Zhang Ming-Zhu, Bian Cai, Ye Run-Ze, Cui Xiao-Ming, Yao Nan-Nan, Yang Ji-Hu, Chu Yan-Li, Su Xiao-Ling, Wu Ya-Fei, Ye Jin-Ling, Liu Shun-Shuai, Shi Xiao-Yu, Shi Wenqiang, Jia Na, Chen Yu-Guo, Zhao Lin, Zheng Yuan-Chun, Zheng Xiao-Min, Jiang Jia-Fu, Cao Wu-Chun
Institute of EcoHealth, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
Mudanjiang Forestry Central Hospital, Mudanjiang, Heilongjiang Province, China.
Lancet Infect Dis. 2025 Apr;25(4):390-398. doi: 10.1016/S1473-3099(24)00616-9. Epub 2024 Nov 7.
Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV.
In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses.
A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations.
Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms.
National Key Research and Development Program of China.
For the Chinese translation of the abstract see Supplementary Materials section.
北海道病毒（YEZV）是一种新出现的蜱传病原体，于2021年在日本首次报道。迄今为止，中国仅报告过1例患者。我们旨在描述一系列患者的流行病学、临床和实验室检查结果，并对YEZV的病毒基因组进行特征分析。
在这项主动监测和基因组分析中，我们在中国东北黑龙江省牡丹江市林业中心医院开展了主动监测。符合以下条件的参与者纳入研究：在2022年和2023年的5月1日至7月31日以及2024年的5月1日至7月10日期间因近期被蜱叮咬而就医。我们采集参与者的血清，通过宏转录组测序、实时逆转录聚合酶链反应（RT-PCR）和间接免疫荧光试验检测YEZV感染。我们通过细胞培养分离YEZV，并通过形态学和系统发育分析对病原体进行特征分析。
在988名参与者中，共识别出18例YEZV感染患者（男性12例，女性6例；中位年龄53岁，四分位间距45 - 60岁）。患者均出现发热（18例，100%）、头痛（10例，56%）、头晕（9例，50%）、乏力（3例，17%）、腰痛（3例，17%）和咳嗽（3例，17%）。9例（50%）患者在蜱叮咬部位周围出现皮疹，4例（22%）有淋巴结病。9例（50%）患者有胃肠道症状，5例（28%）有神经系统症状。在16例接受评估的患者中，10例（63%）出现白细胞减少，5例（31%）出现血小板减少。在所有18例患者中，13例（72%）肝转氨酶浓度升高，9例（50%）乳酸脱氢酶或α-羟丁酸脱氢酶升高，13例（72%）血清淀粉样蛋白A升高，10例（56%）超敏C反应蛋白升高。从参与者身上采集的119只全沟硬蜱中，8只（7%）检测出YEZV阳性。从患者血清中分离出3株YEZV毒株。从5例患者、1只从参与者身上采集的吸血全沟硬蜱以及在患者确诊地区或相邻地区采集的4份宿主搜寻蜱样本中获得了10个病毒基因组。系统发育分析显示，患者或蜱体内的YEZV分为两个进化枝，每个进化枝都有独特的突变。
认识YEZV感染很重要，临床医生在诊断有相应症状的患者时应考虑该病毒。
中国国家重点研发计划。
中文翻译摘要见补充材料部分。
