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West Nile Virus
American crows are highly susceptible to infection and disease. American
Table 1: Year and Symptomatic Classification of West Nile
crows demonstrated a lethal dose (LD)
<10 plaque-forming units (PFU).
Disease Cases in the US
Some populations of this species have decreased by 90% following the
introduction of WNV.
It is not clear why WNV has proved to be so virulent
Year Neurological Fever Unspecified Total Deaths
for birds in North America, but one possible reason is a single amino acid
1999 59 3 0 62 7
residue in the NS3 helicase.
However, while the virus circulating in the US
2000 19 2 0 21 2
was demonstrated to be more virulent for American crows than a Kenyan
2001 64 2 0 66 9
no difference between the strains was evident in house sparrows.
2002 2,946 1,160 50 4,156 284
Therefore, alternative explanations must be considered. One possibility is that
2003 2,860 6,830 166 9,856 264
birds in the US have had relatively little exposure to related flaviviruses, with
2004 1,142 1,269 128 2,539 100
the exception of SLEV. Further studies need to be conducted. Domestic and 2005 1,294 1,607 99 3,000 119
wild mammals become infected, but their role in the transmission cycle is 2006 1,459 2,616 194 4,269 177
probably insignificant because of their generally low levels of viremia.
2007 1,059 2,026 29 3,114 92
Nonetheless, evidence is accumulating that some wild mammals may
TOTAL 10,902 15,515 666 27,083 1,054
contribute to WNV amplification.
Source: Centers for Disease Control and Prevention (CDC), November 6, 2007 (http://www.cdc.gov/ncidod/dvbid/
westnile). Neurological disease data include encephalitis, meningitis, and acute flaccid paralysis.
Culex mosquitoes are the predominant vectors, with the most important
species varying regionally and globally. Approximately 75 mosquito species with 1,054 fatalities (3.9% of all; 9.7% of ND) (see Table 1). The 2002/2003
have been found infected worldwide.
Mosquito species and populations epidemics in the US represent the largest outbreaks of ND ever reported in
vary in vector competence, i.e. the ability to become infected following an the western hemisphere, making WNV the dominant vector-borne viral
infectious blood meal, support replication of virus, and transmit the virus upon pathogen in North America. Approximately 1.4 million total infections have
taking subsequent blood meals. Longevity and host feeding preferences are been estimated.
There have been no reported cases of WN disease in
also critical factors.
Three of the major vector species in the US, the tropical America with a few exceptions, e.g. the Cayman Islands. The
predominantly ornithophilic C. pipiens, C. nigripalpus, and C. tarsalis, have reasons for this are not clear, but hypotheses include the presence of cross-
been demonstrated to shift their feeding from birds to mammals in the late protective flaviviruses,
decreased virulence of the circulating virus, and
summer and early fall,
thereby acting as bridge vectors and facilitating greater biodiversity in the region. Similarly, there have been no overt cases
spillover of the virus from the enzootic cycle to infect equine and human in the UK, even with evidence of serological conversions in sentinel
hosts. An important vector in urban areas in the southern US is chickens.
The lack of human cases in northern Europe compared with
C. quinquefasciatus, which feeds broadly on both avian and mammalian southern Europe may be attributed to the genetics of the predominant
hosts, including man.
Host switching may be due to departure of a preferred vector, C. pipiens,
virus strain differences, and climatic factors, among
host, lack of tolerance by avian hosts as mosquito populations increase, or other possible explanations.
genetic composition of the species in the US.
Other species that feed
frequently on mammals, e.g. C. salinarius, probably become involved as Infection most commonly takes place following a bite from an infected
bridge vectors in areas where they are common, exposing animals not mosquito, and leads to a broad spectrum of disease in humans ranging
involved in enzootic transmission of virus. WNV survives adverse seasons in from fever to severe ND, including meningitis, encephalitis, and acute
temperate environments, most likely in the diapausing adult Culex female flaccid paralysis. This is typical of most Culex-transmitted flavivirus
in hibernacula. However, persistent infection has been observed in infections, such as WNV.
Severe disease is more common in older
experimentally infected animals;
therefore, recrudescence of infectious individuals and immunocompromised hosts are at greatest risk.
virus in birds cannot be ruled out as a possible means of perpetuation of Transplant patients are at extreme risk for ND following blood
the virus. Infected migratory birds may also play an important role in the transfusion, donor transmission, or community exposure.
re-introduction of the virus after harsh winters or dry seasons. In Europe and had been considered mild and unremarkable before the largest outbreaks
Asia, the virus is re-introduced by migrating birds
and possibly may occurred in the US in 2002 and 2003, but it is now clear that the fever
overwinter in adult mosquitoes.
cases also can be serious and may lead to death. Long-term neurological
and functional sequelae are common, with more severe complications
Alternative non-vector-borne modes of transmission have been noted, i.e. following ND.
transfusion and transplantation transmission in humans, ingestion of infected
breast milk, and intra-uterine transmission.
Fecal–oral and peroral Diagnostics
transmission have been observed in experimental animals. WNV has been Serological diagnosis remains the mainstay to confirm WNV infection in
detected in the urine of a patient.
Experimentally infected hamsters have patients following clinical evaluation. Immunoassays are conducted on
been demonstrated to shed the virus in their urine over 52 days and they can serum and cerebrospinal fluid (CSF) for immunoglobulin (Ig) M and IgG
become infected via the oral route.
Cats and other vertebrates also become antibodies. However, confirmation of recent infection in humans is
infected by the oral route following feeding on infected dead animals.
confounded by a long-lasting IgM antibody that has been observed to last
for ≥16 months post-infection.
Other confounding factors include
West Nile Disease flavivirus cross-reactivity, making the more specific cell-culture assay—the
From 1999 to November 6, 2007, approximately 27,083 cases of WN plaque reduction neutralization test—essential. However, this assay requires
disease have been reported in the US, of which 10,902 (40.3%) were ND training and a biosafety level 3 (BSL-3) laboratory.
50 US INFECTIOUS DISEASE 2007