Li Xiaolong, Chen Shouhang, Chen Yu, Han Shujie, Dai Bowen, Li Tianyu, Yuan Xin, Su Dan, Li Zhi, Shen Yuanfang, Zhang Yaodong, Zhang Xiaolong, Jin Yuefei, Wang Fang
Department of Infectious Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, 450018, China.
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.
BMC Pediatr. 2025 Apr 2;25(1):264. doi: 10.1186/s12887-025-05527-6.
Coxsackievirus (CV) A6 has been widely considered as the main cause of global hand, foot, and mouth disease (HFMD) outbreaks. Despite the serious threat to children's health posed by the emerging CV-A6, our knowledge of the epidemiological features and etiology of HFMD caused by the new CV-A6 strains remains limited. In the present study, we aimed to investigate the epidemiological and genetic characterizations of CV-A6-associated HFMD outbreaks in Henan Province, China between 2021 and 2022. Clinical data and biospecimens of 407 children with mild and severe CV-A6 infection from Henan Children's Hospital (Children's Hospital Affiliated to Zhengzhou University) were collected for this prevalence study. Logistic regression analysis was employed to assess potential risk factors for severe illness. We also sequenced the VP1 gene of 4 CV-A6 strains, and a phylogenetic tree was conducted to characterize the evolutionary features of these CV-A6 strains. The majority of patients were 1 ~ 2 years old (236/407, 62.93%). Rash (364/407, 89.43%) and increase of lung markings in both lungs (224/407, 55.04%) were found to account for the highest percentage of clinical manifestations and clinical examination. Logistic regression analysis showed that boys were more likely to develop critical illness (OR: 1.970; 95% CI: 1.220 ~ 3.180), and that persistent high fever (OR: 2.066; 95% CI: 1.375 ~ 3.105), and elevated procalcitonin (PCT) levels (OR: 2.931; 95% CI: 1.590 ~ 5.405) would increase the risk of developing a critical illness (P < 0.01). The phylogenetic tree indicated that the genotype of CV-A6 strains in Henan Province was the D3 subtype. Collectively, in addition to the rash, acute respiratory infections due to CV-A6 infection are becoming increasingly common. Male sex, persistent high fever, and elevated PCT levels are associated with an increased risk of critical illness in patients infected with the D3 subtype of CV-A6. These findings may provide a scientific basis for guiding the prevention of HFMD and increase clinicians' awareness of CV-A6 infection.
柯萨奇病毒A6（CV-A6）被广泛认为是全球手足口病（HFMD）疫情的主要病因。尽管新出现的CV-A6对儿童健康构成严重威胁，但我们对新型CV-A6毒株引起的手足口病的流行病学特征和病因的了解仍然有限。在本研究中，我们旨在调查2021年至2022年中国河南省CV-A6相关手足口病疫情的流行病学和基因特征。本患病率研究收集了来自河南省儿童医院（郑州大学附属儿童医院）的407例轻度和重度CV-A6感染儿童的临床数据和生物标本。采用逻辑回归分析评估重症的潜在危险因素。我们还对4株CV-A6毒株的VP1基因进行了测序，并构建了系统发育树以表征这些CV-A6毒株的进化特征。大多数患者年龄为1至2岁（236/407，62.93%）。皮疹（364/407，89.43%）和双肺肺纹理增多（224/407，55.04%）在临床表现和临床检查中占比最高。逻辑回归分析表明，男孩更易发展为危重症（比值比：1.970；95%置信区间：1.220至3.180），持续高热（比值比：2.066；95%置信区间：1.375至3.105）和降钙素原（PCT）水平升高（比值比：2.931；95%置信区间：1.590至5.405）会增加发展为危重症的风险（P<0.01）。系统发育树表明，河南省CV-A6毒株的基因型为D3亚型。总体而言，除皮疹外，CV-A6感染引起的急性呼吸道感染越来越常见。男性、持续高热和PCT水平升高与感染CV-A6 D3亚型患者发展为危重症的风险增加相关。这些发现可能为指导手足口病的预防提供科学依据，并提高临床医生对CV-A6感染的认识。
