Nath Avindra, Kolson Dennis L
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; and.
Department of Neurology, University of Pennsylvania, Philadelphia.
Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200356. doi: 10.1212/NXI.0000000000200356. Epub 2024 Dec 18.
During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.
在过去十年(及更长时间)里,神经科医生已经意识到一些影响神经系统的常见及新型感染的出现、持续存在及其后果。即使在诸如疱疹病毒、多瘤病毒/JC、流感、虫媒病毒和肝炎等常见的中枢神经系统感染中,在开发有效的抗病毒治疗方法以及感染后后遗症的治疗方面仍然存在挑战。随着环境变化和全球旅行增加,介导人畜共患病传播的节肢动物媒介传播了诸如西尼罗河病毒、登革热、基孔肯雅热、马脑炎和寨卡病毒等不常见病毒。尽管这些疾病对全球健康的影响尚未达到新冠病毒和艾滋病毒的程度,但随着传播媒介的持续传播以及由这些传播媒介介导的新人畜共患病从动物传播给人类的出现,其影响可能会急剧增加。此外,针对虫媒病毒感染的特异性病毒靶向治疗或有效疫苗尚未问世,这是限制这些感染发病率的一个重大挑战。相比之下,艾滋病毒-1是一种最早在20世纪30年代由非人灵长类动物直接传播给人类而起源的疾病,经过多年深入研究,现在有高度特异性和有效的抗病毒药物针对它,这些药物可以限制感染传播并延长所有人群的生命和健康。即使有抑制艾滋病毒复制的这些显著治疗效果,神经功能障碍(主要是认知障碍)仍影响着大量艾滋病毒感染者。这不仅强调了治疗潜在感染的重要性,还强调了即使在抗病毒治疗后也要开发针对初始感染遗留影响的治疗方法的重要性。值得注意的是,新冠病毒感染迅速出现后,迅速实施了高效且特异性的抗病毒疗法。这使得新冠病毒感染的发病率和死亡率早期就大幅降低。尽管如此,新冠病毒感染的感染后并发症(长新冠)现在是全球新出现的人畜共患病感染中成本较高的后果之一。开发能够穿透中枢神经系统的新型抗病毒疗法、疫苗以及针对宿主免疫反应和代谢功能障碍的疗法对于管理已有的和新出现的感染的感染性及感染后并发症将是必要的。