Prevalence And Genetic Characteristics Analysis Of The Human Rhinovirus In Patients With Febrile Respiratory Syndrome In Sentinel Surveillance Hospitals In Hebei Province,China,2013~2015

Background:Febrile respiratory syndrome(FRS)is one of the important syndrome on the list of national surveillance for infectious disease syndromes in China.It plays an important role in analyzing the pathogenic spectrum of acute respiratory infections and the epidemic trend of pathogens.Human rhinovirus(HRV),one of the most important viral pathogens of FRS,has been included in the syndrome as a mandatory detection virus since 2012.It can not only cause common cold,but also cause severe lower respiratory tract infections such as bronchitis,bronchiolitis,pneumonia,and asthma.HRV infection has attracted more and more attention.Several studies on HRV in respiratory infections were reported in Japan,the United States,the Philippines,and Beijing,Shanghai,Hong Kong and some places in China.However,the studies were still limited and still many gaps existed in the prevalence,clinical characteristics,distribution of serotypes and genetic characteristics of HRV in various provinces and cities in China.Distribution of serotypes and genetic characteristics of HRV with FRS in Hebei Province,China,was first carried out in this study.Objective:This study is to identify the HRV infection from the specimens of patients with febrile respiratory syndrome in sentinel surveillance hospitals in Hebei Province,China,from 2013 to 2015 and to clarify the prevalence,clinical characteristics,distribution of serotypes and genetic characteristics of HRV,retrospectively.To provide background data for the distribution of serotypes and disease burden of HRV in Hebei Province,China,and provide scientific basis for formulating the diagnostic method and control measures of HRV.Methods:Specimens were obtained from the sentinel surveillance hospitals in Hebei Province(Shijiazhuang General Hospital,Children's Hospital of Hebei Province,Hebei Center for Disease Control and Prevention).Multiplex real-time reverse transcription-polymerase chain reaction(RT-PCR)was undertaken to detect nine common respiratory viral pathogens.Then the HRV positive specimens were confirmed by real-time RT-PCR method.For HRV-positive specimens,VP4/VP2 gene fragments were amplified by RT-PCR.MEGA and BioEdit were used for constructing phylogenetic tree,analyzing the distribution of serotypes and analyzing genetic characteristics.Results:1.792 samples were collected from the patients with febrile respiratory syndrome in Hebei Province.39.77%of the specimens were detected positive for at least one pathogen.Human parainfluenza virus(HPIV,25.40%)was the pathogen detected most frequently,followed by HRV(19.37%),human influenza virus(Flu,18.10%),human adenovirus(HAdV,10.16%),human respiratory syncytial virus(HRSV,7.62%),human enterovirus(HEV,4.76%),human bocavirus(HBoV,3.81%),human coronavirus(HCoV,3.17%),human metapneumovirus(HMPV,1.90%).Mixed infection was accounted for 5.71%.2.A total of 73 specimens were positive for HRV.Twenty serotypes were detected:11 serotypes of HRV-A and 9 serotypes of HRV-C.HRV-B was not detected.The detected numbers of different serotypes were different.HRV-A81(8/39,20.51%)and HRV-C2(9/28,32.14%)were the dominant serotypes in HRV-A and HRV-C,respectively.3.The number of detection and detection rate of HRV were increasing year by year.The prevalence of detection for hospitalized cases was higher than that for patients in outpatient and emergency departments.4.Children aged<10 years had the highest prevalence of infection.There was no clear seasonal pattern for HRV infection.And there was a co-circulating trend in HRV-A and HRV-C.5.A total of 73 specimens were positive for HRV.12 specimens were HRV mixed with other respiratory viruses(12/73,16.44%),and the most frequently co-detected virus was the HP ?.6.The prevalence of HRV detection in the lower respiratory tract was higher than that in the upper respiratory tract.In addition to the higher incidence of fatigue in HRV-A than HRV-C,there were no statistically significant differences in other clinical symptoms between HRV-A and HRV-C.7.Some HRV serotypes can be prevalent in continous several years and multiple seasons,such as HRV-A20,HRV-A21,HRV81,HRV-C2,HRV-C 15,which were detected in 2013,2014 and 2015.Some serotypes were prevalent in a certain year,such as HRV-A56,HRV-C3,HRV-C6,HRV-C51.Some serotypes may disappear in some years and then begin to be prevalent,such as HRV-54,HRV-A88,HRV-C5.8.None of the prevalent HRV serotypes showed any geographical restriction,suggesting that all serotypes circulated freely worldwide.9.The distribution of different serotypes of HRV in upper or lower respiratory tract infection was different.The serotypes with higher detection rate of upper respiratory tract infection were HRV-A21,HRV-A60,HRV-A88,HRV-C15,HRV-C17.The serotypes with higher detection rate of lower respiratory tract infection were HRV-A10,HRV-A20,HRV-A34,HRV-A54,HRV-A56,HRV-A81,HRV-A82,HRV-A85,HRV-C2,HRV-C3,HRV-C5,HRV-C6,HRV-C30,HRV-C41,HRV-C51.10.The nucleotide homology was 74.4%?100%and the amino acid homology was 87.2%?100%in HRV-A.The nucleotide homology was 67.1%?100%and the amino acid homology was 78%?100%in HRV-C.11.In addition to amino acid synonymous mutations in HRV-A34,non-synonymous amino acid mutations occurred in other serotypes in HRV-A.The mutations in the VP2 region were more frequent than those in the VP4 region.In addition to non-synonymous amino acid mutations in HRV-C3,HRV-C17 and HRV-C41,synonymous mutations occurred in other serotypes in HRV-C.12.Twenty serotypes detected in this study were prevalent in the world and in different years.Except for the low nucleotide homology in HRV-A88(86.4%?95.2%)among the sequence in the world,the nucleotide homology in other serotypes ranged from 88.4%to 100%.Conclusions:1.HRV is an important viral pathogen that causes febrile respiratory syndrome.The prevalence of detection for hospitalized cases was higher and children aged<10 years had the highest prevalence of infection,which suggest that the monitoring of HRV in hospitalized children of FRS should be strengthened.2.HRV is susceptible to mix with other respiratory viruses,which suggest that cross-infection of HRV should be prevented from.Whether it aggravates the clinical symptoms or not will require further study.3.The prevalence of HRV detection in the lower respiratory tract was higher than that in the upper respiratory tract,which suggest that attention should be paid to the lower respiratory tract infection caused by HRV.4.There was a co-circulation of twenty serotypes of HRV in Hebei Province,China,2013?2015.HRV-A81 and HRV-C2 were the dominant serotypes in HRV-A and HRV-C,respectively.5.None of the prevalent HRV types showed any geographical restriction,suggesting the prevalence of HRV is highly globalised.