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临床试验/NCT04401488
NCT04401488Unknown不适用

Paediatric Post Pneumococcal Conjugate Vaccine Nasopharyngeal Carriage Study

University Hospital Southampton NHS Foundation Trust1 个研究点 分布在 1 个国家目标入组 4,000 人开始时间: 2014年10月1日最近更新:
适应症

试验速览

阶段
不适用
入组人数
4,000
试验地点
1
主要终点
Collection of pneumococci

研究概览

简要总结

The investigators intend to investigate the carriage of pneumococci and other respiratory microbes since the introduction of pneumococcal conjugate vaccines (Prevenar 7 and Prevenar 13). The principal aim is to gain a collection of samples that can be used to help investigate any changes that might occur in the epidemiology of microbes that are carried in the upper respiratory tract and which may cause respiratory disease, sepsis or meningitis after the introduction of Prevenar.

Nasopharyngeal and nasal swabs will be taken from up to 2,000 children aged 4 years and under in each year of the study. Swabs will be processed using traditional microbiology and molecular diagnostic techniques and isolated microbes such as S. pneumoniae further characterised using molecular methods. The investigators will also ask parents to complete a short questionnaire requesting: basic demographic data; vaccine history; recent illness; overseas travel and antibiotic usage.

The study will contribute to the success of the introduction of pneumococcal conjugate vaccines and will play a central role in maintaining confidence. The study will also help provide information for future vaccine policy as further vaccines are developed against microbes which cause respiratory disease, sepsis and meningitis.

详细描述

Streptococcus pneumoniae (the pneumococcus) is an important cause of pneumonia, meningitis and bacteraemia worldwide. The prevention of invasive pneumococcal disease (IPD) by immunisation has been a key public health priority. Conjugate vaccines have a good record of eradicating carriage of bacteria as well as protecting against disease because they evoke a T-cell dependent response. For this reason, they are also efficacious in children less than 2 years of age. The first pneumococcal conjugate vaccine, Prevenar 7, was licensed in the UK in 2001 and was added to the routine UK childhood immunisation schedule on 4th September 2006. Prevenar 13 replaced Prevenar 7 from 1st April 2010.

In the US Prevenar 7 was a successful intervention, resulting in decreases of childhood IPD by 69%, which was unsurprising considering that serotypes included in the vaccine (4, 6B, 9V, 14, 18C, 19F and 23F) had been reported to cause 70% of all IPD in young children. Decreases in IPD amongst the adult population were higher than predicted which is thought to have been due to herd immunity. Unfortunately this was also paralleled by an increase in disease caused by non-vaccine types or vaccine-related serotypes which had changed their protective capsule (undergone capsule switching) such as the acquisition of 19A capsular locus by a previously serotype 4 clone .

The introduction of Prevenar 7 into the UK childhood immunisation schedule led to a significant reduction in pneumococcal disease amongst children in the UK and early data after the introduction of Prevenar 13 suggests a further decline in pneumococcal carriage and disease due to the additional six serotypes contained within the vaccine. Recent studies in the UK have characterised collections of pneumococci in an attempt to better understand the clonal distribution of serotypes and sequence types. Such studies are important since pneumococci are highly transformable, with there being ample evidence of capsule switching and serotype replacement amongst pneumococci.

Although Prevenar 7 and 13 have been successful interventions in the UK and elsewhere, improved vaccines will be required to further control pneumococcal disease. Public Health England (previously Health Protection Agency) surveillance data of invasive pneumococcal disease has already indicated that serotype replacement has occurred after the implementation of Prevenar. The investigator's previous study, referred to here as the Southampton pneumococcal carriage study (Full name 'Understanding changes in the molecular epidemiology of pneumococci carried in the nasopharynx amongst children after the introduction of pneumococcal conjugate vaccines', REC No. 06/Q1704/105), also showed serotype replacement during the first three years of Prevenar 7 introduction. The serotypes seen during the investigator's SMART study (full name 'Analysis of the microbial community of the upper respiratory tract to support the development of effective vaccine policy', REC No. 11/SC/0518) similarly suggest the occurrence of serotype replacement in those who have had the Prevenar vaccine due to the low level of vaccine types found within the investigator's data set (data not yet published). There is currently insufficient evidence for the wider use of Prevenar 13 in teenagers and younger adults.

The introduction of vaccines that contain only selected serotypes, as is the case with Prevenar 7 and Prevenar 13, have been shown to promote S. pneumoniae capsule switching or capsule replacement which allows for the evasion of vaccine induced host immunity. It is therefore important to monitor which serotypes of S. pneumoniae are commonly causing disease. It is also important to analyse the nasopharynx as an ecological niche because a reduction in the carriage of pneumococci, due to Prevenar, could lead to a replacement effect such that pneumococci of serotypes not covered by the vaccine or other bacterial/microbe species may fill the niche. It is therefore also important to gain information on the carriage of other bacteria/microbes such as Haemophilus influenzae, Staphylococcus aureus and Neisseria meningitidis.

研究设计

研究类型
Observational
观察模型
Ecologic Or Community
时间视角
Cross Sectional

入排标准

年龄范围
— 至 4 Years(Child)
性别
All
接受健康志愿者

入选标准

  • All children aged 4 years or under, attending the recruitment sites during the recruitment period will be invited to participate through their parents or legal guardian.

排除标准

  • One child per family
  • Children with obstructed nasal passages

结局指标

主要结局

Collection of pneumococci

时间窗: By the end of the study (31/03/2027)

To gain a collection of pneumococci and other microbes of related importance that can be used to help investigate any changes that occur in the epidemiology of pneumococcal disease since the introduction of Prevenar 13

次要结局

  • Understand changes in the molecular epidemiology of pneumococci(By the end of the study (31/03/2027))

研究者

申办方类型
Other
责任方
Sponsor

研究点 (1)

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