Reemerging Infectious Diseases and Neuroimmunologic Complications

Abstract

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.

Figure 1. Pathways of Virus Entry Into the CNS

Multiple routes of entry of infectious virus into the CNS are possible, and individual viruses may use multiple routes. For some viruses, autopsied human tissues of acutely infected decedents have provided confirmation of initial entry routes (e.g., SARS-CoV-2 and HIV-1). For other viruses, presumed routes of entry in humans are based on in vitro cell culture infection studies or animal infection models. Created in BioRender. KOLSON, D. (2024) BioRender.com/w28h898. VZV = varicella zoster virus.

Figure 2. Spread of West Nile Virus After Introduction Into the Northeastern United States in 1999–2000

By 2004, WNV infection spread across the entire country and it remains endemic to this day.

Figure 3. Distribution of Zika Virus Infections and Carrier Mosquito Presence Globally

Light blue represents countries without known presence of the mosquito vector. Medium blue represents countries known to have the mosquito vector but no known Zika virus infection cases. Dark blue represents countries with past or current Zika virus infection cases.