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Summary
Background
Human
infection with avian influenza A H7N9 virus emerged in eastern China in
February, 2013, and has been associated with exposure to poultry. We
report the clinical and microbiological features of patients infected
with influenza A H7N9 virus and compare genomic features of the human
virus with those of the virus in market poultry in Zhejiang, China.
Methods
Between
March 7 and April 8, 2013, we included hospital inpatients if they had
new-onset respiratory symptoms, unexplained radiographic infiltrate, and
laboratory-confirmed H7N9 virus infection. We recorded histories and
results of haematological, biochemical, radiological, and
microbiological investigations. We took throat and sputum samples, used
RT-PCR to detect M, H7, and N9 genes, and cultured samples in
Madin-Darby canine kidney cells. We tested for co-infections and
monitored serum concentrations of six cytokines and chemokines. We
collected cloacal swabs from 86 birds from epidemiologically linked wet
markets and inoculated embryonated chicken eggs with the samples. We
identified and subtyped isolates by RT-PCR sequencing. RNA extraction,
complementary DNA synthesis, and PCR sequencing were done for one human
and one chicken isolate. We characterised and phylogenetically analysed
the eight gene segments of the viruses in the patient's and the
chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and
NS genes.
Findings
We
identified four patients (mean age 56 years), all of whom had contact
with poultry 3—8 days before disease onset. They presented with fever
and rapidly progressive pneumonia that did not respond to antibiotics.
Patients were leucopenic and lymphopenic, and had impaired liver or
renal function, substantially increased serum cytokine or chemokine
concentrations, and disseminated intravascular coagulation with disease
progression. Two patients died. Sputum specimens were more likely to
test positive for the H7N9 virus than were samples from throat swabs.
The viral isolate from the patient was closely similar to that from an
epidemiologically linked market chicken. All viral gene segments were of
avian origin. The H7 of the isolated viruses was closest to that of the
H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest
to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu
and Gly186Val substitutions in human virus H7 (associated with increased
affinity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn
mutation (associated with mammalian adaptation). Ser31Asn mutation,
which is associated with adamantane resistance, was noted in viral M2.
Interpretation
Cross
species poultry-to-person transmission of this new reassortant H7N9
virus is associated with severe pneumonia and multiorgan dysfunction in
human beings. Monitoring of the viral evolution and further study of
disease pathogenesis will improve disease management, epidemic control,
and pandemic preparedness.
Funding
Larry Chi-Kin Yung, National Key Program for Infectious Diseases of China.
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