Cases Of West Nile Virus Infection Research Articles

Abrupt Increase in Detection of Locally Acquired West-Nile-Virus-Lineage-2-Mediated Neuroinvasive Disease in a Previously Non-Endemic Area of Southern Italy (2023).

West Nile virus (WNV) is a public health concern in Europe. Rising temperatures and the migration of potential vectors promote the spread of viruses to previously unaffected areas. In 2023, the Apulia region of Southern Italy experienced an unexpected increase in West Nile neuroinvasive disease (WNND); no such cases had been reported in the previous 10 years. Overall, eight autochthonous cases of WNV infection were identified between July and October 2023, six of which were WNND. All cases were male (median age, 73 years). Two of the cases were blood donors. All WNND cases were hospitalized and all recovered within a few weeks. Surveillance data showed that, in the Apulia region, WNV Lineage 2 was detected in humans, mosquitoes, and horses. Based on the number of WNND cases reported, we can assume that a high number of infections occurred during the summer period. Changes in the climate in the region over recent years could be considered among the main drivers of the rapid increase in WNV infections. Therefore, integrated surveillance should be strengthened to avoid the potential massive spread of WNV in Southern Italy. Moreover, the implementation of whole-genome sequencing of WNV strains, as well as seroepidemiological studies in the area, will facilitate a better understanding of circulation dynamics.

First Detection of West Nile Virus Lineage 2 in Mosquitoes in Switzerland, 2022.

West Nile virus (WNV) is one of the most widespread flaviviruses in the world, and in recent years, it has been frequently present in many Mediterranean and Eastern European countries. A combination of different conditions, such as a favourable climate and higher seasonal average temperatures, probably allowed its introduction and spread to new territories. In Switzerland, autochthonous cases of WNV have never been reported, and the virus was not detected in mosquito vectors until 2022, despite an entomological surveillance in place in Canton Ticino, southern Switzerland, since 2010. In 2022, 12 sites were monitored from July to October, using BOX gravid mosquito traps coupled with honey-baited FTA cards. For the first time, we could detect the presence of WNV in FTA cards and mosquitoes in 8 out of the 12 sampling sites monitored, indicating an unexpectedly widespread circulation of the virus throughout the territory. Positive findings were recorded from the beginning of August until mid-October 2022, and whole genome sequencing analysis identified a lineage 2 virus closely related to strains circulating in Northern Italy. The entomological surveillance has proved useful in identifying viral circulation in advance of possible cases of WNV infection in humans or horses.

West Nile virus emergence in humans in Extremadura, Spain 2020.

In Spain, the largest human West Nile virus (WNV) outbreak among humans was reported in 2020, constituting the second most important outbreak in Europe that season. Extremadura (southwestern Spain) was one of the affected areas, reporting six human cases. The first autochthonous human case in Spain was reported in Extremadura in 2004, and no other human cases were reported until 2020. In this work, we describe the first WNV human outbreak registered in Extremadura, focusing on the most important clinical aspects, diagnostic results, and control actions which followed. In 2020, from September to October, human WNV infections were diagnosed using a combination of molecular and serological methods (an in-house specific qRT-PCR and a commercial ELISA for anti-WNV IgM and IgG antibodies) and by analysing serum, urine, and/or cerebrospinal fluid samples. Serological positive serum samples were further tested using commercial kits against related flaviviruses Usutu and Tick-borne encephalitis in order to analyse serological reactivity and to confirm the results by neutralisation assays. In total, six cases of WNV infection (five with neuroinvasive disease and one with fever) were identified. Clinical presentation and laboratory findings are described. No viral RNA was detected in any of the analysed samples, but serological cross-reactivity was detected against the other tested flaviviruses. Molecular and serological methods for WNV detection in various samples as well as differential diagnosis are recommended. The largest number of human cases of WNV infection ever registered in Extremadura, Spain, occurred in 2020 in areas where circulation of WNV and other flaviviruses has been previously reported in humans and animals. Therefore, it is necessary to enhance surveillance not only for the early detection and implementation of response measures for WNV but also for other emerging flaviviruses that could be endemic in this area.

The 2022 West Nile Virus Season in Greece; A Quite Intense Season.

Since 2010, the West Nile virus (WNV) has been established in Greece. We describe the epidemiology of diagnosed human WNV infections in Greece with a focus on the 2022 season. During the transmission period, clinicians were sending samples from suspected cases for testing. Active laboratory-based surveillance was performed with immediate notification of diagnosed cases. We collected clinical information and interviewed patients on a timely basis to identify their place of exposure. Besides serological and molecular diagnostic methods, next-generation sequencing was also performed. In 2022, 286 cases of WNV infection were diagnosed, including 278 symptomatic cases and 184 (64%) cases with neuroinvasive disease (WNND); 33 patients died. This was the third most intense season concerning the number of WNND cases, following 2018 and 2010. Most (96%) cases were recorded in two regions, in northern and central Greece. The virus strain was a variant of previous years, clustering into the Central European subclade of WNV lineage 2. The 2022 WNV season was quite intense in Greece. The prompt diagnosis and investigation of cases are considered pivotal for the timely response, while the availability of whole genome sequences enables studies on the molecular epidemiology of the disease.

Современные аспекты лихорадки Западного Нила

The problem of arbovirus infections remains relevant in many countries, including Russian Federation. These infections are characterized by a constantly expanding area of their distribution, antigenic variability, and emergence of new genetic variants. Moreover, there are still no effective causal therapy and adequate preventive measures for this group of diseases. One of the important representatives of arboviruses is West Nile virus (WNV). Cases of WNV infection are registered every year in different regions of Russia; however, there is no distinct long-term trend to its further spread or formation of stable infection foci. This review aims to explore the latest data on different aspects of WNV infection, including its etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention. We used descriptive and analytical methods, performed literature analysis, classified and summarized the information. A total of 457 articles were identified in PubMed; 216 articles in Russian were found in e-Library; 282 articles were found in Cyberleninka. We analyzed 169 articles meeting the aims of our review and finally included 25 articles. Key words: West Nile virus, Arboviruses, West Nile fever, epidemiology, pathogenesis, clinical manifestations

Entomological Surveillance Activities in Regions in Greece: Data on Mosquito Species Abundance and West Nile Virus Detection in Culex pipiens Pools (2019-2020).

Human cases of West Nile virus (WNV) infections have been recorded in Greece since 2010, with seasonal outbreaks (summer-autumn) on an almost annual basis, caused mainly by the WNV lineage 2 strain (Nea Santa-Greece-2010). National Public Health Organization (NPHO) in Greece is annually implementing enhanced surveillance of human WNV infection, in order to promptly identify human cases of WNV infection and monitor distribution in terms of time and place. Entomological surveillance activities were carried out on a national basis in 2019 and 2020, under NPHO coordination and the collaboration of several private subcontractors, along with the Unit of Medical Entomology, Laboratory for Surveillance of Infectious Diseases (LSID). The aim was to monitor mosquito species composition, abundance, and WNV circulation in mosquito pools of Culex pipiens s.l. species. Adult mosquito traps were placed in selected sites; collected samples were morphologically characterized and pooled by date of collection, location, and species types. Female Culex pipiens s.l. pools were tested for WNV and WNV infection rates (MIR and MLE) were estimated. Highest mean number of female Culex pipiens s.l. species was recorded in Central Macedonia both for 2019 and 2020. Six hundred and fifty-nine mosquito pools (147 in 2019 and 512 in 2020) of female Culex pipiens s.l. were examined for WNV presence. The highest MLE was detected in Western Macedonia in 2019 and in Thessaly in 2020. Here, we present data on the mosquito species composition in the studied areas and WNV detection in mosquitoes from areas in Greece where the specific national mosquito surveillance program was implemented, for two years, 2019 and 2020.

Development of Antibody-Based Therapeutics Against West Nile Virus in Plants.

Since its discovery in 1937 in the West Nile district of Uganda, West Nile virus (WNV) has been one of the leading causes of mosquito-transmitted infectious diseases (Smithburn, Burke, Am J Trop Med 20:22, 1940). Subsequently, it spread to Europe, Asia, Australia, and finally North America in 1999 (Sejvar, Ochsner 5(3):6-10, 2003). Worldwide outbreaks have continued to increase since the 1990s (Chancey et al, Biomed Res Int 2015:376230, 2015). According to the Center for Disease Control and Prevention, more than 51,000 cases of WNV infection and nearly 2400 cases of WNV-related death were reported in the USA from 1999 to 2019. The estimated economic impact of WNV infections is close to 800 million dollars in the USA from 1999 to 2012 (Barrett, Am J Trop Med Hyg 90:389, 2014).

West Nile Virus Seroprevalence and Cross-Neutralization in Sera from Eastern and Central Sudan

Objectives: In regions with co-existing flaviviruses, the diagnosis of previous West Nile virus (WNV) infections is challenging due to cross-reacting antibodies. The aim of the study was to determine the frequency of previous WNV infections in sera from three Sudanese states by excluding potentially dengue virus (DENV) and ZIKV cross-reacting sera and to determine the percentage of WNV cross-neutralizing sera from individuals with previous DENV infection. Methods: Serum samples from Kassala, North Kordofan, and Red Sea state were screened for antibodies against DENV by ELISA. Sera without DENV antibodies (N = 106) and a matched set of sera with DENV antibodies (N = 108) was selected. In all blood samples the frequency of WNV-neutralizing antibodies and the antibody titers were measured with microplate neutralization assays. DENV and Zika virus (ZIKV) microplate neutralization assays were performed with all WNV neutralizing sera of the DENV negative group. Results: A fraction of 30.2% of the DENV antibody negative sera neutralized WNV. The seroprevalence increased with age from 9.5% to 41.7%. Men and women were equally affected. The percentage of DENV positive sera that neutralized WNV was 83.3%. DENV positive sera had higher WNV neutralization titers than DENV negative sera. Conclusions: A significant fraction of the DENV antibody negative sera from three regions in Sudan showed serologic evidence of previous WNV infection. In comparison, the large majority of DENV antibody positive sera had WNV neutralizing antibodies. Studies are needed to identify clinical cases of WNV infection and to determine whether individuals with cross-neutralizing antibodies are protected from WNV disease.

West Nile Virus Lineage 2 Overwintering in Italy.

In January 2022, West Nile virus (WNV) lineage 2 (L2) was detected in an adult female goshawk rescued near Perugia in the region of Umbria (Italy). The animal showed neurological symptoms and died 15 days after its recovery in a wildlife rescue center. This was the second case of WNV infection recorded in birds in the Umbria region during the cold season, when mosquitoes, the main WNV vectors, are usually not active. According to the National Surveillance Plan, the Umbria region is included amongst the WNV low-risk areas. The necropsy evidenced generalized pallor of the mucous membranes, mild splenomegaly, and cerebral edema. WNV L2 was detected in the brain, heart, kidney, and spleen homogenate using specific RT-PCR. Subsequently, the extracted viral RNA was sequenced. A Bayesian phylogenetic analysis performed through a maximum-likelihood tree showed that the genome sequence clustered with the Italian strains within the European WNV strains among the central-southern European WNV L2 clade. These results, on the one hand, confirmed that the WNV L2 strains circulating in Italy are genetically stable and, on the other hand, evidenced a continuous WNV circulation in Italy throughout the year. In this report case, a bird-to-bird WNV transmission was suggested to support the virus overwintering. The potential transmission through the oral route in a predatory bird may explain the relatively rapid spread of WNV, as well as other flaviviruses characterized by similar transmission patterns. However, rodent-to-bird transmission or mosquito-to-bird transmission cannot be excluded, and further research is needed to better understand WNV transmission routes during the winter season in Italy.

Unprecedented increase of West Nile virus neuroinvasive disease, Spain, summer 2020.

Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.

Evidence for current circulation of an ancient West Nile virus strain (NY99) in Brazil.

INTRODUCTION: In Brazil, West Nile virus (WNV) was first detected, in 2018, in horses with neurological disease. AIM: We report the first case of WNV infection in a horse from Ceará state and the complete genome sequence of an isolate from Espírito Santo state. Both infections occurred in 2019. METHODS: WNV was isolated from the tissues of a horse with neurological signs in Espírito Santo and sequenced by MiSeq. RESULTS: Phylogenetic analysis revealed that the isolate belongs to lineage 1a, clustering with the NY99 strain, a strain that has not circulated in the USA since 2005. CONCLUSIONS: Our findings reinforce the hypothesis that WNV has been silently circulating in Brazil for many years.

West Nile virus in humans, Greece, 2018: the largest seasonal number of cases, 9 years after its emergence in the country.

BackgroundHuman cases of West Nile virus (WNV) infection are recorded since 2010 in Greece, with seasonal outbreaks occurring almost annually. Enhanced surveillance has been implemented since 2010, to promptly characterise cases’ temporal and geographical distribution and inform authorities for implementation of appropriate measures (mosquito control, health education, blood safety).AimWe describe the epidemiology of WNV human infections in Greece focusing on the 2018 season.MethodsThe National Public Health Organization advised physicians to test all suspect WNV infection cases and refer samples to reference laboratories. Laboratories notified diagnosed cases on a daily basis. Treating physicians, patients, and infected blood donors were interviewed within 48 hours after diagnosis and the probable infection location was identified. Hospitalised cases were followed up until discharge.ResultsA total of 317 autochthonous WNV infection cases were diagnosed in 2018. Among them, 243 cases had neuroinvasive disease (WNND), representing a 23% increase of WNND cases compared with 2010, the previous most intense season. There were 51 deaths. Cases started occurring from week 22, earlier than usual. Both rural and urban areas were affected, with 86 (26% of the total) municipalities belonging to seven (54% of the total) regions recording cases. Two major epicentres were identified in Attica and Central Macedonia regions.ConclusionsThe largest number of human cases of WNV infection ever recorded in Greece occurred in 2018, with a wide geographical distribution, suggesting intense virus circulation. Enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

West Nile Virus in Slovenia.

West Nile virus (WNV) is a flavivirus transmitted by mosquitoes. Birds are the reservoir for the virus; humans, horses and other mammals are dead-end hosts. Infections caused by WNV in humans can vary from asymptomatic infections to West Nile fever (WNF) or West Nile neuroinvasive disease (WNND). In 1995, a serosurvey was performed in Slovenia on forest workers, and WNV specific IgG antibodies were confirmed in 6.8% of the screened samples, indicating that WNV is circulating in Slovenia. No human disease cases were detected in Slovenia until 2013, when the first case of WNV infection was confirmed in a retrospective study in a 79-year old man with meningitis. In 2018, three patients with WNND were confirmed by laboratory tests, with detection of IgM antibodies in the cerebrospinal fluid of the patients. In one of the patients, WNV RNA was detected in the urine sample. In 2017, 2018 and 2019, a mosquito study was performed in Slovenia. Mosquitoes were sampled on 14 control locations and 35 additional locations in 2019. No WNV was detected in mosquitoes in 2017 and 2019, but we confirmed the virus in a pool of Culex sp. mosquitoes in 2018. The virus was successfully isolated, and complete genome sequence was acquired. The whole genome of the WNV was also sequenced from the patient’s urine sample. The whole genome sequences of the WNV virus detected in Slovenian patient and mosquito indicate the virus most likely spread from the north, because of the geographic proximity and because the sequences cluster with the Austrian and Hungarian sequences. A sentinel study was performed on dog sera samples, and we were able to confirm IgG antibodies in 1.8% and 4.3% of the samples in 2017 and 2018, respectively. Though Slovenia is not a highly endemic country for WNV, we have established that the virus circulates in Slovenia.

Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018.

BackgroundUsutu virus (USUV) is a mosquito-borne flavivirus, which shares its transmission cycle with the phylogenetically related West Nile virus (WNV). USUV circulates in several European countries and its activity has increased over the last 5 years.AimTo describe human cases of USUV infection identified by surveillance for WNV and USUV infection in the Veneto Region of northern Italy in 2018.MethodsFrom 1 June to 30 November 2018, all cases of suspected autochthonous arbovirus infection and blood donors who had a reactive WNV nucleic acid test were investigated for both WNV and USUV infection by in-house molecular methods. Anti-WNV and anti-USUV IgM and IgG antibodies were detected by ELISA and in-house immunofluorescence assay, respectively; positive serum samples were further tested by WNV and USUV neutralisation assays run in parallel.ResultsEight cases of USUV infection (one with neuroinvasive disease, six with fever and one viraemic blood donor who developed arthralgia and myalgia) and 427 cases of WNV infection were identified. A remarkable finding of this study was the persistence of USUV RNA in the blood and urine of three patients during follow-up. USUV genome sequences from two patients shared over 99% nt identity with USUV sequences detected in mosquito pools from the same area and clustered within lineage Europe 2.ConclusionsClinical presentation and laboratory findings in patients with USUV infection were similar to those found in patients with WNV infection. Cross-reactivity of serology and molecular tests challenged the differential diagnosis.

Detection of flaviviruses and alphaviruses in mosquitoes in Central Macedonia, Greece, 2018

Culex mosquitoes are vectors of several flaviviruses and alphaviruses posing a potential risk to public and veterinary health. In order to gain an insight into the flaviviruses and alphaviruses circulating in the five regional units of Central Macedonia in northern Greece, 17,470 female Culex spp. mosquitoes collected during 2018 were tested for these viruses. Among 229 mosquito pools, West Nile virus (WNV) was detected in 10 (4.4%) pools, while insect-specific flavi- and alphaviruses were detected in 2 (0.9%) and 8 (3.5%) pools, respectively. WNV minimum infection rate (MIR) was 0.57. The highest MIR was identified in Thessaloniki regional unit, where several human cases of WNV infection occurred in 2018. All ten WNV sequences cluster into the Central European subclade of lineage 2. It is of note that the first WNV-positive mosquito pool was detected two weeks prior the report of the first human case in the area, suggesting that testing of mosquitoes could serve as early warning system.

West Nile virus infections are here! Are we prepared to face another flavivirus epidemic?

Emerging arthropod-borne viruses (arboviruses), such as chikungunya and Zika viruses, are a major threat to public health in countries like Brazil where biodiversity is high and medical care is sometimes precarious. West Nile fever is a disease caused by the West Nile Virus (WNV), an RNA virus belonging to the Flaviviridae family. It is transmitted by infected mosquitoes to numerous animals like birds, reptiles and mammals, including human and non-human primates. In the last decade, the number of reported cases of WNV infection in humans and animals has increased in the Americas. Circulation of WNV in forests and rural areas in Brazil has been detected based on serological surveys and, in 2014, the first case of West Nile fever was confirmed in a patient from Piauí State. In 2018, the virus was isolated for the first time from a horse from a rural area in the state of Espírito Santo presenting with a neurological disorder; this raises the possibility that other cases of WNV encephalitis may have occurred without clinical recognition and without laboratory diagnosis by specific assays. The imminent WNV outbreak poses a challenge for Brazilian clinicians and researchers. In this review, we summarize the basic biological and ecological characteristics of this virus and the clinical presentation and treatment of febrile illnesses caused by WNV. We also discuss the epidemiological aspects, prophylaxis of WNV infections, and monitoring strategies that could be applied in the possibility of a WNV outbreak in Brazil.

Detection of West Nile Virus Infection in Viral Encephalitis Cases, China.

This study detected West Nile virus (WNV) infection in serum samples of patients clinically diagnosed with viral encephalitis in the Japanese encephalitis virus (JEV) endemic area (seven provinces) and JEV nonendemic area (Xinjiang province) in China from 2011 to 2012. In JEV endemic areas, there were 22 positive cases of WNV immunoglobulin M (IgM) antibody in serum specimens of 65 JEV patients (JEV IgM antibody positive) in the acute phase, whereas WNV IgM antibodies were not detected in serum specimens of 63 non-JEV patients (JEV IgM antibody negative). However, the titer of JEV-neutralizing antibody was four times higher than that of WNV-neutralizing antibody in WNV-IgM-positive serum specimens. Detection was also conducted in serum specimens collected from 12 patients clinically diagnosed as viral encephalitis in Xinjiang; five serum specimens were WNV IgM antibody positive, and there were fourfold differences in WNV-neutralizing antibody titers between convalescent and acute serum. Meanwhile JEV-neutralizing antibody titer was negative or significantly lower than that of WNV-neutralizing antibody in the same specimens. WNV IgM antibodies positive were detected in acute serum specimens of patients clinically diagnosed with JEV infection in JEV-endemic areas, but no WNV neutralization antibodies were detected fourfold greater than that of the corresponding JEV antibodies. Clinical cases of WNV infection were detected in patients clinically diagnosed with viral encephalitis in Xinjiang.

West Nile virus in horses during the summer and autumn seasons of 2015 and 2016, Portugal

West Nile fever (WNF) is an emergent disease in Europe, under surveillance in the European Union. Following a 5-year period of apparent silence (autumn 2010 to summer 2015), West Nile virus (WNV) reemerged in the South of Portugal, in July 2015.Here we present data from the onset, geographic location within mainland Portugal, and outcome of clinical cases of WNV infection in horses in 2015 and 2016. During the transmission seasons of 2015 and 2016, twenty-seven horses, most symptomatic (n=20) were found positive to IgM, pr-E immunoglobulins and VNT, leading to the subsequent report to Animal Disease Notification System of the European Commission (ADNS) by the Portuguese National Authority for Animal Health.Outbreaks occurred in the middle summer (August) and early/mid autumn (October/November) of 2015 and 2016, in the southern regions of the country (Alentejo and Algarve).Compared with the previous WNV transmission seasons of 2004 and 2010, a higher number of cases were reported in 2015 and 2016.The results of our study contribute to increase information concerning the geographic areas affected and time period for WNV transmission risk in Portugal.

Review of West Nile virus circulation and outbreak risk in Madagascar: Entomological and ornithological perspectives.

West Nile fever (WNF) is a zoonotic disease, occurring nearly globally. In Madagascar, West Nile virus (WNV) was first detected in 1978 from wild birds and the virus is currently distributed across the island, but no epidemic or epizootic period has been recorded. One fatal human case of WNV infection was reported in 2011, suggesting a “tip of the iceberg” phenomenon of a possible WNF epidemic/epizootic on the island. The main objective of this literature-based survey is to review patterns of WNV circulation in Madagascar from the entomological and ornithological points of view. Among the 235 mosquito species described from Madagascar, 29 species are widely associated with WNV infection; 16 of them are found naturally infected with WNV on the island and categorized into major, candidate, and potential vectors of WNV according to their vector capacity. This study upholds the hypothesis that WNV enzooticity is independent of annual movements of migratory birds passing through Madagascar. Moreover, the lack of regular migratory bird flux between Africa and Madagascar would reduce the probability of transmission and the subsequent reintroduction of the virus into locally occurring mosquito species. Given that Palearctic migratory birds are strongly implicated in the transmission of WNV, we highlight notable differences in the movements and species diversity of these birds in Madagascar as compared to eastern and northern Africa. Risk factors from this two-pronged approach are presented for the emergence of WNF outbreak.

Temporal and Spatial Variability of Entomological Risk Indices for West Nile Virus Infection in Northern Colorado: 2006-2013.

West Nile virus (WNV) is enzootic in northern Colorado. Annual surveillance activities in Fort Collins, CO, include collecting female Culex mosquitoes and testing them for the presence of WNV RNA in order to calculate 1) Culex female abundance, 2) WNV infection rate, and 3) the vector index (VI). These entomological risk indices inform public policy regarding the need for emergency adulticiding. Currently, these are calculated on a city-wide basis. In this study, we present descriptive data from historical surveillance records spanning 2006-2013 to discern seasonal and yearly patterns of entomological risk for WNV infection. Also, we retrospectively test the hypothesis that entomological risk is correlated with human transmission risk and is heterogeneous within the City of Fort Collins. Four logistically relevant zones within the city were established and used to test this hypothesis. Zones in the eastern portion of the city consistently had significantly higher Culex abundance and VI compared with zones in the west, leading to higher entomological risk indicators for human WNV infection in the east. Moreover, the relative risk of a reported human case of WNV infection was significantly higher in the eastern zones of the city. Our results suggest that a more spatially targeted WNV management program may better mitigate human risk for WNV infection in Fort Collins, and possibly other cities where transmission is enzootic, while at the same time reducing pesticide use.