(H7N9) Virus in Five Waves from 2013 to 2017 in Zhejiang Province, China
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RESEARCH ARTICLE Spatial characteristics and the epidemiology of human infections with avian influenza A (H7N9) virus in five waves from 2013 to 2017 in Zhejiang Province, China Haocheng Wu1,2☯, XinYi Wang1☯, Ming Xue3, Melanie Xue4, Chen Wu1, Qinbao Lu1, Zheyuan Ding1, Xiaoping Xv1, Junfen Lin1,2* a1111111111 1 Zhejiang Province Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China, 2 Key Laboratory for Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Hangzhou, a1111111111 Zhejiang Province, China, 3 Hangzhou Centre for Disease Control and Prevention, Hangzhou, Zhejiang, a1111111111 Province, China, 4 Kingston University UK, London, United Kingdom a1111111111 a1111111111 ☯ These authors contributed equally to this work. * [email protected] Abstract OPEN ACCESS Citation: Wu H, Wang X, Xue M, Xue M, Wu C, Lu Q, et al. (2017) Spatial characteristics and the Background epidemiology of human infections with avian The five-wave epidemic of H7N9 in China emerged in the second half of 2016. This study influenza A(H7N9) virus in five waves from 2013 to 2017 in Zhejiang Province, China. PLoS ONE 12(7): aimed to compare the epidemiological characteristics among the five waves, estimating the e0180763. https://doi.org/10.1371/journal. possible infected cases and inferring the extent of the possible epidemic in the areas that pone.0180763 have not reported cases before. Editor: Florian Krammer, Icahn School of Medicine at Mount Sinai, UNITED STATES Methods Received: February 17, 2017 The data for the H7N9 cases from Zhejiang Province between 2013 and 2017 was obtained Accepted: June 21, 2017 from the China Information Network System of Disease Prevention and Control. The start Published: July 27, 2017 date of each wave was 16 March 2013, 1 July 2013, 1 July 2014, 1 July 2015 and 1 July 2016. The F test or Pearson's chi-square test were used to compare the characteristics of Copyright: © 2017 Wu et al. This is an open access article distributed under the terms of the Creative the five waves. Global and local autocorrelation analysis was carried out to identify spatial Commons Attribution License, which permits autocorrelations. Ordinary kriging interpolation was analyzed to estimate the number of unrestricted use, distribution, and reproduction in human infections with H7N9 virus and to infer the extent of infections in the areas with no any medium, provided the original author and cases reported before. source are credited. Data Availability Statement: All relevant data are Result within the paper and its Supporting Information files. There were 45, 94, 45, 34 and 80 cases identified from the first wave to the fifth, respec- 2 Funding: This work was supported by grants from tively. The death rate was significantly different among the five waves of epidemics (χ = 2 Provincial Medical Research Fund of Zhejiang, 10.784, P = 0.029). The age distribution (F = 0.903, P = 0.462), gender (χ = 2.674, P = China (grant number were 2015RCB008 and 0.614) and occupation(χ2 = 19.764, P = 0.407) were similar in each period. Most of the 2017KY131). The document in website were http:// cases were males and farmers. A significant trend (χ2 = 70.328, P<0.001) was identified that www.zjmed.org.cn/previewerlet.do?id= 8DD1BAEA38B99297 and http://www.zjmed.org. showed a growing proportion of rural cases. There were 31 high-high clusters and 3 high- cn/previewerlet.do?id=00B32CCF219B843D. The low clusters at the county level among the five waves and 12, 8, 2, 9 and 3 clusters in each PLOS ONE | https://doi.org/10.1371/journal.pone.0180763 July 27, 2017 1 / 17 Epidemiological trend of human infections avian influenza A(H7N9) virus funders had no role in study design, data collection wave, respectively. The total cases infected with the H7N9 virus were far more than those and analysis, decision to publish, or preparation of that have been reported now, and the affected areas continue to expand. The epidemic in the manuscript. the north of Zhejiang Province persisted in all five waves. Since the second wave, the virus Competing interests: The authors have declared spread to the south areas and central areas. There was an obvious decline in the infected that no competing interests exist. cases in the urban areas, and the epidemics mostly occurred in the rural areas after the fourth wave. The epidemic was relatively dispersed since the third wave had fewer than two cases in most of the areas and showed a reinforcing trend again in the fifth wave. Conclusions The study revealed that there were few differences in the epidemiologic characteristics among the five waves of the epidemic. However, the areas where the possible epidemic cir- culated was larger than reported. The epidemic cross-regional expansion continued and mostly occurred in rural areas. Continuous closure of the live poultry market (LPM) is strongly recommended in both rural and urban areas. Illegal and scattered live poultry trad- ing, especially in rural areas, must be forbidden. It is suggested too that a more rigorous management be performed on live poultry trade and wholesale across the area. Health edu- cation, surveillance of cases and pathogenicity should also be strengthened. Introduction The H7N9 virus is a virus that reasserts multiple times and whose gene fragments are obtained from H7N9, H9N2 and H7N3 subtypes of the influenza A virus[1±3]. The first case of human infections with the H7N9 virus occurred in the spring of 2013 in Eastern China[4,5]. The epi- demic caused great concern due to the increasing number of cases, the expansion of the affected areas, the high fatality rate, mutation of the virus and the stigma attached to the virus [6,7]. To date, five waves of H7N9 epidemics have emerged in mainland China. There were 775 laboratory-confirmed infections of A(H7N9) virus across 16 provinces and 3 municipali- ties as of August 31, 2016[8]. In addition, 23 travelers infected with A(H7N9) exported the virus to Hong Kong (sixteen cases), Taiwan (four cases), Canada (two cases), and Malaysia (one case), leading to four deaths [8]. The fifth wave of the epidemic occurred in autumn 2016, and incidences far exceeded those in the corresponding period of 2015. It should be noted that Zhejiang is a province located in the Yangtze River Delta region of southeastern China that is well recognized as the original source of the H7N9 outbreaks [9]. This province was the most seriously affected area, accounting for nearly 30% of total cases reported and 25% of the total fatal cases during the last four waves in mainland China[10]. There are likely to be many more cases than those reported due to there being an unknown number of mild and subclinical infections [11]. The objectives of this study are to identify the epidemiological characteristics and the distribution of H7N9 virus in human infection from 2013 to 2017. The Kriging spatial interpolation methods will be applied to estimate the number of human infections with H7N9 virus and to infer the extent of infections in areas that cur- rently have no reported cases. Methods Definition of the five waves Based on the date of onset, the first wave of H7N9 virus circulation occurred from 13 March to 30 June 2013. In the first wave, the first and last cases occurred on 13 March and 18 April PLOS ONE | https://doi.org/10.1371/journal.pone.0180763 July 27, 2017 2 / 17 Epidemiological trend of human infections avian influenza A(H7N9) virus 2013, respectively. The second wave occurred from 1 July 2013 to 30 June 2014, with the first and last cases occurring on 7 October 2013 and 3 June 2014, respectively. The third wave occurred from 1 July 2014 to 30 June 2015. In the third wave, the first and last cases occurred on 17 November 2014 and 28 May 2015, respectively. The fourth wave occurred from 1 July 2015 to 30 June 2016. In the fourth wave, the first and last cases occurred on 18 September 2015 and 24 June 2016, respectively. The fifth wave occurred from 1 July 2016 to 31 March 2017, with the first case occurring on 28 September 2016. Patient/cluster definition and data collection The patient definition. The diagnosis of the infections confirmed with the H7N9 virus was based on the Chinese Guideline of Diagnosis and Treatment for Human Infections with the Avian Influenza A(H7N9) Virus issued by the National Health and Family Planning Com- mission of the People's Republic of China[7,12,13]. The definition of the confirmed case is clinical manifestation with acute influenza (fever, cough, coryza, difficulty breathing) or a his- tory of contact with a confirmed or suspected case and a laboratory test that includes subtype confirmation by several parameters. These include PCR, viral isolation or no less than a four- fold increase in virus-specific serum antibodies isolated from paired positive sera samples [3,12,13]. The cluster definition. According to the Chinese Guideline of Epidemic Prevention and Control for Human Infections with the Avian Influenza A(H7N9) Virus issued by the National Health and Family Planning Commission of the People's Republic of China[14], the definition of the cluster is that two confirmed cases emerged within 7 days and in small areas, such as one family or one community. The data collection. The confirmed case must be reported through the China Informa- tion Network System of Disease Prevention and Control by medical staff. The data of H7N9 cases in Zhejiang Province from 2013 to 2017 were obtained from this network system(S1 File). Profile of Zhejiang Province. The Zhejiang Province is in the southeast China between longitudes 118oE-123oE and latitudes 27oN-32oN.