van Gent Marjolein, de Greeff Sabine C, van der Heide Han G J, Mooi Frits R
Laboratory for Infectious Diseases and Screening, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands.
Vaccine. 2009 Mar 18;27(13):1898-903. doi: 10.1016/j.vaccine.2009.01.111. Epub 2009 Jan 31.
Despite more than 50 years of vaccination, whooping cough is still an endemic disease in the Netherlands with regular epidemic outbreaks. In the last 20 years, two periods of increased notifications were observed. The causes of the increased notifications in the first period, from 1983 to 1987, are contentious. At the time it was suggested to be a surveillance artifact, caused by changes in diagnostic procedures and increased awareness. An alternative explanation, a reduction in the vaccine dose, was downplayed at the time. The aim of this study was to reinvestigate the causes of the increased notifications by identifying changes in the Bordetella pertussis population. B. pertussis strains, isolated from 1965 to 1992, were characterized by means of fimbrial serotyping, multiple-locus sequence typing of virulence genes (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA). Shifts in fimbrial serotypes and MLVA types were associated with changes in vaccine dose and increased number of notifications. One to three years after lowering of the vaccine dose, the predominant fimbrial serotype changed from Fim3 to Fim2, and the reverse trend was observed when the vaccine dose was increased. Significantly, changes in fimbrial serotypes were evident at least seven years before the increase in notifications. Our results provide evidence that the change in vaccine dose affected host immunity and, consequently, contributed to an increase in pertussis morbidity. Further, we show that MLVA and fimbrial serotyping of strains can be used as early warning for pertussis epidemics.
尽管进行了50多年的疫苗接种，但百日咳在荷兰仍是一种地方病，时有疫情爆发。在过去20年中，观察到两个报告病例增加的时期。1983年至1987年第一个时期报告病例增加的原因存在争议。当时有人认为这是一种监测假象，是由诊断程序的变化和意识提高导致的。另一种解释，即疫苗剂量的减少，当时未被重视。本研究的目的是通过确定百日咳博德特氏菌种群的变化来重新调查报告病例增加的原因。对1965年至1992年分离出的百日咳博德特氏菌菌株进行了菌毛血清分型、毒力基因多位点序列分型（MLST）和多位点可变数目串联重复分析（MLVA）。菌毛血清型和MLVA类型的变化与疫苗剂量的变化和报告病例数的增加有关。疫苗剂量降低后的1至3年，主要菌毛血清型从Fim3变为Fim2，而疫苗剂量增加时则观察到相反的趋势。值得注意的是，菌毛血清型的变化在报告病例增加前至少7年就很明显。我们的结果提供了证据，表明疫苗剂量的变化影响了宿主免疫力，因此导致了百日咳发病率的增加。此外，我们表明菌株的MLVA和菌毛血清分型可作为百日咳疫情的早期预警。
