Camacho Juan, Negredo Anabel, Carrilero Bartolomé, Segovia Manuel, Moreno Antonio, Pozo Francisco, Echevarría Juan-Emilio, Echevarría José-Manuel, Sánchez-Seco M Paz, Tarragó David
National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
CIBER Enfermedades Infecciosas, Madrid, Spain.
Infect Dis Ther. 2023 Nov;12(11):2621-2630. doi: 10.1007/s40121-023-00884-0. Epub 2023 Oct 23.
We report the case of a fatal hemorrhagic varicella primary infection in an immunocompetent man and whole-genome characterization of the virus for the investigation of biomarkers of virulence.
A 38-year-old patient born in Nigeria presented to the emergency department with abdominal pain and subsequently developed fatal hemorrhagic disease without skin rash. Extensive laboratory tests including serology and PCR for arenaviruses, bunyaviruses and ebolaviruses were negative. Varicella-zoster virus (VZV) PCR of sera, liver and spleen tissue samples from autopsy revealed the presence of VZV DNA. Primary infection by varicella-zoster virus with hemorrhagic manifestations was diagnosed after virological testing. The VZV genome was sequenced using a mWGS approach. Bioinformatic analysis showed 53 mutations across the genome, 33 of them producing non-synonymous variants affecting up to 14 genes. Some of them, such as ORF11 and ORF 62, encoded for essential functions related to skin or neurotropism. To our knowledge, the mutations reported here have never been described in a VZV causing such a devastating outcome.
In immunocompetent patients, viral factors should be considered in patients with uncommon symptoms or severe diseases. Some relevant mutations revealed by using whole genome sequencing (WGS) directly from clinical samples may be involved in this case and deserves further investigation.
Differential diagnosis of varicella-zoster virus in immunocompetent adults should be considered among patients with suspected VHF, even if the expected vesicular rash is not present at admission and does not arise thereafter. Whole genome sequencing of strains causing uncommon symptoms and/or mortality is needed for epidemiological surveillance and further characterization of putative markers of virulence. Additionally, this report highlights the recommendation for a VZV vaccination policy in non-immunized migrants from developing countries.
我们报告了一例免疫功能正常男性发生的致命性出血性水痘原发性感染病例，并对病毒进行全基因组特征分析以研究毒力生物标志物。
一名出生于尼日利亚的38岁患者因腹痛就诊于急诊科，随后发展为无皮疹的致命性出血性疾病。包括对沙粒病毒、布尼亚病毒和埃博拉病毒进行血清学和PCR检测在内的广泛实验室检查均为阴性。尸检时采集的血清、肝脏和脾脏组织样本的水痘带状疱疹病毒（VZV）PCR检测显示存在VZV DNA。经病毒学检测后诊断为水痘带状疱疹病毒原发性感染并伴有出血表现。使用mWGS方法对VZV基因组进行了测序。生物信息学分析显示全基因组有53个突变，其中33个产生非同义变体，影响多达14个基因。其中一些基因，如ORF11和ORF 62，编码与皮肤或嗜神经性相关的重要功能。据我们所知，此处报告的突变从未在导致如此严重后果的VZV中被描述过。
在免疫功能正常的患者中，对于出现不常见症状或严重疾病的患者应考虑病毒因素。直接从临床样本中使用全基因组测序（WGS）揭示的一些相关突变可能与该病例有关，值得进一步研究。
对于疑似病毒性出血热的免疫功能正常成年人，即使入院时未出现预期的水疱疹且此后也未出现，也应考虑水痘带状疱疹病毒的鉴别诊断。对引起不常见症状和/或死亡的毒株进行全基因组测序对于流行病学监测和进一步鉴定假定的毒力标志物是必要的。此外，本报告强调了对来自发展中国家未接种疫苗的移民实施VZV疫苗接种政策的建议。
