West Nile virus: lessons from the 21st century

Introduction: West Nile virus (WNV) first appeared in the United States in 1999, causing illness and death in birds, horses, and humans. While the initial outbreak of this sometimes deadly viral disease was limited to the northeastern United States, the virus had an inexorable migration across the continental United States over the next 3 years, causing huge losses among the affected species. The purpose of this review is to present currently available information regarding the epi‐demiology, diagnosis, treatment, and prevention of WNV infection. Veterinarians, particularly those in an emergency practice, serve as an important source of reliable information regarding this disease for animal owners and the public in general. Data sources: Data sources used for the preparation of this review include computer‐based searches of PubMed and Commonwealth Agricultural Bureaux (CAB) abstracts. A search in PubMed using ‘West Nile’ retrieved 1468 ‘hits’ or references, while a similar search in CAB abstracts produced 815 references. Additional information was obtained from various meeting proceedings, particularly data presented in abstract form, and from the Centers for Disease Control (CDC) website dedicated to WNV. Human data synthesis: Prior to the mid‐1990s, reported large‐scale epidemics of WNV infection in humans predominantly presented as acute, mild, febrile disease, sometimes associated with lymphadenopathy and skin rash. The recent large epidemic in the United States, in contrast, has prominently featured encephalitis, particularly among the elderly. Additionally, polio‐encephalomyelitis‐like complications resulting in long‐term neurologic sequelae have been reported. There are many WNV‐permissive native avian and mosquito hosts in the Unites States and there appear to be few limitations to the spread of the disease in the United States. It is expected that the virus will be identified in all 48 continental states, Mexico, and Canada by the end of 2003. Veterinary data synthesis: The horse is the animal species most affected by the recent WNV epidemic in the United States, and losses to the equine industry have been large and unprecedented. A United States Department of Agriculture (USDA)‐approved vaccine against WNV has been in use in horses since 2001 and appears to be effective in limiting the incidence of disease in well‐vaccinated populations. WNV infection has been documented in other species of mammals, including camelids (alpaca/llamas) and dogs, and veterinarians should include WNV as a differential diagnosis for animals presenting with clinical signs consistent with central nervous system infection. A large concern exists for endangered bird populations, particularly birds of prey, whether in zoos or in the wild.     

Pathologic and immunohistochemical findings in naturally occuring West Nile virus infection in horses

The pathologic and peroxidase immunohistochemical features of West Nile flavivirus (WNV) infection were compared in four horses from the northeastern United States and six horses from central Italy. In all 10 animals, there were mild to severe polioencephalomyelitis with small T lymphocyte and lesser macrophage perivascular infiltrate, multifocal glial nodules, neutrophils, and occasional neuronophagia. Perivascular hemorrhages, also noted macroscopically in two animals, were observed in 50% of the horses. In the four American horses, lesions extended from the basal nuclei through the brain stem and to the sacral spinal cord and were more severe than the lesions observed in the six Italian horses, which had moderate to severe lesions mainly in the thoracolumbar spinal cord and mild rhombencephalic lesions. WNV antigen was scant and was identified within the cytoplasm of a few neurons, fibers, glial cells, and macrophages. WNV infection in horses is characterized by lesions with little associated antigen when compared with WNV infection in birds and some fatal human infections and with other important viral encephalitides of horses, such as alphavirus infections and rabies.     

Clinical West Nile virus infection in 2 horses in western Canada

Two horses had a history of ataxia and weakness or recumbency. One recovered and was diagnosed with West Nile virus (WNV) infection by serologic testing. The other was euthanized; it had meningoencephalomyelitis, WNV was detected by polymerase chain reaction. West Nile virus infection is an emerging disease. Year 2002 is the first year in which cases have been seen in Saskatchewan.     

Epidemic West Nile virus encephalomyelitis: a temperature-dependent, spatial model of disease dynamics

Since first being detected in New York in 1999, West Nile virus (WNV) has spread throughout the United States and more than 20,000 cases of equine WNV encephalomyelitis have been reported. A spatial model of disease occurrence was developed, using data from an outbreak of serologically confirmed disease in an unvaccinated population of horses at 108 locations in northern Indiana between 3 August and 17 October 2002. Daily maximum temperature data were recorded at meteorological stations surrounding the study area. The distribution of the total number of degree-days elapsing between July 4 and the date of diagnosis of each case was best described by a normal distribution (mean = 5243 °F, S.D. = 1047). The days on which the average risk was >25, >50 and >75% were predicted (versus observed) to occur on August 23 (August 9), August 31 (September 2) and September 9 (September 9). The epidemic was predicted to occur 3 days earlier, or 4 days later, than observed if temperatures in the study area were uniformly increased, or decreased, by 5 °F, respectively. Maps indicated that WNV encephalomyelitis risk always remained greater in the northwest quadrant of the study area. Since WNV might exist at a hypoendemic level of infection, and occasionally re-emerge as a cause of epidemics in equine populations, by identifying factors that contributed to this epidemic, the potential impact of future epidemics can be reduced. Such studies rely on a GIS framework, availability of meteorological and possibly remotely sensed data and information on host and landscape factors. An early-warning system for WNV transmission in equine populations could be developed.     

Incidence and effects of West Nile virus infection in vaccinated and unvaccinated horses in California

A prospective cohort study was used to estimate the incidence of West Nile virus (WNV) infection in a group of unvaccinated horses (n = 37) in California and compare the effects of natural WNV infection in these unvaccinated horses to a group of co-mingled vaccinated horses (n = 155). Horses initially were vaccinated with either inactivated whole virus (n = 87) or canarypox recombinant (n = 68) WNV vaccines during 2003 or 2004, prior to emergence of WNV in the region. Unvaccinated horses were serologically tested for antibodies to WNV by microsphere immunoassay incorporating recombinant WNV E protein (rE MIA) in December 2003, December 2004, and every two months thereafter until November 2005. Clinical neurologic disease attributable to WNV infection (West Nile disease (WND)) developed in 2 (5.4%) of 37 unvaccinated horses and in 0 of 155 vaccinated horses. One affected horse died. Twenty one (67.7%) of 31 unvaccinated horses that were seronegative to WNV in December, 2004 seroconverted to WNV before the end of the study in November, 2005. Findings from the study indicate that currently-available commercial vaccines are effective in preventing WND and their use is financially justified because clinical disease only occurred in unvaccinated horses and the mean cost of each clinical case of WND was approximately 45 times the cost of a 2-dose WNV vaccination program.     

Detection of antibodies to West Nile virus in equine sera using microsphere immunoassay.

One hundred and ninety-one sera from horses that recently were exposed to West Nile virus (WNV) by either vaccination or natural infection or that were not vaccinated and remained free of infection were used to evaluate fluorescent microsphere immunoassays (MIAs) incorporating recombinant WNV envelope protein (rE) and recombinant nonstructural proteins (rNS1, rNS3, and rNS5) for detection of equine antibodies to WNV. The rE MIA had a diagnostic sensitivity and specificity, respectively, of 99.3% and 97.4% for detection of WNV antibodies in the serum of horses that were recently vaccinated or naturally infected with WNV, as compared to the plaque reduction neutralization test (PRNT). The positive rE MIA results were assumed to be WNV-specific because of the close agreement between this assay and the PRNT and the fact that unvaccinated control horses included in this study were confirmed to be free of exposure to the related St Louis encephalitis virus. The NS protein-based MIA were all less sensitive than either the rE MIA or PRNT (sensitivity 0-48.0), although the rNSI MIA distinguished horses vaccinated with the recombinant WNV vaccine from those that were immunized with the inactivated WNV vaccine (P < 0.0001) or naturally infected with WNV (P < 0.0001). The rE MIA would appear to provide a rapid, convenient, inexpensive, and accurate test for the screening of equine sera for the presence of antibodies to WNV.     

West Nile virus infection in horses in Saudi Arabia (in 2013–2015)

West Nile virus (WNV) is an important emerging zoonotic arbovirus giving rise to clinical syndromes of varying severity in humans and horses. Culex mosquitoes are the main vector. Although WNV has been reported in many countries in the Middle East and Asia, little is known about its prevalence in equine populations in the Arabian Peninsula. We have carried out a serological study on 200 horses to assess WNV infection in the Eastern and Central regions of Saudi Arabia in 2013–2015. Sera were tested for the presence of WNV antibodies in parallel using a commercial enzyme‐linked immunosorbent assay (ELISA) kit and microneutralization (MN) tests. In comparison with the MN assay used as “gold standard,” we find the ELISA had a sensitivity of 94.7% and specificity of 80.1%. The prevalence of WNV neutralizing antibody ranged from 5 (17.3%) of 29 sera collected in Riyadh up to 15 (55.6%) of 27 sera collected from Al‐Qateef. These findings highlight the need to be aware of the possibility of WNV disease in humans and horses presenting with central nervous system disease in the Kingdom of Saudi Arabia.     

The anamnestic serologic response to vaccination with a canarypox virus-vectored recombinant West Nile virus (WNV) vaccine in horses previously vaccinated with an inactivated WNV vaccine

A new recombinant West Nile virus (WNV) vaccine has been licensed for use in horses. Prior to the availability of the recombinant vaccine in 2004, the only equine WNV vaccine available on the market had been an inactivated vaccine. Since the recombinant vaccine only expresses selected viral genes, the question could be posed as to whether a single dose of the recombinant vaccine would be effective in producing an anamnestic serologic response in horses previously vaccinated with an inactivated WNV vaccine. In this study we demonstrate that vaccination of horses with a canarypox-vectored recombinant vaccine, under field conditions, results in a marked anamnestic response in horses previously vaccinated with an inactivated WNV vaccine.     

West Nile virus and its emergence in the United States of America

Zoonotic West Nile virus (WNV) circulates in natural transmission cycles involving certain mosquitoes and birds, horses, humans, and a range of other vertebrates are incidental hosts. Clinical infections in humans can range in severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its introduction to the Western Hemisphere in 1999, WNV had spread across North America, Central and South America and the Caribbean, although the vast majority of severe human cases have occurred in the United States of America (USA) and Canada. By 2002-2003, the WNV outbreaks have involved thousands of patients causing severe neurologic disease (meningoencephalitis and poliomyelitis-like syndrome) and hundreds of associated fatalities in USA. The purpose of this review is to present recent information on the epidemiology and pathogenicity of WNV since its emergence in North America.     

Investigation of an outbreak of encephalomyelitis caused by West Nile virus in 136 horses

OBJECTIVE: To describe an outbreak of encephalomyelitis caused by West Nile virus (WNV) in horses in northern Indiana. DESIGN: Case series. ANIMALS: 170 horses. PROCEDURES: Horses with clinical signs suggestive of encephalomyelitis caused by WNV were examined. Date, age, sex, breed, and survival status were recorded. Serum samples were tested for anti-WNV antibodies, and virus isolation was attempted from samples of brain tissue. Climate data from local weather recording stations were collected. An epidemic curve was constructed, and case fatality rate was calculated. RESULTS: The most common clinical signs were ataxia, hind limb paresis, and muscle tremors and fasciculations. Eight horses had been vaccinated against WNV from 2 to 21 days prior to the appearance of clinical signs. West Nile virus was isolated from brain tissue of 2 nonvaccinated horses, and anti-WNV IgM antibodies were detected in 132 nonvaccinated horses; in 2 other nonvaccinated horses, anti-WNV antibodies were detected and WNV was also isolated from brain tissue. Thirty-one (22.8%) horses died or were euthanatized. The peak of the outbreak occurred on September 6, 2002. Ambient temperatures were significantly lower after the peak of the outbreak, compared with prior to the peak. CONCLUSIONS AND CLINICAL RELEVANCE: The peak risk period for encephalomyelitis caused by WNV in northern Indiana was mid-August to mid-September. Reduction in cases coincided with decreasing ambient temperatures. Because of a substantial case fatality rate, owners of horses in northern Indiana should have their horses fully protected by vaccination against WNV before June. In other regions of the United States with a defined mosquito breeding season, vaccination of previously nonvaccinated horses should commence at least 4 months before the anticipated peak in seasonal mosquito numbers, and for previously vaccinated horses, vaccine should be administered no later than 2 months before this time.     

The economic impact of West Nile virus infection in horses in the North Dakota equine industry in 2002

This study estimated economic impacts associated with the West Nile virus (WNV) outbreak in horses for North Dakota in 2002.The 2002 epidemic in the United States was the largest meningoencephalitis epidemic reported in the Western Hemisphere. Over 15,257 horse cases were reported in 43 states with most cases occurring in central United States. North Dakota reported over 569 horse cases, with a mortality rate of 22%. The total costs incurred by the state were approximately US$1.9 million. The costs incurred by horse owners were about US$1.5 million. Of the US$1.5 million, about US$781,203 and US$802,790 were spent on medical costs and losses due to inability to use animals because of the disease, respectively. Medical costs included the cost of vaccinating 152 horses, and the treatment costs for 345 horses which were US$4,803 and US$524,400 respectively. Costs associated with mortality were US$252,000 for the 126 horses which died of WNV. The state government spent US*$400,000 on WNV monitoring, control, and surveillance under the WNV-control program in 2002. Despite these conservative estimates, the data suggest that economic costs attributable to WNV epidemic to horse owners in North Dakota were substantial.     

Efficacy, duration, and onset of immunogenicity of a West Nile virus vaccine, live Flavivirus chimera, in horses with a clinical disease challenge model

REASON FOR PERFORMING STUDY: West Nile virus (WNF) is a Flavivirus responsible for a life-threatening neurological disease in man and horses. Development of improved vaccines against Flavivirus infections is therefore important. OBJECTIVES: To establish that a single immunogenicity dose of live Flavivirus chimera (WN-FV) vaccine protects horses from the disease and it induces a protective immune response, and to determine the duration of the protective immunity. METHODS: Clinical signs were compared between vaccinated (VACC) and control (CTRL) horses after an intrathecal WNV challenge given at 10 or 28 days, or 12 months post vaccination. RESULTS: Challenge of horses in the immunogenicity study at Day 28 post vaccination resulted in severe clinical signs of WNV infection in 10/10 control (CTRL) compared to 1/20 vaccinated (VACC) horses (P<0.01). None of the VACC horses developed viraemia and minimal histopathology was noted. Duration of immunity (DPI) was established at 12 months post vaccination. Eight of 10 CTRL exhibited severe clinical signs of infection compared to 1 of 9 VACC horses (P<0.05). There was a significant reduction in the occurrence of viraemia and histopathology lesion in VACC horses relative to CTRL horses. Horses challenged at Day 10 post vaccination experienced moderate or severe clinical signs of WNV infection in 3/3 CTRL compared to 5/6 VACC horses (P<0.05). CONCLUSIONS: This novel WN-FV chimera vaccine generates a protective immune response to WNV infection in horses that is demonstrated 10 days after a single vaccination and lasts for up to one year. POTENTIAL RELEVANCE: This is the first USDA licensed equine WNV vaccine to utilise a severe challenge model that produces the same WNV disease observed under field conditions to obtain a label claim for prevention of viraemia and aid in the prevention of WNV disease and encephalitis with a duration of immunity of 12 months.     

West Nile virus infection of horses

West Nile virus (WNV) is a flavivirus closely related to Japanese encephalitis and St. Louis encephalitis viruses that is primarily maintained in nature by transmission cycles between mosquitoes and birds. Occasionally, WNV infects and causes disease in other vertebrates, including humans and horses. West Nile virus has re-emerged as an important pathogen as several recent outbreaks of encephalomyelitis have been reported from different parts of Europe in addition to the large epidemic that has swept across North America. This review summarises the main features of WNV infection in the horse, with reference to complementary information from other species, highlighting the most recent scientific findings and identifying areas that require further research.     

Predictive risk mapping of West Nile virus (WNV) infection in Saskatchewan horses

The objective of this study was to develop a model using equine data from geographically limited surveillance locations to predict risk categories for West Nile virus (WNV) infection in horses in all geographic locations across the province of Saskatchewan. The province was divided geographically into low-, medium-, or high-risk categories for WNV, based on available serology information from 923 horses obtained through 4 studies of WNV infection in horse populations in Saskatchewan. Discriminant analysis was used to build models using the observed risk of WNV in horses and geographic division-specific environmental data as well as to predict the risk category for all areas, including those beyond the surveillance zones. High-risk areas were indicated by relatively lower rainfall, higher temperatures, and a lower percentage of area covered in trees, water, and wetland. These conditions were most often identified in the southwest corner of the province. Environmental conditions can be used to identify those areas that are at highest risk for WNV. Public health managers could use prediction maps, which are based on animal or human information and developed from annual early season meteorological information, to guide ongoing decisions about when and where to focus intervention strategies for WNV.     

Transmission dynamics and changing epidemiology of West Nile virus

West Nile virus (WNV) is a flavivirus that is maintained in a bird-mosquito transmission cycle. Humans, horses and other non-avian vertebrates are usually incidental hosts, but evidence is accumulating that this might not always be the case. Historically, WNV has been associated with asymptomatic infections and sporadic disease outbreaks in humans and horses in Africa, Europe, Asia and Australia. However, since 1994, the virus has caused frequent outbreaks of severe neuroinvasive disease in humans and horses in Europe and the Mediterranean Basin. In 1999, WNV underwent a dramatic expansion of its geographic range, and was reported for the first time in the Western Hemisphere during an outbreak of human and equine encephalitis in New York City. The outbreak was accompanied by extensive and unprecedented avian mortality. Since then, WNV has dispersed across the Western Hemisphere and is now found throughout the USA, Canada, Mexico and the Caribbean, and parts of Central and South America. WNV has been responsible for >27,000 human cases, >25,000 equine cases and hundreds of thousands of avian deaths in the USA but, surprisingly, there have been only sparse reports of WNV disease in vertebrates in the Caribbean and Latin America. This review summarizes our current understanding of WNV with particular emphasis on its transmission dynamics and changing epidemiology.     

Clinical findings, lesions, and viral antigen distribution in great gray owls (Strix nebulosa) and barred owls (Strix varia) with spontaneous West Nile virus infection

West Nile Virus (WNV) infection manifests itself clinically a nd pathologically differently in various species of birds. The clinicopathologic findings and WNV antigen tissue distribution of six great gray owls (Strix nebulosa) and two barred owls (Strix varia) with WNV infection are described in this report. Great gray owls usually live in northern Canada, whereas the phylogenetically related barred owls are native to the midwestern and eastern United States and southern Canada. Naturally acquired WNV infection caused death essentially without previous signs of disease in the six great gray owls during a mortality event. Lesions of WNV infection we re dominated by hepatic and splenic necrosis, with evidence o f disseminatedintravascular coagulation in the great gray owls. WNV antigen was widely distributed in th e organs of the great gray owls and appeared totarget endothelial cells, macrophages, and hepatocytes. The barred owls represented two sporadic cases. They had neurologic disease with mental dullness that led to euthanasia. These birds had mild to moderate lymphoplasmacytic encephalitis with glial nodules and lymphoplasmacytic pectenitis. WNV antigen was sparse in barred owls and only present in a few brain neurons and renaltubular epithelial cells. The cause of the different manifestations of WNV disease in these fairly closely related owl species is uncertain.     

Immunologic responses to West Nile virus in vaccinated and clinically affected horses

OBJECTIVE: To compare neutralizing antibody response between horses vaccinated against West Nile virus (WNV) and horses that survived naturally occurring infection. DESIGN: Cross-sectional observational study. ANIMALS: 187 horses vaccinated with a killed WNV vaccine and 37 horses with confirmed clinical WNV infection. PROCEDURE: Serum was collected from vaccinated horses prior to and 4 to 6 weeks after completion of an initial vaccination series (2 doses) and 5 to 7 months later. Serum was collected from affected horses 4 to 6 weeks after laboratory diagnosis of infection and 5 to 7 months after the first sample was obtained. The IgM capture ELISA, plaque reduction neutralization test (PRNT), and microtiter virus neutralization test were used. RESULTS: All affected horses had PRNT titers > or = 1:100 at 4 to 6 weeks after onset of disease, and 90% (18/20) maintained this titer for 5 to 7 months. After the second vaccination, 67% of vaccinated horses had PRNT titers > or = 1:100 and 14% had titers < 1:10. Five to 7 months later, 33% (28/84) of vaccinated horses had PRNT titers > or = 1:100, whereas 29% (24/84) had titers < 1:10. Vaccinated and clinically affected horses' end point titers had decreased by 5 to 7 months after vaccination. CONCLUSIONS AND CLINICAL RELEVANCE: A portion of horses vaccinated against WNV may respond poorly. Vaccination every 6 months may be indicated in certain horses and in areas of high vector activity. Other preventative methods such as mosquito control are warranted to prevent WNV infection in horses.