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先天性巨细胞病毒感染:诊断与治疗的最新进展

Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment.

作者信息

Chiopris Giulia, Veronese Piero, Cusenza Francesca, Procaccianti Michela, Perrone Serafina, Daccò Valeria, Colombo Carla, Esposito Susanna

机构信息

Paediatric Clinic Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.

Neonatology Clinic, Pietro Barilla Children's Hospital, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy.

出版信息

Microorganisms. 2020 Oct 1;8(10):1516. doi: 10.3390/microorganisms8101516.

Abstract

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

摘要

先天性巨细胞病毒(cCMV)感染是最常见的先天性病毒感染,是感音神经性听力损失(SNLH)的主要非遗传病因,也是神经发育障碍的重要病因。孕期发生原发性感染时,宫内传播风险最高,感染时孕周较大的母亲垂直传播率更高,而如果胎儿在妊娠前半期发生感染,胎儿出现不良影响的风险会显著增加。尽管cCMV感染在新生儿群体中很普遍且发病率高,但目前尚无针对cCMV感染的标准化诊断检测方法和治疗方案。本叙述性综述旨在探讨cCMV感染诊断和治疗的最新进展。文献分析表明,除孕期行为措施外,仍缺乏预防性干预措施,尽管目前正在进行许多临床试验以制定孕前女性疫苗。目前,我们建议对疑似cCMV感染的新生儿进行血液、尿液和唾液的PCR检测。目前,尚无证据表明抗病毒治疗对无症状婴儿有益。对于有症状的cCMV感染,我们实际上建议口服缬更昔洛韦治疗12个月。该治疗方案的有效性和耐受性已被证明对听力和神经发育的长期结局有效。缬更昔洛韦仅用于出生时患有症状性疾病的先天性感染新生儿,如小头畸形、颅内钙化、脑脊液指标异常、脉络膜视网膜炎或感音神经性听力损失。由于研究证据不足,对于出生时患有轻度症状性疾病的新生儿、孕周小于32周的新生儿或出生30天以上的婴儿,不常规推荐使用抗病毒药物治疗。然而,由于这些人群占cCMV感染新生儿和婴儿的绝大多数,且他们有发生迟发性后遗症的风险,因此还应找到一种能够预测长期后遗症的生物标志物,以证明开始治疗的合理性并减轻CMV相关并发症的负担。

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