van Twillert Inonge, Bonačić Marinović Axel A, van Gaans-van den Brink Jacqueline A M, Kuipers Betsy, Berbers Guy A M, van der Maas Nicoline A T, Verheij Theo J M, Versteegh Florens G A, Teunis Peter F M, van Els Cécile A C M
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
Julius Center Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
PLoS One. 2016 Feb 5;11(2):e0148507. doi: 10.1371/journal.pone.0148507. eCollection 2016.
Bordetella pertussis circulates even in highly vaccinated countries affecting all age groups. Insight into the scale of concealed reinfections is important as they may contribute to transmission. We therefore investigated whether current single-point serodiagnostic methods are suitable to estimate the prevalence of pertussis reinfection. Two methods based on IgG-Ptx plasma levels alone were used to evaluate the proportion of renewed seroconversions in the past year in a cohort of retrospective pertussis cases ≥ 24 months after a proven earlier symptomatic infection. A Dutch population database was used as a baseline. Applying a classical 62.5 IU/ml IgG-Ptx cut-off, we calculated a seroprevalence of 15% in retrospective cases, higher than the 10% observed in the population baseline. However, this method could not discriminate between renewed seroconversion and waning of previously infection-enhanced IgG-Ptx levels. Two-component cluster analysis of the IgG-Ptx datasets of both pertussis cases and the general population revealed a continuum of intermediate IgG-Ptx levels, preventing the establishment of a positive population and the comparison of prevalence by this alternative method. Next, we investigated the complementary serodiagnostic value of IgA-Ptx levels. When modelling datasets including both convalescent and retrospective cases we obtained new cut-offs for both IgG-Ptx and IgA-Ptx that were optimized to evaluate renewed seroconversions in the ex-cases target population. Combining these cut-offs two-dimensionally, we calculated 8.0% reinfections in retrospective cases, being below the baseline seroprevalence. Our study for the first time revealed the shortcomings of using only IgG-Ptx data in conventional serodiagnostic methods to determine pertussis reinfections. Improved results can be obtained with two-dimensional serodiagnostic profiling. The proportion of reinfections thus established suggests a relatively increased period of protection to renewed infection after clinical pertussis.
百日咳博德特氏菌即使在疫苗接种率很高的国家也有传播，影响所有年龄组。了解隐匿性再感染的规模很重要，因为它们可能会导致传播。因此，我们调查了当前的单点血清诊断方法是否适合估计百日咳再感染的患病率。仅基于IgG-Ptx血浆水平的两种方法被用于评估一组回顾性百日咳病例在过去一年中再次血清转化的比例，这些病例在早期确诊有症状感染后≥24个月。一个荷兰人口数据库被用作基线。应用经典的62.5 IU/ml IgG-Ptx临界值，我们计算出回顾性病例中的血清阳性率为15%，高于在人群基线中观察到的10%。然而，这种方法无法区分再次血清转化和先前感染增强的IgG-Ptx水平的下降。对百日咳病例和普通人群的IgG-Ptx数据集进行的双组分聚类分析揭示了IgG-Ptx中间水平的连续性，这使得无法确定阳性人群，也无法通过这种替代方法比较患病率。接下来，我们研究了IgA-Ptx水平的补充血清诊断价值。在对包括恢复期病例和回顾性病例的数据集进行建模时，我们获得了针对IgG-Ptx和IgA-Ptx的新临界值，这些临界值经过优化以评估既往病例目标人群中的再次血清转化。二维结合这些临界值，我们计算出回顾性病例中的再感染率为8.0%，低于基线血清阳性率。我们的研究首次揭示了在传统血清诊断方法中仅使用IgG-Ptx数据来确定百日咳再感染的缺点。二维血清诊断分析可以获得更好的结果。如此确定的再感染比例表明临床百日咳后对再次感染的保护期相对延长。
