Acute neurologic emerging flaviviruses

Abstract

The COVID-19 pandemic has shed light on the challenges we face as a global society in preventing and containing emerging and re-emerging pathogens. Multiple intersecting factors, including environmental changes, host immunological factors, and pathogen dynamics, are intimately connected to the emergence and re-emergence of communicable diseases. There is a large and expanding list of communicable diseases that can cause neurological damage, either through direct or indirect routes. Novel pathogens of neurotropic potential have been identified through advanced diagnostic techniques, including metagenomic next-generation sequencing, but there are also known pathogens which have expanded their geographic distribution to infect non-immune individuals. Factors including population growth, climate change, the increase in animal and human interface, and an increase in international travel and trade are contributing to the expansion of emerging and re-emerging pathogens. Challenges exist around antimicrobial misuse giving rise to antimicrobial-resistant infectious neurotropic organisms and increased susceptibility to infection related to the expanded use of immunomodulatory treatments. In this article, we will review key concepts around emerging and re-emerging pathogens and discuss factors associated with neurotropism and neuroinvasion. We highlight several neurotropic pathogens of interest, including West Nile virus (WNV), Zika Virus, Japanese Encephalitis Virus (JEV), and Tick-Borne Encephalitis Virus (TBEV). We emphasize neuroinfectious diseases which impact the central nervous system (CNS) and focus on flaviviruses, a group of vector-borne pathogens that have expanded globally in recent years and have proven capable of widespread outbreak.

Mechanisms of Zika astrocyte infection and neuronal toxicity

“…But the long-term consequences of ZIKV infection in the mother and fetus are still active and ongoing. Currently, several Flaviviruses are neurotropic such as dengue viruses, West Nile, and yellow fever viruses, but also emerging viruses, such as Japanese encephalitic, tick-borne encephalitis and Usutu viruses [ 68 ], [ 69 ], [ 70 ], [ 71 ]. Despite extensive investigation and vaccines (experimental and under ongoing use), these viruses still pose a serious public health challenge and concern due to the infection and the expansion of the vectors worldwide [ 71 ].…”

“…Overall, the clinical symptoms of acute flavivirus infection range from mild to severe life-threatening diseases, including hemorrhagic fever, shock, encephalitis, paralysis, hepatic failure, and congenital defects. Several groups determine that severe disease is correlated with polymorphisms in critical host genes, including CCR5 for West Nile, DC-SIGN for Dengue, age, comorbidities, immune status, and prior flavivirus immunity [ 70 , 72 ], [ 73 ], [ 74 ]. In the case of ZIKV, direct and indirect neuronal and neuroprogenitor cell damage has been described [ 6 , 11 , 12 , 25 , 26 , 29 , 59 ].…”

“…This is partly due to the timeline of maternal ZIKV infection, breach of the placental barrier and the resulting developmental problems in the fetus can be traced as 6 wpc until as late as 29 wpc [ 75 ], but the main consensus is indicated in Figure 1 . Also, despite the evolution of several animal models, most data are limited to ultrasound, postmortem tissues, and newborn information, however, the specific developmental windows and consequences in the fetus development still are not well understood [ 6 , 9 , 59 , 70 , 73 ].…”

Congenital Zika syndrome

“…ZIKV has a strong tropism to ectodermal derivatives, which confers greater dissemination potential with a wide variety of clinical manifestations and specific alterations according to the infected tissue 35,45 . It has been reported that ZIKV presents neuronal tropism and towards other organs, such as the liver, kidney, heart, spleen, testicle, and ovary since viral RNA has been found in these tissues 30,46,47 .…”

Influence of mosquito-borne biological agents on health risks among soldiers and military personnel

“…In humans, the infection predominantly manifests with flu-like symptoms, while about 1% of patients develop a severe form accompanied by encephalitis (mortality rate up to 30%). The disease occurs mainly in Southeast Asia, as well as Pakistan, India, Sri Lanka, Nepal, Papua New Guinea, and Australia [51,65,66,67,68].…”