West Nile Virus Neuroinvasive Disease

Abstract

West Nile virus (WNV), first recognized in North America in 1999, was responsible for the largest arboviral epidemic of human encephalitis in history and continues to be the most frequent cause of epidemic meningoencephalitis in North America. WNV neuroinvasive disease (WNND) occurs in fewer than 1% of infected individuals, with presentations including aseptic meningitis, encephalitis, and poliomyelitis. Between 1999 and 2009, over 12,000 cases of WNND were reported in the United States, with the peak annual incidence occurring in epidemics of 2002 and 2003. In this review, we first summarize the epidemiology of WNV over the past decade and the salient clinical features of WNND, including a discussion of laboratory and radiographic findings, risk factors, morbidity, and mortality. In addition, we review recent progress in our understanding of virus and host determinants of the pathogenesis of WNND, as well as the prospects for the development of specific therapeutic targets.

The role of chemokines in the pathogenesis of neurotropic flaviviruses

“…However, in the mid1990s, the epidemiology and ecology changed, with frequent outbreaks occurring in new geographic areas characterized by high rates of severe neurological disease and death. In 1999, WNV was identified as the causative agent of seven human fatalities as well as a large number of avian deaths in New York City and the surrounding areas [10,11]. From there, the virus spread westward across the US and into Canada, and southward into Mexico, the Caribbean, and Central/South America, decimating bird populations and causing 31,257 cases and 1,254 (4 %) associated deaths [12,13].…”

“…From there, the virus spread westward across the US and into Canada, and southward into Mexico, the Caribbean, and Central/South America, decimating bird populations and causing 31,257 cases and 1,254 (4 %) associated deaths [12,13]. WNV has been detected in over 300 bird and 60 mosquito species in North America and appears to be firmly implanted in the New World [10]. The success of WNV can be attributed to several factors, such as the presence of numerous competent Culex species for transmission, and the naive and highly susceptible bird populations of North America.…”

Investigation of neuropathogenesis and control of an equine-pathogenic Australian West Nile virus isolate in an established CD1 Swiss white mouse and a novel rabbit model

“…However, since the 1990's, outbreaks involving patients with fatal encephalitis has been observed globally [6][7][8][9]. In 1999, the first WNV case was identified in the US and since then WNV has been responsible for several human and equine outbreaks across the country with neurological disease being a notable feature of infected individuals [9,10]. In 2012, the USA Centers for Disease Control and Prevention (CDC) reported the highest number of human WNV cases in the US since 2003 [11].…”

“…Of the 5674 cases, 51% were reported to be neuroinvasive, amounting to the highest number of human neuroinvasive cases caused by an arbovirus in US history [3]. Prior to 2012, US patients with neuroinvasive disease per year accounted for less than 1% of symptomatic cases [10,[12][13][14]. Meningitis, encephalitis and poliomyelitis appear to be the main pathological features in human disease [10].…”

“…Prior to 2012, US patients with neuroinvasive disease per year accounted for less than 1% of symptomatic cases [10,[12][13][14]. Meningitis, encephalitis and poliomyelitis appear to be the main pathological features in human disease [10]. Horses present with similar neurological disease, with neurological cases in WNV-infected equids reported to be approximately 10% [13,15].…”