Obeid Michele, Gakhal Inderdeep, McDonald Philip J
Department of Internal Medicine, Hurley Medical Center/Michigan State University, Flint, Michigan, USA.
Access Microbiol. 2021 Aug 4;3(8):000256. doi: 10.1099/acmi.0.000256. eCollection 2021.
Human herpesvirus-6 (HHV-6), the virus which causes roseola, has traditionally been associated with benign and self-limited childhood illness. However, HHV-6 establishes lifelong latency and can reactivate in immunocompromised adult patients. In about 1% of cases, it integrates into the human genome as inherited chromosomally integrated HHV-6 (iciHHV-6). We report the case of a 70-year-old man presenting with altered mental status and agitation. His infectious workup revealed a cerebrospinal fluid sample positive for HHV-6 with virus detectable in the blood as well. He was subsequently treated with ganciclovir. HHV-6 viremia (DNAemia) persisted, and the antiviral medications were switched to foscarnet under the assumption of treatment failure due to drug resistance. After several admissions to the hospital for the same complaint, and after noticing that DNAemia persisted despite adequate treatment for HHV-6, infectious disease specialists ordered testing for chromosomally integrated virus. Test results confirmed the presence of iciHHV-6, explaining his consistently elevated serum viral load. Primary HHV-6 infection in adults causes a transient increase in viral load with resolution and clearance after a few weeks while iciHHV-6 is characterized by persistent detection of viral DNA at a high copy number. Individuals with iciHHV-6 can develop HHV-6 disease and are at increased risk for active viral replication when treated with immunosuppressive medications, but only mRNA testing, which is not widely available can differentiate between latent and active infection. This makes the decision to treat challenging in this patient population. When faced with a positive HHV-6 DNA result in the setting of equivocal symptoms, clinicians should consider the possibility of chromosomally integrated virus rather than drug-resistant virus in order to reduce exposure to potentially toxic antiviral medications.
人类疱疹病毒6型（HHV-6）是引起幼儿急疹的病毒，传统上一直与儿童期的良性自限性疾病相关。然而，HHV-6会建立终身潜伏感染，并且在免疫功能低下的成年患者中可能重新激活。在大约1%的病例中，它会整合到人类基因组中，成为遗传性染色体整合HHV-6（iciHHV-6）。我们报告了一例70岁男性患者，表现为精神状态改变和烦躁不安。他的感染性疾病检查显示脑脊液样本中HHV-6呈阳性，血液中也可检测到病毒。随后他接受了更昔洛韦治疗。HHV-6病毒血症（DNA血症）持续存在，由于假定治疗失败是由于耐药性，抗病毒药物换成了膦甲酸钠。在因同样的症状多次住院后，并且注意到尽管对HHV-6进行了充分治疗但DNA血症仍持续存在，传染病专家下令对染色体整合病毒进行检测。检测结果证实存在iciHHV-6，这解释了他的血清病毒载量持续升高的原因。成人原发性HHV-6感染会导致病毒载量短暂升高，几周后病毒载量会消退和清除，而iciHHV-6的特征是持续检测到高拷贝数的病毒DNA。患有iciHHV-6的个体可能会发生HHV-6疾病，并且在接受免疫抑制药物治疗时病毒活跃复制的风险增加，但只有mRNA检测（目前尚未广泛应用）才能区分潜伏感染和活跃感染。这使得在这一患者群体中做出治疗决策具有挑战性。当在症状不明确的情况下HHV-6 DNA检测结果呈阳性时，临床医生应考虑染色体整合病毒而非耐药病毒的可能性，以减少接触潜在有毒的抗病毒药物。
