Etiological Characteristics Of Human Infection With Avian Influenza A (H7N9) Virus In Fujian Province,China

Objective:This study was aimed at describing epidemiological characteristics of all human infection with avian influenza A(H7N9)cases,exploring the probable sources and evolution of avian influenza A(H7N9)viruses in Fujian from April 2013 to September 2017 and to provide the scientific evidence for the future adjustment of prevention and control strategy.Methods:Establishing databases via Excel 2010 based on the information of H7N9 cases form flu and avian flu surveillance system,public health emergency monitoring system and surveillance system for pneumonia of unknown origin.Descriptive epidemiologic studies were applied to describe epidemiological characteristics of all H7N9 cases from April 2013 to September 2017 in Fujian Province.Phylogenetic tree of all eight genes were constructed and the mutation of key amino acid site of whole genome on all H7N9 viruses in Fujian were analyzed via bioinformatical software.Results:1.There were 5 epidemic peaks of H7N9 from April 2013 to September 2017 in Fujian Province.The seasonal distribution of H7N9 cases were the majority in winter and spring.As time went on,the H7N9 cases were reported in all season in Fujian.The age distribution of infected population showed left skewed distribution,with a median of 56 years and an inter-quartile range of 29 years.There was a statistically significant difference in gender between different age groups,and more male cases than females in all age groups.Cases of H7N9 mostly concentrated on coastal areas.2.Homology analysis demonstrated that the nucleotide and amino acid homology of all H7N9 strains of Fujian were above 92.5% and 95.1% by comparing with the vaccine strain A/Anhui/1/2013(H7N9).Complete sequences of all H7N9 viruses in the fourth and fifth wave in Fujian were above 90.3% and 95.3% identical with the new vaccine strain A/Hunan/02650/2016(H7N9)respectively.However,the HA and NA gene of all H7N9 viruses in Fujian during 2013 to 2017 kept a high homology(above 97%)with A/Anhui/1/2013 and A/Hunan/02650/2016.3.Phylogenetic analysis suggested that the surface genes(HA and NA)of H7N9 virus in Fujian Province were divided into two branches from the third wave epidemic.HA and NA genes of H7N9 virus mostly belonged to the Yangtze River Delta lineage from April 2013 to September 2017,but other internal genes were scattered in the Yangtze River Delta and the Pearl River Delta lineages.The majority of strains in the fifth wave,whether they were internal genes or surface genes,clustered together and became independent branches.4.Analysis of molecular characteristics showed that all viruses contained the Q226L(except for Q226 I of one strain)and G186 V in HA receptor binding site.The amino acid at position 135 of the HA receptor binding site 130 loop was 135 A in the first two wave epidemics.It began to increase from the third wave at 135 V.The 135 th position of all strains in the fourth and fifth epidemic wave were became 135 V.Our study did not find the mutation of neuraminidase inhibitor drug resistance site in NA(except for two H274 Y in the fifth wave),but five amino acid deletions occurred in the stalk region.All viruses in Fujian Province had S31 N mutation and some strains had V27 I mutation in M2,which led to amantadine resistance.The 588 th position in PB2 is one of the sites that enhance the virulence of H7N9 virus.In the first wave and the second wave,all the strains were 588 A in this site.Nevertheless,the A to V mutation occurred at position 588 since the third wave,and by the fifth epidemic wave,all strains were 588 V.conclusions:The seasonal distribution of Fujian's H7N9 cases are the majority in winter and spring from April 2013 to September 2017.There are high homology of HA and NA gene between all strains and the vaccine strain,which contributes to promote vaccine.HA and NA genes of human infection with avian influenza A(H7N9)virus in Fujian Province mostly derive from H7N9 virus of Yangtze River Delta.With epidemic in past five years,H7N9 viruses in Fujian Province have adapted well to the local host and formed a stable branch.Viruses have a susceptibility to people.It is effective to use neuraminidase inhibitors for treatment of most H7N9 cases.