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儿童干细胞移植后多种腺病毒血清型的序贯出现。

Sequential emergence of multiple adenovirus serotypes after pediatric stem cell transplantation.

作者信息

Kroes Aloys C M, de Klerk Erik P A, Lankester Arjan C, Malipaard Corry, de Brouwer Caroline S, Claas Eric C J, Jol-van der Zijde Els C, van Tol Maarten J D

机构信息

Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

J Clin Virol. 2007 Apr;38(4):341-7. doi: 10.1016/j.jcv.2007.01.001. Epub 2007 Feb 20.

DOI:10.1016/j.jcv.2007.01.001
PMID:17317293
Abstract

BACKGROUND

Adenovirus infections after allogeneic stem cell transplantation (SCT), particularly in children, may be severe and protracted. Up to 51 different serotypes of adenovirus are presently recognized but serotyping is usually limited to initial viral isolates.

OBJECTIVES

A systematic and sustained analysis of adenovirus serotypes in a cohort of adenovirus-infected pediatric SCT recipients, correlated to transplant-associated variables.

STUDY DESIGN

Eighty-three consecutive pediatric SCT recipients were studied by culture of feces and adenoviruses isolated were serotyped by neutralization. Upon persistent viral excretion, serotyping was repeated for at least two isolates of any infectious episode, including initial and final isolates, and patients with single and multiple serotypes were compared. In a subset of cases, serotyping of fecal isolates was compared to genotypic analysis.

RESULTS

In 33 patients, adenovirus was isolated at least once after SCT. Serotyping uncovered 49 different adenoviruses, including three isolates without an assigned serotype. In 16 patients, a single serotype was present for a sustained period, whereas 12 patients (36%) showed multiple serotypes. Comparison of these groups demonstrated more frequent non-malignant primary disease with multiple infections (p<0.01), but otherwise no significant differences were observed, although single serotype infections had a lower survival rate. Remarkably, serotype 31 appeared initially in 7 out of 12 patients with multiple infections. Genotyping by sequencing confirmed neutralization assays at least at the species level in 14 of 18 isolates.

CONCLUSION

In 36% of adenovirus infections after SCT more than one serotype could be detected by sequential analysis. Multiple serotypes occurred more often with non-malignant disorders. Adenovirus serotype 31 was often included. This finding is relevant for diagnostic purposes and immunotherapeutic interventions and provides insight into the pathogenesis of this problem.

摘要

背景

异基因干细胞移植(SCT)后腺病毒感染,尤其是在儿童中,可能较为严重且病程迁延。目前已识别出多达51种不同血清型的腺病毒,但血清分型通常仅限于初始病毒分离株。

目的

对一组腺病毒感染的儿科SCT受者的腺病毒血清型进行系统且持续的分析,并与移植相关变量相关联。

研究设计

对83例连续的儿科SCT受者进行粪便培养研究,分离出的腺病毒通过中和试验进行血清分型。在病毒持续排泄时,对任何感染发作的至少两个分离株(包括初始和最终分离株)重复进行血清分型,并比较单一血清型和多种血清型的患者。在部分病例中,将粪便分离株的血清分型与基因分型进行比较。

结果

33例患者在SCT后至少有一次分离出腺病毒。血清分型发现了49种不同的腺病毒,包括3株未指定血清型的分离株。16例患者在一段时间内呈现单一血清型,而12例患者(36%)表现出多种血清型。这些组别的比较显示,多种感染的非恶性原发性疾病更为常见(p<0.01),但除此之外未观察到显著差异,但单一血清型感染的存活率较低。值得注意的是,12例多种感染患者中有7例最初出现31型血清型。通过测序进行的基因分型在18株分离株中的14株中至少在种水平上证实了中和试验结果。

结论

在SCT后的腺病毒感染中,36%的病例通过序贯分析可检测到不止一种血清型。多种血清型在非恶性疾病中更常出现。31型腺病毒血清型常被包含在内。这一发现对于诊断目的和免疫治疗干预具有重要意义,并为该问题的发病机制提供了见解。

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