West Nile Virus Outbreaks Research Articles

Encephalitis in the Pediatric Population

1. Stephen J. Falchek, MD* 1. *Division of Pediatric Neurology, Alfred I. duPont Hospital for Children/Thomas Jefferson University, Wilmington, DE, and Philadelphia, PA. * Abbreviations: ADEM: : acute disseminated encephalomyelitis CEP: : California Encephalitis Project CNS: : central nervous system CPP: : cerebral perfusion pressure CSF: : cerebrospinal fluid HSV: : herpes simplex virus IVIG: : intravenous immune globulin MS: : multiple sclerosis PCR: : polymerase chain reaction WNV: : West Nile virus Management of encephalitis, which can be fatal, requires understanding of a broad range of causative agents, pathophysiologic mechanisms, clinical syndromes, and outcomes. After completing this article, readers should be able to: 1. Know the many causes of encephalitis, including infectious, parainfectious, and noninfectious disorders. 2. Recognize the clinical features of encephalitis. 3. Be able to conduct a diagnostic investigation of a patient with encephalitis by using clinical and laboratory criteria. 4. Know the anticipated clinical course of different types of encephalitis. 5. Be familiar with the modalities used to treat encephalitis. 6. Understand the factors that influence the outcome in a patient who has encephalitis. The broad definition of the term “encephalitis,” that is, inflammation of the brain , necessitates acknowledgment of the enormous inclusivity of the topic. The most common interpretation of the term implies a direct invasion of the brain by an infectious pathogen, most commonly, viral, fungal, or parasitic. The topic also includes examples of meningitis mediated by bacteria or other agents, which can produce extrameningeal symptoms such as lethargy or seizures, in which case, the combined term “meningoencephalitis” is used. There are also many examples of encephalitis not due to direct central nervous system (CNS) infections. Inflammatory processes due to an acute or chronic illness can result in an acute immune-mediated encephalitis, such as acute disseminated encephalomyelitis (ADEM), lupus cerebritis, and paraneoplastic syndromes. Agents or conditions that produce slowly progressive CNS symptoms, such as tertiary syphilis or “slow viruses” (the prion protein encephalopathies), also are considered examples of encephalitis. Table 1 lists only a limited number of the many pathogens and pathologic conditions that can cause either acute or subacute encephalitis. In this discussion, …

High cerebrospinal fluid protein level in West Nile virus ncephalitis: report of five cases

An outbreak of West Nile virus (WNV) occurred in Greece, Russia, and Turkey in 2010. We diagnosed 5 WNV encephalitis patients, who presented with high cerebrospinal fluid (CSF) protein level and encephalitis relevant symptoms in the last days of summer or in the first days of autumn. Here, we aimed to present a retrospective analysis of 5 WNV encephalitis cases in Turkey in terms of their clinical and laboratory findings.

Monitoring of the West Nile Virus epidemic in Spain between 2010 and 2011

West Nile virus (WNV) is a mosquito-transmitted flavivirus recognized as an emerging and re-emerging pathogen in different countries. This study describes the monitoring of the first WNV epidemic in Spain between 2010 and 2011. Between September and December 2010, 36 outbreaks of WNV in horses were reported in three different provinces of Andalusia (southern Spain), with no apparent spread outside this area. The temporal distribution and the clinical signs observed during the WNV epidemic in Spain were, in general, similar to those reported in Europe and in the Mediterranean Basin. Morbidity, mortality and fatality rate in the affected herds were 4.6, 1.4 and 35.3%, respectively. Thirty-six of 75 (47.4%) suspected herds investigated presented at least one IgM seropositive animal. The individual seroprevalence in unvaccinated animals from the infected holdings was 51.7%. RNA WNV lineage 1 virus was confirmed from blood and cerebrospinal fluid samples in a lethally infected horse. The entomological survey showed that the most abundant mosquito species detected in the affected area was Culex pipiens. A cross-sectional study was carried out in non-suspected herds between April 2010 and February 2011 in the affected area. The individual seroprevalence was 11.0%, and six of the 38 herds sampled (15.8%) presented at least one seropositive animal. The results showed active WNV circulation several months before the first outbreak was reported in horses. The seropositivity found in municipalities where clinical cases were not reported indicates a higher geographical dissemination of the virus. Significantly higher seroprevalences were detected in areas close to Morocco. Furthermore, 90 wild ruminants were tested for the presence of antibodies against WNV, but the results were all negative.

Environmental Factors and Risk Areas of West Nile Virus in Southern California, 2007–2009

The West Nile virus (WNV) may post a significant health risk for mammals, including humans and insects. This study examines the spatial–temporal effects of environmental factors on WNV dissemination with a case study of ten counties in the southern California, where the epidemic was recently most prevalent within the USA. WNV surveillance data were obtained from the California Vectorborne Disease Surveillance System and Centers for Disease Control and Prevention. Remote sensing and Geographic Information Systems (GIS) techniques were combined to derive environmental variables. Principal component analysis was performed to select the most relevant environmental variables. Two ecological zones were identified based on the selected variables. Identification of risk areas for WNV was limited to a zone with 95% mosquitoes surveillance records. Three time windows, the epidemiological weeks 18–26, 27–35, and 36–44 in each year of 2007–2009, were examined in details with risk area mapping. It is found that the southern part of San Joaquin Valley in Kern County and Los Angeles County (especially its southern part) were the most vulnerable locations for WNV outbreak. Main factors contributing to the WNV propagation included summer mean temperature, annual mean deviation from the mean temperature, land surface temperature, elevation, landscape complexity, landscape diversity, and vegetation water content. The result of this study improves understanding of WNV ecology and provides tools for detecting, tracking, and predicting the epidemic. The holistic approach developed for this study, which integrated remotely sensed, GIS-based, and in situ-measured environmental data with landscape metrics, may be applied to studies of other vector-borne diseases.

Exposure of Eurasian magpies and turtle doves to West Nile virus during a major human outbreak, Greece, 2011

A major number of West Nile virus (WNV) infections in humans occurred in 2010 in northern Greece, with 262 laboratory confirmed cases. In 2011, fewer cases were reported, but the pattern was more dispersed throughout the Greek mainland. Isolated strains were similar to lineage 2 strains detected in previous years in Austria and Hungary from birds of prey. We conducted a serological surveillance study on hunter-harvested wild birds, to determine possible exposure of avian species during the current outbreak. Serum samples from a total of 113 Eurasian magpies and 85 turtle doves (abundant resident and migratory avian species, respectively, with potential roles in WNV epidemiology) were tested. These birds were hunter-harvested during 2011 from various prefectures both affected and not affected by the WNV outbreak in Greece. Sera were tested for the presence of WNV IgG antibodies by indirect immunofluorescence assay (IFA). Verification of positive results by a micro-virus neutralization test (VNT) was also performed. A total of 23 out of 113 (20.4%) Eurasian magpies and 6/85 (7.1%) turtle doves were found positive. Results showed association of human cases with wild birds’ exposure to the virus; no avian sera were found positive in prefectures not affected by the WNV outbreak. In contrast, positive avian sera were found in every prefecture that human WNV cases occurred in 2011. High seroprevalence in Eurasian magpies suggests high activity of WNV in the areas. Findings of past exposure of migratory birds like turtle doves to WNV upon their arrival in resting areas in Greece suggest various avian species with similar migration traits as target species for viral isolation studies, as they can be considered candidates for the introduction of WNV lineage 2 in Greece from Central Europe.

Spatio-temporal patterns of distribution of West Nile virus vectors in eastern Piedmont Region, Italy

BackgroundWest Nile Virus (WNV) transmission in Italy was first reported in 1998 as an equine outbreak near the swamps of Padule di Fucecchio, Tuscany. No other cases were identified during the following decade until 2008, when horse and human outbreaks were reported in Emilia Romagna, North Italy. Since then, WNV outbreaks have occurred annually, spreading from their initial northern foci throughout the country. Following the outbreak in 1998 the Italian public health authority defined a surveillance plan to detect WNV circulation in birds, horses and mosquitoes. By applying spatial statistical analysis (spatial point pattern analysis) and models (Bayesian GLMM models) to a longitudinal dataset on the abundance of the three putative WNV vectors [Ochlerotatus caspius (Pallas 1771), Culex pipiens (Linnaeus 1758) and Culex modestus (Ficalbi 1890)] in eastern Piedmont, we quantified their abundance and distribution in space and time and generated prediction maps outlining the areas with the highest vector productivity and potential for WNV introduction and amplification.ResultsThe highest abundance and significant spatial clusters of Oc. caspius and Cx. modestus were in proximity to rice fields, and for Cx. pipiens, in proximity to highly populated urban areas. The GLMM model showed the importance of weather conditions and environmental factors in predicting mosquito abundance. Distance from the preferential breeding sites and elevation were negatively associated with the number of collected mosquitoes. The Normalized Difference Vegetation Index (NDVI) was positively correlated with mosquito abundance in rice fields (Oc. caspius and Cx. modestus). Based on the best models, we developed prediction maps for the year 2010 outlining the areas where high abundance of vectors could favour the introduction and amplification of WNV.ConclusionsOur findings provide useful information for surveillance activities aiming to identify locations where the potential for WNV introduction and local transmission are highest. Such information can be used by vector control offices to stratify control interventions in areas prone to the invasion of WNV and other mosquito-transmitted pathogens.

Identification of suitable areas for West Nile virus outbreaks in equid populations for application in surveillance plans: the example of the Castile and Leon region of Spain

The introduction and rapid spread of West Nile virus (WNV) into new areas such as the American continent, associated also with the severity of the disease in humans and equids has increased concerns regarding the need to better prevent and control future WNV incursions. WNV outbreaks in equids usually occur under specific climatic and environmental conditions and, typically, before detection of WNV cases in humans. Targeting surveillance strategies in areas and time periods identified as suitable for WNV outbreaks in equids may act as an early-warning system to prevent disease in both equids and humans. This study used a GIS-based framework to identify suitable areas and time periods for WNV outbreak occurrence in one of the most important areas of equid production in Spain, i.e. Castile and Leon. Methods and results presented here may help to improve the early detection and control of future WNV outbreaks in Spain and other regions.

Multi-species interactions in West Nile virus infection

In this paper, we analyse the interaction of different species of birds and mosquitoes on the dynamics of West Nile virus (WNV) infection. We study the different transmission efficiencies of the vectors and birds and the impact on the possible outbreaks. We show that the basic reproductive number is the weighted mean of the basic reproductive number of each species, weighted by the relative abundance of its population in the location. These results suggest a possible explanation of why there are no outbreaks of WNV in Mexico.

Non-neuroinvasive West Nile virus infections during the outbreak in Greece

A major outbreak of West Nile virus (WNV) infections took place in 2010 in Greece. Apart from the neuroinvasive cases, many additional cases without involvement of the nervous system were observed, characterized by high fever, myalgia, rash, leukopenia, and long-lasting recovery. West Nile nonneuroinvasive disease is a distinct clinical syndrome, and is not always mild.

Climatic Controls on West Nile Virus and Sindbis Virus Transmission and Outbreaks in South Africa

The processes influencing the magnitude of West Nile virus (WNV) transmission from 1 year to the next require thorough investigation. The intensity of WNV transmission is related to the dynamics and interactions between the pathogen, vector, vertebrate hosts, and environment. Climatic variability is one process that can influence interannual disease transmission. South Africa has a long WNV and Sindbis virus (SINV) record where consistent climate and disease relationships can be identified. We relate climate conditions to historic mosquito infection rates. Next, we detect similar associations with reported human outbreaks dating back to 1941. Both concurrent summer precipitation and the change in summer precipitation from the previous to the current summer were strongly associated with WNV and SINV transmission and recorded human outbreaks. Each 100 mm interannual summer precipitation change increased WNV infection rates by 0.39 WNV-positive Culex univittatus/1000 tested Cx. univittatus. An improved understanding of biotic and abiotic disease transmission dynamics may help anticipate and mitigate future outbreaks.

Enhancing temporal resolution of satellite imagery for public health studies: A case study of West Nile Virus outbreak in Los Angeles in 2007

Although remotely sensed data have been used in public health studies, these studies are often limited by the critical choice that has to be made in data selection: either using data with high spatial but low temporal resolution, or data with high temporal but low spatial resolution. This choice creates significant limitations for time-dependent epidemiological studies, since it is often essential to have datasets with high spatial and temporal resolution. Effectively synthesizing high temporal resolution imagery with high spatial resolution imagery can potentially ease this limitation. To this end, we conducted an experiment by creating a series of simulated ASTER datasets by fusing ASTER and MODIS data with the STARFM image fusion model. These simulated datasets are then used to derive the following urban environmental variables: normalized difference vegetation index, normalized difference water index, and land surface temperature. These variables are used to quantitatively examine the effects of urban environmental characteristics on West Nile Virus dissemination in Los Angeles County, California, where the epidemic was most prevalent in the United States in 2007. Mosquito surveillance data were collected from the weekly summary reports published in the California West Nile Virus website. A spatial–temporal analysis of WNV dissemination was conducted by synthesizing remote sensing variables and mosquito surveillance records. We focused on assessment of WNV risk areas in July through September due to data sufficiency of tested-positive mosquito pools. Moderate- and high-risk areas of WNV infections in mosquitoes were identified for five selected time windows, i.e., epidemiological weeks 30–31, 32–33, 34–35, 36–37, and 38–39. The results show that elevation and urban built-up conditions were negatively associated with the WNV propagation, while LST positively correlated with viral transmission. NDVI was not significantly associated with WNV transmission during the studied time intervals. San Fernando Valley was found to be the most vulnerable to mosquito infections of WNV within the City of Los Angeles. With the complementation of high-spatial resolution ASTER and high-temporal resolution MODIS images, the fused image datasets allow for estimating environmental parameters at desired epidemiological weeks. This paper provides important insights into how high temporal resolution remote sensing imagery might be used to study time-dependant events in public health, especially in the operational surveillance and control of vector-borne or other epidemic diseases.

Acute West Nile virus neuroinvasive infections: Cross‐reactivity with dengue virus and tick‐borne encephalitis virus

Cross-reactions in serology are common among flaviviruses. During the outbreak of West Nile virus (WNV) infections in Greece in 2010, WNV IgM-positive serum and cerebrospinal fluid samples were tested for the presence of IgM and IgG antibodies against Dengue virus (DENV) and tick-borne encephalitis virus. Higher cross-reactivity was observed in IgM antibodies between WNV and DENV; however, the index of the WNV antibodies was in all cases higher than that of the DENV antibodies. There is a need for caution when evaluating serologic results of flaviviral infections, while efforts have to be focused on the development of diagnostic assays with increased specificity.

Persistence of West Nile virus immunoglobulin M antibodies, Greece

A major outbreak of West Nile virus (WNV) lineage 2 infections was observed in 2010 in Greece. In order to check the persistence of WNV IgM antibodies, a second serum sample taken 75-180 days after onset of the illness from 29 patients with WNV infection was tested. A third sample was obtained 181-270 days after onset of the illness from 8 of the 12 patients with IgM-positive second sample. Mixed effects linear regression analysis indicated that the approximate time at which IgM index became negative was 164 (95% confidence interval, 95% CI 99-236) days after the symptoms' onset. Persistence of IgM antibodies was observed in 12% of patients at 181-270 days of follow-up. A sharp decrease in the IgM levels was observed, mainly in patients who had high IgM index value in the acute phase. All patients were WNV IgG positive at the follow-up.

Detection of West Nile virus lineage 2 in mosquitoes during a human outbreak in Greece

A human outbreak of West Nile virus (WNV) infections occurred in 2010 in central Macedonia, northern Greece. Most cases were observed close to four rivers forming a large Delta, a major Mediterranean wetland. WNV lineage 2 sequences were obtained from two pools of Culex pipiens mosquitoes trapped in sites where encephalitis cases occurred a few days before the trapping. The Greek strain showed the highest homology to Hungarian and South African strains, differing from the Russian WNV lineage 2 strain, which suggests that at least two lineage 2 strains have been introduced and established in Europe, causing severe disease to humans.

Retrospective Diagnosis of West Nile Virus Infection in a Patient with Meningoencephalitis in Tuscany, Italy

We report a case of West Nile virus (WNV) infection in a symptomatic woman living in Tuscany in 2007. A retrospective analysis on cerebrospinal fluids drawn from people affected by neurological diseases with unknown etiology allowed the identification of a case of WNV infection before the WNV outbreak in the Northeast Italy in 2008. This emphasizes the importance of maintaining a high level of epidemiological surveillance all over the Italian territory.

Abundance and population trends of mangrove landbirds in southwest Florida

ABSTRACT The avifauna of south Florida's mangrove forests is unique and relatively unstudied. The population status of landbirds that breed in these forests is currently unknown, and this lack of information is especially problematic for species that have North American ranges limited almost exclusively to Florida's mangroves. To address this information gap, we estimated trends in abundance using data generated during bird surveys conducted from 2000 to 2008 at 101 points in mangrove forests in southwestern Florida. We found that populations of two of three mangrove-dependent species that breed in these forests, Black-whiskered Vireos (Vireo altiloquus) and Mangrove Cuckoos (Coccyzus minor), declined significantly during our study. In contrast, only one of seven species with a broader North American range (Red-bellied Woodpecker, Melanerpes carolinensis) declined in abundance. No species increased in abundance. The Mangrove Cuckoo population exhibited the greatest decline, with numbers declining 87.1% from 2000 to 2008. Numbers of Black-whiskered Vireos declined 63.9%. These declines coincided with the outbreak of West Nile virus that has been linked to population declines of other North American birds, but we could not rule out other potential causes, including changes in the quality or extent of breeding or wintering habitat. La avifauna de los manglares del sur de la Florida, es única y ha sido poco estudiada. Actualmente se desconoce el estatus poblacional de las aves terrestres que anidan en estos bosques y esta falta de información es especialmente problemática para especies que tienen límites en su distribución a Norte America y que están limitadas exclusivamente a los manglares de la Florida. Para llenar este vacío de información, estimamos las tendencias en abundancia de estas aves, utilizando los datos generados durante los censos conducidos del 2000 al 2008 en 101 puntos de manglares en el sur de Florida. En dos de tres manglares encontramos que las poblaciones de especies, que son dependientes de estos, como el Julián Chiví (Vireo altiloquus) y el Pájaro Bobo Menor (Coccyzus minor), se redujeron significativamente, durante el periodo de estudio. En contraste, solo una de siete especies con una distribución más amplia (Melanerpes carolinensis) se redujo en abundancia. Ninguna especie mostró aumentos en su abundancia. El Pájaro Bobo Menor mostró el mayor descenso, con una reducción de 87.1% del 2000 al 2008. Por su parte el Julián Chiví se redujo en 63.9%. Estas reducciones coinciden con la llegada del virus de la fiebre del Nilo a Norte America que ha sido asociado a la reducción de otras aves, aunque no podemos dejar fuera otras causas incluyendo los cambios en la calidad y extensión del hábitat de anidamiento o el invernal.

Development time of IgG antibodies to West Nile virus

Following an outbreak of West Nile virus (WNV) infections in Greece during summer/autumn 2010, a study was conducted to investigate the patterns of WNV IgG reactivity in 255 patients with respect to the day of illness and the type of clinical syndrome. IgG antibodies were detectable after a mean of 8.1 ± 4.9 and 12.6 ± 11.3 days after onset of illness in neuroinvasive and non-neuroinvasive cases, respectively (p < 0.001), suggesting that a delay in the development of WNV IgG antibodies is seen in non-neuroinvasive cases.

Molecular detection and phylogenetic analysis of West Nile virus lineage 2 in sedentary wild birds (Eurasian magpie), Greece, 2010

A West Nile virus (WNV) lineage 2 strain was molecularly identified and characterised in a Eurasian magpie hunted in Greece in 2010, during a WNV outbreak in humans. Phylogenetic analysis revealed the highest sequence similarity (>99%) with other WNV lineage 2 strains derived from birds of prey in Austria and Hungary (2004–2009). This first molecular detection of WNV in sedentary wild birds in Greece, which are possible reservoirs of the virus, is a public health concern.

Dix ans de diagnostic génomique viral : leçons et perspectives

Nucleic acid testing has been routinely performed in all blood donations in France since July 1st 2001. This is the story of a controversial decision. “The unacceptable HIV risk” in the context of the early 2000s influenced the decision. The results achieved over these past 10 years are analyzed given the expected progress of this new screening tool for infectious agents in transfusion. They confirm the relevance of models used by experts in 2000. Out of 22.3 million donations over the period (2001–2009), 22 donations have been rejected because of nucleic acid testing positive for hepatitis C virus ( n = 11) and human immunodeficiency virus ( n = 11). Nucleic acid testing has contributed to improve the functioning of the transfusion chain activities in order to ensure the availability of blood products. In terms of reactivity against emerging infectious agents, its role in the West Nile virus (WNV) outbreak is exemplary, but it did not play a similar role in crises of the same order. ALT determination has been stopped thanks to nucleic acid testing. The risk of contamination of the method by amplification products has been confirmed and caution is still required. Nucleic acid testing is being maintained and reached a new milestone in 2010 with the implementation of a full automated system, meanwhile pool screening was given up and hepatitis B virus screening became widespread. Nucleic acid tests will probably be revised when all blood products are pathogen-inactivated.

West Nile virus: a seasonal threat?

With the report of an outbreak of West Nile virus in mainland Greece, Barry Hill provides an update on its prevalence and of its potential impact on UK blood services