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葡萄牙全国免疫计划引入 PCV13 后儿童肺炎链球菌携带、血清型、基因型和抗生素耐药趋势的横断面研究。

Streptococcus pneumoniae carriage, serotypes, genotypes, and antimicrobial resistance trends among children in Portugal, after introduction of PCV13 in National Immunization Program: A cross-sectional study.

机构信息

Laboratory of Molecular Microbiology of Human Pathogens, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal.

MOSTMICRO Unit, ITQB NOVA, Oeiras, Portugal.

出版信息

Vaccine. 2024 Sep 17;42(22):126219. doi: 10.1016/j.vaccine.2024.126219. Epub 2024 Aug 14.

Abstract

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance.

摘要

肺炎链球菌带菌研究对于监测使用肺炎球菌结合疫苗引起的变化以及为疫苗接种政策提供信息至关重要。在这项横断面研究中,我们研究了 2015 年葡萄牙国家免疫计划(NIP)引入 PCV13 后肺炎链球菌人群的变化。在 2018-2020 年(NIP-PCV13)期间,我们从≤6 岁的日托儿童中获得了 1450 份鼻咽样本。我们评估了血清型、抗菌药物耐药性和基因型(MLST 和 GPSC),并将结果与早期时期进行了比较:2009-2010 年(PCV13 前)、2011-2012 年(PCV13 早期)和 2015-2016 年(PCV13 晚期)。肺炎链球菌带菌率保持在 60.2%。PCV13 血清型的带菌率为 10.7%,与 PCV13 前时期相比显著降低(47.6%)。最常见的 PCV13 血清型为 19F、3 和 19A,与 PCV13 前时期相比均呈显著下降趋势(分别从 7.1%降至 4.7%、10.1%降至 1.8%和 14.1%降至 1.8%),这是一个值得注意的观察结果,因为 PCV13 对血清型 3 的效力有限。未接种疫苗的儿童和 4-6 岁的儿童更有可能携带 PCV13 血清型(分别为 2.5 倍,95%CI [1.1-5.6]和 2.9 倍,95%CI [1.3-6.8])。最常见的非 PCV13 血清型为 15B/C、11A、23B、23A 和 NT,合计占所有分离株的 51.9%。总共,30.5%的肺炎球菌可能被 PCV20 覆盖。青霉素(低水平)和大环内酯类药物的耐药性显著增加,从 PCV13 晚期的 9.3%和 13.4%分别增加到接近 20%,这主要是由于表达非 PCV13 血清型的谱系引起的,接近 PCV13 前时期的水平。CC156-GPSC6(血清型 14)和 CC193-GPSC11(血清型 19F)等传统上与 PCV13 血清型相关的谱系的扩张,但现在主要表达非 PCV13 血清型(GPSC6 的 11A、15B/C 和 24F;GPSC11 的 15A 和 21)。这些发现表明,肺炎链球菌人群正在适应 PCV13 和抗菌药物使用带来的压力,并表明需要保持密切监测。

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