百日咳患儿血清百日咳毒素-IgG抗体水平及其影响因素的分析

Levels and influencing factors of serum pertussis toxin-IgG antibody in children with pertussis

目的探究百日咳患儿的血清百日咳毒素(pertussis toxin,PT)-IgG抗体水平及其影响因素。方法收集2015年7月至2018年12月深圳市儿童医院实验室确诊为百日咳且完成PT-IgG抗体检测的患儿的年龄、病程、疫苗接种状况等临床资料,采集患儿静脉血检测PT-IgG抗体水平,采集鼻咽拭子进行聚合酶链反应(polymerase chain reaction,PCR)检测百日咳鲍特菌核酸,并进行百日咳鲍特菌培养。两组间比较采用曼-惠特尼U检验,多组间比较采用Kruskal-Wallis检验。采用多元线性回归分析PT-IgG抗体水平的影响因素。结果共纳入871例百日咳患儿,年龄为4(2,7)个月,年龄<6月龄者592例(68.0%),<1岁者754例(86.6%),病程为15(11,20)d。871例患儿中,PCR和(或)培养阳性者864例(99.2%),其中仅PCR阳性者696例,仅培养阳性者35例,PCR和培养均阳性者133例。疫苗未接种、已接种至少1剂者分别为452例(51.9%)和346例(39.7%)。年龄为0~2月龄、3~5月龄、6月龄~2岁、≥3岁组患儿PT-IgG抗体水平分别为0.7(0,8.2)IU/mL、2.3(0,23.0)IU/mL、24.6(0,112.3)IU/mL和24.9(0,114.7)IU/mL,病程为0~2周、>2~4周、>4~8周、>8周组患儿PT-IgG抗体水平分别为0(0,7.9)IU/mL、8.7(0,56.0)IU/mL、26.6(5.1,82.9)IU/mL和68.0(15.3,118.8)IU/mL,不同年龄和病程组患儿PT-IgG抗体水平差异均有统计学意义(H=88.346、94.076,均P<0.01)。疫苗未接种、已接种至少1剂者PT-IgG抗体水平分别为0.9(0,12.7)IU/mL、14.6(0,86.3)IU/mL,差异有统计学意义(Z=-8.520,P<0.01)。PT-IgG≥80 IU/mL者在全年龄组占16.0%(139/871),在年龄≥3岁组中占34.3%(12/35),13例年龄≥3岁且病程>2周的患儿中6例为PT-IgG≥80 IU/mL。年龄、病程、疫苗接种状态是PT-IgG抗体水平的独立影响因素(β=0.108、0.189、0.250,均P<0.01)。结论百日咳患儿的PT-IgG抗体水平受年龄、病程、疫苗接种状态影响,单份血清以80 IU/mL为诊断界值可能导致漏诊率增加,需进一步探索适合我国儿童的标准。

Objective To investigate the levels and influencing factors of serum pertussis toxin(PT)-IgG antibody in children with pertussis.Methods The clinical data including age,course of disease and vaccination status of children with laboratory-confirmed pertussis and tested for PT-IgG antibody in Shenzhen Children′s Hospital from July 2015 to December 2018 were collected.Venous blood samples were obtained to detect PT-IgG antibody levels.Nasopharyngeal swabs were taken for polymerase chain reaction(PCR)test to detect Bordetella pertussis nucleic acid and culture of Bordetella pertussis.Mann-Whitney U test was used for comparison between two groups.Kruskal-Wallis test was used for comparison among multiple groups.Multiple linear regression was used to analyze the influencing factors of PT-IgG antibody levels.Results A total of 871 children aged 4(2,7)months were included,among whom,592(68.0%)cases were under six months and 754(86.6%)cases were under one year old.The course of disease was 15(11,20)days.Among 871 cases,864(99.2%)cases were PCR test and(or)culture positive,including 696 cases positive only for PCR test,35 cases positive only for culture and 133 cases positive for both PCR test and culture.There were 452(51.9%)children who were not vaccinated and 346(39.7%)children vaccinated with at least one dose.In terms of age,the PT-IgG amtibody levels of children aged 0 to two months,three to five months,six months to two years and≥three years were 0.7(0,8.2)IU/mL,2.3(0,23.0)IU/mL,24.6(0,112.3)IU/mL and 24.9(0,114.7)IU/mL,respectively.The PT-IgG antibody levels of children after onset of symptoms at 0 to two weeks,more than two to four weeks,more than four to eight weeks and more than eight weeks were 0(0,7.9)IU/mL,8.7(0,56.0)IU/mL,26.6(5.1,82.9)IU/mL and 68.0(15.3,118.8)IU/mL,respectively.The differences were both statistically significant(H=88.346 and 94.076,respectively,both P<0.01).The PT-IgG antibody levels in children who were unvaccinated and vaccinated with at least one dose were 0.9(0,12.7)IU/mL and 14.6(0,86.3)IU/mL,respectively.The difference was statistically significant(Z=-8.520,P<0.01)PT-IgG≥80 IU/mL accounted for 16%(139/871)in the whole range of age,34.3%(12/35)in children≥three years old.There were 13 patients aged≥three years old with a disease course>two weeks,among whom,six patients had PT-IgG≥80 IU/mL.Age,course of disease and vaccination status were independent influencing factors of PT-IgG levels(β=0.108,0.189 and 0.250,respectively,all P<0.01).Conclusions The levels of PT-IgG antibody in children with pertussis are influenced by age,course of disease and vaccination status.The single serum PT-IgG of 80 IU/mL as cut-off value in the diagnosis of pertussis may lead to a increase of missed diagnosis.Therefore,it is necessary to further explore the standards suitable for children in China.