2005-2007年广州儿童医院住院肺炎患儿三种病毒感染的临床特征
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摘要
背景与目的
肺炎是全世界5岁之下儿童第一位的死亡原因,约占全世界5岁之下儿童死亡人数的19%。中国每年的肺炎患儿总计2100万人次,肺炎也是中国5岁以下儿童第一位的死亡原因。因此需积极加强儿童肺炎的临床防治工作,降低儿童肺炎尤其是儿童重症肺炎的发病率和死亡率。
呼吸道合胞病毒(Respiratory syncytial virus,RSV)、甲型流感病毒(Influenza A virus,FV)和腺病毒(Adenovirus,ADV)是儿童肺炎的常见病原体,重症肺炎可以导致患儿死亡,并会造成流行传播。但至今对儿童RSV、FV和ADV感染肺炎没有特效治疗药物。目前认为对儿童RSV、FV和ADV感染肺炎的控制关键在于预防,其前提是了解儿童RSV、FV和ADV感染肺炎的性别、年龄、季节及年度分布等临床特征,在以上三种病毒感染肺炎的高发季节对高危儿童采一取临床防护工作。
前人研究表明,儿童RSV、FV及ADV感染的性别、年龄、季节及年度分布等临床特征在不同地区存在差异。因此,不同地区儿童RSV、FV及ADV感染肺炎的临床防治工作,要结合本地区RSV、FV及ADV感染肺炎患儿性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征进行。但目前对广州地区儿童RSV、FV和ADV感染临床特征进行研究的文献不多,对广州地区RSV、FV和ADV感染肺炎患儿的性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征尚不明确。
基于以上背景,本课题对2005-2007在广州儿童医院住院、来自于广州地区的12195例肺炎患儿中RSV、FV及ADV等三种病毒病毒感染肺炎患儿的临床资料进行回顾性分析和比较,旨在认识广州地区RSV、FV和ADV感染肺炎患儿的性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征,为广州地区儿童以上三种病毒感染肺炎的临床防治提供参考。广州儿童医院是广州市三级甲等儿童专科医院,年门诊量150余万人次,年住院患儿3万人次,广州儿童医院住院肺炎患儿常规进行FV及ADV等三种病毒的检测,对了解广州地区RSV、FV及ADV感染肺炎患儿临床特征具有一定的代表性。
研究对象与方法
1.研究对象及诊断标准
研究对象：收集2005年1月1日至2007年12月31日、年龄在0-14岁(0岁<年龄≤14岁)之间、来自于广州市市区及周边等广州地区、在广州儿童医院住院,根据病史、临床症状、体格检查和胸部X片检查确诊为肺炎的全部患儿的资料。肺炎诊断标准参考儿科学第七版。重症肺炎诊断标准参考中华医学会儿科分会呼吸学组制定的重症肺炎诊断标准。
2.三种病毒的检测方法
所有住院肺炎患儿均常规进行RSV、FV和ADV感染的检测。标本采集均得到了患儿监护人的同意。
RSV和ADV的检测方法：均采集患儿空腹外周静脉血,分离出血清,用ELISA方法,分别使用抗RSV抗体IgM检测试剂盒进行特异性RSV-IgM血清抗体的测定、使用抗ADV抗体IgM检测试剂盒进行特异性ADV-IgM血清抗体的测定,把特异性RSV-IgM血清抗体阳性患儿的病例资料纳入统计学分析,并把特异性ADV-IgM抗体阳性患儿的病例资料纳入统计学分析。
FV检测方法：取患儿咽分泌物,接种到MDCK细胞上,再33℃温箱培养72h,上清液进行血凝试验,对血凝试验阳性病例进行流感病毒分型鉴定,把流感病毒分型鉴定为甲型流感的患儿的病例资料纳入统计学分析。
3.观察项目
患儿的性别、年龄、发病日期、住院天数及重症肺炎情况等。
4.统计学处理
采用SPSS13.0软件进行,率的比较采用卡方检验,住院天数两组间比较采用t检验、多组间比较采用方差分析多重比较方法,以P<0.05为差异具有显著性。均数的表达采用x±s表示。
结果
确诊肺炎患儿共计12195例,其中男性患儿8432例,女性患儿3763例,男女比例2.24：1。0-1岁((0<年龄≤1岁)6277例(其中0-6月年龄段患儿4366例),1-3岁(1岁<年龄≤3岁)3405例,3-6岁(3岁<年龄≤6岁)1633例,6-14岁(6岁<年龄≤14岁)880例。春季(3,4,5月)4441例,夏季(6,7,8月)3464例,秋季(9,10,11月)2512例,冬季(12,1,2月)1778例。2005年3699例,2006年4483例,2007年4013例。12195例住院肺炎患儿中诊断重症肺炎的患儿共计1022人。
1.住院肺炎患儿呼吸道合胞病毒感染临床特征
12195例住院肺炎患儿中共检测到RSV-IgM特异性抗体阳性的肺炎患儿903例,感染率7.4%(903／12195)。RSV感染肺炎患儿平均住院天数为7.87±3.44天。
1.1性别分布
RSV感染肺炎患儿中男性635例,女性268例,男女比例2.37：1。男、女住院肺炎患儿RSV感染率分别为7.53%(635／8432)和7.12%(268／3763),男女感染率差异不具有显著性(χ2=0.634,P=0.426)。男女RSV肺炎患儿住院天数差异不具有显著性(P>0.05)。
1.2年龄分布
RSV感染肺炎患儿中0-1岁、1-3岁、3-6岁和6-14岁各年龄段患儿分别为607例、232例、57例和7例,以上各年龄段住院肺炎患儿RSV感染率依次为：9.67%(607／6277)、6.81%(232／3405)、3.49%(57／1633)和0.80%(7／880),各年龄段之间RSV感染率差异均具有显著性(均P<0.05),提示随年龄段增加RSV感染率下降。0-3岁年龄段RSV肺炎患儿共839例,占92.91%(839／903),是RSV感染的高峰年龄段。RSV肺炎患儿0-1岁组住院天数显著长于1-3岁组和6-14岁组(均P<0.05),3-6岁组长于6-14岁组(P<0.05),其他各年龄组间住院天数差异不具有显著性(P>0.05)。
1.3季节分布
RSV感染肺炎患儿中春、夏、秋、冬四季患儿分别为496例、219例、89例和99例,以上四季住院肺炎患儿RSV感染率感染率依次为11.17%(496／8432)、6.32%(219／3464)、3.54%(89／2512)和5.57%(99／1778)。春季感染率显著高于夏季、秋季和冬季感染率(分别为χ2=55.562,P=0.000；χ2=121.079,P=0.000；χ2=46.030,P=0.000),秋季感染率显著低于夏季和冬季(分别为,=23.007,P=0.000；χ2=10.189,P=0.001),夏、冬感染率差异不具有显著性(P>0.05),提示RSV在春季住院肺炎患儿病原学中更重要。春夏季(3-8月)RSV感染肺炎患儿共715例,占RSV感染肺炎患儿总数的79.18%,是感染的主要季节,其中4月份是发病的最高峰。春、夏、秋、冬四季间住院天数均无显著性差异(P>0.05)。
1.4年度分布
2005年、2006年和2007年RSV感染肺炎患儿数分别为148例、400例和355例,以上各年度住院肺炎患儿RSV感染率依次为4.00%(148／3699)、8.92%(400/483)和8.85%(355／4013)。2005年感染率显著低于2006(χ2=78.556,P=0.000)、2007年(χ2=74.113,P=0.000<0.05)感染率(均P<0.05)。2005-2007年各年度RSV感染性肺炎患儿发病高峰年龄段均为0-3岁,每年的春夏季均是发病的高峰季节且以4月份为最高峰月份。不同年度患儿住院天数均无显著性差异(P>0.05)。
1.5重症肺炎患儿特征
903例RSV感染肺炎患儿中重症肺炎患儿69例,重症肺炎发生率为7.64%(69／903),其中2例患儿死亡。重症肺炎患儿住院天数长于普通肺炎患儿(P<0.05)。
2.住院肺炎患儿甲型流感病毒感染临床特征
12195例住院肺炎患儿中共检测到流感病毒A型阳性患儿242例,感染率1.98%(242／12195)。FV感染肺炎患儿的平均住院天数为8.26±4.73天。
2.1性别分布
甲型流感病毒感染肺炎患儿男性175例,女性67例,男女之比2.61：1。男、女住院肺炎患儿FV感染率分别为2.08%(175／8432)与1.78%(67／3763),差异不具有显著性(χ2=1.164,P=0.281)。男女FV感染肺炎患儿平均住院天数无显著差异(t=-0.047,P=0.962)。
2.2年龄分布
0-1岁、1-3岁、3-6岁和6-14岁FV感染肺炎患儿分别为88例、93例、45例和16例,以上各年龄段住院肺炎患儿FV感染率依次为：1.40%(88／6277)、2.73%(93／3405)、2.76%(45／1633)和1.82%(16／880)。1-3岁和3-6岁年龄段感染率显著高于0-1岁年龄段感染率(分别为χ2=21.264,P=0.000和／χ214.365,P=0.000),其他每两个年龄段间感染率无显著性差异(P>0.05)。0-3岁患儿占FV感染肺炎患儿总数的74.79%(181／242),是感染的高峰年龄段。0.1岁组患儿较3-6岁和6-14岁组FV感染肺炎患儿住院天数显著延长(P<0.05),而其他各个组别之间住院肺炎患儿住院天数均无显著性差异(P>0.05)。
2.3季节分布
春、夏、秋、冬四季FV感染肺炎患几分别为98例、94例、32例和18例,以上四季住院肺炎患儿FV感染率依次为：2.21%(98／4441)、2.71%(94／3464)、1.27%(32／2512)、1.01%(18／1778)。春季与秋季(χ2=7.609,P=0.006)、春季与冬季(χ2=9.894,P=0.002)、夏季与秋季(χ2=14.623,P=0.000)、夏季与冬季(χ2=16.263,P=0.000)之间感染率均具有显著性差异(P<0.05),而春季与夏季(χ2=2.110,P=0.146)、秋季与冬季(χ2=0.618,P=0.432)感染率均无显著性差异(P>0.05)。FV感染肺炎患儿春夏季节(3-8月)占79.34%(192／242),是高峰感染季节。春、夏、秋、冬四季间住院天数均无显著性差异(P>0.05)。
2.4年度分布
2005、2006和2007年FV感染肺炎患儿分别为20例、136例和86例,以上各年度住院肺炎患儿FV感染率依次为0.54%(20／3699)、3.30%(136／4483)和2.14%(86／4013)。2005年感染率显著低于2006年和2007年(分别为χ2=67.349,P=0.000和,=34.456,P=0.000),2006感染率显著高2007年(χ2=67.349,P=0.010)。2005、2006和2007年FV感染肺炎患儿发病高峰年龄段均为0-3岁,发病高峰季节均为3-8月。2005、2006和2007年FV感染肺炎患儿住院天数年度间均无显著性差异(P>0.05)。
2.5重症肺炎患儿特征
242例FV感染肺炎患儿中重症肺炎患儿共计12例,重症肺炎发生率为4.96%(12／242),其中1例患儿死亡。重症FV感染肺炎患儿住院天数长于普通肺炎患儿,但二者差异不具有显著性(P>0.05)。
3.住院肺炎患儿腺病毒感染临床特征
12195例住院肺炎患儿中共检测到ADV感染肺炎患儿737例,感染率6.04%(737／12195)。737例ADV感染肺炎患儿平均住院天数为7.98±3.55天。
3.1性别分布
ADV感染肺炎患儿中男、女患儿分别为439例和298例,男女比例1.47：1。男女住院肺炎患儿ADV感染率分别为5.21%(439／8432)和7.92%(298／3763),男女感染率有显著性差异(χ2=33.723,P=0.000)。男女ADV感染肺炎患儿住院天数无显著性差异(P>0.05)。
3.2年龄分布
0-1岁、1-3岁、3-6岁和6-14岁ADV感染肺炎患儿分别为233例、272例、162例和70例,以上各年龄段住院肺炎患儿ADV感染率分别为：3.71%(233／6277)、7.99%(272／3405)、9.92%(162／1633)和7.95%(70／880)。0-1岁年龄段感染率显著低于1-3岁(χ2=81.654,P=0.000)、3-6岁(χ2=105.281,P=0.000)和6-14岁(χ2=34.264,P=0.000)等各年龄段感染率(P<0.05)。3-6岁年龄段感染率高于0-1岁(χ2=105.281,P=0.000)、1-3岁(χ2=5.324,P=0.022)和6-14岁(χ2=0.001,P=0.976)各年龄段感染率(P<0.05),其余各年龄段之间感染率无显著性差异(P>0.05)。0-3岁患儿占ADV感染肺炎患儿的68.52%(505／737),是感染的高峰年龄段。各年龄段患儿之间住院天数无显著性差异(P>0.05)。
3.3季节分布
春、夏、秋、冬四季ADV感染肺炎患儿分别为236例、207例、144例和150例,以上四季住院肺炎患儿ADV感染率分别为5.31%(236／4441)、5.98%(207／3464)、5.73%(144／2512)和8.44%(150／1778)。冬季感染率显著高于春(χ2=21.262,P=0.000)、夏(χ2=11.210,P=0.001)、秋(χ2=11.924,P=0.001)各季感染率(均P<0.05)。ADV感染肺炎患儿发病情况全年波动性小,但春夏季(3-8月)患儿占ADV感染肺炎患儿的60.11%(443／737),是主要的感染季节。各季节ADV感染肺炎患儿住院天数比较差异均无显著性(P>0.05)。
3.4年度分布
2005、2006和2007年ADV感染肺炎患儿数分别为263例、301例和173例,以上各年度住院肺炎患儿ADV感染率分别为7.11%(263／3299)、6.71%(301／4483)和4.31%(173／1778)。2007年感染率显著低于2005年、2006年感染率(P<0.05)。2005、2006、2007年ADV感染高峰年龄段均为0-3岁,感染高峰季节均为春夏季。2006年ADV感染肺炎患儿住院天数显著短于2005年住院天数(P<0.05),其他各个年度ADV肺炎患儿住院天数差异不具有显著性(P>0.05)。
3.5重症肺炎患儿特征
737例ADV感染肺炎患儿中重症肺炎患儿共计26例,重症肺炎患儿发生率3.53%(26／737),无死亡患儿。ADV感染重症肺炎患儿住院天数显著长于ADV感染普通肺炎患儿(t=3.073,P=0.005<0.05)。
4.住院肺炎患儿呼吸道合胞病毒、甲型流感病毒和腺病毒感染特征比较
4.1总体比较
住院肺炎患儿RSV、FV和ADV感染率分别为7.40%(903／12195)、1.98%(242／12195)和6.04%(737／12195)。RSV感染率高于FV和ADV(均P=0.000<0.05)；ADV感染率高于FV感染率(P=0.000<0.05)。
4.2性别比较
男性患儿RSV、FA和ADV感染率分别为7.53%(635／8432)、2.08%(175／8432)和5.21%(439／3432),男性患儿三种病毒感染率均具有显著性差异(均为P=0.000<0.05)。女性患儿RSV、FA和ADV感染率分别为7.12%(268/3763)、1.78%(67／3763)和7.92%(298／3763),女性患儿RSV和FV感染率、ADV和FV感染率均具有显著性差异(均为P=0.000<0.05),RSV和ADV感染率无显著性差异(P=0.190>0.05)。RSV、FA和ADV感染男女比例分别为2.37：1、2.61：1和1.47：1。
4.3年龄比较
0-1岁住院肺炎患儿RSV、FA和ADV感染率分别为9.67%(607／6277)、8.71%(233／6277)和1.40%(88／6277),三种病毒感染率两两比较均具有显著性差异(均P<0.05)。1-3岁住院肺炎患儿RSV、FV和ADV感染率分别为6.81%(232／3405)、2.73%(93／3405)和7.99%(272／3405),三种病毒感染率两两比较差异均具有显著性(均P<0.05)。3-6岁年龄段住院肺炎患儿RSV、FA和ADV感染率分别为：3.49%(57／1633)、2.76%(45／1633)和9.92%(162／1633),感染率ADV与RSV(χ2=53.961,P=0.000)、FV(χ2=70.605,P=0.000)间两两比较均具有显著性差异(P<0.05),RSV与FV间比较无显著性差异(P>0.05)。6-14岁住院肺炎患儿RSV、FA和ADV感染率分别为：0.80%(7／880)、1.82%(16／880)和7.95%(70／880),ADV与RSV(χ2=53.904,P=0.000)、FV(χ2=35.649,P=0.000)感染率差异均有显著性(均P<0.05),RSV与FV感染率无显著性差异(P>0.05)。0-3岁在RSV、FV、ADV感染肺炎患儿中分别占92.91%(839／903)、74.79%(181／242)和68.52%(505／737),是三种病毒共同的高峰感染年龄段。
4.4季节比较
春季住院肺炎患儿RSV、FA、ADV感染率分别为11.17%(496／4441)、2.21%(98／4441)和5.31%(236／4441),三种病毒感染率均有显著性差异(均为P=0.000<0.05)。夏季住院肺炎患儿RSV、FA、ADV感染率分别为6.32%(219／3464)、2.71%(94／3464)、5.98%(207／3464),RSV与FV(χ2=52.282,P=0.000)、ADV与FV(χ2=44.349,P=0.000)感染率差异均有显著性(均P<0.05),FV与ADV感染率无显著性差异(P>0.05)。秋季住院肺炎患儿RSV、FA、ADV感染率分别为3.54%(89／2512)、1.27%(32／2512)、5.73%(144／2512),三种病毒感染率均具有显著性差异(均为P=0.000<0.05)。冬季住院肺炎患儿RSV、FA、ADV感染率分别为5.57%(99／1778)、1.01%(18／1778)、8.44%(150／1778),三种病毒感染率均具有显著性差异(RSV与FV比较：χ2=57.937,P=0.000；RSV与ADV比较：χ2=11.263,P=0.001；FV与ADV比较：χ2=108.857,P=0.000)。RSV感染肺炎患儿春夏季占79.18%(715／903),FV感染肺炎患儿春夏季占79.34%(192／242),ADV感染肺炎患儿春夏季占60.11%(443/737),春夏季是三种病毒感染肺炎共同的高峰发病季节。
4.5年度比较
2005年住院肺炎患儿RSV、FA和ADV感染率分别为4.00%(148／3699)、0.54%(20／3699)和7.11%(263／3699),三种病毒两两间感染率均具有显著性差异(均P<0.05)。2006年住院肺炎患儿RSV、FV和ADV感染率分别为8.92%(400／4483)、3.30%(136／4483)和6.71%(301／4483),三种病毒感染率两两间比较均具有显著性差异(均P<0.05)。2007年住院肺炎患儿RSV、FV和ADV感染率分别为8.85%(355／4013)、2.14%(86／3927)和4.31%(173／4013),三种病毒感染率两两间比较均具有显著性差异(均P<0.05)。
4.6重症肺炎特征比较
RSV、FV和ADV感染肺炎患儿重症肺炎发生率分别为7.64%(69／903)、4.96%(12／242)和3.53%(26／737)。RSV和ADV感染重症肺炎发生率差异具有显著性(χ2=12.582,P=0.000),而RSV与FV、FV与ADV感染重症肺炎发生率差异不具有显著性(P>0.05)。RSV、FV和ADV重症肺炎患儿中0-3岁年龄段患儿所占比例分别为100%(69／69)、100%(12／12)和96.25%(25／26)。经过综合治疗,重症RSV感染肺炎患儿痊愈率98.55%(68／69),死亡率1.45%(1／69)；重症FV感染肺炎患儿痊愈率83.33%(10／12),死亡率16.67%(2／12)；重症ADV感染肺炎患儿中痊愈率88.46%(23／26),病情好转率11.54%(3／26),无死亡病例。
结论
本课题对2005-2007年广州儿童医院RSV、FV和ADV感染住院肺炎患儿临床特征进行分析及比较,结果表明：
1、RSV、FV和ADV均是住院肺炎患儿的常见病原,其感染率分别为7.40%、1.98%和6.04%,三种病毒中RSV是住院肺炎患儿中最常见的病原体。
2.男性住院肺炎患儿RSV、FV和ADV感染率分别为7.53%、2.08%和5.21%,三种病毒中RSV是男性住院肺炎患儿最常见的病原体。女性住院肺炎患儿RSV、FV和ADV感染率分别为7.12%、1.78%与7.92%,三种病毒中FV是女性肺炎患儿最少见的病原体。RSV、FV和ADV感染肺炎患儿男女之比分别为2.37：1、2.61：1和1.47：1,三种病毒感染肺炎患儿中男性患儿数量均多于女性患儿。
3.0-1岁住院肺炎患儿RSV、FV和ADV感染率分别为9.67%、1.40%和3.71%；1-3岁住院肺炎患儿RSV、FV和ADV感染率分别为6.81%、2.73%和7.99%；3-6岁住院肺炎患儿RSV、FV和ADV感染率分别为3.49%、2.76%和9.92%；6-14岁住院肺炎患儿RSV、FV和ADV感染率分别为0.80%、1.82%和7.95%。RSV是0-1岁年龄段住院肺炎患儿最常见的病原体,而ADV是3-6岁和6-14岁住院肺炎患儿最常见的病原体。RSV、FV、ADV感染肺炎患儿中0-3岁年龄段患儿分别占92.91%、74.79%和68.52%,0-3岁年龄段是三种病毒共同的高峰感染年龄段。
4.春季住院肺炎患儿RSV、FV和ADV感染率分别为11.17%、2.21%和5.31%；夏季住院肺炎患儿RSV、FV和ADV感染率分别为6.32%、2.71%和5.98%；秋季住院肺炎患儿RSV、FV和ADV感染率分别3.54%、1.27%和5.73%；冬季住院肺炎患儿RSV、FV和ADV感染率分别为5.57%、1.01%和8.44%。RSV是春季住院肺炎患儿最常见的病原体,而ADV是秋季和冬季住院肺炎患儿最常见的病原体。RSV、FV和ADV感染肺炎患儿中春夏季(3-8月)患儿分别占79.18%、79.34%和60.11%,春夏季节(3-8月)是三种病毒感染肺炎共同的高峰发病季节。
5.2005年RSV、FV和ADV感染率分别为4.00%、0.54%和7.11%；2006年RSV、FV和ADV感染率分别为8.92%、3.30%和6.71%；2007年RSV、FV和ADV感染率分别为8.85%、2.14%和4.31%。三种病毒中ADV是2005年住院肺炎患儿最常见的病原体,RSV是2006和2007年住院肺炎患儿中最常见的病原体。
6.RSV、FV、ADV三种病毒感染肺炎患儿重症肺炎发生率分别为7.64%、4.96%和3.53%。三种病毒感染重症肺炎发生的高危年龄段均为0-3岁。综合治疗对三种病毒感染重症肺炎患儿均有效。
总之,本研究提示,广州地区、RSV、FV及ADV感染肺炎患儿临床特征具有一定的地域独特性。广州地区儿童RSV、FV和ADV感染肺炎的重点防治对象均为0-3岁儿童尤其是男童、重点防治季节均为3-8月、要根据不同年度的病毒感染情况进行防治。对RSV、FV和ADV感染肺炎患儿中0-3岁年龄段患儿要防止其发展成重症肺炎,对重症肺炎患儿可进行综合治疗。研究成果可以为广州地区儿童RSV、FV和ADV感染肺炎的临床防治提供参考,具有实际的临床应用价值。
BACKGRANDS AND OBJECTIVES
Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years, and is responsible for about 19% of all deaths in children aged less than 5 years worldwide. There are about 21 million new childhood pneumonia episodes each year in China. Pneumonia is also the leading cause of mortality for Chinese children aged less than 5 years. Therefore it is important to strengthen the prevention and treatment of clinical pneumonia, espicallly of severe pneumonia in children, thus to reduce morbidity and mortality of childhood pneumonia.
RSV (Respiratory syncytial virus, RSV), influenza A virus (Influenza A virus, FV) and adenovirus (Adenovirus, ADV) are all common pathogen of childhood pneumonia. Childhood severe pneumonia can cause death, and may cause epidemic spread. But so far, there are limited effective treatments for childhood pneumonia infected with RSV, FV and ADV. It is considered that prevention is the key. This requires understanding clinical characteristics by sex, age, seasonal and annual distribution of children's RSV, FV and ADV infected pneumonia and clinical features of severe pneumonia of them, for children with RSV, FV and ADV virus pneumonia prevention and control of reference.
Previous studies showed that clinical features by sex, age, season and annual distribution of children with RSV, FV and ADV infection are different in different regions. Thus, the prevention and control work of childhood pneumonia infected with RSV, FV and ADV in different regions should be executed according to clinical features by sex, age, season, annual distribution and clinical features of severe pneumonia of the three viruses infected pneumonia children in regions themselves. Guangzhou is the same. However, there are few literatures about clinical features by sex, age, season, annual distribution and clinical features of severe pneumonia of the three viruses infected pneumonia children in Guangzhou, and there are no comparative literatures for them three in Guangzhou.
Based on the above background, clinical features of childhood pneumonia with RSV, FV and ADV infection in 12,195 cases of hospitalized pneumonia children in Guangzhou Children's Hospital in 2005-2007 were retrospectively analyzed and compared, thus to understand the clinical characteristics by sex, age, season, the annual distribution and severe pneumonia clinical features of RSV, FV and ADV pneumonia for hospitalized pneumonia children in Guangzhou, to provide reference for prevention and control work of hospitalized pneumonia children infected with the three viruses in Guangzhou.
METHODS
1. All the cases were from the hospitalized patients of Guangzhou children's hospital, the largest children's hospital of south China. All the cases selected from January 1st,2005,to December 31st,2007. The age of them were 0-14 years old (0 2.RSV,FV and ADV were detected for all of the cases. The RSV and ADV infected cases were detected by Anti-RSV IgM and Anti-ADV IgM Test, using blood serum of the hospitalized pneumonia children, those positive of RSV and ADV were analized. The FV infected cases were detected by methods of taking all the specimens from viral isolation with swabs from throats of pneumonia children and inoculated into MDCK cells, then supernatant of cultured cells was tested with hemagglutination reaction, those positive of FV were analized.
3.Clinical datas of sex, age, date of onset, hospitalized stay of RSV, FV and ADV infected hospitalized pneumonia children and severe pneumonia clinical datas of them were collected.
4. Statistic analyses were dealt with by SPSS13.0. Chi-square test was used to analysize the infection rate between different sex, different age, different season and different year. T-test or One-way ANOVA test were used to analyze the average of hospitalized stay of two or more groups. P<0.05 was indicated as significant difference.Mean was expressed as x±s.
RESULTS
The total pneumonia cases were 12,195, within them male were 8,432 and female were 3,763;within them 0-1(0 1.Features of the respiratory syncytial virus infected pneumonia cases
903 cases of RSV-IgM positive hospitalized pneumonia children were detected and the infection rate was 7.40%. The average hospitalized days of them were 7.87±3.44d.
1.1 Sex distribution
The infection rate between male(7.53%) and female (7.12%) had no significant difference(χ2=0.634, P=0.426>0.05).The average hospitalized days between them were also had no significance (P>0.05).
1.2 Age distribution
The infection rate of 0-1,1-3,3-6 and 6-14 years old was 9.67%、6.811%、3.49% and 0.80%,respectively. The infection rate between each two age stags had significantly difference(P<0.05).Cases of 0-3 years old occupied 92.03%. The average hospitalized days of 0-1 years old were longer than 3-6 and 6-14 years old(P <0.05),and those of 3-6 years old were longer than 6-14 years old.However, those between each two of the other age stages had no significantly difference (P>0.05).
1.3 Season distribution
The infection rate of spring, summer, autumn and winter was 11.17%、6.32%、3.54% and 5.57%, respectively. The infection rate of spring was significantly higher than that of summer, autumn and winter(P<0.05).Cases from March to August accounted for 79.18%. The average hospitalized days between each two of them had no significantly difference (P>0.05).
1.4 Year distribution
The RSV infection rate in 2005,2006 and 2007 were 4.00%,8.92% and 8.85%, respectively. The infection rate between 2005 and 2006(χ2=78.556,P=0.000), between 2005 and 2007 (χ2=74.113,P=0.000)were both significant(P<0.05),while infection rate between 2006 and 2007 had no significantly difference(P>0.05).The peak infected age stage in 2005,2006 and 2007 were all 0-3 years old, and the peak season in 2005,2006 and 2007 were all in spring and summer, Apil was the most peakest month. The average hospitalized days between each two of them had no significantly difference (P>0.05).
1.5 Severe pneumonia cases
There were 69 cases RSV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of RSV was 7.64%. Two cases of severe pneumonia children cases died.The average hospitalized days of the servere cases were significantly longer than the common cases(P<0.05)
2. Features of the influenza A virus infected pneumonia cases
242 cases of FV positive hospitalized pneumonia cases were detected and the infection rate was 1.98%.
2.1 Sex distribution
The difference of infection rate between male (2.08%) and female(1.78%) had no significance(χ2=1.164,P=0.281).The average hospitalized days between them had no significantly difference (P>0.05).
2.2 Age distribution
The infection rate of 0-lyears old, 1-3years old,3-6 years old and 6-14 years old was 1.40%,2.73%,2.76% and 1.82%, respectively. And the infection rate of 1-3 years old and 3-6 years old both were significantly different from that of the 0-1 years old(P<0.05). FV infected children for 0 to 3 years old occupied 74.79%. The average hospitalized days of 0-1 years old were longer than 3-6 and 6-14 years old (P<0.05), and those between each two of the other age stages had no significantly difference (P >0.05).
2.3 Season distribution
The infection rate of spring, summer, autumn and winter was 2.21%,2.71%, 1.27% and 1.01%,respectively. And the infection rate between spring and autum (χ2=7.609, P=0.006),between spring and winter (/=9.894, P=0.002),between summer and autumn (χ2=14.623,P=0.000),between summer and winte (χ2=16.263,P=0.000) were all had significantly difference(P<0.05). Cases of spring and summer occupied 79.34%.The average hospitalized days between each two of the seasons had no significantly difference (P>0.05).
2.4 Year distribution
FV Infected cases in 2005,2006 and 2007 were 20,136 and 86 cases, respectively. And the infection rate of 2005,2006 and 2007 were 0.54%,3.30% and 2.14%, respectively. The infection rate of 2005 was significantly less than 2006 and 2007 (χ2=67.349,P=0.000 and =34.456,P=0.000),the infection rate of 2006 was significantly higher than 2007(χ2=67.349,P=0.010).The peak infected age stage in 2005,2006 and 2007 were all 0-3 years old, and the peak season in 2005,2006 and 2007 were all in spring and summer.The average hospitalized days between each two of the years had no significantly difference (P>0.05).
2.5 Severe pneumonia cases
There were 12 cases of FV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of FV was 4.96%. One case of severe pneumonia children died. The average hospitalized days of the severe cases were longer than the common cases, while had no significantly difference (P>0.05).
3. Features of the adenovirus infected pneumonia cases
737 case for ADV-IgM positive of hospitalized pneumonia cases were detected and the total ADV infection rate was 6.04%.The average hospitalized days of them were 7.98±3.55d.
3.1 Sex distribution
The infection rate of female (7.92%) was significantly(P<0.05)higher than the infection rate of male (5.21%).The average hospitalized days between them had no significance (P>0.05).
3.2 Age distribution
The infection rate of 0-1、1-3、3-6 and 6-14 years old was 3.71%、7.99%、9.92% and 7.95%,respectively.Furthermore,the infection rate of 0-1 years old was significantly less than that of the other age stages(P<0.05),and the infection rate of 3-6 years old was significantly higher than that of all the other age stases(P<0.05) ADV infected pneumonia cases of 0-3 years old occupied 68.52%.The average hospitalized days of 0-1 years old were longer than 3-6 years old(P<0.05),and those between each two of the other age stages had no significant difference (P>0.05).
3.3 Season distribution
The infection rate of spring, summer, autumn and winter was 5.31%,5.98%, 5.73% and 8.44%, respectively. And the infection rate of winter is significantly higher than the infection rate of spring(χ2=21.262, P=0.000),summer (χ2=11.210,P=0.001)and autum(χ2=11.924,P=0.001).Cases from March to August accounted 60.11% of all the ADV infected cases.The average hospitalized days each two of the seasons had no significantly difference (P>0.05).
3.4 Year distribution
ADV infected hospitalized pneumonia cases in 2005,2006 and 2007 were 263 cases,301 cases and 173 cases, respectively. And the ADV infection rate of 2005, 2006 and 2007 were 7.11%,6.71% and 4.31%, respectively. Infection rate of 2007 was significantly less than that of 2005 and 2006. The peak age stage in 2005,2006 and 2007 were all 0-3 years old, while the peak months had some difference in different years. The average hospitalized days between each two of them had no significantly difference (P>0.05).
3.5 Severe pneumonia cases
There were 26 cases of ADV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of ADV was 3.53%.The average hospitalized days between the severe and the common pneumonia had no significantly difference (P>0.05).
4. Comparison of the three viruses infected pneumonia cases
4.1 Comparison as a whole
The differences of infection rate between each two of the viruses were significant (between RSV and FV:χ2=400.387,P=0.000;between RSV and ADV:χ2=18.014,P=0.000;between ADV and FV:χ2=260.747,P=0.000).
4.2 Comparison by Sex
The infected rates of the male of RSV, FV and ADV were 7.53%、2.08% and 5.21%,respectively.The infected rates of the female of RSV, FV and ADV were 7.12%.1.78% and 7.92%,respectively. The infected rates of the male between each two viruses had significantly difference:between RSV and FVχ2=274.415,P=0.000; RSV and ADV:χ2=38.202,P=0.000;ADV and FV:χ2=117.800,P=0.000).As for the female:between RSV and FV:χ2=126.218,P=0.000<0.05;between RSV and ADV:χ2=1.719,P=0.190>0.05;between ADV and FV:χ2=153.646,P=0.000<0.05.
4.3 Comparison by age
For children of 0-1 years old, the infection rate of RSV、FV and was ADV 9.67%、8.71% and 1.40%,respectively, each of two of them had significant difference (P<0.05).For children of 1-3 years old, the infection rate of RSV、FV and was 6.81%,7.99% and 2.73%,respectively, and the infection rate between RSV and ADV (χ2=62.429,P=0.000)、between FV and ADV(χ2=92.755,P=0.000)were both had significant difference(P<0.05).For children of 3-6 years old, the infection rate of RSV、FV and ADV was 3.49%,9.92% and 2.76%,respectively, and the infection rate between FV and RSV(χ2=53.961,P=0.000)、between FV and ADV(χ2=70.605, P=0.000)were both had significant difference(P<0.05).For children of 6-14 years old, the infection rate of RSV、FV and ADV was 0.80%、1.82% and 7.95%,respectively. The infection rate between ADV and RSV(χ2=53.904, P=0.000)、between ADV and FV(χ2=35.649,P=0.000)were both had significant difference(P<0.05).All of the most prevalent infected age of RSV, FV and ADV were 0-3 years old.
4.4 Comparison by year
The infection rate of RSV, FV and ADV in 2005 were 4.00%,0.54% and 7.11%,respectivey, each two of them had significantly difference(P<0.05).The infection rate of RSV, FV and ADV in 2006 were 8.92%,3.30% and 6.71%, respectivey,each two of them had significantly difference(P<0.05). The infection rate of RSV, FV and ADV in 2007 were 8.85%,2.14% and 4.31%,respectivey,each two of them had significantly difference(P<0.05)
4.5 Comparison by season
The infection rate for RSV、FV and ADV in spring was 11.17%、2.21% and 5.31%,respectively,each two of them had significant difference(between RSV and FV:χ2=285.786, P=0.000;between RSV and ADV:χ2=100.644, P=0.000;between ADV and FV:χ2=59.246,P=0.000. The infection rate of RSV、FV and ADV in summer was 6.32%,2.71% and 5.98%,respectively. And the infection rate between RSV and FV(χ2=52.282,P=0.000)、ADV and FV(χ2=44.349,P=0.000)both had signifficant difference(P<0.05).The infection rate of RSV,FV and ADV in autumn was 3.54%，1.27% and 5.73%,respectively. Each of them had significant difference (RSV and FV:χ2=27.514,P=0.000; RSV and ADV:χ2=13.614,P=0.000;FV and ADV:χ2=73.860,P=0.000;The infection rate of RSV、FV and ADV in winter was 5.57%,1.01% and 8.44%,respectively, each of them had significant difference(RSV and FV:χ2=57.937,P=0.000;RSV and ADV:χ2=11.263, P=0.001;FV and ADV:χ2=108.857,P=0.000).5)The infection rate of RSV、FV and ADV in 2005 was 4.00%,0.54% and 7.11%,respectively; in 2006 was 8.92%,3.30% and 6.71%,respectively; in 2007 was 8.85%、2.14% and 4.31%,respectively.Each of them in the three years were different significantly(P<0.05).
4.6 Comparison by the severe cases
Severe pneumonia incidence rates of RSV, FV and ADV were 7.64%,4.96% and 3.53%,respectively. Severe pneumonia incidence rates between RSV and ADV had significantly difference (χ2=12.582, P=0.000), while which between RSV and FV, between FV and ADV had no significantly difference (P> 0.05). As for RSV, FV and ADV, severe pneumonia in children aged 0-3 were 100%,100% and 96.15%, respectively. Comprehensive treatments with antibiotics, ribavirin, inhaled bronchodilators, systemic hormones, intravenous immunoglobulin and mechanical ventilatory support had good therapeutic effect to severe RSV, FV and ADV infected hospitalized pneumonia children.
CONCLUSIONS
Clinical features of RSV、FV and ADV infected hospitalized pneumonia children in Guangzhou Children's Hospital in 2005-2007 were analyzed in this paper, results were as follows:
1.RSV, FV, and ADV were all common pathogens of hospitalized pneumonia children,and RSV-was the most common pneumonia cause of the three viruses.
2.Infection rates of the male of RSV, FV and ADV pneumonia cases were 7.53%,2.08% and 5.21%,respectively. For female of them were 7.12%,1.78% and 7.92%, respectively. RSV was the most important pneumonia causes of the three viruses for the male, and FV was the least important pneumonia causes of the three viruses for the female. Male to female ratio of RSV, FV and ADV pneumonia cases were 2.37:1,2.61:1 and 1.47:1,respectively.For three of them, the male cases were all more than the female.
3.RSV was the most common causes in 0-1 age stages of the three viruses, and ADV were the most common causes in 3-6 and 6-14 age stages. Pneumonia case of 0-3 years old occupied 92.91%,74.79% and 68.52% of all the RSV, FV and ADV cases, respectively, were the common peak infected age stages for all of the three viruses.
4. RSV was the most common causes in spring of the three viruses, and ADV were the most common causes in autumn and winter. Pneumonia cases in spring and summer occupied 79.18%,79.34% and 60.11% cases of RSV, FV and ADV pneumonia cases, respectively, were the common peak seasons for the three viruses.
5.RSV was the most common causes in spring of the three viruses in 2006 and 2007, however, ADV were the most common causes in 2005.
6. Severe pneumonia cases incidence rates of RSV, FV and ADV were 7.64%、4.96% and 3.53%,respectively. Cases of 0-3 years old occupied 100%,100% and 96.25% of severe pneumonia cases of RSV, FV and ADV infected pneumonia cases, respectively. Complex treat had functions to RSV, FV and ADV infected pneumonia cases.
In conclusion, this study suggests that prevention and therapy works for RSV, FV and ADV infected childhood pneumonia in Guangzhou should be focused on age stage of 0-3 years old, particularly boys; and should also be focused on seasons of March-August and be adjusted in different years to the epidemic circumstances of the year. Severe pneumonia cases caused by the three viruses musted mostly in 0-3 year old children and these severe pneumonia cases should be complex treated.
肺炎是全世界5岁之下儿童第一位的死亡原因,约占全世界5岁之下儿童死亡人数的19%。中国每年的肺炎患儿总计2100万人次,肺炎也是中国5岁以下儿童第一位的死亡原因。因此需积极加强儿童肺炎的临床防治工作,降低儿童肺炎尤其是儿童重症肺炎的发病率和死亡率。
呼吸道合胞病毒(Respiratory syncytial virus,RSV)、甲型流感病毒(Influenza A virus,FV)和腺病毒(Adenovirus,ADV)是儿童肺炎的常见病原体,重症肺炎可以导致患儿死亡,并会造成流行传播。但至今对儿童RSV、FV和ADV感染肺炎没有特效治疗药物。目前认为对儿童RSV、FV和ADV感染肺炎的控制关键在于预防,其前提是了解儿童RSV、FV和ADV感染肺炎的性别、年龄、季节及年度分布等临床特征,在以上三种病毒感染肺炎的高发季节对高危儿童采一取临床防护工作。
前人研究表明,儿童RSV、FV及ADV感染的性别、年龄、季节及年度分布等临床特征在不同地区存在差异。因此,不同地区儿童RSV、FV及ADV感染肺炎的临床防治工作,要结合本地区RSV、FV及ADV感染肺炎患儿性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征进行。但目前对广州地区儿童RSV、FV和ADV感染临床特征进行研究的文献不多,对广州地区RSV、FV和ADV感染肺炎患儿的性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征尚不明确。
基于以上背景,本课题对2005-2007在广州儿童医院住院、来自于广州地区的12195例肺炎患儿中RSV、FV及ADV等三种病毒病毒感染肺炎患儿的临床资料进行回顾性分析和比较,旨在认识广州地区RSV、FV和ADV感染肺炎患儿的性别、年龄、季节、年度分布等临床特征及重症肺炎临床特征,为广州地区儿童以上三种病毒感染肺炎的临床防治提供参考。广州儿童医院是广州市三级甲等儿童专科医院,年门诊量150余万人次,年住院患儿3万人次,广州儿童医院住院肺炎患儿常规进行FV及ADV等三种病毒的检测,对了解广州地区RSV、FV及ADV感染肺炎患儿临床特征具有一定的代表性。
研究对象与方法
1.研究对象及诊断标准
研究对象：收集2005年1月1日至2007年12月31日、年龄在0-14岁(0岁<年龄≤14岁)之间、来自于广州市市区及周边等广州地区、在广州儿童医院住院,根据病史、临床症状、体格检查和胸部X片检查确诊为肺炎的全部患儿的资料。肺炎诊断标准参考儿科学第七版。重症肺炎诊断标准参考中华医学会儿科分会呼吸学组制定的重症肺炎诊断标准。
2.三种病毒的检测方法
所有住院肺炎患儿均常规进行RSV、FV和ADV感染的检测。标本采集均得到了患儿监护人的同意。
RSV和ADV的检测方法：均采集患儿空腹外周静脉血,分离出血清,用ELISA方法,分别使用抗RSV抗体IgM检测试剂盒进行特异性RSV-IgM血清抗体的测定、使用抗ADV抗体IgM检测试剂盒进行特异性ADV-IgM血清抗体的测定,把特异性RSV-IgM血清抗体阳性患儿的病例资料纳入统计学分析,并把特异性ADV-IgM抗体阳性患儿的病例资料纳入统计学分析。
FV检测方法：取患儿咽分泌物,接种到MDCK细胞上,再33℃温箱培养72h,上清液进行血凝试验,对血凝试验阳性病例进行流感病毒分型鉴定,把流感病毒分型鉴定为甲型流感的患儿的病例资料纳入统计学分析。
3.观察项目
患儿的性别、年龄、发病日期、住院天数及重症肺炎情况等。
4.统计学处理
采用SPSS13.0软件进行,率的比较采用卡方检验,住院天数两组间比较采用t检验、多组间比较采用方差分析多重比较方法,以P<0.05为差异具有显著性。均数的表达采用x±s表示。
结果
确诊肺炎患儿共计12195例,其中男性患儿8432例,女性患儿3763例,男女比例2.24：1。0-1岁((0<年龄≤1岁)6277例(其中0-6月年龄段患儿4366例),1-3岁(1岁<年龄≤3岁)3405例,3-6岁(3岁<年龄≤6岁)1633例,6-14岁(6岁<年龄≤14岁)880例。春季(3,4,5月)4441例,夏季(6,7,8月)3464例,秋季(9,10,11月)2512例,冬季(12,1,2月)1778例。2005年3699例,2006年4483例,2007年4013例。12195例住院肺炎患儿中诊断重症肺炎的患儿共计1022人。
1.住院肺炎患儿呼吸道合胞病毒感染临床特征
12195例住院肺炎患儿中共检测到RSV-IgM特异性抗体阳性的肺炎患儿903例,感染率7.4%(903／12195)。RSV感染肺炎患儿平均住院天数为7.87±3.44天。
1.1性别分布
RSV感染肺炎患儿中男性635例,女性268例,男女比例2.37：1。男、女住院肺炎患儿RSV感染率分别为7.53%(635／8432)和7.12%(268／3763),男女感染率差异不具有显著性(χ2=0.634,P=0.426)。男女RSV肺炎患儿住院天数差异不具有显著性(P>0.05)。
1.2年龄分布
RSV感染肺炎患儿中0-1岁、1-3岁、3-6岁和6-14岁各年龄段患儿分别为607例、232例、57例和7例,以上各年龄段住院肺炎患儿RSV感染率依次为：9.67%(607／6277)、6.81%(232／3405)、3.49%(57／1633)和0.80%(7／880),各年龄段之间RSV感染率差异均具有显著性(均P<0.05),提示随年龄段增加RSV感染率下降。0-3岁年龄段RSV肺炎患儿共839例,占92.91%(839／903),是RSV感染的高峰年龄段。RSV肺炎患儿0-1岁组住院天数显著长于1-3岁组和6-14岁组(均P<0.05),3-6岁组长于6-14岁组(P<0.05),其他各年龄组间住院天数差异不具有显著性(P>0.05)。
1.3季节分布
RSV感染肺炎患儿中春、夏、秋、冬四季患儿分别为496例、219例、89例和99例,以上四季住院肺炎患儿RSV感染率感染率依次为11.17%(496／8432)、6.32%(219／3464)、3.54%(89／2512)和5.57%(99／1778)。春季感染率显著高于夏季、秋季和冬季感染率(分别为χ2=55.562,P=0.000；χ2=121.079,P=0.000；χ2=46.030,P=0.000),秋季感染率显著低于夏季和冬季(分别为,=23.007,P=0.000；χ2=10.189,P=0.001),夏、冬感染率差异不具有显著性(P>0.05),提示RSV在春季住院肺炎患儿病原学中更重要。春夏季(3-8月)RSV感染肺炎患儿共715例,占RSV感染肺炎患儿总数的79.18%,是感染的主要季节,其中4月份是发病的最高峰。春、夏、秋、冬四季间住院天数均无显著性差异(P>0.05)。
1.4年度分布
2005年、2006年和2007年RSV感染肺炎患儿数分别为148例、400例和355例,以上各年度住院肺炎患儿RSV感染率依次为4.00%(148／3699)、8.92%(400/483)和8.85%(355／4013)。2005年感染率显著低于2006(χ2=78.556,P=0.000)、2007年(χ2=74.113,P=0.000<0.05)感染率(均P<0.05)。2005-2007年各年度RSV感染性肺炎患儿发病高峰年龄段均为0-3岁,每年的春夏季均是发病的高峰季节且以4月份为最高峰月份。不同年度患儿住院天数均无显著性差异(P>0.05)。
1.5重症肺炎患儿特征
903例RSV感染肺炎患儿中重症肺炎患儿69例,重症肺炎发生率为7.64%(69／903),其中2例患儿死亡。重症肺炎患儿住院天数长于普通肺炎患儿(P<0.05)。
2.住院肺炎患儿甲型流感病毒感染临床特征
12195例住院肺炎患儿中共检测到流感病毒A型阳性患儿242例,感染率1.98%(242／12195)。FV感染肺炎患儿的平均住院天数为8.26±4.73天。
2.1性别分布
甲型流感病毒感染肺炎患儿男性175例,女性67例,男女之比2.61：1。男、女住院肺炎患儿FV感染率分别为2.08%(175／8432)与1.78%(67／3763),差异不具有显著性(χ2=1.164,P=0.281)。男女FV感染肺炎患儿平均住院天数无显著差异(t=-0.047,P=0.962)。
2.2年龄分布
0-1岁、1-3岁、3-6岁和6-14岁FV感染肺炎患儿分别为88例、93例、45例和16例,以上各年龄段住院肺炎患儿FV感染率依次为：1.40%(88／6277)、2.73%(93／3405)、2.76%(45／1633)和1.82%(16／880)。1-3岁和3-6岁年龄段感染率显著高于0-1岁年龄段感染率(分别为χ2=21.264,P=0.000和／χ214.365,P=0.000),其他每两个年龄段间感染率无显著性差异(P>0.05)。0-3岁患儿占FV感染肺炎患儿总数的74.79%(181／242),是感染的高峰年龄段。0.1岁组患儿较3-6岁和6-14岁组FV感染肺炎患儿住院天数显著延长(P<0.05),而其他各个组别之间住院肺炎患儿住院天数均无显著性差异(P>0.05)。
2.3季节分布
春、夏、秋、冬四季FV感染肺炎患几分别为98例、94例、32例和18例,以上四季住院肺炎患儿FV感染率依次为：2.21%(98／4441)、2.71%(94／3464)、1.27%(32／2512)、1.01%(18／1778)。春季与秋季(χ2=7.609,P=0.006)、春季与冬季(χ2=9.894,P=0.002)、夏季与秋季(χ2=14.623,P=0.000)、夏季与冬季(χ2=16.263,P=0.000)之间感染率均具有显著性差异(P<0.05),而春季与夏季(χ2=2.110,P=0.146)、秋季与冬季(χ2=0.618,P=0.432)感染率均无显著性差异(P>0.05)。FV感染肺炎患儿春夏季节(3-8月)占79.34%(192／242),是高峰感染季节。春、夏、秋、冬四季间住院天数均无显著性差异(P>0.05)。
2.4年度分布
2005、2006和2007年FV感染肺炎患儿分别为20例、136例和86例,以上各年度住院肺炎患儿FV感染率依次为0.54%(20／3699)、3.30%(136／4483)和2.14%(86／4013)。2005年感染率显著低于2006年和2007年(分别为χ2=67.349,P=0.000和,=34.456,P=0.000),2006感染率显著高2007年(χ2=67.349,P=0.010)。2005、2006和2007年FV感染肺炎患儿发病高峰年龄段均为0-3岁,发病高峰季节均为3-8月。2005、2006和2007年FV感染肺炎患儿住院天数年度间均无显著性差异(P>0.05)。
2.5重症肺炎患儿特征
242例FV感染肺炎患儿中重症肺炎患儿共计12例,重症肺炎发生率为4.96%(12／242),其中1例患儿死亡。重症FV感染肺炎患儿住院天数长于普通肺炎患儿,但二者差异不具有显著性(P>0.05)。
3.住院肺炎患儿腺病毒感染临床特征
12195例住院肺炎患儿中共检测到ADV感染肺炎患儿737例,感染率6.04%(737／12195)。737例ADV感染肺炎患儿平均住院天数为7.98±3.55天。
3.1性别分布
ADV感染肺炎患儿中男、女患儿分别为439例和298例,男女比例1.47：1。男女住院肺炎患儿ADV感染率分别为5.21%(439／8432)和7.92%(298／3763),男女感染率有显著性差异(χ2=33.723,P=0.000)。男女ADV感染肺炎患儿住院天数无显著性差异(P>0.05)。
3.2年龄分布
0-1岁、1-3岁、3-6岁和6-14岁ADV感染肺炎患儿分别为233例、272例、162例和70例,以上各年龄段住院肺炎患儿ADV感染率分别为：3.71%(233／6277)、7.99%(272／3405)、9.92%(162／1633)和7.95%(70／880)。0-1岁年龄段感染率显著低于1-3岁(χ2=81.654,P=0.000)、3-6岁(χ2=105.281,P=0.000)和6-14岁(χ2=34.264,P=0.000)等各年龄段感染率(P<0.05)。3-6岁年龄段感染率高于0-1岁(χ2=105.281,P=0.000)、1-3岁(χ2=5.324,P=0.022)和6-14岁(χ2=0.001,P=0.976)各年龄段感染率(P<0.05),其余各年龄段之间感染率无显著性差异(P>0.05)。0-3岁患儿占ADV感染肺炎患儿的68.52%(505／737),是感染的高峰年龄段。各年龄段患儿之间住院天数无显著性差异(P>0.05)。
3.3季节分布
春、夏、秋、冬四季ADV感染肺炎患儿分别为236例、207例、144例和150例,以上四季住院肺炎患儿ADV感染率分别为5.31%(236／4441)、5.98%(207／3464)、5.73%(144／2512)和8.44%(150／1778)。冬季感染率显著高于春(χ2=21.262,P=0.000)、夏(χ2=11.210,P=0.001)、秋(χ2=11.924,P=0.001)各季感染率(均P<0.05)。ADV感染肺炎患儿发病情况全年波动性小,但春夏季(3-8月)患儿占ADV感染肺炎患儿的60.11%(443／737),是主要的感染季节。各季节ADV感染肺炎患儿住院天数比较差异均无显著性(P>0.05)。
3.4年度分布
2005、2006和2007年ADV感染肺炎患儿数分别为263例、301例和173例,以上各年度住院肺炎患儿ADV感染率分别为7.11%(263／3299)、6.71%(301／4483)和4.31%(173／1778)。2007年感染率显著低于2005年、2006年感染率(P<0.05)。2005、2006、2007年ADV感染高峰年龄段均为0-3岁,感染高峰季节均为春夏季。2006年ADV感染肺炎患儿住院天数显著短于2005年住院天数(P<0.05),其他各个年度ADV肺炎患儿住院天数差异不具有显著性(P>0.05)。
3.5重症肺炎患儿特征
737例ADV感染肺炎患儿中重症肺炎患儿共计26例,重症肺炎患儿发生率3.53%(26／737),无死亡患儿。ADV感染重症肺炎患儿住院天数显著长于ADV感染普通肺炎患儿(t=3.073,P=0.005<0.05)。
4.住院肺炎患儿呼吸道合胞病毒、甲型流感病毒和腺病毒感染特征比较
4.1总体比较
住院肺炎患儿RSV、FV和ADV感染率分别为7.40%(903／12195)、1.98%(242／12195)和6.04%(737／12195)。RSV感染率高于FV和ADV(均P=0.000<0.05)；ADV感染率高于FV感染率(P=0.000<0.05)。
4.2性别比较
男性患儿RSV、FA和ADV感染率分别为7.53%(635／8432)、2.08%(175／8432)和5.21%(439／3432),男性患儿三种病毒感染率均具有显著性差异(均为P=0.000<0.05)。女性患儿RSV、FA和ADV感染率分别为7.12%(268/3763)、1.78%(67／3763)和7.92%(298／3763),女性患儿RSV和FV感染率、ADV和FV感染率均具有显著性差异(均为P=0.000<0.05),RSV和ADV感染率无显著性差异(P=0.190>0.05)。RSV、FA和ADV感染男女比例分别为2.37：1、2.61：1和1.47：1。
4.3年龄比较
0-1岁住院肺炎患儿RSV、FA和ADV感染率分别为9.67%(607／6277)、8.71%(233／6277)和1.40%(88／6277),三种病毒感染率两两比较均具有显著性差异(均P<0.05)。1-3岁住院肺炎患儿RSV、FV和ADV感染率分别为6.81%(232／3405)、2.73%(93／3405)和7.99%(272／3405),三种病毒感染率两两比较差异均具有显著性(均P<0.05)。3-6岁年龄段住院肺炎患儿RSV、FA和ADV感染率分别为：3.49%(57／1633)、2.76%(45／1633)和9.92%(162／1633),感染率ADV与RSV(χ2=53.961,P=0.000)、FV(χ2=70.605,P=0.000)间两两比较均具有显著性差异(P<0.05),RSV与FV间比较无显著性差异(P>0.05)。6-14岁住院肺炎患儿RSV、FA和ADV感染率分别为：0.80%(7／880)、1.82%(16／880)和7.95%(70／880),ADV与RSV(χ2=53.904,P=0.000)、FV(χ2=35.649,P=0.000)感染率差异均有显著性(均P<0.05),RSV与FV感染率无显著性差异(P>0.05)。0-3岁在RSV、FV、ADV感染肺炎患儿中分别占92.91%(839／903)、74.79%(181／242)和68.52%(505／737),是三种病毒共同的高峰感染年龄段。
4.4季节比较
春季住院肺炎患儿RSV、FA、ADV感染率分别为11.17%(496／4441)、2.21%(98／4441)和5.31%(236／4441),三种病毒感染率均有显著性差异(均为P=0.000<0.05)。夏季住院肺炎患儿RSV、FA、ADV感染率分别为6.32%(219／3464)、2.71%(94／3464)、5.98%(207／3464),RSV与FV(χ2=52.282,P=0.000)、ADV与FV(χ2=44.349,P=0.000)感染率差异均有显著性(均P<0.05),FV与ADV感染率无显著性差异(P>0.05)。秋季住院肺炎患儿RSV、FA、ADV感染率分别为3.54%(89／2512)、1.27%(32／2512)、5.73%(144／2512),三种病毒感染率均具有显著性差异(均为P=0.000<0.05)。冬季住院肺炎患儿RSV、FA、ADV感染率分别为5.57%(99／1778)、1.01%(18／1778)、8.44%(150／1778),三种病毒感染率均具有显著性差异(RSV与FV比较：χ2=57.937,P=0.000；RSV与ADV比较：χ2=11.263,P=0.001；FV与ADV比较：χ2=108.857,P=0.000)。RSV感染肺炎患儿春夏季占79.18%(715／903),FV感染肺炎患儿春夏季占79.34%(192／242),ADV感染肺炎患儿春夏季占60.11%(443/737),春夏季是三种病毒感染肺炎共同的高峰发病季节。
4.5年度比较
2005年住院肺炎患儿RSV、FA和ADV感染率分别为4.00%(148／3699)、0.54%(20／3699)和7.11%(263／3699),三种病毒两两间感染率均具有显著性差异(均P<0.05)。2006年住院肺炎患儿RSV、FV和ADV感染率分别为8.92%(400／4483)、3.30%(136／4483)和6.71%(301／4483),三种病毒感染率两两间比较均具有显著性差异(均P<0.05)。2007年住院肺炎患儿RSV、FV和ADV感染率分别为8.85%(355／4013)、2.14%(86／3927)和4.31%(173／4013),三种病毒感染率两两间比较均具有显著性差异(均P<0.05)。
4.6重症肺炎特征比较
RSV、FV和ADV感染肺炎患儿重症肺炎发生率分别为7.64%(69／903)、4.96%(12／242)和3.53%(26／737)。RSV和ADV感染重症肺炎发生率差异具有显著性(χ2=12.582,P=0.000),而RSV与FV、FV与ADV感染重症肺炎发生率差异不具有显著性(P>0.05)。RSV、FV和ADV重症肺炎患儿中0-3岁年龄段患儿所占比例分别为100%(69／69)、100%(12／12)和96.25%(25／26)。经过综合治疗,重症RSV感染肺炎患儿痊愈率98.55%(68／69),死亡率1.45%(1／69)；重症FV感染肺炎患儿痊愈率83.33%(10／12),死亡率16.67%(2／12)；重症ADV感染肺炎患儿中痊愈率88.46%(23／26),病情好转率11.54%(3／26),无死亡病例。
结论
本课题对2005-2007年广州儿童医院RSV、FV和ADV感染住院肺炎患儿临床特征进行分析及比较,结果表明：
1、RSV、FV和ADV均是住院肺炎患儿的常见病原,其感染率分别为7.40%、1.98%和6.04%,三种病毒中RSV是住院肺炎患儿中最常见的病原体。
2.男性住院肺炎患儿RSV、FV和ADV感染率分别为7.53%、2.08%和5.21%,三种病毒中RSV是男性住院肺炎患儿最常见的病原体。女性住院肺炎患儿RSV、FV和ADV感染率分别为7.12%、1.78%与7.92%,三种病毒中FV是女性肺炎患儿最少见的病原体。RSV、FV和ADV感染肺炎患儿男女之比分别为2.37：1、2.61：1和1.47：1,三种病毒感染肺炎患儿中男性患儿数量均多于女性患儿。
3.0-1岁住院肺炎患儿RSV、FV和ADV感染率分别为9.67%、1.40%和3.71%；1-3岁住院肺炎患儿RSV、FV和ADV感染率分别为6.81%、2.73%和7.99%；3-6岁住院肺炎患儿RSV、FV和ADV感染率分别为3.49%、2.76%和9.92%；6-14岁住院肺炎患儿RSV、FV和ADV感染率分别为0.80%、1.82%和7.95%。RSV是0-1岁年龄段住院肺炎患儿最常见的病原体,而ADV是3-6岁和6-14岁住院肺炎患儿最常见的病原体。RSV、FV、ADV感染肺炎患儿中0-3岁年龄段患儿分别占92.91%、74.79%和68.52%,0-3岁年龄段是三种病毒共同的高峰感染年龄段。
4.春季住院肺炎患儿RSV、FV和ADV感染率分别为11.17%、2.21%和5.31%；夏季住院肺炎患儿RSV、FV和ADV感染率分别为6.32%、2.71%和5.98%；秋季住院肺炎患儿RSV、FV和ADV感染率分别3.54%、1.27%和5.73%；冬季住院肺炎患儿RSV、FV和ADV感染率分别为5.57%、1.01%和8.44%。RSV是春季住院肺炎患儿最常见的病原体,而ADV是秋季和冬季住院肺炎患儿最常见的病原体。RSV、FV和ADV感染肺炎患儿中春夏季(3-8月)患儿分别占79.18%、79.34%和60.11%,春夏季节(3-8月)是三种病毒感染肺炎共同的高峰发病季节。
5.2005年RSV、FV和ADV感染率分别为4.00%、0.54%和7.11%；2006年RSV、FV和ADV感染率分别为8.92%、3.30%和6.71%；2007年RSV、FV和ADV感染率分别为8.85%、2.14%和4.31%。三种病毒中ADV是2005年住院肺炎患儿最常见的病原体,RSV是2006和2007年住院肺炎患儿中最常见的病原体。
6.RSV、FV、ADV三种病毒感染肺炎患儿重症肺炎发生率分别为7.64%、4.96%和3.53%。三种病毒感染重症肺炎发生的高危年龄段均为0-3岁。综合治疗对三种病毒感染重症肺炎患儿均有效。
总之,本研究提示,广州地区、RSV、FV及ADV感染肺炎患儿临床特征具有一定的地域独特性。广州地区儿童RSV、FV和ADV感染肺炎的重点防治对象均为0-3岁儿童尤其是男童、重点防治季节均为3-8月、要根据不同年度的病毒感染情况进行防治。对RSV、FV和ADV感染肺炎患儿中0-3岁年龄段患儿要防止其发展成重症肺炎,对重症肺炎患儿可进行综合治疗。研究成果可以为广州地区儿童RSV、FV和ADV感染肺炎的临床防治提供参考,具有实际的临床应用价值。
BACKGRANDS AND OBJECTIVES
Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years, and is responsible for about 19% of all deaths in children aged less than 5 years worldwide. There are about 21 million new childhood pneumonia episodes each year in China. Pneumonia is also the leading cause of mortality for Chinese children aged less than 5 years. Therefore it is important to strengthen the prevention and treatment of clinical pneumonia, espicallly of severe pneumonia in children, thus to reduce morbidity and mortality of childhood pneumonia.
RSV (Respiratory syncytial virus, RSV), influenza A virus (Influenza A virus, FV) and adenovirus (Adenovirus, ADV) are all common pathogen of childhood pneumonia. Childhood severe pneumonia can cause death, and may cause epidemic spread. But so far, there are limited effective treatments for childhood pneumonia infected with RSV, FV and ADV. It is considered that prevention is the key. This requires understanding clinical characteristics by sex, age, seasonal and annual distribution of children's RSV, FV and ADV infected pneumonia and clinical features of severe pneumonia of them, for children with RSV, FV and ADV virus pneumonia prevention and control of reference.
Previous studies showed that clinical features by sex, age, season and annual distribution of children with RSV, FV and ADV infection are different in different regions. Thus, the prevention and control work of childhood pneumonia infected with RSV, FV and ADV in different regions should be executed according to clinical features by sex, age, season, annual distribution and clinical features of severe pneumonia of the three viruses infected pneumonia children in regions themselves. Guangzhou is the same. However, there are few literatures about clinical features by sex, age, season, annual distribution and clinical features of severe pneumonia of the three viruses infected pneumonia children in Guangzhou, and there are no comparative literatures for them three in Guangzhou.
Based on the above background, clinical features of childhood pneumonia with RSV, FV and ADV infection in 12,195 cases of hospitalized pneumonia children in Guangzhou Children's Hospital in 2005-2007 were retrospectively analyzed and compared, thus to understand the clinical characteristics by sex, age, season, the annual distribution and severe pneumonia clinical features of RSV, FV and ADV pneumonia for hospitalized pneumonia children in Guangzhou, to provide reference for prevention and control work of hospitalized pneumonia children infected with the three viruses in Guangzhou.
METHODS
1. All the cases were from the hospitalized patients of Guangzhou children's hospital, the largest children's hospital of south China. All the cases selected from January 1st,2005,to December 31st,2007. The age of them were 0-14 years old (0
3.Clinical datas of sex, age, date of onset, hospitalized stay of RSV, FV and ADV infected hospitalized pneumonia children and severe pneumonia clinical datas of them were collected.
4. Statistic analyses were dealt with by SPSS13.0. Chi-square test was used to analysize the infection rate between different sex, different age, different season and different year. T-test or One-way ANOVA test were used to analyze the average of hospitalized stay of two or more groups. P<0.05 was indicated as significant difference.Mean was expressed as x±s.
RESULTS
The total pneumonia cases were 12,195, within them male were 8,432 and female were 3,763;within them 0-1(0
903 cases of RSV-IgM positive hospitalized pneumonia children were detected and the infection rate was 7.40%. The average hospitalized days of them were 7.87±3.44d.
1.1 Sex distribution
The infection rate between male(7.53%) and female (7.12%) had no significant difference(χ2=0.634, P=0.426>0.05).The average hospitalized days between them were also had no significance (P>0.05).
1.2 Age distribution
The infection rate of 0-1,1-3,3-6 and 6-14 years old was 9.67%、6.811%、3.49% and 0.80%,respectively. The infection rate between each two age stags had significantly difference(P<0.05).Cases of 0-3 years old occupied 92.03%. The average hospitalized days of 0-1 years old were longer than 3-6 and 6-14 years old(P <0.05),and those of 3-6 years old were longer than 6-14 years old.However, those between each two of the other age stages had no significantly difference (P>0.05).
1.3 Season distribution
The infection rate of spring, summer, autumn and winter was 11.17%、6.32%、3.54% and 5.57%, respectively. The infection rate of spring was significantly higher than that of summer, autumn and winter(P<0.05).Cases from March to August accounted for 79.18%. The average hospitalized days between each two of them had no significantly difference (P>0.05).
1.4 Year distribution
The RSV infection rate in 2005,2006 and 2007 were 4.00%,8.92% and 8.85%, respectively. The infection rate between 2005 and 2006(χ2=78.556,P=0.000), between 2005 and 2007 (χ2=74.113,P=0.000)were both significant(P<0.05),while infection rate between 2006 and 2007 had no significantly difference(P>0.05).The peak infected age stage in 2005,2006 and 2007 were all 0-3 years old, and the peak season in 2005,2006 and 2007 were all in spring and summer, Apil was the most peakest month. The average hospitalized days between each two of them had no significantly difference (P>0.05).
1.5 Severe pneumonia cases
There were 69 cases RSV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of RSV was 7.64%. Two cases of severe pneumonia children cases died.The average hospitalized days of the servere cases were significantly longer than the common cases(P<0.05)
2. Features of the influenza A virus infected pneumonia cases
242 cases of FV positive hospitalized pneumonia cases were detected and the infection rate was 1.98%.
2.1 Sex distribution
The difference of infection rate between male (2.08%) and female(1.78%) had no significance(χ2=1.164,P=0.281).The average hospitalized days between them had no significantly difference (P>0.05).
2.2 Age distribution
The infection rate of 0-lyears old, 1-3years old,3-6 years old and 6-14 years old was 1.40%,2.73%,2.76% and 1.82%, respectively. And the infection rate of 1-3 years old and 3-6 years old both were significantly different from that of the 0-1 years old(P<0.05). FV infected children for 0 to 3 years old occupied 74.79%. The average hospitalized days of 0-1 years old were longer than 3-6 and 6-14 years old (P<0.05), and those between each two of the other age stages had no significantly difference (P >0.05).
2.3 Season distribution
The infection rate of spring, summer, autumn and winter was 2.21%,2.71%, 1.27% and 1.01%,respectively. And the infection rate between spring and autum (χ2=7.609, P=0.006),between spring and winter (/=9.894, P=0.002),between summer and autumn (χ2=14.623,P=0.000),between summer and winte (χ2=16.263,P=0.000) were all had significantly difference(P<0.05). Cases of spring and summer occupied 79.34%.The average hospitalized days between each two of the seasons had no significantly difference (P>0.05).
2.4 Year distribution
FV Infected cases in 2005,2006 and 2007 were 20,136 and 86 cases, respectively. And the infection rate of 2005,2006 and 2007 were 0.54%,3.30% and 2.14%, respectively. The infection rate of 2005 was significantly less than 2006 and 2007 (χ2=67.349,P=0.000 and =34.456,P=0.000),the infection rate of 2006 was significantly higher than 2007(χ2=67.349,P=0.010).The peak infected age stage in 2005,2006 and 2007 were all 0-3 years old, and the peak season in 2005,2006 and 2007 were all in spring and summer.The average hospitalized days between each two of the years had no significantly difference (P>0.05).
2.5 Severe pneumonia cases
There were 12 cases of FV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of FV was 4.96%. One case of severe pneumonia children died. The average hospitalized days of the severe cases were longer than the common cases, while had no significantly difference (P>0.05).
3. Features of the adenovirus infected pneumonia cases
737 case for ADV-IgM positive of hospitalized pneumonia cases were detected and the total ADV infection rate was 6.04%.The average hospitalized days of them were 7.98±3.55d.
3.1 Sex distribution
The infection rate of female (7.92%) was significantly(P<0.05)higher than the infection rate of male (5.21%).The average hospitalized days between them had no significance (P>0.05).
3.2 Age distribution
The infection rate of 0-1、1-3、3-6 and 6-14 years old was 3.71%、7.99%、9.92% and 7.95%,respectively.Furthermore,the infection rate of 0-1 years old was significantly less than that of the other age stages(P<0.05),and the infection rate of 3-6 years old was significantly higher than that of all the other age stases(P<0.05) ADV infected pneumonia cases of 0-3 years old occupied 68.52%.The average hospitalized days of 0-1 years old were longer than 3-6 years old(P<0.05),and those between each two of the other age stages had no significant difference (P>0.05).
3.3 Season distribution
The infection rate of spring, summer, autumn and winter was 5.31%,5.98%, 5.73% and 8.44%, respectively. And the infection rate of winter is significantly higher than the infection rate of spring(χ2=21.262, P=0.000),summer (χ2=11.210,P=0.001)and autum(χ2=11.924,P=0.001).Cases from March to August accounted 60.11% of all the ADV infected cases.The average hospitalized days each two of the seasons had no significantly difference (P>0.05).
3.4 Year distribution
ADV infected hospitalized pneumonia cases in 2005,2006 and 2007 were 263 cases,301 cases and 173 cases, respectively. And the ADV infection rate of 2005, 2006 and 2007 were 7.11%,6.71% and 4.31%, respectively. Infection rate of 2007 was significantly less than that of 2005 and 2006. The peak age stage in 2005,2006 and 2007 were all 0-3 years old, while the peak months had some difference in different years. The average hospitalized days between each two of them had no significantly difference (P>0.05).
3.5 Severe pneumonia cases
There were 26 cases of ADV infected severe pneumonia cases from 2005 to 2007, and the severe pneumonia incidence rate of ADV was 3.53%.The average hospitalized days between the severe and the common pneumonia had no significantly difference (P>0.05).
4. Comparison of the three viruses infected pneumonia cases
4.1 Comparison as a whole
The differences of infection rate between each two of the viruses were significant (between RSV and FV:χ2=400.387,P=0.000;between RSV and ADV:χ2=18.014,P=0.000;between ADV and FV:χ2=260.747,P=0.000).
4.2 Comparison by Sex
The infected rates of the male of RSV, FV and ADV were 7.53%、2.08% and 5.21%,respectively.The infected rates of the female of RSV, FV and ADV were 7.12%.1.78% and 7.92%,respectively. The infected rates of the male between each two viruses had significantly difference:between RSV and FVχ2=274.415,P=0.000; RSV and ADV:χ2=38.202,P=0.000;ADV and FV:χ2=117.800,P=0.000).As for the female:between RSV and FV:χ2=126.218,P=0.000<0.05;between RSV and ADV:χ2=1.719,P=0.190>0.05;between ADV and FV:χ2=153.646,P=0.000<0.05.
4.3 Comparison by age
For children of 0-1 years old, the infection rate of RSV、FV and was ADV 9.67%、8.71% and 1.40%,respectively, each of two of them had significant difference (P<0.05).For children of 1-3 years old, the infection rate of RSV、FV and was 6.81%,7.99% and 2.73%,respectively, and the infection rate between RSV and ADV (χ2=62.429,P=0.000)、between FV and ADV(χ2=92.755,P=0.000)were both had significant difference(P<0.05).For children of 3-6 years old, the infection rate of RSV、FV and ADV was 3.49%,9.92% and 2.76%,respectively, and the infection rate between FV and RSV(χ2=53.961,P=0.000)、between FV and ADV(χ2=70.605, P=0.000)were both had significant difference(P<0.05).For children of 6-14 years old, the infection rate of RSV、FV and ADV was 0.80%、1.82% and 7.95%,respectively. The infection rate between ADV and RSV(χ2=53.904, P=0.000)、between ADV and FV(χ2=35.649,P=0.000)were both had significant difference(P<0.05).All of the most prevalent infected age of RSV, FV and ADV were 0-3 years old.
4.4 Comparison by year
The infection rate of RSV, FV and ADV in 2005 were 4.00%,0.54% and 7.11%,respectivey, each two of them had significantly difference(P<0.05).The infection rate of RSV, FV and ADV in 2006 were 8.92%,3.30% and 6.71%, respectivey,each two of them had significantly difference(P<0.05). The infection rate of RSV, FV and ADV in 2007 were 8.85%,2.14% and 4.31%,respectivey,each two of them had significantly difference(P<0.05)
4.5 Comparison by season
The infection rate for RSV、FV and ADV in spring was 11.17%、2.21% and 5.31%,respectively,each two of them had significant difference(between RSV and FV:χ2=285.786, P=0.000;between RSV and ADV:χ2=100.644, P=0.000;between ADV and FV:χ2=59.246,P=0.000. The infection rate of RSV、FV and ADV in summer was 6.32%,2.71% and 5.98%,respectively. And the infection rate between RSV and FV(χ2=52.282,P=0.000)、ADV and FV(χ2=44.349,P=0.000)both had signifficant difference(P<0.05).The infection rate of RSV,FV and ADV in autumn was 3.54%，1.27% and 5.73%,respectively. Each of them had significant difference (RSV and FV:χ2=27.514,P=0.000; RSV and ADV:χ2=13.614,P=0.000;FV and ADV:χ2=73.860,P=0.000;The infection rate of RSV、FV and ADV in winter was 5.57%,1.01% and 8.44%,respectively, each of them had significant difference(RSV and FV:χ2=57.937,P=0.000;RSV and ADV:χ2=11.263, P=0.001;FV and ADV:χ2=108.857,P=0.000).5)The infection rate of RSV、FV and ADV in 2005 was 4.00%,0.54% and 7.11%,respectively; in 2006 was 8.92%,3.30% and 6.71%,respectively; in 2007 was 8.85%、2.14% and 4.31%,respectively.Each of them in the three years were different significantly(P<0.05).
4.6 Comparison by the severe cases
Severe pneumonia incidence rates of RSV, FV and ADV were 7.64%,4.96% and 3.53%,respectively. Severe pneumonia incidence rates between RSV and ADV had significantly difference (χ2=12.582, P=0.000), while which between RSV and FV, between FV and ADV had no significantly difference (P> 0.05). As for RSV, FV and ADV, severe pneumonia in children aged 0-3 were 100%,100% and 96.15%, respectively. Comprehensive treatments with antibiotics, ribavirin, inhaled bronchodilators, systemic hormones, intravenous immunoglobulin and mechanical ventilatory support had good therapeutic effect to severe RSV, FV and ADV infected hospitalized pneumonia children.
CONCLUSIONS
Clinical features of RSV、FV and ADV infected hospitalized pneumonia children in Guangzhou Children's Hospital in 2005-2007 were analyzed in this paper, results were as follows:
1.RSV, FV, and ADV were all common pathogens of hospitalized pneumonia children,and RSV-was the most common pneumonia cause of the three viruses.
2.Infection rates of the male of RSV, FV and ADV pneumonia cases were 7.53%,2.08% and 5.21%,respectively. For female of them were 7.12%,1.78% and 7.92%, respectively. RSV was the most important pneumonia causes of the three viruses for the male, and FV was the least important pneumonia causes of the three viruses for the female. Male to female ratio of RSV, FV and ADV pneumonia cases were 2.37:1,2.61:1 and 1.47:1,respectively.For three of them, the male cases were all more than the female.
3.RSV was the most common causes in 0-1 age stages of the three viruses, and ADV were the most common causes in 3-6 and 6-14 age stages. Pneumonia case of 0-3 years old occupied 92.91%,74.79% and 68.52% of all the RSV, FV and ADV cases, respectively, were the common peak infected age stages for all of the three viruses.
4. RSV was the most common causes in spring of the three viruses, and ADV were the most common causes in autumn and winter. Pneumonia cases in spring and summer occupied 79.18%,79.34% and 60.11% cases of RSV, FV and ADV pneumonia cases, respectively, were the common peak seasons for the three viruses.
5.RSV was the most common causes in spring of the three viruses in 2006 and 2007, however, ADV were the most common causes in 2005.
6. Severe pneumonia cases incidence rates of RSV, FV and ADV were 7.64%、4.96% and 3.53%,respectively. Cases of 0-3 years old occupied 100%,100% and 96.25% of severe pneumonia cases of RSV, FV and ADV infected pneumonia cases, respectively. Complex treat had functions to RSV, FV and ADV infected pneumonia cases.
In conclusion, this study suggests that prevention and therapy works for RSV, FV and ADV infected childhood pneumonia in Guangzhou should be focused on age stage of 0-3 years old, particularly boys; and should also be focused on seasons of March-August and be adjusted in different years to the epidemic circumstances of the year. Severe pneumonia cases caused by the three viruses musted mostly in 0-3 year old children and these severe pneumonia cases should be complex treated.
引文
[1]Rudan I,Boschi Pinto C,Biloglav Z,et al. Epidemiology and etiology of childhood pneumonia[J].Bull World Health Organ,2008,86(5):408-416.
[2]沈晓明,王卫平主编.儿科学第7版[M],人民卫生出版社：272-281.
[3]Meury S,Zeller S,Heininger U. Comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents[J].Eur J Pediatr,2004,163(7):359-363.
[4]Fouchief R,Munster AM,Wallensten V,et al. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls[J].J Virol,2005,79:2814-2822.
[5]Jong JC,Wermenbol AG,Verweijj-Uijterwaal MW,et al.Adenoviruses from human immunodeficiency virus-infected individuals,including two strains that represent new candidate serotypes Ad50 and Ad51 of species B1 and D,respectively[J].J Clin Microbiol,1999,37(12):3940-3945.
[6]Tchatalbachev S,Flick R, Hobom G.The packaging signal of influenza viral RNA molecules[J].RNA,2001,7(7):979-989.
[7]龙智钢,刘运芝,张烨,等.湖南省2004年流感病毒优势流行毒株甲3亚型基因特性分析[J].中国卫生检验杂志,2006,16(2)：164-166.
[8]Barrera CA,Reyes-Teran G Influenza:Forecast for a Pandemic[J].Archives of Medical Research,2005,36(6):628-636.
[9]常敏.腺病毒感染与多脏器损伤[J].现代中西医结合杂志,2006,15(1)：66-67.
[10]Corsello G,Di Carlo P,Salsa L,et al. Respiratory syncytial virus infection in a Sicilian pediatric population:risk factors,epidemiology,and severity[J].Allergy Asthma Proc,2008,29(2):205-210.
[11]Mlinaric-Galinovic QWelliver RC,et al. The biennial cycle of respiratory syncytial virus outbreaks in Croatia[J].Virol J,2008,28(5):18.
[12]Nokes DJ,Ngama M,Bett A,et al.Incidence and severity of respiratory syncytial virus pneumonia in rural Kenyan children identified through hospital surveillance[J].Clin Infect Dis,2009,49(9):1341-1349.
[13]Simmerman JM,Chitttaganpitch M,Levy J,et al.Incidence,seasonality and mortality associated with influenza pneumonia in Thailand:2005-2008[J].PloS One,2009,4(11):e7776.
[14]Brooks WA,Goswami D,Rahman M, et al.Influenza is a major contributor to childhood pneumonia in a tropical developing country. Pediatr Infect Dis J, 2010,29(3):216-221.
[15]Samransamruajkit R,Hiranrat T,Chieochansin T,Sritippayawan S,et al. Prevalence,clinical presentations and complications among hospitalized children with influenza pneumonia[J].Jpn J Infect Dis,2008,61(6):446-449.
[16]Ou ZY,Zeng QY,Wang FH,et al.Retrospective study of adenovirus in autopsied pulmonary tissue of pediatric fatal pneumonia in south China[J].BMC Infect Dis,2008,21(8):122.
[17]谢健屏,常汝虚,何翠娟,等.1978-1996年广州地区呼吸道合胞病毒感染分析[J].中华儿科杂志,1997,35(8)：402-404.
[18]谢健屏,赖桂香,陈正珊,等.广州地区1998-2003年儿童流行性感冒病毒检测分析[J].实用儿科临床杂志,2005,20(10)：980-982.
[19]谢健屏,赖桂香,何翠娟,等.1998-2002年广州地区儿童流感病毒检测与分析[J].中华儿科杂志,2002,40(9)：530-532.
[20]李静,麦贤弟,陈环等.儿童腺病毒感染的临床分析—附124例分析报告[J].新医学,2006,37(3)：169-170.
[21]余嘉璐,邓力,张建涛,等.腺病毒3型感染489例临床分析[J].中国实用 儿科杂志,2009,24(12)：957-958.
[22]RSV肺炎220例临床分析[J].周卫芳,季伟.苏州大学学报(医学版),2008,28(1)：159-160.
[23]Snow A,Dayyat E,Montgomery-Downs He,et al.Pediatric obstructive sleep apnea:a potential late consequence of respiratory syncytial virus bronchiolitis[J].Pediatr Pulmonol,2009,44(12):1186-1191.
[24]顾勇,姚泽忠.231例婴儿呼吸道合胞病毒性肺炎血清心肌酶分析[J].浙江实用医学,2007,12(1)：28-29.
[25]Cassimos DC,Tsalkidis A, TripsianisGA, et al.Asihma, lung function and sensitization in school children with a history of bronchiolitis[J].Pediatr Int,2008,50(1):51-56.
[26]Perez-Yarza EQMoreno A,Lazaro P, et al.The association between respiratory syncytial virus infection and the development of childhood asthma:a systematic review of the literature[J].Pediatr Infect Dis J,2007,26(8):733-739.
[27]刘国荣,申昆玲,江载芳,等.北京地区呼吸道合胞病毒感染的临床特点[J].实用儿科临床杂志,2002,17(3)：177-179.
[28]张学兰,朱雪明,季伟,等.婴幼儿呼吸道合胞病毒感染特点及支气管肺炎细胞免疫等指标的变化[J].实用儿科临床杂志,2003,18(9)：717-718.
[29]万诚,颜胜宇,郑钢.112例呼吸道合胞病毒下呼吸道感染临床特征分析[J].浙江临床医学.2008,8(4)：396--397.
[30]尹月英,尹志宏,王史远,等.儿童呼吸道合胞病毒肺炎流行特征分析[J].疾病监测,2007,22(1)：40-43.
[31]江远长.小儿呼吸道合胞病毒感染分析[J].临床和实验医学杂志,2006,5(5：544-545.
[32]仲玉强,曹海霞.2003年.2005年青海地区支气管肺炎患儿呼吸道合胞病毒的流行特点分析[J].青海医药杂志,2007,37(5)：32-33.
[33]郑季彦,李海峰,汤宏峰.小儿呼吸道合胞病毒感染的肝脏损害[J].浙江 预防医学,2005,17(10)：48-50.
[34]吴小青,伍严安,曾秀雅,等.福州地区急性呼吸道感染患儿呼吸道合胞病毒检测及亚型分析[J].实用医学杂志,2008,24(1)：50-52.
[35]赵明波,吴澄清,赵波.昆明地区小儿急性下呼吸道合胞病毒感染的临床研究[J].中国实用儿科杂志,2008,23(1)：34-36.
[36]Centers for Disease Control and Prevention (CDC).Brief report:respiratory syncytial virus activity--United States,July 2006-November 2007[J].MMWR Morb Mortal Wkly Rep,2007,56(48):1263-1265.
[37]Medici MC,Arcangeltti MC,Merolla R, et al. Incidence of respiratory syncytial virus infection in infants and young children referred to the emergency departments for lower respiratory tract diseases in Italy[J].Acta Biomed, 2004,75(1):26-33.
[38]Calegari T,Queiroz DA,Yokosawa J, et al. Clinical-epidemiological evaluation of respiratory syncytial virus infection in children attended in a public hospital in midwestern Brazil[J].Braz J Infect Dis,2005,9(2):156-161.
[39]芝敏,刘涌,张斌,等.住院呼吸道感染儿童呼吸道合胞病毒与腺病毒感染的调查[J].中国儿童保健杂志,2008,16(2)：247-248.
[40]Robinson RF.Impact of respiratory syncytial virus in the United States[J].Am J Health Syst Pharm,2008,65(8):3-6.
[41]Light M,Bauman J,Mavunda K, et al. Correlation between respiratory syncytial virus (RSV) test data and hospitalization of children for RSV lower respiratory tract illness in Florida[J].Pediatr Infect Dis J,2008,27(6):512-518.
[42]谢健屏,何翠娟,赖桂香,等.儿童呼吸道感染临床病毒学研究[J].现代临床学生物工程学杂志,2001,7(4)：259-260.
[43]谢健屏,常汝虚,张美德,等.从尸解肺组织分离呼吸道合胞病毒2例分析[J].中华实验和临床病毒学杂志,1994,(1)：79.
[44]中华医学会儿科学分会呼吸学组,《中华儿科杂志》编辑委员会.儿童社区获得性肺炎管理指南(试行)(上)[J].中华儿科杂志,2007,45：8390.
[45]Stensballe LG,Kofoed PE,Nantes EJ,et al.Duration of secretory IgM and IgA antibodies to respirtory syncytial virus in a community study in Guinea-Bissau[J].Acta Paediatr,2000,89(4):421-426.
[46]王光亮,吴雪梅,宋晓南,等.病毒IgM抗体及细胞学检测对病毒性脑炎的诊断价值[J].中风与神经疾病杂志,2008,24(6)：704-706.
[47]阳隽,黄海鹭,徐军,等.广州地区呼吸道合胞病毒分离株G蛋白基因序列分析[J].广东医学,2003,24(6)：580-582.
[48]Nagayama Y,Tsubaki T,Sawada K, et al. Age and sex as factors of response to RSV infections among those with previous history of wheezing[J].Pediatr Allergy Immunol,2006,17(5):376-381.
[49]Jensen-Fangel,Mohey R,Johnsen SP,et al.Gender differences in hospitalization rates for respiratory tract infections in Danish youth[J].Scand J Infect Dis,2004,36(1):31-36.
[50]吴福玲,宋秀凤,李营营,等.不同年龄患儿对呼吸道合胞病毒感染的免疫反应[J].滨州医学院学报,2009,29(5)：353-354,367.
[51]Chen ZM,Mao JH,Du LZ,et al.Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection[J].Acta Paediatr,2002,91(9):914-922.
[52]Vieira SE,Gilio AE,Durigon EL,et al. Lower respiratory tract infection caused by respiratory syncytial virus in infants:the role played by specific antibodies [J].Clinics,2007,62(6):709-716.
[53]Corsello G,Di Carlo P,Salsa L,et al.Respiratory syncytial virus infection in a Sicilian pediatric population:risk factors,epidemiology,and severity[J].Allergy Asthma Porc,2008,29(2):205-210.
[54]张明智,王立波,陆爱珍,等.IFNγCA重复序列多态性与呼吸道合胞病毒毛细支气管炎易感性的关系[J].临床儿科杂志,2008,26(1)：16-19.
[55]Puthothu B,Krueger M,Forster J, et al.Interleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory syncytial virus infection[J].Pediatr Infect Dis J,2007,26(12):1094-1098.
[56]Aurivillius M,Oymar K,Oxelius VA. Immunoglobulin heavy G2 chain(IGHG2) gene restriction in the development of severe respiratory syncytial virus infection[J].Acta Paediatr,2005,94(4):414-418.
[57]Tasker RC,Roe MF,Bloxham DM, et al. The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy[J]. Intensive Care Med,2004,30(12):2257
[58]Lai SH,Stein DA,Guerero-Plata A, et al.Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice[J].Mol Ther, 2008,16(6):1120-1128.
[59]Prodhan P,Westra SJ,Lin J,et al.Chest radiological patterns predict the duration of mechanical ventilation in children with RSV infection[J].Pediatr Radiol,2009,39(2):117-123.
[60]Chavez-Bueno S,Mejias A,Merryman RA,et al.Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients[J].Pediatr Infect Dis J.2007,26(12):1089-1093.
[61]Tahan F,Ozcan A,Koc N. Clarithromycin in the treatment of RSV bronchiolitis:a double-blind,randomised,placebo-controlled trial[J].Europe Respiratory J,2007,29(1):91-97.
[62]Morris SK,Dzolganovski B,Beyene J,et al.A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection[J].BMC Infect Dis,2009,9:106.
[63]Numata M,Chu HW,Dakhama A,et al.Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection[J].Proc Natl Acad Sci USA,2010,107(1):320-325.
[64]Thorburn K,Harigopal S,Reddy V,et al.High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV)bronchiolitis[J].Thorax,2006,61(7):611-5.
[65]Ohba K,Yoshida S,Dewan Z,et al. Mutant influenza A virus nucleoprotein is preferentially localized in the cytoplasm and its immunization in mice shows higher immunogenicity and cross-reactivity[J].Vaccine,2007, 25(21):4291-4300.
[66]Sawada T,Hashimoto T, Nakano H,et al. Influenza viral hemagglutinin complicated shape is advantageous to its binding affinity for sialosaccharide receptor[J].Biochemical and Biophysical Research Communications,2007, 355(1):6-9.
[67]John Watkins. Influenza:burden of disease in childhood[C].International Congress Series 1263,2004:263-266.
[68]陈焕辉,陈翊,刘晓敏,等.广州地区婴幼儿非细菌性下呼吸道感染病原研究[J].现代临床医学生物工程学杂志,2004,10(6)：474-475.
[69]Schrag S,Shay DK,Gershman K,et al. Multistate surveillance for laboratory-confirmed,influenza-associated hospitalizations in children: 2003-2004[J].Pediatr Infect Dis J,2006,25(5):395-400.
[70]中华医学会呼吸病学分会.流行性感冒临床诊断和治疗指南(2004年修订稿)[J].中华结核和呼吸杂志.2005,28(1)：5-9.
[71]Schrag S,Shay DK,Gershman K,et al. Multistate surveillance for laboratory-confirmed,influenza-associated hospitalizations in children: 2003-2004[J].Pediatr Infect Dis J,2006,25(5):395-400.
[72]Nicholson KG,Teresa MB,Silverman MB,et al. Rates of hospitalisation for influenza, respiratory syncytial virus and human metapneumovirus among infants and young children[J].Zambonc Vaccine 24.2006,102-108.
[73]Xiao H,Lu SH,Ou Q,et al.Hospitalizeed patients with novel influenza A (H1N1)virus infection:Shanghai,June-July 2009.Chin Med J,2010, 123(4):401-405.
[74]Bren L. Influenza:vaccination still the best protection[J].FDA Consum, 2006,40(5):12-19.
[75]Epstein SL,Kong WP,Misplon JA,et al. Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein[J]. Vaccine,2005,23(46-47):5404-5410.
[76]Wright PF,Sannella E,Shi JR,et al. Antibody responses after inactivated influenza vaccine in young children[J].Pediatr Infect Dis J,2008 27(11):1004-1008.
[77]Halasa NB,Gerber MA,Chen Q,et al.Safety and immunogenicity of tribalent inactivated influenza vaccine in infants[J].J Infect Dis,2008, 197(10):1448-1454.
[78]Anatoly N. Slepushkin,Elena BI,et al. Influenza morbidity and some peculiarities of antiinfluenza immunity and prevention during influenza pandemics[J].International Congress Series 1263,2004,787-790.
[79]Nguyenv HH,Zemlin M,Ivanov II,et al. Heterosubtypic Immunity to Influenza A Virus Infection Requires a Properly Diversified Antibody Repertoire[J].J Virol,2007,81(17):9331-9338.
[80]Yuichi H,Muramatsu M,Shibata T,et al.Unmutated immunoglobulin M can protect micefrom death by influenza virus infection[J].J E Med,2004, 197(12):1779-1785.
[81]郭元吉,郭忠明.我国流感监测(1990-1993)[J].中华实验和临床病毒学志,1994,8(1)：11-15.
[82]梁爽,怀清杰,谷鸿喜,等.哈尔滨市2006-2007年度儿童流行性感冒监测结果分析[J].中国自然医学杂志,2008,10(1)：51-52.
[83]于伟,姚文清,张眉眉,等.辽宁省儿童流行性感冒病原学检测分析[J].中国公共卫生,2007,23(5)：547.
[84]朱大方,祖荣强,潘浩,等.江苏省2004-2007年流行性感冒监测分析[J].中国公共卫生2008,24(2)：232-234.
[85]逯建华,程小雯,何建凡,等.深圳市2006年流行性感冒流行特征分析[J].疾病控制杂志,2008,12(1)：33-36.
[86]张静,陈遂,徐淑娟,等.我院2004-2006年门诊病人流行性感冒监测结果分析[J].江西医学院学报,2008,48(1)：74-75.
[87]Simmerman JM,Chitttaganpitch M,Levy J,et al.Incidence,seasonality and mortality associated with influenza pneumonia in Thailand:2005-2008[J].PloS One,2009,4(11):e7776.
[88]张欣,倪汉忠,邓爱萍,等.2006年广东省流感病毒流行的分子基础[J].热带医学杂志,2007,7(6)：525-527.
[89]Baya A,Etlik AF,Arslan H,et al. Radiological and clinical course of pneumonia in patients with avian influenza H5N1[J].European Journal of Radiology,2007,61:245-250.
[90]Phipps LP,Essen SC,Brown IH. Genetic subtyping of influenza A viruses using RT-PCR with a single set of primers based on conserved sequences within the HA2 coding region. Journal of Viro Methods[J],2004, 122(1):119-122.
[91]朱汝南,钱渊,王芳,等.分子生物学方法在儿童流行性感冒监测中的应用[J].中华流行病学杂志,2003,24(1)：9-14.
[92]Xie ZX,Pang YS,Liu JB,et al. A multiplex RT-PCR for detection of type A influenza virus and differentiation of avian H5,H7,and H9 hemagglutinin subtypes[J].Molecular and Cellular Probes,2006,20(3-4):245-249.
[93]Minosse C,Selleri M,Zaniratti MS,et al. Improved detection of human influenza A and B viruses in respiratory tract specimens by hemi-nested PCR[J].Journal of Virological Methods,2007,141(2):225-228.
[94]温秋芳,孙晓强,吴忠兰,等.全国流感监测网络宁夏监测点2007-2008年度流行性感冒监测结果分析.宁夏医学杂志,2008,30(11)：1045-1046.
[95]梅玉发,赵国兵,王建平,等.2004-2007年十堰市流行性感冒监测结果分析.疾病监测,2008,11：682-684.
[96]曾照丽,白瑞婷,张晓熙.北京市朝阳区2005-2006年流感病原学监测分析.现代预防医学,2007,22：4356-4357.
[97]毛晓健,钱新华,曾其毅,等.2005-2006年广州地区儿童甲型流行性感冒病毒感染情况[J].实用儿科临床杂志,2008,23(10)：733-735.
[98]Chiu SS,Chan KH,Chen H, et al.Virologically confirmed population-based burden of hospitalized caused by influenza A and B among children in Hong Kong[J].Clin Infect Dis,2009,49(7):1016-1021.
[99]Wutzler P,Schmidt-Ott R, Hoyer H,et al.Prevalence of influenza A and B antibodies in pregnant women and their offspring.J Clin Virol,2009, 46(2):161-164.
[100]Hwang SD,Shin JS,Ku KB,et al.Protection of pregnant mice,fetuses and neonates from lethality of H5N1 influenza viruses by maternal vaccination[J].Vaccine,2010 Feb 25.[Epub ahead of print]
[101]李威,宋艳玲,王长科.甲型H1N1流感在美国传播期和墨西哥爆发期的气象条件与中国初夏气候特点的相似分析[J].科技导报,2009,27(11)：19-22.
[102]曲东,任晓旭,王菲,等.甲型H1N1流感危重患儿5例临床特点分析[J].中国实用儿科杂志,2009,12：923-925.
[103]Sugaya N. Influenza-associated encephalopathy in Japan[J].Seminars in Pediatric Infection Disease,2002,13:79-84.
[104]Karen LK,Shu Y Lam,Tak L Que,et al. Influenza A and Febrile Seizures in Childhood[J].Pediatr Neurol,2006,35(6):395-399.
[105]Newland JG,Laurich VN,Rosenquist AW,et al. Neurologic complications in children hospitalized with influenza:characteristics,incidence,and risk factors[J].J Pediatr,2007,150(3):306-310.
[106]Sivadon-Tardy V,Orlikowski D,Porcher R,et al. Guillain-Barre syndrome and influenza virus infection[J].Clin Infect Dis,2009,48(1):48-56.
[107]Mizuguchi M,Yamanouchi H,Ichiyama T,et al. Acute encephalopathy associated with influenza and other viral infections[J].Acta Neurol Scand, 2007,115(186):45-56.
[108]Hernandez E,Ramisse F,Lhonneux A,et al. Compared protective effect of nasal immunoprophylaxis using a new human monoclonal IgM antibody, human polyclonal antibodies,F(ab')2,amantadine,and zanamivir for prophylaxis of influenza A virus pneumonia in mice[J].Mil Med,2003, 168(3):246-251.
[109]Manxin Z,Darya Z,Krystyna M,et al.Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus[J].Molecular Immunology,2006,43:2195-2206.
[110]Ascione A,Capecchi B,Campetelli L,Lmperiale V,et al.Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1[J].Antiviral Res,2009,83(3):238-244.
[111]Lewis PF,Schmidt MA,Lu X,et al.A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14[J]J Infect Dis, 2009,199(10):1427-1434.
[112]Centers for Disease Control and Prevention(CDC).Outbreak of adenovirus 14 respiratory illness-Prince of Wales Island,Alaska,2008[J].MMWR Morb Mortal Wkly Rep,2010,59(1):6-10.
[113]Lee JA,Kim NH,Kim S J,et al.Rapid identification of human adenovirus types 3 and 7 from respiratory specimens via multiplex type-specific PCR [J]. J Clin Microbiol,2005,43(11):5509-5514.
[114]Wong S,Pabbaraju K,Pang XL,et al.Detection of a broad range of human adenoviruses in respiratory tract samples using a sensitive multiplex real-time PCR assay[J].J Med Virol,2008,80(5):856-865.
[115]Gray GC,McCarthy T,Lebeck MG,et al.Genotype prevalence and risk factors for severe clinical adenovirus infection,United States 2004-2006[J].Clin Infect Dis,2007,45(9):1120-1131.
[116]Baure U,Fllwker G,Bruss K,et al. Detection of antibodies against adenovirus protein IX,fiber,and hexon in human sera by immunoblot assay[J].J ClinMicrobiol,2005,43(9):4426-4433.
[117]Moro MR,Bonville CA,Suryadevara M,et al.Clinical features,adenovirus types,and local production of inflammatory mediators in adenovirus infections.Pediatr Infect Dis J,2009,28(5):376-380.
[118]杨祖钦,周晓聪,李昌崇,等.儿童呼吸道腺病毒感染50例诊治分析[J].浙江临床医学,2008,10(2)：175-176.
[119]Vaideewar P,Bavdekar SB,Jadhav SM,et al.Necrotizing adenoviral pneumonia:manifestation of nosocomial infection in pediatric intensive care unit[J].Indian J Pediatr,2008,75(11):1171-1174.
[120]范丽萍,张学兰,孙惠泉,等.苏州地区呼吸道感染住院患儿腺病毒感染分析[J].临床儿科杂志,2008,26(10)：866-868.
[121]张辉,刘春艳,王燕,等.北京儿童医院下呼吸道感染住院患儿血清腺病毒抗体检测分析[J].中华流行病学杂志,2007,28(7)：686-687.
[122]Hsieh WY,Chiu NC,Chi H,et al. Respiratory adenoviral infections in Taiwanese children:a hospital-based study[J].J Microbiol Immunol Infect, 2009,42(5):371-377.
[123]Lin YC,Lin KH,Ke GM,et al.Secular trend of genome types of respiratory adenovirus type 3 during 1983-2005:a study from Taiwan[J].Arch Virol,2010, 155(2):287-292.
[124]Chen HL,Chiou SS,Hsiao HP,et al.Respiratory adenoviral infections in children:a study of hospitalized cases in southern Taiwan in 2001-2002[J].J Trop Pediatr,2004,50(5):279-284.
[125]Zhang Q,Su X,Gong S,et al. Comparative genomic analysis of two strains of human adenovirus type 3 isolated from children with acute respiratory infection in southern China[J].J Gen Virol,2006,87(6):1531-1541.
[126]Murtagh P,Giubergia V,Viale D,et al.Lower respiratory infections by adenovirus in children. Clinical features and risk factors for bronchiolitis obliterans and mortality[J].Pediatr Pulmonol,2009,44(5):450-456.
[127]Chiu CY,Wong KS,Huang YC,et al.Bronchiolitis boliterans in children:clinical presentation,therapy and long-term follow-up[J].J Paediatr Child Health,2008,44(3):129-133.
[128]Hatherill M, Levin M, Lawrenson J,et al. Evolution of an adenovirus outbreak in a multidisciplinary children's hospital[J].J Paediatr Child Health. 2004,40(8):449-454.
[129]祝国红,王财富,陈志敏.腺病毒肺炎50例临床分析[J].实用儿科临床杂志,2002,17(5)：534-535.
[130]Bourgeois FT,Valim C,Wei JC.Influenza and other respiratory virus-related emergency department visits among young children[J].Pediatrics,2006, 118(1):1-8.
[131]Fabbiani M,Terrosi C, Martorelli B,et al.Epidemiological and clinical study of viral respiratory tract infections in children from Italy[J].J Med Virol,2009, 81(4):750-756.
[132]Schanzer DL,Langley JM,Tam TW.Hospitalization attributable to influenza and other viral respiratory illnesses in Canadian children[J].Pediatr Infect Dis J,2006,25(9):795-800.
[133]Zhang HY,Li ZM,Zhang GL,et al.Respiratory viruses in hospitalized children with acute lower respiratory tract infections in harbin,China[J].Jpn J Infect Dis,2009,62(6):458-460.
[134]Melendi GA,Laham FR,Monsalvo AC,et al.Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus,or influenza virus in infans[J].Pediatrics,2007, 120(2):410-415.
[135]Byeon JH,Lee JC,Choi IS,et al.Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections[J].Acta Paediatr,2009,98(4):725-730.
[136]Tang LF,Wang TL,Tang HF,et al.Viral pathogens of acute lower respiratory tract infection in China[J].Indian Pediatr,2008,45(12):971-975.
[137]Sung RY,Chan PK,Tsen T,et al.Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays[J].J Med Virol,2009,81(1):153-159.
[138]Lopez PG,Morfin Maciel BM,et al.Identification of influenza,parainfluenza, adenovirus and respiratory syncytial virus during rhinopharyngitis in a group of Mexican children with asthma and wheezing[J].Rev Alerg Mex,2009, 56(3):86-91.
[139]Farshad N,Saffar MJ,Khalilian AR,et al.Respiratory viruses in hospitalized children with acute lower respiratory tract infections,Mazandaran Province, Iran[J].Indian Pediatr,2008,45(7):590-592.
[140]Palomino MA,Larranaga C,Villagra E,et al.Adenovirus and respiratory sync, ytial virus-adenovirus mixed acute lower respiratory infections in Chilean infants[J].Pediatr Infect Dis J,2004,23(4):337-341.
[141]Gilla G,OnateE,Perez-Yarza EG,et al.Viruses in community-acquiared pneumonia in children aged less than 3 years old:high rate of viral coinfection[J].J Med Virol,2008,80(10):1843-1849.
[142]Ei Sayed Zaki M,Goda T.Clinico-pathological study of atypical pathogens in community-acquired pneumonia:a prospective study[J].J Infect Dev Ctries, 2009,3(3):199-205.
[143]Tie K,Lodha R,Pandey RM,et al.Factors determining the outcome of children hospitalized with severe pneumonia[J].BMC Pediatr,2009,9-15.
[2]沈晓明,王卫平主编.儿科学第7版[M],人民卫生出版社：272-281.
[3]Meury S,Zeller S,Heininger U. Comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents[J].Eur J Pediatr,2004,163(7):359-363.
[4]Fouchief R,Munster AM,Wallensten V,et al. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls[J].J Virol,2005,79:2814-2822.
[5]Jong JC,Wermenbol AG,Verweijj-Uijterwaal MW,et al.Adenoviruses from human immunodeficiency virus-infected individuals,including two strains that represent new candidate serotypes Ad50 and Ad51 of species B1 and D,respectively[J].J Clin Microbiol,1999,37(12):3940-3945.
[6]Tchatalbachev S,Flick R, Hobom G.The packaging signal of influenza viral RNA molecules[J].RNA,2001,7(7):979-989.
[7]龙智钢,刘运芝,张烨,等.湖南省2004年流感病毒优势流行毒株甲3亚型基因特性分析[J].中国卫生检验杂志,2006,16(2)：164-166.
[8]Barrera CA,Reyes-Teran G Influenza:Forecast for a Pandemic[J].Archives of Medical Research,2005,36(6):628-636.
[9]常敏.腺病毒感染与多脏器损伤[J].现代中西医结合杂志,2006,15(1)：66-67.
[10]Corsello G,Di Carlo P,Salsa L,et al. Respiratory syncytial virus infection in a Sicilian pediatric population:risk factors,epidemiology,and severity[J].Allergy Asthma Proc,2008,29(2):205-210.
[11]Mlinaric-Galinovic QWelliver RC,et al. The biennial cycle of respiratory syncytial virus outbreaks in Croatia[J].Virol J,2008,28(5):18.
[12]Nokes DJ,Ngama M,Bett A,et al.Incidence and severity of respiratory syncytial virus pneumonia in rural Kenyan children identified through hospital surveillance[J].Clin Infect Dis,2009,49(9):1341-1349.
[13]Simmerman JM,Chitttaganpitch M,Levy J,et al.Incidence,seasonality and mortality associated with influenza pneumonia in Thailand:2005-2008[J].PloS One,2009,4(11):e7776.
[14]Brooks WA,Goswami D,Rahman M, et al.Influenza is a major contributor to childhood pneumonia in a tropical developing country. Pediatr Infect Dis J, 2010,29(3):216-221.
[15]Samransamruajkit R,Hiranrat T,Chieochansin T,Sritippayawan S,et al. Prevalence,clinical presentations and complications among hospitalized children with influenza pneumonia[J].Jpn J Infect Dis,2008,61(6):446-449.
[16]Ou ZY,Zeng QY,Wang FH,et al.Retrospective study of adenovirus in autopsied pulmonary tissue of pediatric fatal pneumonia in south China[J].BMC Infect Dis,2008,21(8):122.
[17]谢健屏,常汝虚,何翠娟,等.1978-1996年广州地区呼吸道合胞病毒感染分析[J].中华儿科杂志,1997,35(8)：402-404.
[18]谢健屏,赖桂香,陈正珊,等.广州地区1998-2003年儿童流行性感冒病毒检测分析[J].实用儿科临床杂志,2005,20(10)：980-982.
[19]谢健屏,赖桂香,何翠娟,等.1998-2002年广州地区儿童流感病毒检测与分析[J].中华儿科杂志,2002,40(9)：530-532.
[20]李静,麦贤弟,陈环等.儿童腺病毒感染的临床分析—附124例分析报告[J].新医学,2006,37(3)：169-170.
[21]余嘉璐,邓力,张建涛,等.腺病毒3型感染489例临床分析[J].中国实用 儿科杂志,2009,24(12)：957-958.
[22]RSV肺炎220例临床分析[J].周卫芳,季伟.苏州大学学报(医学版),2008,28(1)：159-160.
[23]Snow A,Dayyat E,Montgomery-Downs He,et al.Pediatric obstructive sleep apnea:a potential late consequence of respiratory syncytial virus bronchiolitis[J].Pediatr Pulmonol,2009,44(12):1186-1191.
[24]顾勇,姚泽忠.231例婴儿呼吸道合胞病毒性肺炎血清心肌酶分析[J].浙江实用医学,2007,12(1)：28-29.
[25]Cassimos DC,Tsalkidis A, TripsianisGA, et al.Asihma, lung function and sensitization in school children with a history of bronchiolitis[J].Pediatr Int,2008,50(1):51-56.
[26]Perez-Yarza EQMoreno A,Lazaro P, et al.The association between respiratory syncytial virus infection and the development of childhood asthma:a systematic review of the literature[J].Pediatr Infect Dis J,2007,26(8):733-739.
[27]刘国荣,申昆玲,江载芳,等.北京地区呼吸道合胞病毒感染的临床特点[J].实用儿科临床杂志,2002,17(3)：177-179.
[28]张学兰,朱雪明,季伟,等.婴幼儿呼吸道合胞病毒感染特点及支气管肺炎细胞免疫等指标的变化[J].实用儿科临床杂志,2003,18(9)：717-718.
[29]万诚,颜胜宇,郑钢.112例呼吸道合胞病毒下呼吸道感染临床特征分析[J].浙江临床医学.2008,8(4)：396--397.
[30]尹月英,尹志宏,王史远,等.儿童呼吸道合胞病毒肺炎流行特征分析[J].疾病监测,2007,22(1)：40-43.
[31]江远长.小儿呼吸道合胞病毒感染分析[J].临床和实验医学杂志,2006,5(5：544-545.
[32]仲玉强,曹海霞.2003年.2005年青海地区支气管肺炎患儿呼吸道合胞病毒的流行特点分析[J].青海医药杂志,2007,37(5)：32-33.
[33]郑季彦,李海峰,汤宏峰.小儿呼吸道合胞病毒感染的肝脏损害[J].浙江 预防医学,2005,17(10)：48-50.
[34]吴小青,伍严安,曾秀雅,等.福州地区急性呼吸道感染患儿呼吸道合胞病毒检测及亚型分析[J].实用医学杂志,2008,24(1)：50-52.
[35]赵明波,吴澄清,赵波.昆明地区小儿急性下呼吸道合胞病毒感染的临床研究[J].中国实用儿科杂志,2008,23(1)：34-36.
[36]Centers for Disease Control and Prevention (CDC).Brief report:respiratory syncytial virus activity--United States,July 2006-November 2007[J].MMWR Morb Mortal Wkly Rep,2007,56(48):1263-1265.
[37]Medici MC,Arcangeltti MC,Merolla R, et al. Incidence of respiratory syncytial virus infection in infants and young children referred to the emergency departments for lower respiratory tract diseases in Italy[J].Acta Biomed, 2004,75(1):26-33.
[38]Calegari T,Queiroz DA,Yokosawa J, et al. Clinical-epidemiological evaluation of respiratory syncytial virus infection in children attended in a public hospital in midwestern Brazil[J].Braz J Infect Dis,2005,9(2):156-161.
[39]芝敏,刘涌,张斌,等.住院呼吸道感染儿童呼吸道合胞病毒与腺病毒感染的调查[J].中国儿童保健杂志,2008,16(2)：247-248.
[40]Robinson RF.Impact of respiratory syncytial virus in the United States[J].Am J Health Syst Pharm,2008,65(8):3-6.
[41]Light M,Bauman J,Mavunda K, et al. Correlation between respiratory syncytial virus (RSV) test data and hospitalization of children for RSV lower respiratory tract illness in Florida[J].Pediatr Infect Dis J,2008,27(6):512-518.
[42]谢健屏,何翠娟,赖桂香,等.儿童呼吸道感染临床病毒学研究[J].现代临床学生物工程学杂志,2001,7(4)：259-260.
[43]谢健屏,常汝虚,张美德,等.从尸解肺组织分离呼吸道合胞病毒2例分析[J].中华实验和临床病毒学杂志,1994,(1)：79.
[44]中华医学会儿科学分会呼吸学组,《中华儿科杂志》编辑委员会.儿童社区获得性肺炎管理指南(试行)(上)[J].中华儿科杂志,2007,45：8390.
[45]Stensballe LG,Kofoed PE,Nantes EJ,et al.Duration of secretory IgM and IgA antibodies to respirtory syncytial virus in a community study in Guinea-Bissau[J].Acta Paediatr,2000,89(4):421-426.
[46]王光亮,吴雪梅,宋晓南,等.病毒IgM抗体及细胞学检测对病毒性脑炎的诊断价值[J].中风与神经疾病杂志,2008,24(6)：704-706.
[47]阳隽,黄海鹭,徐军,等.广州地区呼吸道合胞病毒分离株G蛋白基因序列分析[J].广东医学,2003,24(6)：580-582.
[48]Nagayama Y,Tsubaki T,Sawada K, et al. Age and sex as factors of response to RSV infections among those with previous history of wheezing[J].Pediatr Allergy Immunol,2006,17(5):376-381.
[49]Jensen-Fangel,Mohey R,Johnsen SP,et al.Gender differences in hospitalization rates for respiratory tract infections in Danish youth[J].Scand J Infect Dis,2004,36(1):31-36.
[50]吴福玲,宋秀凤,李营营,等.不同年龄患儿对呼吸道合胞病毒感染的免疫反应[J].滨州医学院学报,2009,29(5)：353-354,367.
[51]Chen ZM,Mao JH,Du LZ,et al.Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection[J].Acta Paediatr,2002,91(9):914-922.
[52]Vieira SE,Gilio AE,Durigon EL,et al. Lower respiratory tract infection caused by respiratory syncytial virus in infants:the role played by specific antibodies [J].Clinics,2007,62(6):709-716.
[53]Corsello G,Di Carlo P,Salsa L,et al.Respiratory syncytial virus infection in a Sicilian pediatric population:risk factors,epidemiology,and severity[J].Allergy Asthma Porc,2008,29(2):205-210.
[54]张明智,王立波,陆爱珍,等.IFNγCA重复序列多态性与呼吸道合胞病毒毛细支气管炎易感性的关系[J].临床儿科杂志,2008,26(1)：16-19.
[55]Puthothu B,Krueger M,Forster J, et al.Interleukin (IL)-18 polymorphism 133C/G is associated with severe respiratory syncytial virus infection[J].Pediatr Infect Dis J,2007,26(12):1094-1098.
[56]Aurivillius M,Oymar K,Oxelius VA. Immunoglobulin heavy G2 chain(IGHG2) gene restriction in the development of severe respiratory syncytial virus infection[J].Acta Paediatr,2005,94(4):414-418.
[57]Tasker RC,Roe MF,Bloxham DM, et al. The neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy[J]. Intensive Care Med,2004,30(12):2257
[58]Lai SH,Stein DA,Guerero-Plata A, et al.Inhibition of respiratory syncytial virus infections with morpholino oligomers in cell cultures and in mice[J].Mol Ther, 2008,16(6):1120-1128.
[59]Prodhan P,Westra SJ,Lin J,et al.Chest radiological patterns predict the duration of mechanical ventilation in children with RSV infection[J].Pediatr Radiol,2009,39(2):117-123.
[60]Chavez-Bueno S,Mejias A,Merryman RA,et al.Intravenous palivizumab and ribavirin combination for respiratory syncytial virus disease in high-risk pediatric patients[J].Pediatr Infect Dis J.2007,26(12):1089-1093.
[61]Tahan F,Ozcan A,Koc N. Clarithromycin in the treatment of RSV bronchiolitis:a double-blind,randomised,placebo-controlled trial[J].Europe Respiratory J,2007,29(1):91-97.
[62]Morris SK,Dzolganovski B,Beyene J,et al.A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection[J].BMC Infect Dis,2009,9:106.
[63]Numata M,Chu HW,Dakhama A,et al.Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus-induced inflammation and infection[J].Proc Natl Acad Sci USA,2010,107(1):320-325.
[64]Thorburn K,Harigopal S,Reddy V,et al.High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV)bronchiolitis[J].Thorax,2006,61(7):611-5.
[65]Ohba K,Yoshida S,Dewan Z,et al. Mutant influenza A virus nucleoprotein is preferentially localized in the cytoplasm and its immunization in mice shows higher immunogenicity and cross-reactivity[J].Vaccine,2007, 25(21):4291-4300.
[66]Sawada T,Hashimoto T, Nakano H,et al. Influenza viral hemagglutinin complicated shape is advantageous to its binding affinity for sialosaccharide receptor[J].Biochemical and Biophysical Research Communications,2007, 355(1):6-9.
[67]John Watkins. Influenza:burden of disease in childhood[C].International Congress Series 1263,2004:263-266.
[68]陈焕辉,陈翊,刘晓敏,等.广州地区婴幼儿非细菌性下呼吸道感染病原研究[J].现代临床医学生物工程学杂志,2004,10(6)：474-475.
[69]Schrag S,Shay DK,Gershman K,et al. Multistate surveillance for laboratory-confirmed,influenza-associated hospitalizations in children: 2003-2004[J].Pediatr Infect Dis J,2006,25(5):395-400.
[70]中华医学会呼吸病学分会.流行性感冒临床诊断和治疗指南(2004年修订稿)[J].中华结核和呼吸杂志.2005,28(1)：5-9.
[71]Schrag S,Shay DK,Gershman K,et al. Multistate surveillance for laboratory-confirmed,influenza-associated hospitalizations in children: 2003-2004[J].Pediatr Infect Dis J,2006,25(5):395-400.
[72]Nicholson KG,Teresa MB,Silverman MB,et al. Rates of hospitalisation for influenza, respiratory syncytial virus and human metapneumovirus among infants and young children[J].Zambonc Vaccine 24.2006,102-108.
[73]Xiao H,Lu SH,Ou Q,et al.Hospitalizeed patients with novel influenza A (H1N1)virus infection:Shanghai,June-July 2009.Chin Med J,2010, 123(4):401-405.
[74]Bren L. Influenza:vaccination still the best protection[J].FDA Consum, 2006,40(5):12-19.
[75]Epstein SL,Kong WP,Misplon JA,et al. Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein[J]. Vaccine,2005,23(46-47):5404-5410.
[76]Wright PF,Sannella E,Shi JR,et al. Antibody responses after inactivated influenza vaccine in young children[J].Pediatr Infect Dis J,2008 27(11):1004-1008.
[77]Halasa NB,Gerber MA,Chen Q,et al.Safety and immunogenicity of tribalent inactivated influenza vaccine in infants[J].J Infect Dis,2008, 197(10):1448-1454.
[78]Anatoly N. Slepushkin,Elena BI,et al. Influenza morbidity and some peculiarities of antiinfluenza immunity and prevention during influenza pandemics[J].International Congress Series 1263,2004,787-790.
[79]Nguyenv HH,Zemlin M,Ivanov II,et al. Heterosubtypic Immunity to Influenza A Virus Infection Requires a Properly Diversified Antibody Repertoire[J].J Virol,2007,81(17):9331-9338.
[80]Yuichi H,Muramatsu M,Shibata T,et al.Unmutated immunoglobulin M can protect micefrom death by influenza virus infection[J].J E Med,2004, 197(12):1779-1785.
[81]郭元吉,郭忠明.我国流感监测(1990-1993)[J].中华实验和临床病毒学志,1994,8(1)：11-15.
[82]梁爽,怀清杰,谷鸿喜,等.哈尔滨市2006-2007年度儿童流行性感冒监测结果分析[J].中国自然医学杂志,2008,10(1)：51-52.
[83]于伟,姚文清,张眉眉,等.辽宁省儿童流行性感冒病原学检测分析[J].中国公共卫生,2007,23(5)：547.
[84]朱大方,祖荣强,潘浩,等.江苏省2004-2007年流行性感冒监测分析[J].中国公共卫生2008,24(2)：232-234.
[85]逯建华,程小雯,何建凡,等.深圳市2006年流行性感冒流行特征分析[J].疾病控制杂志,2008,12(1)：33-36.
[86]张静,陈遂,徐淑娟,等.我院2004-2006年门诊病人流行性感冒监测结果分析[J].江西医学院学报,2008,48(1)：74-75.
[87]Simmerman JM,Chitttaganpitch M,Levy J,et al.Incidence,seasonality and mortality associated with influenza pneumonia in Thailand:2005-2008[J].PloS One,2009,4(11):e7776.
[88]张欣,倪汉忠,邓爱萍,等.2006年广东省流感病毒流行的分子基础[J].热带医学杂志,2007,7(6)：525-527.
[89]Baya A,Etlik AF,Arslan H,et al. Radiological and clinical course of pneumonia in patients with avian influenza H5N1[J].European Journal of Radiology,2007,61:245-250.
[90]Phipps LP,Essen SC,Brown IH. Genetic subtyping of influenza A viruses using RT-PCR with a single set of primers based on conserved sequences within the HA2 coding region. Journal of Viro Methods[J],2004, 122(1):119-122.
[91]朱汝南,钱渊,王芳,等.分子生物学方法在儿童流行性感冒监测中的应用[J].中华流行病学杂志,2003,24(1)：9-14.
[92]Xie ZX,Pang YS,Liu JB,et al. A multiplex RT-PCR for detection of type A influenza virus and differentiation of avian H5,H7,and H9 hemagglutinin subtypes[J].Molecular and Cellular Probes,2006,20(3-4):245-249.
[93]Minosse C,Selleri M,Zaniratti MS,et al. Improved detection of human influenza A and B viruses in respiratory tract specimens by hemi-nested PCR[J].Journal of Virological Methods,2007,141(2):225-228.
[94]温秋芳,孙晓强,吴忠兰,等.全国流感监测网络宁夏监测点2007-2008年度流行性感冒监测结果分析.宁夏医学杂志,2008,30(11)：1045-1046.
[95]梅玉发,赵国兵,王建平,等.2004-2007年十堰市流行性感冒监测结果分析.疾病监测,2008,11：682-684.
[96]曾照丽,白瑞婷,张晓熙.北京市朝阳区2005-2006年流感病原学监测分析.现代预防医学,2007,22：4356-4357.
[97]毛晓健,钱新华,曾其毅,等.2005-2006年广州地区儿童甲型流行性感冒病毒感染情况[J].实用儿科临床杂志,2008,23(10)：733-735.
[98]Chiu SS,Chan KH,Chen H, et al.Virologically confirmed population-based burden of hospitalized caused by influenza A and B among children in Hong Kong[J].Clin Infect Dis,2009,49(7):1016-1021.
[99]Wutzler P,Schmidt-Ott R, Hoyer H,et al.Prevalence of influenza A and B antibodies in pregnant women and their offspring.J Clin Virol,2009, 46(2):161-164.
[100]Hwang SD,Shin JS,Ku KB,et al.Protection of pregnant mice,fetuses and neonates from lethality of H5N1 influenza viruses by maternal vaccination[J].Vaccine,2010 Feb 25.[Epub ahead of print]
[101]李威,宋艳玲,王长科.甲型H1N1流感在美国传播期和墨西哥爆发期的气象条件与中国初夏气候特点的相似分析[J].科技导报,2009,27(11)：19-22.
[102]曲东,任晓旭,王菲,等.甲型H1N1流感危重患儿5例临床特点分析[J].中国实用儿科杂志,2009,12：923-925.
[103]Sugaya N. Influenza-associated encephalopathy in Japan[J].Seminars in Pediatric Infection Disease,2002,13:79-84.
[104]Karen LK,Shu Y Lam,Tak L Que,et al. Influenza A and Febrile Seizures in Childhood[J].Pediatr Neurol,2006,35(6):395-399.
[105]Newland JG,Laurich VN,Rosenquist AW,et al. Neurologic complications in children hospitalized with influenza:characteristics,incidence,and risk factors[J].J Pediatr,2007,150(3):306-310.
[106]Sivadon-Tardy V,Orlikowski D,Porcher R,et al. Guillain-Barre syndrome and influenza virus infection[J].Clin Infect Dis,2009,48(1):48-56.
[107]Mizuguchi M,Yamanouchi H,Ichiyama T,et al. Acute encephalopathy associated with influenza and other viral infections[J].Acta Neurol Scand, 2007,115(186):45-56.
[108]Hernandez E,Ramisse F,Lhonneux A,et al. Compared protective effect of nasal immunoprophylaxis using a new human monoclonal IgM antibody, human polyclonal antibodies,F(ab')2,amantadine,and zanamivir for prophylaxis of influenza A virus pneumonia in mice[J].Mil Med,2003, 168(3):246-251.
[109]Manxin Z,Darya Z,Krystyna M,et al.Fine specificity and sequence of antibodies directed against the ectodomain of matrix protein 2 of influenza A virus[J].Molecular Immunology,2006,43:2195-2206.
[110]Ascione A,Capecchi B,Campetelli L,Lmperiale V,et al.Human monoclonal antibodies in single chain fragment variable format with potent neutralization activity against influenza virus H5N1[J].Antiviral Res,2009,83(3):238-244.
[111]Lewis PF,Schmidt MA,Lu X,et al.A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14[J]J Infect Dis, 2009,199(10):1427-1434.
[112]Centers for Disease Control and Prevention(CDC).Outbreak of adenovirus 14 respiratory illness-Prince of Wales Island,Alaska,2008[J].MMWR Morb Mortal Wkly Rep,2010,59(1):6-10.
[113]Lee JA,Kim NH,Kim S J,et al.Rapid identification of human adenovirus types 3 and 7 from respiratory specimens via multiplex type-specific PCR [J]. J Clin Microbiol,2005,43(11):5509-5514.
[114]Wong S,Pabbaraju K,Pang XL,et al.Detection of a broad range of human adenoviruses in respiratory tract samples using a sensitive multiplex real-time PCR assay[J].J Med Virol,2008,80(5):856-865.
[115]Gray GC,McCarthy T,Lebeck MG,et al.Genotype prevalence and risk factors for severe clinical adenovirus infection,United States 2004-2006[J].Clin Infect Dis,2007,45(9):1120-1131.
[116]Baure U,Fllwker G,Bruss K,et al. Detection of antibodies against adenovirus protein IX,fiber,and hexon in human sera by immunoblot assay[J].J ClinMicrobiol,2005,43(9):4426-4433.
[117]Moro MR,Bonville CA,Suryadevara M,et al.Clinical features,adenovirus types,and local production of inflammatory mediators in adenovirus infections.Pediatr Infect Dis J,2009,28(5):376-380.
[118]杨祖钦,周晓聪,李昌崇,等.儿童呼吸道腺病毒感染50例诊治分析[J].浙江临床医学,2008,10(2)：175-176.
[119]Vaideewar P,Bavdekar SB,Jadhav SM,et al.Necrotizing adenoviral pneumonia:manifestation of nosocomial infection in pediatric intensive care unit[J].Indian J Pediatr,2008,75(11):1171-1174.
[120]范丽萍,张学兰,孙惠泉,等.苏州地区呼吸道感染住院患儿腺病毒感染分析[J].临床儿科杂志,2008,26(10)：866-868.
[121]张辉,刘春艳,王燕,等.北京儿童医院下呼吸道感染住院患儿血清腺病毒抗体检测分析[J].中华流行病学杂志,2007,28(7)：686-687.
[122]Hsieh WY,Chiu NC,Chi H,et al. Respiratory adenoviral infections in Taiwanese children:a hospital-based study[J].J Microbiol Immunol Infect, 2009,42(5):371-377.
[123]Lin YC,Lin KH,Ke GM,et al.Secular trend of genome types of respiratory adenovirus type 3 during 1983-2005:a study from Taiwan[J].Arch Virol,2010, 155(2):287-292.
[124]Chen HL,Chiou SS,Hsiao HP,et al.Respiratory adenoviral infections in children:a study of hospitalized cases in southern Taiwan in 2001-2002[J].J Trop Pediatr,2004,50(5):279-284.
[125]Zhang Q,Su X,Gong S,et al. Comparative genomic analysis of two strains of human adenovirus type 3 isolated from children with acute respiratory infection in southern China[J].J Gen Virol,2006,87(6):1531-1541.
[126]Murtagh P,Giubergia V,Viale D,et al.Lower respiratory infections by adenovirus in children. Clinical features and risk factors for bronchiolitis obliterans and mortality[J].Pediatr Pulmonol,2009,44(5):450-456.
[127]Chiu CY,Wong KS,Huang YC,et al.Bronchiolitis boliterans in children:clinical presentation,therapy and long-term follow-up[J].J Paediatr Child Health,2008,44(3):129-133.
[128]Hatherill M, Levin M, Lawrenson J,et al. Evolution of an adenovirus outbreak in a multidisciplinary children's hospital[J].J Paediatr Child Health. 2004,40(8):449-454.
[129]祝国红,王财富,陈志敏.腺病毒肺炎50例临床分析[J].实用儿科临床杂志,2002,17(5)：534-535.
[130]Bourgeois FT,Valim C,Wei JC.Influenza and other respiratory virus-related emergency department visits among young children[J].Pediatrics,2006, 118(1):1-8.
[131]Fabbiani M,Terrosi C, Martorelli B,et al.Epidemiological and clinical study of viral respiratory tract infections in children from Italy[J].J Med Virol,2009, 81(4):750-756.
[132]Schanzer DL,Langley JM,Tam TW.Hospitalization attributable to influenza and other viral respiratory illnesses in Canadian children[J].Pediatr Infect Dis J,2006,25(9):795-800.
[133]Zhang HY,Li ZM,Zhang GL,et al.Respiratory viruses in hospitalized children with acute lower respiratory tract infections in harbin,China[J].Jpn J Infect Dis,2009,62(6):458-460.
[134]Melendi GA,Laham FR,Monsalvo AC,et al.Cytokine profiles in the respiratory tract during primary infection with human metapneumovirus, respiratory syncytial virus,or influenza virus in infans[J].Pediatrics,2007, 120(2):410-415.
[135]Byeon JH,Lee JC,Choi IS,et al.Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections[J].Acta Paediatr,2009,98(4):725-730.
[136]Tang LF,Wang TL,Tang HF,et al.Viral pathogens of acute lower respiratory tract infection in China[J].Indian Pediatr,2008,45(12):971-975.
[137]Sung RY,Chan PK,Tsen T,et al.Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays[J].J Med Virol,2009,81(1):153-159.
[138]Lopez PG,Morfin Maciel BM,et al.Identification of influenza,parainfluenza, adenovirus and respiratory syncytial virus during rhinopharyngitis in a group of Mexican children with asthma and wheezing[J].Rev Alerg Mex,2009, 56(3):86-91.
[139]Farshad N,Saffar MJ,Khalilian AR,et al.Respiratory viruses in hospitalized children with acute lower respiratory tract infections,Mazandaran Province, Iran[J].Indian Pediatr,2008,45(7):590-592.
[140]Palomino MA,Larranaga C,Villagra E,et al.Adenovirus and respiratory sync, ytial virus-adenovirus mixed acute lower respiratory infections in Chilean infants[J].Pediatr Infect Dis J,2004,23(4):337-341.
[141]Gilla G,OnateE,Perez-Yarza EG,et al.Viruses in community-acquiared pneumonia in children aged less than 3 years old:high rate of viral coinfection[J].J Med Virol,2008,80(10):1843-1849.
[142]Ei Sayed Zaki M,Goda T.Clinico-pathological study of atypical pathogens in community-acquired pneumonia:a prospective study[J].J Infect Dev Ctries, 2009,3(3):199-205.
[143]Tie K,Lodha R,Pandey RM,et al.Factors determining the outcome of children hospitalized with severe pneumonia[J].BMC Pediatr,2009,9-15.
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