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在一项咽炎的人体感染控制试验中 的传播潜力。

Transmission potential of during a controlled human infection trial of pharyngitis.

机构信息

Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia, Nedlands, Western Australia, Australia.

Medical School, University of Western Australia, Crawley, Western Australia, Australia.

出版信息

mSphere. 2024 Oct 29;9(10):e0051324. doi: 10.1128/msphere.00513-24. Epub 2024 Sep 10.

DOI:10.1128/msphere.00513-24
PMID:39254050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11520304/
Abstract

Controlled human infection (CHI) models can provide insights into transmission of pathogens such as (Strep A). As part of the Controlled Human Infection with Penicillin for (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain. Three approaches to understanding transmission were employed: the use of agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of distance droplets could spread during conversation; and environmental swabbing of high-touch items to detect Strep A on surfaces. Of the 60 (27%) CHIPS trial participants across five cohorts, 16 were enrolled in this sub-study; availability of study staff was the primary reason for selection. In total, 189 plates and 260 swabs were collected. Strep A was grown on one settle plate from a participant on the second day, using plates placed 30 cm away. This participant received the placebo dose of penicillin and had met the primary endpoint of pharyngitis. Whole-genome sequencing identified this to be the challenge strain. Strep A was not detected on any swabs. In this small sample of CHI participants, we did not find evidence of Strep A transmission by the airborne route or fomites, and just one instance of droplet spread while acutely symptomatic with streptococcal pharyngitis. Although these experiments provide evidence of minimal transmission within controlled clinical settings, greater efforts are required to explore Strep A transmission in naturalistic settings.IMPORTANCE remains a significant driver of morbidity and mortality, particularly in under-resourced settings. Understanding the transmission modalities of this pathogen is essential to ensuring the success of prevention methods. This proposed paper presents a nascent attempt to determine the transmission potential of nested within a larger controlled human infection model.

摘要

受控人体感染(CHI)模型可以提供有关病原体传播的深入了解,例如A 组链球菌(Strep A)。作为青霉素控制性人体感染用于 A 组链球菌(CHIPS)试验的一部分,我们探索了参与者故意感染 Strep A emm75 菌株的潜在传播可能性。采用了三种方法来了解传播:使用琼脂沉降平板捕捉可能的飞沫或空气传播的 Strep A;测量谈话期间飞沫可以传播的距离;以及对高接触物品进行环境擦拭以检测表面上的 Strep A。在五个队列的 60 名(27%)CHIPS 试验参与者中,有 16 名参加了这项子研究;研究人员的可用性是选择的主要原因。总共收集了 189 个平板和 260 个拭子。在第二天,一名参与者的一个沉降平板上长出了 Strep A,使用放置在 30 厘米远的平板。该参与者接受了青霉素的安慰剂剂量,并达到了咽炎的主要终点。全基因组测序确定这是挑战菌株。在任何拭子上均未检测到 Strep A。在这个小型 CHI 参与者样本中,我们没有发现 Strep A 通过空气传播途径或媒介物传播的证据,并且只有一例在急性链球菌性咽炎时的飞沫传播。尽管这些实验在受控临床环境中提供了最小传播的证据,但仍需要更大的努力来探索自然环境中的 Strep A 传播。意义仍然是发病率和死亡率的主要驱动因素,尤其是在资源匮乏的环境中。了解这种病原体的传播方式对于确保预防方法的成功至关重要。本文提出了一种新兴的尝试,即在更大的受控人体感染模型中确定 Strep A 的传播潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd2/11520304/28dabdeb0857/msphere.00513-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd2/11520304/28dabdeb0857/msphere.00513-24.f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abd2/11520304/28dabdeb0857/msphere.00513-24.f001.jpg

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本文引用的文献

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Microbiology (Reading). 2024 Jan;170(1). doi: 10.1099/mic.0.001421.
2
Searching for Strep A in the clinical environment during a human challenge trial: a sub-study protocol.在人体激发试验的临床环境中检测A群链球菌:一项子研究方案
Access Microbiol. 2023 Sep 20;5(9). doi: 10.1099/acmi.0.000650.v3. eCollection 2023.
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Pathogenesis, epidemiology and control of Group A Streptococcus infection.A 组链球菌感染的发病机制、流行病学和控制。
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Detection of Streptococcus pyogenes M1 in Australia and characterization of the mutation driving enhanced expression of superantigen SpeA.检测澳大利亚的酿脓链球菌 M1 并鉴定驱动超抗原 SpeA 过度表达的突变。
Nat Commun. 2023 Feb 24;14(1):1051. doi: 10.1038/s41467-023-36717-4.
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BMJ Open. 2022 Dec 8;12(12):e064022. doi: 10.1136/bmjopen-2022-064022.
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