Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay

Modelling anti-pertussis toxin IgG antibody decay following primary and preschool vaccination with an acellular pertussis vaccine in UK subjects using a modified oral fluid assay
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DOI:
10.1099/jmm.0.062000-0
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发表时间:
2013-09-01
影响因子:
3
通讯作者:
Harrison, Timothy G.
Harrison, Timothy G.
中科院分区:
医学3区
文献类型:
--
作者:
Fry, Norman K.;Litt, David J.;Harrison, Timothy G.

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最近接种百日咳疫苗可能会混淆血清学和口腔液(OF)检测,这些检测以抗百日咳毒素(抗PT)IgG抗体作为近期感染的标志物。本研究旨在根据实验数据确定最小潜在混淆时间段,以帮助解读英国受试者提交的百日咳诊断样本。使用改良的OF IgG抗体捕获ELISA(GACELISA)在接种后测量抗PT IgG抗体应答和衰减。数据来自72名婴儿在第三次无细胞百日咳疫苗接种后的主要计划(4个月大)和119名儿童在学龄前(3岁4个月至5岁8个月大)单次接种后。在初次免疫(第三剂)后9个月和学龄前加强免疫(PSB)后13个月,每隔约1个月采集一次标本。改良GACELISA的灵敏度为52/56(92.9 ok:95% CI 82.7-98.0),特异性为120/128(93.8%:95%CI 88.0-97.3),与国家参考实验室标准抗PT IgG血清ELISA结果一致(等级相关性=0.80)和原始OF测定(等级相关性=0.79)。对抗体滴度下降的建模显示,对于第三次初次给药后和PSB后受试者,第14天后每次加倍的时间分别降低54%和34%。这些数据表明,对于初次免疫后获得的样本,最小混杂时间段约为300天,对于PSB免疫后提交的英国儿童样本,最小混杂时间段至少为3年。当免疫后天数和流行率已知或假设时,这些数据将通过估计阳性预测值极大地帮助解释单个高诊断性抗PT IgG滴度。
Recent vaccination with pertussis vaccine can confound serological and oral fluid (OF) assays targeting anti-pertussis toxin (anti-PT) IgG antibodies as a marker of recent infection. This study sought to establish the minimum potentially confounding time period based on experimental data to assist interpretation from such samples submitted from UK subjects for pertussis diagnosis. Anti-PT IgG antibody response and decay were measured post-vaccination using a modified OF IgG antibody-capture ELISA (GACELISA). Data were obtained from 72 infants after the third acellular pertussis vaccine dose in the primary schedule (4 months of age) and from 119 children after the single dose at preschool age (3 years 4 months to 5 years 8 months of age). Specimens were taken at approximately 1 month intervals for 9 months post-primary immunization (third dose) and 13 months post-preschool booster (PSB). The modified GACELISA demonstrated a sensitivity of 52/56 (92.9 ok: 95% CI 82.7-98.0) and a specificity of 1 20/1 28 (93.8 %: 95% Cl 88.0-97.3) and showed good agreement with the National Reference Laboratory standard anti-PT IgG serum ELISA (rank correlation=0.80) and the original OF assay (rank correlation=0.79). Modelling of the decline in antibody titres showed a reduction of 54 % and 34% for each doubling of time after day 14 for the post-third primary dose and post-PSB subjects, respectively. These data suggest that the minimum confounding time period is approximately 300 days for samples obtained post-primary immunization and at least 3 years for samples submitted from UK children following immunization with the PSB. These data will greatly assist the interpretation of single high diagnostic anti-PT IgG titres by allowing an estimate of the positive predictive value, when the number of days post-immunization and prevalence are known or assumed.