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肺炎球菌结合疫苗对蒙古国2至59个月住院儿童肺炎球菌携带情况的影响:一项活动性肺炎监测项目

Effect of pneumococcal conjugate vaccination on pneumococcal carriage in hospitalised children aged 2-59 months in Mongolia: an active pneumonia surveillance programme.

作者信息

von Mollendorf Claire, Mungun Tuya, Ulziibayar Munkhchuluun, Nguyen Cattram D, Batsaikhan Purevsuren, Suuri Bujinlkham, Luvsantseren Dashtseren, Narangerel Dorj, Tsolmon Bilegtsaikhan, Demberelsuren Sodbayar, Ortika Belinda D, Pell Casey L, Wee-Hee Ashleigh, Nation Monica L, Hinds Jason, Dunne Eileen M, Mulholland E K, Satzke Catherine

机构信息

Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.

National Center for Communicable Diseases, Ulaanbaatar, Mongolia.

出版信息

Lancet Microbe. 2024 Dec;5(12):100929. doi: 10.1016/S2666-5247(24)00171-X. Epub 2024 Oct 30.

DOI:10.1016/S2666-5247(24)00171-X
PMID:
39486429
Abstract

BACKGROUND

Data on changes in pneumococcal serotypes in hospitalised children following the introduction of the pneumococcal conjugate vaccine (PCV) in low-income and middle-income countries are scarce. In 2016, Mongolia introduced the 13-valent PCV (PCV13) into the national immunisation programme. We aimed to describe the trend and impact of PCV13 introduction on pneumococcal carriage in hospitalised children aged 2-59 months with pneumonia in Mongolia over a 6-year period.

METHODS

In this active surveillance programme, children aged 2-59 months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50 beats per min, oxygen saturation <90%, or clinical diagnosis of severe pneumonia) were enrolled between April 1, 2015, and June 30, 2021, from four districts in Ulaanbaatar. We tested nasopharyngeal samples collected at enrolment for pneumococci using lytA real-time quantitative PCR and conducted molecular serotyping and detection of antimicrobial resistance (AMR) genes with DNA microarray. We used log-binomial regression to estimate prevalence ratios (PRs) of pneumococcal carriage, comparing prevalence in the periods before and after the introduction of PCV13 and between vaccinated and unvaccinated children for three outcomes: overall, PCV13 vaccine-type, and non-PCV13 vaccine-type carriage. PRs were adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature.

FINDINGS

A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411 collected nasopharyngeal swabs were tested for pneumococci. In all age groups, a similar prevalence of pneumococcal carriage was shown between the pre-PCV13 period and post-PCV13 period (882 [48·0%] of 1837 vs 2174 [46·2%] of 4708; adjusted PR 0·98 [95% CI 0·92-1·04]; p=0·60). Overall, vaccine-type carriage reduced by 43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23 months) showed a 47·7% reduction in vaccine-type carriage (95% CI 41·2-53·5; adjusted PR 0·52 [95% CI 0·46-0·59]; p<0·0001), whereas children aged 24-59 months had a 29·3% reduction (12·6-42·8; 0·71 [0·57-0·87]; p=0·0014). Prevalence of 6A, 6B, 14, 19F, and 23F decreased following the introduction of PCV13; however, 19F and 6A remained common (5·8% and 2·9%). Non-vaccine-type carriage increased (adjusted PR 1·49 [95% CI 1·32-1·67]), with 15A, NT2, and 15B/C being the most prevalent serotypes. Overall, 1761 (89·3%) of 1978 analysed samples contained at least one AMR gene. The percentage of samples with any AMR gene decreased with vaccine introduction (92·3% in the pre-PCV13 period vs 85·3% in the post-PCV13 period; adjusted odds ratio 0·49 [95% CI 0·34-0·70]), with similar decreases for samples with at least three AMR genes (46·8% vs 27·6%; 0·44 [0·36-0·55]).

INTERPRETATION

6 years after the introduction of PCV13 in Mongolia, the prevalence of vaccine-type carriage and AMR genes showed a reduction among young hospitalised children with pneumonia. Reductions in vaccine-type carriage are likely to result in reductions in pneumococcal pneumonia.

FUNDING

GAVI, the Vaccine Alliance.

摘要

背景

在低收入和中等收入国家引入肺炎球菌结合疫苗(PCV)后,关于住院儿童肺炎球菌血清型变化的数据稀缺。2016年,蒙古将13价肺炎球菌结合疫苗(PCV13)纳入国家免疫规划。我们旨在描述在6年期间,PCV13引入对蒙古2至59个月患肺炎住院儿童肺炎球菌携带情况的趋势和影响。

方法

在这个主动监测项目中,2015年4月1日至2021年6月30日期间,从乌兰巴托的四个区招募符合研究病例定义(咳嗽或呼吸困难,呼吸频率≥50次/分钟、血氧饱和度<90%或临床诊断为重症肺炎)的2至59个月患肺炎儿童。我们使用lytA实时定量PCR检测入组时采集的鼻咽样本中的肺炎球菌,并通过DNA微阵列进行分子血清分型和抗菌药物耐药(AMR)基因检测。我们使用对数二项回归估计肺炎球菌携带的患病率比(PRs),比较PCV13引入前后以及接种和未接种儿童中三种结果的患病率:总体、PCV13疫苗型和非PCV13疫苗型携带。PRs用通过使用有向无环图确定的协变量进行调整,相关文献提供了参考。

结果

共纳入17688名儿童,其中17607名(99.5%)符合研究病例标准。在采集的15411份鼻咽拭子中,6545份(42.5%)检测了肺炎球菌。在所有年龄组中,PCV13引入前和引入后肺炎球菌携带率相似(1837份中的882份[48.0%] vs 4708份中的2174份[46.2%];调整后的PR为0.98[95%CI 0.92 - 1.04];p = 0.60)。总体而言,引入PCV13后疫苗型携带率降低了43.6%(调整后的PR为0.56[95%CI 0.51 - 0.62];p<0.0001)。年龄较小的儿童(2至23个月)疫苗型携带率降低了47.7%(95%CI 41.2 - 53.5;调整后的PR为0.52[95%CI 0.46 - 0.59];p<0.0001),而24至59个月的儿童降低了29.3%(12.6 - 42.8;0.71[0.57 - 0.87];p = 0.0014)。引入PCV13后,6A、6B、14、19F和23F的患病率下降;然而,19F和6A仍然常见(5.8%和2.9%)。非疫苗型携带率增加(调整后的PR为1.49[95%CI 1.32 - 1.67]),15A、NT2和15B/C是最常见的血清型。总体而言,在1978份分析样本中,1761份(89.3%)至少含有一种AMR基因。随着疫苗的引入,含有任何AMR基因的样本百分比下降(PCV13引入前为92.3%,引入后为85.3%;调整后的优势比为0.49[95%CI 0.34 - 0.70]),至少含有三种AMR基因的样本也有类似下降(46.8%对27.6%;0.44[0.36 - 0.55])。

解读

在蒙古引入PCV13六年后,患肺炎住院的幼儿中疫苗型携带率和AMR基因患病率有所降低。疫苗型携带率的降低可能会导致肺炎球菌肺炎发病率下降。

资助

全球疫苗免疫联盟(GAVI)

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