急性呼吸道感染住院病例病毒性病原谱及流感季节性研究
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摘要
背景：急性呼吸道感染(Acute respiratory infections, ARI)是中国和全球范围内感染性疾病发病和死亡的主要原因之一。其中,病毒是引起ARI的重要病原。在我国未见全国范围或区域性的、覆盖多个季节的ARI住院病例病毒性病原谱结果的报道。流感对人类健康危害严重,其每年冬春季周而复始循环的季节性在温带地区已有广泛研究。然而,在热带和亚热带地区不同型别流感病毒的季节性变化规律及其驱动因素一直是困扰国际科学界的难题。
目的：确定引起我国儿童和成人ARI住院病例的主要病毒性病原体及其构成；定义不同型别流感在中国不同地理、气候区域的季节性模式,为我国流感疫苗预防接种政策的制定提供建议。
方法：1.2009-2013年ARI住院病例病毒性病原谱研究：2009年1月至2013年9月,在我国24个省的108家哨点医院开展ARI住院病例监测,收集其人口统计学、临床症状和体征等信息,采集其呼吸道标本,进行呼吸道合胞病毒(RSV)、流感病毒、腺病毒、副流感病毒、偏肺病毒、冠状病毒和博卡病毒的实验室检测。分不同年份、年龄组对ARI住院病例的病毒性病原体进行分析,并描述各种呼吸道病毒阳性病例的季节性分布特征。2.中国不同区域的流感季节性模式时空模型研究：收集和整理2005-2011年全国30个省的193家流感监测哨点医院每周报告的流感样病例数、检测标本数和实验室确诊的A型、B型流感病例数,以及各监测省、城市的人口、人群移动模式、社会经济水平、地理和气象等资料,利用带有谐波的线性回归模型定量测量流感的季节性,包括不同型别流感病毒活动的年度周期和半年周期、振幅、振幅比值、流行高峰时间和流行持续时间。采用分层贝叶斯模型识别流感季节性的预测因素,采用分层聚类法和逐步线性判别分析,确定流感广义流行病学区域。
结果：1.2009-2013年ARI住院病例病毒性病原谱研究：经对监测数据质控,剔除了2009-2013年纳入并检测7种病毒的住院ARI病例数<40的哨点医院,最终纳入22个省的81家哨点医院的28369例住院ARI病例进行分析。至少一种病毒检测阳性的10387例(阳性率36.6%)。 RSV的检测阳性率最高(9.9%),以下依次是流感病毒(6.6%)、副流感病毒(4.8%)、腺病毒(3.4%)、博卡病毒(1.9%)、偏肺病毒(1.5%)和冠状病毒(1.4%)。7.2%的病例两种及以上病毒检测呈阳性。2岁以下儿童中,RSV是最常见的病毒性病原(17.0%)。流感病毒是成年和老年住院ARI病例的主要病毒性病原。副流感病毒、博卡病毒、偏肺病毒和腺病毒感染在儿童中最常见,而冠状病毒感染在各年龄组分布较均衡、RSV、流感病毒、副流感病毒、博卡病毒和偏肺病毒有明显的季节性。
2.中国不同区域的流感季节性模式时空模型研究：2005-2011年,我国A型流感的年度周期性随纬度增加而增强(北方平均发病率标准化的年度周期振幅均值为140%[95%CI128%-151%],南方为37%[95%CI27%-47%]),呈多样化的空间模式和季节性特征：≥33°N的北方省份,每年1-2月份单一年度高峰；<27°N的最南部省份,每年4-6月份单一年度高峰；27.4-31.3°N的中纬度地区,每年1-2月份和6-8月份的双周期高峰(周期比>0.6的省份处于纬度27.4-31.3°N之间,纬度梯度的斜率为-0.016[95%CI-0.025至-0.008],p<0.001)。而B型流感在中国大部分地区呈单一的冬季高发模式。气候因素是流感季节性的最强预测因素,包括最低温度、日照时数和最大降雨量。
结论：ARI住院病例的病毒性病原谱研究结果为我国将来开展急性呼吸道感染监测和研究工作提供了基线资料,对我国制定ARI的预防控制策略有一定的参考价值。鉴于RSV感染在婴幼儿中较常见,因此采用疫苗预防接种、特异性治疗等防治措施将具有重要的公共卫生意义。流感病毒感染在学龄儿童和成年人较常见,应推动流感疫苗在这两类人群及其他高危人群中更大范围的应用。
流感季节性模式研究表明,中国应分不同区域制定流感疫苗预防接种策略。北方省份的流感疫苗最佳接种时机应遵循世界卫生组织推荐的北半球疫苗接种时间,即每年10月份启动疫苗接种；最南部省份的流感活动高峰在4-6月份,疫苗接种时间最好在每年2-3月份。考虑到中纬度地区流感季节性模式的复杂性,应进一步加强这一地区的流感监测。
Background:Acute respiratory infections (ARIs) are an important cause of acute illnesses and mortality worldwide and in China. Viral etiologies play impaort role in ARI. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Influenza can cause seveve impact to human health, and its seasonality has been well studied in temperate regions. However, seasonality of influenza by each type of virus strain remains poorly characterized in tropical and subtropical areas.
Objectives:To discribe the viral etiologies associated with hospitalized ARI patients in children and adults; and to characterize the diversity of influenza seasonality in virious regions of China and make recommendations to guide future vaccination programs.
Methods:1. Study on Viral Etiologiesof Hospitalized Acute Respiratory Infection: Active surveillance for hospitalized ARI patients in108sentinel hospitals in24provinces of China was conducted from January2009to September2013. We enrolled all-age hospitalized patients with ARI, and collected respiratory specimens, blood or serum for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). Demographic information, symptoms, signs, and viral etiologies of ARI were analyzied by season and age group. Seasonal pattern of ARI casescaused by virus were described.
2. Spatio-Temporal Modeling Study on Regional Influenza Seasonality Patterns in China:We compiled weekly reports of laboratory-confirmed influenza A and B infections from193sentinel hospitals in cities representing30Chinese provinces,2005-2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, amplitude ratio, and peak timing. Predictors of influenza seasonal characteristics were assessed by hierarchical Bayesian models. Hierarchical clustering and stepwise linear discriminant analysis were used to identify epidemiological relevant regions.
Results:1. Study on Viral Etiologiesof Hospitalized Acute Respiratory Infection:We excluded879patients from hospitals in which<40patients enrolled through quality control of surveillance data, and included28,369ARI patients from81(of the108) sentinel hospitals in22(of the24) provinces during2009-2013for final analysis.10,387(36.6%) were positive for one virus at least. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in7.2%of patients. RSV was the most common etiology (17.0%) in young children aged<2years. Influenza viruses were the main cause of hospitalized patients of ARI in adult and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections.
2. Spatio-Temporal Modeling Study on Regional Influenza Seasonality Patterns in China:During2005-2011, the annual epidemic periodicity of influenza A is more distinct as the latitude increased (mean amplitude of annual cycle standardized by mean incidence,140%[95%CI128%-151%] in the north versus37%[95%CI27%-47%] in the south,p<0.0001). Epidemics peaked in January-February in Northern China (latitude≥33°N) and April-June in southernmost regions (latitude<27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January-February and June-August (periodicity ratio>0.6in provinces located between27.4°N-31.3°N, slope of latitudinal gradient with latitude-0.016[95%CI-0.025to-0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall.
Conclusions:Our findings on viral etiologies of ARI could provide baseline information for surveillance and study on ARI in China, and serve as scientific evidence for public health authorities in drawing up further plans to prevent and control ARIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in school-age children and adults, and influenza vaccination should be implemented on a wider scale in China.
Analysis of seasonality of influenza suggests, regional-specific influenza vaccination strategies would be optimal in China; it is optimal for Northern China to follow the timing of vaccination typically recommended for the Northern Hemisphere, with annual campaigns starting in October. In contrast, southernmost Chinese provinces have to accommodate influenza activity peaking in April-June, and hence vaccination would be best initiated in February-March of each year. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region.
目的：确定引起我国儿童和成人ARI住院病例的主要病毒性病原体及其构成；定义不同型别流感在中国不同地理、气候区域的季节性模式,为我国流感疫苗预防接种政策的制定提供建议。
方法：1.2009-2013年ARI住院病例病毒性病原谱研究：2009年1月至2013年9月,在我国24个省的108家哨点医院开展ARI住院病例监测,收集其人口统计学、临床症状和体征等信息,采集其呼吸道标本,进行呼吸道合胞病毒(RSV)、流感病毒、腺病毒、副流感病毒、偏肺病毒、冠状病毒和博卡病毒的实验室检测。分不同年份、年龄组对ARI住院病例的病毒性病原体进行分析,并描述各种呼吸道病毒阳性病例的季节性分布特征。2.中国不同区域的流感季节性模式时空模型研究：收集和整理2005-2011年全国30个省的193家流感监测哨点医院每周报告的流感样病例数、检测标本数和实验室确诊的A型、B型流感病例数,以及各监测省、城市的人口、人群移动模式、社会经济水平、地理和气象等资料,利用带有谐波的线性回归模型定量测量流感的季节性,包括不同型别流感病毒活动的年度周期和半年周期、振幅、振幅比值、流行高峰时间和流行持续时间。采用分层贝叶斯模型识别流感季节性的预测因素,采用分层聚类法和逐步线性判别分析,确定流感广义流行病学区域。
结果：1.2009-2013年ARI住院病例病毒性病原谱研究：经对监测数据质控,剔除了2009-2013年纳入并检测7种病毒的住院ARI病例数<40的哨点医院,最终纳入22个省的81家哨点医院的28369例住院ARI病例进行分析。至少一种病毒检测阳性的10387例(阳性率36.6%)。 RSV的检测阳性率最高(9.9%),以下依次是流感病毒(6.6%)、副流感病毒(4.8%)、腺病毒(3.4%)、博卡病毒(1.9%)、偏肺病毒(1.5%)和冠状病毒(1.4%)。7.2%的病例两种及以上病毒检测呈阳性。2岁以下儿童中,RSV是最常见的病毒性病原(17.0%)。流感病毒是成年和老年住院ARI病例的主要病毒性病原。副流感病毒、博卡病毒、偏肺病毒和腺病毒感染在儿童中最常见,而冠状病毒感染在各年龄组分布较均衡、RSV、流感病毒、副流感病毒、博卡病毒和偏肺病毒有明显的季节性。
2.中国不同区域的流感季节性模式时空模型研究：2005-2011年,我国A型流感的年度周期性随纬度增加而增强(北方平均发病率标准化的年度周期振幅均值为140%[95%CI128%-151%],南方为37%[95%CI27%-47%]),呈多样化的空间模式和季节性特征：≥33°N的北方省份,每年1-2月份单一年度高峰；<27°N的最南部省份,每年4-6月份单一年度高峰；27.4-31.3°N的中纬度地区,每年1-2月份和6-8月份的双周期高峰(周期比>0.6的省份处于纬度27.4-31.3°N之间,纬度梯度的斜率为-0.016[95%CI-0.025至-0.008],p<0.001)。而B型流感在中国大部分地区呈单一的冬季高发模式。气候因素是流感季节性的最强预测因素,包括最低温度、日照时数和最大降雨量。
结论：ARI住院病例的病毒性病原谱研究结果为我国将来开展急性呼吸道感染监测和研究工作提供了基线资料,对我国制定ARI的预防控制策略有一定的参考价值。鉴于RSV感染在婴幼儿中较常见,因此采用疫苗预防接种、特异性治疗等防治措施将具有重要的公共卫生意义。流感病毒感染在学龄儿童和成年人较常见,应推动流感疫苗在这两类人群及其他高危人群中更大范围的应用。
流感季节性模式研究表明,中国应分不同区域制定流感疫苗预防接种策略。北方省份的流感疫苗最佳接种时机应遵循世界卫生组织推荐的北半球疫苗接种时间,即每年10月份启动疫苗接种；最南部省份的流感活动高峰在4-6月份,疫苗接种时间最好在每年2-3月份。考虑到中纬度地区流感季节性模式的复杂性,应进一步加强这一地区的流感监测。
Background:Acute respiratory infections (ARIs) are an important cause of acute illnesses and mortality worldwide and in China. Viral etiologies play impaort role in ARI. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Influenza can cause seveve impact to human health, and its seasonality has been well studied in temperate regions. However, seasonality of influenza by each type of virus strain remains poorly characterized in tropical and subtropical areas.
Objectives:To discribe the viral etiologies associated with hospitalized ARI patients in children and adults; and to characterize the diversity of influenza seasonality in virious regions of China and make recommendations to guide future vaccination programs.
Methods:1. Study on Viral Etiologiesof Hospitalized Acute Respiratory Infection: Active surveillance for hospitalized ARI patients in108sentinel hospitals in24provinces of China was conducted from January2009to September2013. We enrolled all-age hospitalized patients with ARI, and collected respiratory specimens, blood or serum for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). Demographic information, symptoms, signs, and viral etiologies of ARI were analyzied by season and age group. Seasonal pattern of ARI casescaused by virus were described.
2. Spatio-Temporal Modeling Study on Regional Influenza Seasonality Patterns in China:We compiled weekly reports of laboratory-confirmed influenza A and B infections from193sentinel hospitals in cities representing30Chinese provinces,2005-2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, amplitude ratio, and peak timing. Predictors of influenza seasonal characteristics were assessed by hierarchical Bayesian models. Hierarchical clustering and stepwise linear discriminant analysis were used to identify epidemiological relevant regions.
Results:1. Study on Viral Etiologiesof Hospitalized Acute Respiratory Infection:We excluded879patients from hospitals in which<40patients enrolled through quality control of surveillance data, and included28,369ARI patients from81(of the108) sentinel hospitals in22(of the24) provinces during2009-2013for final analysis.10,387(36.6%) were positive for one virus at least. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in7.2%of patients. RSV was the most common etiology (17.0%) in young children aged<2years. Influenza viruses were the main cause of hospitalized patients of ARI in adult and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections.
2. Spatio-Temporal Modeling Study on Regional Influenza Seasonality Patterns in China:During2005-2011, the annual epidemic periodicity of influenza A is more distinct as the latitude increased (mean amplitude of annual cycle standardized by mean incidence,140%[95%CI128%-151%] in the north versus37%[95%CI27%-47%] in the south,p<0.0001). Epidemics peaked in January-February in Northern China (latitude≥33°N) and April-June in southernmost regions (latitude<27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January-February and June-August (periodicity ratio>0.6in provinces located between27.4°N-31.3°N, slope of latitudinal gradient with latitude-0.016[95%CI-0.025to-0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall.
Conclusions:Our findings on viral etiologies of ARI could provide baseline information for surveillance and study on ARI in China, and serve as scientific evidence for public health authorities in drawing up further plans to prevent and control ARIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in school-age children and adults, and influenza vaccination should be implemented on a wider scale in China.
Analysis of seasonality of influenza suggests, regional-specific influenza vaccination strategies would be optimal in China; it is optimal for Northern China to follow the timing of vaccination typically recommended for the Northern Hemisphere, with annual campaigns starting in October. In contrast, southernmost Chinese provinces have to accommodate influenza activity peaking in April-June, and hence vaccination would be best initiated in February-March of each year. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region.
引文
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