The effects of influenza-like illness definitions on influenza surveillance in hospitalized children
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摘要:
目的 了解不同流感样病例定义对住院儿童流感监测结果的影响。 方法 利用2017年10月-2018年5月苏州大学附属儿童医院呼吸道疾病综合监测的病原学和临床症状等数据, 计算符合中国、欧盟疾病预防控制中心(European center for disease prevention and control, ECDC)和世界卫生组织(world health organization, WHO)的流感样病例定义时的流感病毒检出率, 以流感病毒检出为金标准, 分别分析三种流感样病例定义确诊的灵敏度、特异度、阳性预测值、阴性预测值与受试者工作特征曲线(receiver operator characteristic curve, ROC)下面积, 并采用多因素Logistic回归分析模型分析流感病毒阳性率的相关因素。 结果 研究共纳入1 459例呼吸道感染住院病例, 其中流感病毒阳性者204例, 阳性率14.0%。ECDC定义的灵敏度最高(91.7%, 95% CI:87.9%~95.5%), 但其特异度最低(44.6%, 95% CI:41.9%~47.4%); WHO定义的灵敏度最低(70.6%, 95% CI:64.3%~76.8%); 中国定义的灵敏度(91.2%, 95% CI:87.3%~95.1%)和特异度(51.5%, 95% CI:48.8%~54.3%)均较高, 且其ROC曲线下面积最大(71.2%, 95% CI:67.9%~74.5%)。多因素分析发现有发热症状(≥38℃)患儿的流感病毒检出率高于不发热患儿(OR=7.03, 95% CI:3.89~12.70)。 结论 在住院儿童中开展流感监测时, 采用中国流感监测的流感样病例定义可以获得较好的效果。 Abstract:Objective To evaluate clinical factors associated with laboratory-confirmed influenza infection and probe into the effects of different influenza-like illness(ILI) definitions on influenza surveillance in hospitalized children. Methods The influenza surveillance on the hospitalized children with acute respiratory infection was carried out in Soochow university affiliated children's hospital from October 2017 to May 2018. The definition of influenza-like illness(ILI), which proposed by world health organization(WHO), the European center for disease prevention and control(ECDC) and ministry of public health of China, was analyzed to determine the area under receiver operating characteristic curve(ROC), sensibility, specificity, and the positive and negative predictive values of the ILI definition using the laboratory evidence of influenza virus infection as golden criteria. Logistic regression model was employed to explore the risk factors of the laboratory confirmed influenza infection among the hospitalized children. Results Of the enrolled 1 459 hospitalized children, 204(14.0%) were lab-confirmed influenza cases. The ECDC definition had the highest sensitivity(91.7%, 95% CI: 87.9%-95.5%) but the lowest specificity(44.6%, 95% CI: 41.9%-47.4%). The WHO definition had the lowest specificity(70.6%, 95% CI: 64.3%-76.8%). China's definition was the most discriminant definition with relatively high sensitivity(91.2%, 95% CI: 87.3%-95.1%) and specificity(51.5%, 95% CI: 48.8%-54.3%), and its positive area under curve value(71.2%, 95% CI: 67.9%-74.5%) was the highest. Multivariate analysis model showed that the detection rate of influenza virus in children with fever(≥38 ℃) was higher than that in children without fever(OR=7.03, 95% CI:3.89-12.70). Conclusions It is suggested to adopt China's ILI definition to get better output during influenza surveillance among hospitalized children. -
表 1 2017年10月-2018年6月纳入分析的住院患儿的基本特征[n(%)]
Table 1. General characteristics of hospitalized children from October 2017 to June 2018 [n(%)]
特征 流感病毒阳性
(n=204)流感病毒阴性
(n=1 255)合计
(n=1 459)性别 男 127(62.3) 804(64.1) 931(63.8) 女 77(37.7) 451(35.9) 528(36.2) 年龄组(岁) 0~ 24(11.8) 533(42.5) 557(38.2) 0.5~ 87(42.7) 388(30.9) 475(32.6) 2~ 66(32.4) 230(18.3) 296(20.3) ≥5 27(13.2) 104(8.3) 131(9.0) 发病至采样时间(d) 1~ 40(19.6) 385(30.7) 425(29.1) 5~ 75(13.8) 456(36.3) 531(36.4) 8~ 39(19.1) 163(13.0) 202(13.9) ≥11 50(24.5) 251(20.0) 301(20.6) 临床症状 咳嗽 201(98.5) 1 234(98.3) 1 435(98.4) 咽痛 202(99.0) 1 231(98.1) 1 433(98.2) 发热 186(91.2) 608(48.5) 794(54.4) 流涕 58(28.4) 403(32.1) 461(31.6) 喘息 66(32.4) 530(42.2) 596(32.4) 气促 6(2.9) 114(9.1) 120(8.2) 呕吐 8(3.9) 127(10.1) 135(3.9) 呼吸困难 2(1.0) 22(1.8) 24(1.0) 疾病诊断 支气管肺炎 166(81.4) 1 040(82.9) 1 206(82.7) 肺炎 13(7.8) 98(6.4) 111(7.6) 大叶性肺炎 10(4.9) 27(2.2) 37(2.5) 支气管炎 4(2.0) 25(2.0) 29(2.0) 毛细支气管炎 0(0.0) 21(2.0) 21(1.4) 其他 11(5.9) 44(3.5) 55(3.8) 合计 204(100.0) 1 255(100.0) 1 459(100.0) 表 2 影响流感病毒检出率的单因素和多因素Logistic回归分析模型分析结果
Table 2. Univariate and multivariate analysis results of risk factors associated with positive rate of influenza by Logistic regression analysis model
变量 调查例数
(n=1 459)阳性例数
(n=204)阳性率
(%, 95%CI)OR(95%CI)值a P值 OR(95%CI)值b P值 年龄(岁) 0~ 557 24 4.3(2.6~6.0) 1.00 1.00 0.5~ 475 87 18.3(14.9~22.1) 4.98(3.11~9.98) < 0.001 2.76(1.55~4.94) 0.001 2~ 296 66 22.3(17.7~27.5) 6.37(3.90~10.42) < 0.001 3.12(1.67~5.84) < 0.001 ≥5 131 27 20.6(13.7~27.5) 5.77(3.20~10.39) < 0.001 1.91(0.91~4.01) 0.086 发病至采样时间(d) ≤3 425 40 9.4(6.6~12.2) 1.00 1.00 4~ 531 75 14.1(11.2~17.1) 1.58(1.05~2.37) 0.027 1.39(0.91~2.27) 0.185 8~ 202 39 19.3(13.9~24.8) 2.30(1.43~3.71) < 0.001 1.84(1.01~3.35) 0.045 ≥11 301 50 16.6(12.4~20.8) 1.92(1.23~3.00) 0.004 2.31(1.32~4.05) 0.004 流感季发病 427 188 44.0(39.3~48.7) 22.78(13.50~38.46) < 0.001 28.22(16.37~48.67) < 0.001 发热 794 186 23.4(20.5~26.4) 11.00(6.70~18.06) < 0.001 7.03(3.89~12.70) < 0.001 咳嗽 1 435 201 14.0(12.2~15.8) 1.14(0.34~3.86) 0.833 3.62(0.95~13.77) 0.059 咽痛 1 433 202 14.1(12.3~15.9) 1.97(0.46~8.40) 0.360 1.78(0.32~10.11) 0.513 流涕 461 58 12.6(9.6~15.6) 0.84(0.61~1.16) 0.295 0.73(0.48~1.10) 0.135 气促 120 6 5.0(1.1~8.9) 0.30(0.13~0.70) 0.005 0.36(0.14~0.94) 0.037 呼吸困难 24 2 8.3(-3.0~19.6) 0.55(0.13~2.38) 0.428 0.33(0.06~1.75) 0.192 喘息 596 66 11.1(8.6~13.6) 0.65(0.48~0.90) 0.008 0.94(0.62~1.43) 0.778 呕吐 135 8 5.9(1.9~9.9) 0.36(0.18~0.75) 0.007 0.30(0.13~0.68) 0.004 注:a以是否检出流感病毒为因变量(阳性=1,阴性=0),以年龄、发病至采样间隔时间、是否处于流感季(1=是,0=否)、发热(1=发热,0=体温正常)、咳嗽(1=咳嗽,0=无咳嗽)、咽痛(1=咽痛,0=无咽痛)、流涕(1=流涕,0=无流涕)、气促(1=气促,0=无气促)、呼吸困难(1=呼吸困难,0=无呼吸困难)、喘息(1=喘息,0=无喘息)和呕吐(1=呕吐,0=无呕吐)作为自变量分别进行单因素分析。b以是否检出流感病毒为因变量,将单因素分析中所有自变量纳入,采用多因素Logistic回归分析模型进行分析。 表 3 不同ILI定义的灵敏度、特异度和ROC曲线下面积[n(%)]
Table 3. Sensitivity, specificity and the area under ROC curve defined by different ILI[n(%)]
特征 合计 流感病毒阳性 流感病毒阴性 灵敏度(%, 95% CI) 特异度(%, 95% CI) AUC(%, 95% CI) 总病例数 1 459(100.0) 204(14.0) 1 255(86.0) ILI病例(WHO) 647(44.3) 144(22.3) 503(77.7) 70.6(64.3~76.8) 59.9(57.2~62.6) 65.3(61.3~69.2) ILI病例(ECDC) 882(60.5) 187(21.2) 695(78.8) 91.7(87.9~95.5) 44.6(41.9~47.4) 68.1(64.8~71.5) ILI病例(中国) 794(54.4) 186(23.4) 608(76.6) 91.2(87.3~95.1) 51.5(48.8~54.3) 71.2(67.9~74.5) 表 4 不同流感样病例定义的阳性预测值和阴性预测值
Table 4. Positive predictive value and negative predictive value of different ILI definitions
特征 阳性预测值(%, 95%CI) 阴性预测值(%, 95%CI) ECDC定义 WHO定义 中国定义 ECDC定义 WHO定义 中国定义 合计 21.2(18.5~23.9) 22.3(19.1~25.5) 23.5(20.6~26.5) 97.1(95.7~98.4) 92.6(90.8~94.4) 96.9(95.6~98.2) 年龄(岁) 0~ 8.9(4.4~13.3) 9.3(3.5~15.1) 11.2(5.5~17.0) 97.5(96.0~99.0) 96.7(95.1~98.4) 83.5(80.3~86.6) 0.5~ 23.0(18.6~27.3) 25.4(20.1~30.7) 25.2(20.3~30.0) 95.1(91.2~98.9) 90.0(86.0~93.9) 95.0(91.7~98.4) 2~ 25.2(20.0~31.0) 24.9(19.1~30.7) 26.5(21.0~32.1) 97.4(92.3~100) 84.3(76.5~92.2) 98.0(89.6~100) ≥5 23.9(16.0~31.7) 21.0(12.1~29.9) 25.5(17.0~33.9) 100.0 80.0(68.9~91.1) 96.5(90.0~100) 流感分型 A/H1N1 15.1(12.7~17.4) 14.8(12.1~17.6) 16.9(14.2~19.5) 98.6(97.7~99.6) 94.5(92.9~96.0) 98.5(97.6~99.4) A/H3N2 0.3(0.2~1.5) 1.2(0.3~2.1) 1.0(0.3~1.7) 99.8(99.5~100) 99.9(99.6~100.0) 99.9(99.5~100) B/Yamagata 4.3(3.0~5.7) 5.1(3.4~6.8) 4.6(3.3~6.4) 99.0(98.1~99.8) 98.7(97.9~99.4) 98.9(98.0~99.6) B/Victoria 1.4(0.6~2.1) 1.6(0.6~2.5) 1.5(0.1~2.4) 99.7(99.2~100) 99.5(99.0~100.0) 99.7(99.3~100) 流感季 是 47.8(42.7~52.9) 46.0(40.3~51.8) 48.9(43.6~54.1) 94.4(91.6~97.3) 83.1(79.1~87.2) 93.6(90.6~96.5) 否 2.5(6.9~3.9) 3.1(1.3~4.9) 2.8(1.2~4.4) 99.1(98.0~100.0) 99.0(98.1~99.9) 99.0(98.1~100.0) -
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