Surveillance and Diagnosis of West Nile Virus in the Face of Flavivirus Cross-Reactivity

Abstract

West Nile Virus (WNV) is an arthropod-borne flavivirus whose zoonotic cycle includes both mosquitoes and birds as amplifiers and humans and horses as dead-end hosts. In recent years WNV has been spreading globally and is currently endemic in Africa, The Middle East, India, Australia, central and southern Europe, and the Americas. Integrated surveillance schemes and environmental data aim to detect viral circulation and reduce the risk of infection for the human population emphasizing the critical role for One Health principles in public health. Approximately 20% of WNV infected patients develop West Nile Fever while in less than 1%, infection results in West Nile Neurological Disease. Currently, the diagnosis of WNV infection is primarily based on serology, since molecular identification of WNV RNA is unreliable due to the short viremia. The recent emergence of Zika virus epidemic in America and Asia has added another layer of complexity to WNV diagnosis due to significant cross-reactivity between several members of the Flaviviridae family such as Zika, dengue, Usutu, and West Nile viruses. Diagnosis is especially challenging in persons living in regions with flavivirus co-circulation as well as in travelers from WNV endemic countries traveling to Zika or dengue infected areas or vise-versa. Here, we review the recent studies implementing WNV surveillance of mosquitoes and birds within the One Health initiative. Furthermore, we discuss the utility of novel molecular methods, alongside traditional molecular and serological methods, in WNV diagnosis and epidemiological research.

Influence of flavivirus co‐circulation in serological diagnostics and surveillance: A model of study using West Nile, Usutu and Bagaza viruses

“…At least five genetic lineages have been identified, but only two of them (lineages 1 and 2) have shown high expansion and relevance for animal and human health. In response to this emerging threat, many affected (or at risk) countries are implementing surveillance programs which rely, at least in part, on monitoring animal populations at risk of exposure, including wild bird reservoirs (Gossner et al, ; Lustig, Sofer, Bucris, & Mendelson, ). Identification of WNV circulation by viral RNA detection is not practical due to the difficulties to find positive samples as a result of the short period of viremia (usually 4–6 days) caused by infections (Komar et al, ).…”

Diagnosis of West Nile virus encephalitis in a returned traveller

“…Rogers and colleagues relied on paired flavivirus serology for diagnosis, whereas our case relied on urine flavivirus PCR for diagnosis. Flavivirus diagnosis can be difficult due to low viraemia levels, potential for serological cross‐reactivity, or false negative results in the presence of hypogammaglobulinaemia. Emerging evidence suggests flavivirus PCR may be detectable for a number of weeks in urine and whole blood, particularly in neuroinvasive disease, compared with serum, which may remain positive for up to a week after symptom onset …”

In vitro and in vivo RNAi screening with a West Nile virus library encoding artificial microRNAs identifies novel host restriction factors

“…Mosquito-borne flaviviruses include Murray valley encephalitis virus (MVEV), St. Louis encephalitis virus (SLEV), yellow fever virus (YFV), dengue virus (DENV) serotypes 1-4, Japanese encephalitis virus (JEV), Zika virus (ZIKV) and West Nile virus (WNV) whereas tickborne encephalitis virus is the most prominent flavivirus spread by ticks [1]. Most flavivirus infections are reported in tropical and temperate regions where climatic conditions allow arthropods to thrive and favour flavivirus replicative lifecycles in arthropods [8,9]. Emergence of new flaviviruses in areas where they were not known as endemic has been attributed to urbanisation, tourism, travel and improved surveillance programs [10,11].…”

“…During a blood meal, WNV-infected mosquitoes transfer the virus to the dermis and to some extent directly into the blood stream of a vertebrate host [55]. The incubation period of WNV infection in human is [2][3][4][5][6][7][8][9][10][11][12][13][14] days and infections in immunocompetent humans are either asymptomatic or self-limited febrile illness with general body weakness, muscle and joint pains, headache, gastrointestinal complaints, skin rash and lymphadenopathy. However in immunocompromised individuals, infants, elderly and rare situations, a small proportion of WNV cases develop neurological infections characterised by flaccid paralysis, meningitis and encephalitis, which can often lead to death [56].…”

“…RNA replication stages (5, 6, 7 and 8) occur in the vesicle packets formed in the endoplasmic reticulum membrane. Immature virions are shuttled through host secretory pathway causing WNV-E glycosylation and cleavage of prM into mature M by furin (9). Consequently, mature virions are shuttled and released from the plasma membrane by exocytosis (10).…”