Cases Of West Nile Neuroinvasive Disease 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.

Demographic characteristics associated with West Nile virus neuroinvasive disease - A retrospective study on the wider European area 2006-2021.

With a case-fatality-risk ranging from 3.0 to >20.0% and life-long sequelae, West Nile neuroinvasive disease (WNND) is the most dangerous outcome of West Nile virus (WNV) infection in humans. As no specific prophylaxis nor therapy is available for these infections, focus is on preventive strategies. We aimed to find variables associated with WNND diagnosis, hospitalisation or death, to identify high-risk sub-groups of the population, on whom to concentrate these strategies. We used data from The European Surveillance System-TESSy, provided by National Public Health Authorities, and released by the European Centre for Disease Prevention and Control (ECDC). In two Firth-penalised logistic regression models, we considered age, sex, clinical criteria, epidemiological link to other cases (epi-link), calendar year, and season as potential associated variables. In one model we considered also the rural/urban classification of the place of infection (RUC), while in the other the specific reporting country. Among confirmed West Nile Virus cases, 2,916 WNND cases were registered, of which 2,081 (71.4%), and 383 (13.1%) resulted in the hospitalisation and death of the patient, respectively. Calendar year, RUC/country, age, sex, clinical criteria, and epi-link were associated with WNND diagnosis. Hospitalisation was associated with calendar year and RUC/country; whereas death was associated with age, sex and country. Our results support previous findings on WNND associated variables (most notably age and sex); while by observing the whole population of WNND cases in the considered area and period, they also allow for stronger generalizations, conversely to the majority of previous studies, which used sample populations.

Epidemiology and Clinical Manifestation of West Nile Virus Infections of Equines in Hungary, 2007-2020.

West Nile virus (WNV) is an emerging pathogen in Hungary, causing severe outbreaks in equines and humans since 2007. The aim of our study was to provide a comprehensive report on the clinical signs of West Nile neuroinvasive disease (WNND) in horses in Hungary. Clinical details of 124 confirmed equine WNND cases were collected between 2007 and 2019. Data about the seasonal and geographical presentation, demographic data, clinical signs, treatment protocols, and disease progression were evaluated. Starting from an initial case originating from the area of possible virus introduction by migratory birds, the whole country became endemic with WNV over the subsequent 12 years. The transmission season did not expand significantly during the data collection period, but vaccination protocols should be always reviewed according to the recent observations. There was not any considerable relationship between the occurrence of WNND and age, breed, or gender. Ataxia was by far the most common neurologic sign related to the disease, but weakness, behavioral changes, and muscle fasciculation appeared frequently. Apart from recumbency combined with inappetence, no other clinical sign or treatment regime correlated with survival. The survival rate showed a moderate increase throughout the years, possibly due to the increased awareness of practitioners.

West Nile virus transfusion-transmission risk in Australia associated with a seasonal outbreak in the United States.

West Nile virus (WNV) is a potentially transfusion-transmissible virus endemic in the US. The aim of this study was to estimate the monthly WNV transfusion transmission (TT) risk in Australia associated with donors returning from the US in 2018 and consider the implications for mitigation strategies. We used a probabilistic risk model to estimate the monthly WNV TT risks for each outbreak state/district in the US for the 2018 transmission season and the cumulative monthly risk for all US states/districts. The highest monthly cumulative transfusion risk in Australia occurred in August 2018 when 746 West Nile neuroinvasive disease cases were reported in the US and the estimated mean WNV TT risk in Australia was 1 in 1.0× 108 donations (95% confidence interval [CI]: 1.6× 108 -7.0× 107 ). The highest risk during August was associated with California, with a mean risk of 1 in 4.1× 108 donations (95% CI: 2.9× 108 -6.6× 108 ), representing 24% of the total risk in Australia. The cumulative TT risk in Australia for the other 11 months varied from 1 in 1.5× 108 donations (95% CI: 2.3× 108 -1.0× 108 ) in September to 1 in 3.9× 1010 donations (95% CI: 6.1× 1010 -2.7× 1010 ) in February. Our modeling indicates that the WNV TT risk in Australia associated with seasonal outbreaks in the US is extremely small and may not warrant donation restrictions for donors returning from the US.

Three case reports of West Nile virus neuroinvasive disease: lessons from real-life clinical practice

BackgroundDespite being an uncommon cause of meningoencephalitis, West Nile virus (WNV) recently provoked significant outbreaks throughout Europe. West Nile neuroinvasive disease (WNND) is associated with significant morbidity and mortality in older and compromised individuals, while its diagnosis may be demanding for the clinician. Here discussed are three cases of WNND with a focus on the diagnostic challenges they presented due to atypical clinical presentation and laboratory findings.Case presentationBetween July and September 2020 three patients presented to our attention with signs and symptoms compatible with meningoencephalitis. Among routine procedures, they underwent lumbar puncture and imaging. In the absence of microbiological isolates, biological samples were sent for serology and NAATs for WNV. Following diagnosis, the patients gradually recovered and were discharged either home or to rehabilitation facilities.ConclusionsThe laboratory findings here discussed, in particular CSF parameters, are only partially consistent with those described in the literature, which highlights the need for further research. While serology and NAATs on blood and urine appear the most reliable techniques in the diagnostic work-up of WNND, utility of NAATs on CSF specimens is limited by the kinetics of WNV viremia in biological fluids. This report underlines that WNND should always be included in the differential diagnosis of meningoencephalitis during WNV transmission period.

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.

Epidemiology of West Nile Virus Infections in Humans, Italy, 2012-2020: A Summary of Available Evidences.

In Italy, human cases of West Nile virus (WNV) infection have been recorded since 2008, and seasonal outbreaks have occurred almost annually. In this study, we summarize available evidences on the epidemiology of WNV and West Nile neuro-invasive disease (WNND) in humans reported between 2012 and 2020. In total, 1145 WNV infection cases were diagnosed; of them 487 (42.5%) had WNND. A significant circulation of the pathogen was suggested by studies on blood donors, with annual incidence rates ranging from 1.353 (95% confidence intervals (95% CI) 0.279–3.953) to 19.069 cases per 100,000 specimens (95% CI 13.494–26.174). The annual incidence rates of WNND increased during the study period from 0.047 cases per 100,000 (95% CI 0.031–0.068) in 2012, to 0.074 cases per 100,000 (95% CI 0.054–0.099) in 2020, peaking to 0.377 cases per 100,000 (95% CI 0.330–0.429) in 2018. There were 60 deaths. Cases of WNND were clustered in Northern Italy, particularly in the Po River Valley, during the months of August (56.7%) and September (27.5%). Higher risk for WNND was reported in subjects of male sex (risk ratio (RR) 1.545, 95% CI 1.392–1.673 compared to females), and in older age groups (RR 24.46, 95% CI 15.61–38.32 for 65–74 y.o.; RR 43.7, 95% CI 28.33–67.41 for subjects older than 75 years), while main effectors were identified in average air temperatures (incidence rate ratio (IRR) 1.3219, 95% CI 1.0053–1.7383), population density (IRR 1.0004, 95% CI 1.0001–1.0008), and occurrence of cases in the nearby provinces (IRR 1.0442, 95% CI 1.0340–1.0545). In summary, an enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

Human West Nile Meningo-Encephalitis in a Highly Endemic Country: A Complex Epidemiological Analysis on Biotic and Abiotic Risk Factors.

West Nile virus (WNV) is one of the most prevalent mosquito-borne viruses. Although the infection in humans is mostly asymptomatic, 15–20% of cases show flu-like symptoms with fever. In 1% of infections, humans develop severe nervous symptoms and even die, a condition known as West Nile neuroinvasive disease (WNND). The aim of our study was to analyze the influence of abiotic and biotic factors with the human WNND cases during the period 2015–2019. A database containing all the localities in Romania was developed. Abiotic and biotic predictors were included for each locality: geographic variables, climatic data, and biotic factors. Spatial distribution of the WNND infections was analyzed using directional distribution (DD). The Spearman’s rank correlation coefficient was employed to assess the strength of association between the WNND infections and predictors. A model was generated using the random forest ensemble learning method. A total number of 535 human WNND cases were confirmed in 308 localities. The DD showed a south-eastern geographical distribution. Weak correlation was observed between the number of human WNND cases for each year and the predictors. The highest predicted probability was around urbanized patches in the south and southeast. Increased surveillance and control measures of vectors in risk areas should be implemented and educational campaigns should be made available for the general public in order to raise awareness of the disease and inform the population about prophylactic measures.

Contrasted Epidemiological Patterns of West Nile Virus Lineages 1 and 2 Infections in France from 2015 to 2019.

Since 2015, annual West Nile virus (WNV) outbreaks of varying intensities have been reported in France. Recent intensification of enzootic WNV circulation was observed in the South of France with most horse cases detected in 2015 (n = 49), 2018 (n = 13), and 2019 (n = 13). A WNV lineage 1 strain was isolated from a horse suffering from West Nile neuro-invasive disease (WNND) during the 2015 episode in the Camargue area. A breaking point in WNV epidemiology was achieved in 2018, when WNV lineage 2 emerged in Southeastern areas. This virus most probably originated from WNV spread from Northern Italy and caused WNND in humans and the death of diurnal raptors. WNV lineage 2 emergence was associated with the most important human WNV epidemics identified so far in France (n = 26, including seven WNND cases and two infections in blood and organ donors). Two other major findings were the detection of WNV in areas with no or limited history of WNV circulation (Alpes-Maritimes in 2018, Corsica in 2018–2019, and Var in 2019) and distinct spatial distribution of human and horse WNV cases. These new data reinforce the necessity to enhance French WNV surveillance to better anticipate future WNV epidemics and epizootics and to improve the safety of blood and organ donations.

Recent rapid changes in the spatio-temporal distribution of West Nile Neuro-invasive Disease in Italy.

In Italy, the first human case of West Nile Virus (WNV) infection was reported in 2008 and, since then, the number of cases has been steadily increasing. In this study, we describe the temporal and spatial pattern of WNV infection risk among humans in Italy, focusing on the human cases of West Nile Neuro-invasive Disease (WNND) observed between 2008 and 2017. Incidence rates are estimated for each year and province under study. The incidence temporal trend is estimated using Poisson regression, and a spatio-temporal cluster detection analysis is performed to detect high-risk areas. In total, 231 WNND cases were notified in Italy between 2008 and 2017. The annual incidence rates increased during the study period (annual percentage change: 11.7%; 95%CI: -0.9%; 26.1%). A geographical spread of the disease was observed during the study period throughout Northern Italy, with an increasing number of affected provinces. Provinces close to the Po River (the main river in the north of Italy) and the Oristano province (in the Sardinia Island) experienced the highest incidence rates during the study period. Our study shows a gradual, but rapid spread of WNND across Northern Italy from east to west and suggests the hypothesis that provinces close to Po River might present ecological and climatic conditions favourable to the virus circulation.

443. West Nile Virus in Humans in Greece, 2010–2017

BackgroundIn 2010, the first West Nile (WN) virus outbreak was recorded in Central Macedonia, northern Greece, with 197 WN neuroinvasive disease (WNND) cases; the largest reported in Europe since 1996. In the consecutive years, seasonal outbreaks continued to occur. We investigated the 2010–2017 outbreaks to determine their extent, describe the geographical and temporal distribution of human cases and implement appropriate control measures.MethodsWe supported the investigation of suspected human cases and strengthened the laboratory surveillance. We interviewed cases and treating physicians and recorded suspected place of exposure, type of disease (WNND or non-WNND) and disease outcome. We estimated case fatality (CF) of neuro-invasive disease (WNND). PCR-positive samples were sequenced.ResultsSince 2010, a total of 672 human cases were recorded, from June to October, including 474 (71%) WNND cases. Cases were recorded for five consecutive years, in 2010 (n = 262), 2011 (n = 100), 2012 (n = 161), 2013 (n = 86), and 2014 (n = 15); and then in 2017 (n = 48), after a 2-year period with no cases diagnosed. Since 2010, a total of 81 (CF=17%) fatalities occurred among WNND cases, with a median age of 80 (49–95) years. Cases were recorded, in both urban and rural areas, in half (37/74) of the Regional Units (NUT-3 level), in all 13 Regions. In 2011, the virus dispersed southwards to newly affected Regional Units, and in the following years cases were recorded both in previously affected and in new areas, during each transmission season. In 2017, cases were also recorded for the first time in the two last—previously non-affected—Regions of the country. Sequences from PCR-positive samples revealed WNV lineage 2, with high genetic similarity to the 2010 strain.ConclusionThe reoccurrence of human cases and the spread of the virus in newly affected areas suggests that WNV lineage 2 has been established in Greece; its circulation and occurrence of cases remain likely in the following transmission periods, in previously affected and in new areas. Enhanced surveillance throughout Greece is critical to timely implement targeted control and prevention measures (i.e., communication campaigns, vector control, and blood safety measures).Disclosures All authors: No reported disclosures.

Re-emergence of severe West Nile virus neuroinvasive disease in humans in Romania, 2012 to 2017-implications for travel medicine.

In Romania, after a major outbreak in 1996, West Nile neuroinvasive disease (WNND) was reported only in a limited number of cases annually. During 2016-2017, a significant increase in the number of WNND cases was reported at the national level, associated with high mortality rates. A retrospective analysis of all cases confirmed with WNND, hospitalized during 2012-2017 in a single tertiary facility from Bucharest was performed in order to determine the annual prevalence and mortality rate and the risk factors associated with a severe outcome. 47 cases were confirmed as WNND. The mortality rate was 25.5%, all death occurred during 2016-2017. Coma, confusion, obtundation, sleepiness and depressed deep tendon reflexes were symptoms predicting a severe outcome. In a univariate analysis age (p < 0.001), associated cancers (p = 0.012) and low levels of chloride in the CSF (p = 0.008) were risk factors for mortality. In a multinomial logistic analysis, age older than 75 years remained the only independent predictor of death in WNND. The increase in both the number and the mortality rate of WNND cases suggest a changing pattern of WNV infection in Romania. Public health authorities and clinicians should be aware of the risk of severe WNV infection in travelers returning from Romania.

Impacts of Increasing Temperature on the Future Incidence of West Nile Neuroinvasive Disease in the United States

Multiple studies have identified links between climate and West Nile virus disease since the virus arrived in North America. Here we sought to extend these results by developing a Health Impact Function (HIF) to generate county-level estimates of the expected annual number of West Nile neuroinvasive disease (WNND) cases based on the county’s historical WNND incidence, annual average temperature, and population size. To better understand the potential impact of projected temperature change on WNND risk, we used the HIF to project the change in expected annual number of WNND cases attributable to changing temperatures by 2050 and by 2090 using data from five global climate models under two representative concentration pathways (RCP4.5 and RCP8.5). To estimate the costs of anticipated changes, as well as to enable comparisons with other public health impacts, projected WNND cases were allocated to nonfatal and fatal outcomes, then monetized using a cost-of-illness estimate and the U.S. Environmental Protection Agency’s value of a statistical life, respectively. We found that projected future temperature and population changes could increase the expected annual number of WNND cases to ≈2000 - 2200 cases by 2050 and to ≈2700 - 4300 cases by 2090, from a baseline of 970 cases. Holding population constant at future levels while varying temperature from a 1995 baseline, we estimated projected temperature change alone is responsible for ≈590 and ≈960 incremental WNND cases in 2050 and 2090 (respectively) under the RCP4.5 scenario, and ≈820 and ≈2500 cases in 2050 and 2090 (respectively) for the RCP8.5 scenario, with substantial regional variation. The monetized impact of these temperature-attributable incremental cases is estimated at $0.5 billion in 2050 and $1.0 billion in 2090 under the RCP4.5 scenario, and $0.7 billion in 2050 and $2.6 billion in 2090 under the RCP8.5 scenario (undiscounted 2015 U.S. dollars).

Identification of genetic variants associated with susceptibility to West Nile virus neuroinvasive disease.

West Nile virus (WNV) infection results in a diverse spectrum of outcomes, and host genetics are likely to influence susceptibility to neuroinvasive disease (WNND). We performed whole exome sequencing of 44 individuals with WNND and identified alleles associated with severe disease by variant filtration in cases, kernel association testing in cases and controls, and SNP imputation into a larger cohort of WNND cases and seropositive controls followed by genome-wide association analysis. Variant filtration prioritized genes based on the enrichment of otherwise rare variants, but did not unambiguously implicate variants shared by a majority of cases. Kernel association demonstrated enrichment for risk and protective alleles in the HLA-A and HLA-DQB1 loci, which have well understood roles in antiviral immunity. Two loci, HERC5 and an intergenic region between CD83 and JARID2, were implicated by multiple imputed SNPs and exceeded genome-wide significance in a discovery cohort (n=862). SNPs at two additional loci, TFCP2L1 and CACNA1H, achieved genome-wide significance after association testing of directly genotyped and imputed SNPs in a discovery cohort (n=862) and a separate replication cohort (n=1387). The context of these loci suggests that immunoregulatory, ion channel, and endothelial barrier functions may be important elements of the host response to WNV.

The experience of West Nile virus integrated surveillance system in the Emilia-Romagna region: five years of implementation, Italy, 2009 to 2013.

Predicting West Nile virus (WNV) circulation and the risk of WNV epidemics is difficult due to complex interactions of multiple factors involved. Surveillance systems that timely detect virus activity in targeted areas, and allow evidence-based risk assessments may therefore be necessary. Since 2009, a system integrating environmental (mosquitoes and birds) and human surveillance has been implemented and progressively improved in the Emilia-Romagna region, Italy. The objective is to increase knowledge of WNV circulation and to reduce the probability of virus transmission via blood, tissue and organ donation. As of 2013, the system has shown highly satisfactory results in terms of early detection capacity (the environmental surveillance component allowed detection of WNV circulation 3–4 weeks before human cases of West Nile neuroinvasive disease (WNND) occurred), sensitivity (capacity to detect virus circulation even at the enzootic level) and area specificity (capacity to indicate the spatial distribution of the risk for WNND). Strong correlations were observed between the vector index values and the number of human WNND cases registered at the province level. Taking into consideration two scenarios of surveillance, the first with environmental surveillance and the second without, the total costs for the period from 2009 to 2013 were reduced when environmental surveillance was considered (EUR 2.093 million for the first scenario vs EUR 2.560 million for the second). Environmental surveillance helped to reduce costs by enabling a more targeted blood unit testing strategy. The inclusion of environmental surveillance also increased the efficiency of detecting infected blood units and further allowed evidence-based adoption of preventative public health measures.

Economic Burden of West Nile Virus in the United States

Economic Burden of West Nile Virus in the United States

Clinical features of West Nile virus epidemic in Dallas, Texas, 2012

In 2012, Texas has reported the highest number of West Nile virus (WNV) cases in the United States to the Centers for Disease Control and Prevention. In this report, we conducted a retrospective chart review of 57 patients with WNV disease and analyzed the clinical features of these patients. Our results revealed that 25 (44%) patients were diagnosed with West Nile fever and 32 (56%) with West Nile neuroinvasive disease (WNND). The median age for patients with WNND was 54.5 years, and those with encephalitis were more likely to be >60 years old. Pre-existing conditions such as hypertension and diabetes were more frequent in patients with WNND. Testing both serum and cerebrospinal fluid (CSF) for antibodies diagnosed more cases of WNND than just testing serum or CSF alone. The increasing number of WNV cases during this epidemic highlights the need to increase efforts to control mosquito populations and educate the general public.

The 2012 West Nile Encephalitis Epidemic in Dallas, Texas

After progressive declines over recent years, in 2012 West Nile virus epidemics resurged nationwide, with the greatest number of cases centered in Dallas County, Texas. To analyze the epidemiologic, meteorologic, and geospatial features of the 2012 Dallas West Nile virus epidemic to guide future prevention efforts. Public health surveillance of Dallas County, an area of 2257 km2 and population of 2.4 million. Surveillance data included numbers of residents diagnosed with West Nile virus infection between May 30, 2012, and December 3, 2012; mosquito trap results; weather data; and syndromic surveillance from area emergency departments. Incidence and age-adjusted incidence rates of West Nile neuroinvasive disease (WNND), daily prevalence of emergency department visits for asthma and skin rash, and Culex quinquefasciatus species-specific vector index (an estimate of the average number of West Nile virus-infected mosquitoes per trap-night). The investigation identified 173 cases of WNND, 225 of West Nile fever, 17 West Nile virus-positive blood donors, and 19 deaths in 2012. The incidence rate for WNND was 7.30 per 100,000 residents in 2012, compared with 2.91 per 100,000 in 2006, the largest previous Dallas County outbreak. An unusually rapid and early escalation of large numbers of human cases closely followed increasing infection trends in mosquitoes. The Cx quinquefasciatus species-specific vector index predicted the onset of symptoms among WNND cases 1 to 2 weeks later (count regression β = 2.97 [95% CI, 2.34 to 3.60]; P < .001). Although initially widely distributed, WNND cases soon clustered in neighborhoods with high housing density in the north central area of the county, reflecting higher vector indices and following geospatial patterns of West Nile virus in prior years. During the 11 years since West Nile virus was first identified in Dallas, the log-transformed annual prevalence of WNND was inversely associated with the number of days with low temperatures below 28°F (-2.2°C) in December through February (β = -0.29 [95% CI, -0.36 to -0.21]; P < .001). Aerial insecticide spraying was not associated with increases in emergency department visits for respiratory symptoms (β = -4.03 [95% CI, -13.76 to 5.70]; P = .42) or skin rash (β = -1.00 [95% CI, -6.92 to 4.92]; P = .74). Large West Nile virus epidemics in Dallas County begin early after unusually warm winters, revisit similar geographical distributions, and are strongly predicted by the mosquito vector index. Consideration of weather patterns and historical geographical hot spots and acting on the vector index may help prevent West Nile virus-associated illness.

West Nile Virus Lineage 2 Strain in Greece, 2012

West Nile Virus Lineage 2 Strain in Greece, 2012

Antecedent Avian Immunity Limits Tangential Transmission of West Nile Virus to Humans

BackgroundWest Nile virus (WNV) is a mosquito-borne flavivirus maintained and amplified among birds and tangentially transmitted to humans and horses which may develop terminal neuroinvasive disease. Outbreaks typically have a three-year pattern of silent introduction, rapid amplification and subsidence, followed by intermittent recrudescence. Our hypothesis that amplification to outbreak levels is contingent upon antecedent seroprevalence within maintenance host populations was tested by tracking WNV transmission in Los Angeles, California from 2003 through 2011.MethodsPrevalence of antibodies against WNV was monitored weekly in House Finches and House Sparrows. Tangential or spillover transmission was measured by seroconversions in sentinel chickens and by the number of West Nile neuroinvasive disease (WNND) cases reported to the Los Angeles County Department of Public Health.ResultsElevated seroprevalence in these avian populations was associated with the subsidence of outbreaks and in the antecedent dampening of amplification during succeeding years. Dilution of seroprevalence by recruitment resulted in the progressive loss of herd immunity following the 2004 outbreak, leading to recrudescence during 2008 and 2011. WNV appeared to be a significant cause of death in these avian species, because the survivorship of antibody positive birds significantly exceeded that of antibody negative birds. Cross-correlation analysis showed that seroprevalence was negatively correlated prior to the onset of human cases and then positively correlated, peaking at 4–6 weeks after the onset of tangential transmission. Antecedent seroprevalence during winter (Jan – Mar) was negatively correlated with the number of WNND cases during the succeeding summer (Jul–Sep).ConclusionsHerd immunity levels within after hatching year avian maintenance host populations <10% during the antecedent late winter and spring period were followed on three occasions by outbreaks of WNND cases during the succeeding summer. Because mosquitoes feed almost exclusively on these avian species, amplification was directly related to the availability of receptive non-immune hosts.