基于中断时间序列和间断线性回归分析法百日咳免疫策略转换效果评价

Effectiveness of immunization strategy transition of pertussis vaccines:an evaluation with interrupted time series and segmented regression analysis

目的评价无细胞百白破疫苗(DTaP)替换全细胞百白破疫苗(DTwP)免疫策略的转换效果。方法收集山东省济南市1965—2016年百日咳报告发病率数据,应用中断时间序列(ITS)和间断线性回归分析(SRA)方法定量评价百日咳疫苗预防接种及DTaP替代DTwP的免疫策略转换对百日咳发病率影响的近期影响和长期效应。结果1978年济南市DTwP大规模预防接种后,百日咳年均报告发病率较接种前的164.47/10万下降了145.77/10万(P=0.017),但长期效应平均每年上升7.32/10万(P=0.004);2002年开始DTaP作为二类苗接种并未对发病率产生近期影响和长期效应(均P>0.05);2008年DTaP替代第4针DTwP、2009年DTaP替代第2~4针DTwP和2010年DTaP全面替代DTwP的3种免疫策略使百日咳报告发病率当年分别下降5.97/10万、7.39/10万和8.03/10万(均P<0.01),同时DTaP接种产生长期效应,使百日咳报告发病率每年上升0.29/10万、0.35/10万和0.39/10万(均P<0.001)。结论DTwP与DTaP组合免疫策略的效果可能优于单独接种DTwP;全程接种DTaP的短期效果优于DTwP,但DTaP诱导免疫的持续时间不理想,中国百日咳疫苗研发和免疫策略有待进一步研究。

Objective To evaluate the effectiveness of pertussis immunization strategy transition from diphtheria,tetanus and whole-cell pertussis vaccine(DTwP)to diphtheria,tetanus and acellular pertussis vaccine(DTaP)in Ji'nan city of Shandong province.Methods We collected data on yearly pertussis incidence in Ji'nan city from 1965 through 2016 from the Notifiable Diseases Registry Database.We used interrupted time series(ITS)and segmented regression analysis(SRA)to quantitatively assess short-and long-term effect of pertussis vaccine inoculation and the transition of vaccination schedule from DTwP to DTaP on pertussis incidence in the city.Results The reported pertussis incidence decreased significantly from 164.47/100000 before the pertussis vaccine inoculation in to 145.77/100000 following the implementation of DTwP inoculation in 1978(P=0.017)and the average long-term effect increased by 7.32/100000 per year between 1978 and 2001.No significant short-and long-term variations in reported pertussis incidence were observed when the implementation of DTaP vaccination as a second class vaccine in 2002(both P>0.05).The reported yearly pertussis incidence declined significantly by 5.97,7.39,and 8.03 per 100000 population in 2008,2009,and 2010 when the fourth dose,the second/third/fourth,and all doses of DTwP vaccinations were replaced by DTaP in the year,respectively(P<0.01 for all);but an increasing trend in the reported yearly pertussis incidence was observed after the replacements of various doses of DTwP with DTaP for the periods from 2008,2009,and 2010 to 2016,with the average annual increases of 0.29,0.35,0.39 per 100000 population.Conclusion The study showed that the effectiveness of an all-DTwP vaccination schedule may be less than the effectiveness of a sequential DTwP/DTaP vaccination schedule.Short-term effectiveness of DTaP vaccination was better than that of DTwP,but the duration of DTaP-induced protection is not ideal.Effective pertussis vaccines and vaccination schedules in China need to be developed.