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儿童白喉-破伤风-无细胞百日咳疫苗的免疫持续时间和有效性。

Duration of Immunity and Effectiveness of Diphtheria-Tetanus-Acellular Pertussis Vaccines in Children.

机构信息

Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases Unit, Institut Pasteur, Inserm U1181, University of Versailles St-Quentin-en-Yvelines, Versailles, France.

Odum School of Ecology, University of Georgia, Athens.

出版信息

JAMA Pediatr. 2019 Jun 1;173(6):588-594. doi: 10.1001/jamapediatrics.2019.0711.

Abstract

IMPORTANCE

The United States has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high estimated vaccine coverage. Short-lived immunity induced by diphtheria-tetanus-acellular pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden, but the duration of protection conferred by DTaP vaccines remains incompletely quantified.

OBJECTIVE

To assess the duration of immunity and the effectiveness of DTaP vaccines in US children.

DESIGN, SETTING, AND PARTICIPANTS: A mathematical, age-structured model of pertussis transmission, previously validated empirically on incidence data in Massachusetts, was used in this simulation study to assess the duration of DTaP immunity most consistent with the empirical values of the relative increase in the odds of acquiring pertussis from recent epidemiologic studies in the United States. The study included 5 simulated cohorts of children born between January 1, 2001, and December 31, 2005, followed up between the ages of 5 and 9 years (study period, January 1, 2006, to December 31, 2014). Statistical analysis was performed from May 1 to December 1, 2017.

INTERVENTIONS

Vaccination with DTaP according to the US immunization schedule, with a range of assumptions regarding the degree of waning immunity.

MAIN OUTCOMES AND MEASURES

Vaccine effectiveness and relative change in the odds of acquiring pertussis (odds ratio) in children aged 5 to 9 years, duration of DTaP immunity, and vaccine population-level impact.

RESULTS

This study found a marked association between the degree of waning immunity, vaccine effectiveness, and the odds ratio. Counterintuitively, the odds ratio was positively associated with vaccine effectiveness, as a consequence of nonlinear, age-assortative transmission dynamics. Based on the empirical odds ratios (1.33; 95% CI, 1.23-1.43), it was estimated that vaccine effectiveness exceeded 75% in children aged 5 to 9 years and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.

CONCLUSIONS AND RELEVANCE

The results of this study suggest that temporal trends in the odds of acquiring pertussis are an unreliable measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. Control strategies should be based on the best available estimates of vaccine properties and the age structure of the transmission network.

摘要

重要性

自 20 世纪 70 年代中期以来,尽管估计疫苗接种率很高,但美国仍经历了百日咳的全国性反弹。幼儿接种白喉-破伤风-无细胞百日咳(DTaP)疫苗所产生的短暂免疫力被广泛认为是导致这种日益加重的负担的原因,但 DTaP 疫苗提供的保护持续时间仍不完全量化。

目的

评估 DTaP 疫苗在美国儿童中的免疫持续时间和有效性。

设计、环境和参与者:本模拟研究使用了一种先前在马萨诸塞州的发病率数据上进行了实证验证的百日咳传播的数学、年龄结构模型,以评估与美国最近流行病学研究中获得百日咳的几率相对增加的经验值最一致的 DTaP 免疫持续时间。该研究包括 5 个模拟队列,队列中的儿童于 2001 年 1 月 1 日至 2005 年 12 月 31 日期间出生,在 5 至 9 岁期间进行随访(研究期间为 2006 年 1 月 1 日至 2014 年 12 月 31 日)。统计分析于 2017 年 5 月 1 日至 12 月 1 日进行。

干预措施

根据美国免疫计划接种 DTaP,接种方案中对免疫衰减程度有一系列假设。

主要结果和措施

5 至 9 岁儿童的疫苗效力和获得百日咳的几率(比值比)的相对变化,DTaP 免疫持续时间以及疫苗对人群的影响。

结果

本研究发现免疫衰减程度,疫苗效力和比值比之间存在明显的关联。反直觉的是,由于非线性,年龄相关的传播动力学,比值比与疫苗效力呈正相关。根据经验比值比(1.33;95%CI,1.23-1.43),估计 5 至 9 岁儿童的疫苗效力超过 75%,并且在最后一剂 DTaP 后 5 年,超过 65%的儿童仍对百日咳具有免疫力。

结论和相关性

这项研究的结果表明,获得百日咳的几率的时间趋势是衡量疫苗诱导保护持久性的不可靠指标。它们进一步表明 DTaP 疫苗提供了不完美但持久的保护。控制策略应基于对疫苗特性和传播网络年龄结构的最佳可用估计。

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