,   
Issue Date: 05 September 2013
URL:     OR
CharacteristicsFirst confirmed influenza A (H7N9) fatality in Zhejiang
Date of specimen collectionAge (year)39
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)
Septic shockNo
Respiratory failureYes
Acute renal damageYes
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-
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
Glycosylation sites30NGTKNGTKNGTKNGTK
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.
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