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迅速进展、致命、类似吸入性炭疽的人类感染:病例报告、病原体基因组测序、病理学和协调应对。

Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response.

机构信息

Department of Pathology and Laboratory Medicine, The Methodist Hospital System, Houston, Texas, USA.

出版信息

Arch Pathol Lab Med. 2011 Nov;135(11):1447-59. doi: 10.5858/2011-0362-SAIR.1. Epub 2011 Aug 9.

DOI:10.5858/2011-0362-SAIR.1
PMID:21882964
Abstract

CONTEXT

Ten years ago a bioterrorism event involving Bacillus anthracis spores captured the nation's interest, stimulated extensive new research on this pathogen, and heightened concern about illegitimate release of infectious agents. Sporadic reports have described rare, fulminant, and sometimes fatal cases of pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus , a species closely related to Bacillus anthracis.

OBJECTIVES

To describe and investigate a case of rapidly progressive, fatal, anthrax-like pneumonia and the overwhelming infection caused by a Bacillus species of uncertain provenance in a patient residing in rural Texas.

DESIGN

We characterized the genome of the causative strain within days of its recovery from antemortem cultures using next-generation sequencing and performed immunohistochemistry on tissues obtained at autopsy with antibodies directed against virulence proteins of B anthracis and B cereus.

RESULTS

We discovered that the infection was caused by a previously unknown strain of B cereus that was closely related to, but genetically distinct from, B anthracis . The strain contains a plasmid similar to pXO1, a genetic element encoding anthrax toxin and other known virulence factors. Immunohistochemistry demonstrated that several homologs of B anthracis virulence proteins were made in infected tissues, likely contributing to the patient's death.

CONCLUSIONS

Rapid genome sequence analysis permitted us to genetically define this strain, rule out the likelihood of bioterrorism, and contribute effectively to the institutional response to this event. Our experience strongly reinforced the critical value of deploying a well-integrated, anatomic, clinical, and genomic strategy to respond rapidly to a potential emerging, infectious threat to public health.

摘要

背景

十年前,涉及炭疽芽孢杆菌孢子的生物恐怖主义事件引起了全国的关注,刺激了对这种病原体的广泛新研究,并加剧了对非法释放传染性制剂的关注。有零星报道描述了人类和非人类灵长类动物中由蜡状芽孢杆菌引起的罕见、暴发性和有时致命的肺炎病例,蜡状芽孢杆菌是与炭疽芽孢杆菌密切相关的一种物种。

目的

描述和调查一起在德克萨斯州农村居住的患者发生的快速进展、致命的炭疽样肺炎和来源不明的芽孢杆菌属引起的严重感染病例。

设计

我们在从生前培养物中回收致病菌株后的几天内使用下一代测序技术对其基因组进行了特征描述,并使用针对炭疽芽孢杆菌和蜡状芽孢杆菌毒力蛋白的抗体对尸检获得的组织进行了免疫组织化学染色。

结果

我们发现感染是由一种以前未知的蜡状芽孢杆菌菌株引起的,该菌株与炭疽芽孢杆菌密切相关,但在遗传上是不同的。该菌株含有类似于 pXO1 的质粒,这是一种编码炭疽毒素和其他已知毒力因子的遗传元件。免疫组织化学显示,感染组织中产生了几种炭疽芽孢杆菌毒力蛋白的同源物,可能导致了患者的死亡。

结论

快速的基因组序列分析使我们能够在遗传上定义该菌株,排除生物恐怖主义的可能性,并有效地为应对这一事件的机构响应做出贡献。我们的经验强烈强调了部署综合的、解剖学的、临床的和基因组的策略来快速应对公共卫生潜在新发传染病威胁的重要性。

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