Culex pipiens and Stegomyia albopicta (= Aedes albopictus) populations as vectors for lineage 1 and 2 West Nile virus in Europe

The emerging disease West Nile fever is caused by West Nile virus (WNV), one of the most widespread arboviruses. This study represents the first test of the vectorial competence of European Culex pipiens Linnaeus 1758 and Stegomyia albopicta (= Aedes albopictus) (both: Diptera: Culicidae) populations for lineage 1 and 2 WNV isolated in Europe. Culex pipiens and S. albopicta populations were susceptible to WNV infection, had disseminated infection, and were capable of transmitting both WNV lineages. This is the first WNV competence assay to maintain mosquito specimens under environmental conditions mimicking the field (day/night) conditions associated with the period of maximum expected WNV activity. The importance of environmental conditions is discussed and the issue of how previous experiments conducted in fixed high temperatures may have overestimated WNV vector competence results with respect to natural environmental conditions is analysed. The information presented should be useful to policymakers and public health authorities for establishing effective WNV surveillance and vector control programmes. This would improve preparedness to prevent future outbreaks.     

Predicting the spatio-temporal spread of West Nile virus in Europe

West Nile virus is a widely spread arthropod-born virus, which has mosquitoes as vectors and birds as reservoirs. Humans, as dead-end hosts of the virus, may suffer West Nile Fever (WNF), which sometimes leads to death. In Europe, the first large-scale epidemic of WNF occurred in 1996 in Romania. Since then, human cases have increased in the continent, where the highest number of cases occurred in 2018. Using the location of WNF cases in 2017 and favorability models, we developed two risk models, one environmental and the other spatio-environmental, and tested their capacity to predict in 2018: 1) the location of WNF; 2) the intensity of the outbreaks (i.e. the number of confirmed human cases); and 3) the imminence of the cases (i.e. the Julian week in which the first case occurred). We found that climatic variables (the maximum temperature of the warmest month and the annual temperature range), human-related variables (rain-fed agriculture, the density of poultry and horses), and topo-hydrographic variables (the presence of rivers and altitude) were the best environmental predictors of WNF outbreaks in Europe. The spatio-environmental model was the most useful in predicting the location of WNF outbreaks, which suggests that a spatial structure, probably related to bird migration routes, has a role in the geographical pattern of WNF in Europe. Both the intensity of cases and their imminence were best predicted using the environmental model, suggesting that these features of the disease are linked to the environmental characteristics of the areas. We highlight the relevance of river basins in the propagation dynamics of the disease, as outbreaks started in the lower parts of the river basins, from where WNF spread towards the upper parts. Therefore, river basins should be considered as operational geographic units for the public health management of the disease.     

Culex pipiens, an experimental efficient vector of West Nile and Rift Valley fever viruses in the Maghreb region

West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 10(7.8) and 10(8.5) plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14-21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology.     

Remote Sensing of Climatic Anomalies and West Nile Virus Incidence in the Northern Great Plains of the United States

The northern Great Plains (NGP) of the United States has been a hotspot of West Nile virus (WNV) incidence since 2002. Mosquito ecology and the transmission of vector-borne disease are influenced by multiple environmental factors, and climatic variability is an important driver of inter-annual variation in WNV transmission risk. This study applied multiple environmental predictors including land surface temperature (LST), the normalized difference vegetation index (NDVI) and actual evapotranspiration (ETa) derived from Moderate-Resolution Imaging Spectroradiometer (MODIS) products to establish prediction models for WNV risk in the NGP. These environmental metrics are sensitive to seasonal and inter-annual fluctuations in temperature and precipitation, and are hypothesized to influence mosquito population dynamics and WNV transmission. Non-linear generalized additive models (GAMs) were used to evaluate the influences of deviations of cumulative LST, NDVI, and ETa on inter-annual variations of WNV incidence from 2004–2010. The models were sensitive to the timing of spring green up (measured with NDVI), temperature variability in early spring and summer (measured with LST), and moisture availability from late spring through early summer (measured with ETa), highlighting seasonal changes in the influences of climatic fluctuations on WNV transmission. Predictions based on these variables indicated a low WNV risk across the NGP in 2011, which is concordant with the low case reports in this year. Environmental monitoring using remote-sensed data can contribute to surveillance of WNV risk and prediction of future WNV outbreaks in space and time.     

The Israeli strain IS-98-ST1 of West Nile virus as viral model for West Nile encephalitis in the Old World

West Nile virus (WNV) recently became a major public health concern in North America, the Middle East, and Europe. In contrast with the investigations of the North-American isolates, the neurovirulence properties of Middle-Eastern strains of WNV have not been extensively characterized. Israeli WNV strain IS-98-ST1 that has been isolated from a white stork in 1998, was found to be highly neuroinvasive in adult C57BL/6 mice. Strain IS-98-ST1 infects primary neuronal cells from mouse cortex, causing neuronal death. These results demonstrate that Israeli strain IS-98-ST1 provides a suitable viral model for WNV-induced disease associated with recent WNV outbreaks in the Old World.     

Permissive Summer Temperatures of the 2010 European West Nile Fever Upsurge

Background

In the summer of 2010, Europe experienced outbreaks of West Nile Fever (WNF) in humans, which was preceded by hot spells. The objective of this study was to identify potential drivers of these outbreaks, such as spring and summer temperatures, relative humidity (RH), and precipitation.

Methods

Pearson and lag correlations, binary and multinomial logistic regressions were used to assess the relationship between the climatic parameters and these outbreaks.

Results

For human morbidity, significant (<0.05) positive correlations were observed between a number of WNF cases and temperature, with a geographic latitude gradient: northern (“colder”) countries displayed strong correlations with a lag of up to four weeks, in contrast to southern (“warmer”) countries, where the response was immediate. The correlations with RH were weaker, while the association with precipitation was not consistent. Horse morbidity started three weeks later than in humans where integrated surveillance was conducted, and no significant associations with temperature or RH were found for lags of 0 to 4 weeks.

Conclusions

Significant temperature deviations during summer months might be considered environmental precursors of WNF outbreaks in humans, particularly at more northern latitudes. These insights can guide vector abatement strategies by health practitioners in areas at risk for persistent transmission cycles.     

A continental risk assessment of West Nile virus under climate change

Since first introduced to North America in 1999, West Nile virus (WNV) has spread rapidly across the continent, threatening wildlife populations and posing serious health risks to humans. While WNV incidence has been linked to environmental factors, particularly temperature and rainfall, little is known about how future climate change may affect the spread of the disease. Using available data on WNV infections in vectors and hosts collected from 2003–2011 and using a suite of 10 species distribution models, weighted according to their predictive performance, we modeled the incidence of WNV under current climate conditions at a continental scale. Models were found to accurately predict spatial patterns of WNV that were then used to examine how future climate may affect the spread of the disease. Predictions were accurate for cases of human WNV infection in the following year (2012), with areas reporting infections having significantly higher probability of presence as predicted by our models. Projected geographic distributions of WNV in North America under future climate for 2050 and 2080 show an expansion of suitable climate for the disease, driven by warmer temperatures and lower annual precipitation that will result in the exposure of new and naïve host populations to the virus with potentially serious consequences. Our risk assessment identifies current and future hotspots of West Nile virus where mitigation efforts should be focused and presents an important new approach for monitoring vector‐borne disease under climate change.     

West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation

West Nile virus (WNV) is a recently re-emerged health problem in Europe. In Italy, an increasing number of outbreaks of West Nile disease, with occurrences of human cases, have been reported since 2008. This is particularly true in northern Italy, where entomological surveillance systems have been implemented at a regional level. The aim of this study was to use, for the first time, all the entomological data collected in the five regions undergoing surveillance for WNV in northern Italy to characterize the viral circulation (at a spatial and temporal scale), identify potential mosquito vectors, and specify relationships between virus circulation and meteorological conditions. In 2013, 286 sites covering the entire Pianura Padana area were monitored. A total of 757,461 mosquitoes were sampled. Of these, 562,079 were tested by real-time PCR in 9,268 pools, of which 180 (1.9%) were positive for WNV. The largest part of the detected WNV sequences belonged to lineage II, demonstrating that, unlike those in the past, the 2013 outbreak was mainly sustained by this WNV lineage. This surveillance also detected the Usutu virus, a WNV-related flavivirus, in 241 (2.6%) pools. The WNV surveillance systems precisely identified the area affected by the virus and detected the viral circulation approximately two weeks before the occurrence of onset of human cases. Ninety percent of the sampled mosquitoes were Culex pipiens, and 178/180 WNV-positive pools were composed of only this species, suggesting this mosquito is the main WNV vector in northern Italy. A significantly higher abundance of the vector was recorded in the WNV circulation area, which was characterized by warmer and less rainy conditions and greater evapotranspiration compared to the rest of the Pianura Padana, suggesting that areas exposed to these conditions are more suitable for WNV circulation. This observation highlights warmer and less rainy conditions as factors able to enhance WNV circulation and cause virus spillover outside the sylvatic cycle.     

Influence of Warming Tendency on <Emphasis Type="Italic">Culex pipiens</Emphasis> Population Abundance and on the Probability of West Nile Fever Outbreaks (Israeli Case Study: 2001–2005)

Climate change and West Nile fever (WNV) are both subjects of global importance. Many mosquitoes and the diseases they carry, including West Nile virus (WNV), are sensitive to temperature increase. The current study analyzes the lag correlations between weather conditions (especially air temperature) and 1) Culex pipiens mosquito population abundance, and 2) WNF frequency in humans, between 2001 and 2005 in Israel. These 5 years follow a long period with a documented tendency for temperature increase in the hot season in the country. Monthly anomalies of minimum and maximum temperatures, relative seasonal rainfall contribution, mosquito samplings (hazard level), and WNF cases (hospital admission dates and patients’ addresses) were analyzed. Logistic regression was calculated between the climatic data and the mosquito samples, as Spearman correlations and Pearson cross-correlations were calculated between daily temperature values (or daily precipitation amounts) and the hospital admission dates. It was found that the disease appearance reflects the population distribution, while the risk tends to escalate around the metropolis characterized by an urban heat island. Positive anomalies of the temperature during the study period appear to have facilitated the mosquito abundance and, consequently, the disease emergence in humans. An important finding is the potential influence of extreme heat in the early spring on the vector population increase and on the disease’s appearance weeks later. Awareness of such situations at the beginning of the spring may help authorities to reduce the disease risk before it becomes a real danger.     

Protection of a Single Dose West Nile Virus Recombinant Subviral Particle Vaccine against Lineage 1 or 2 Strains and Analysis of the Cross-Reactivity with Usutu Virus

West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus. High WNV virulence was mainly associated with lineage 1 strains, but recent outbreaks have unveiled circulation of highly virulent lineage 2 strains. Co-expression of flavivirus prM and E glycoproteins drives the assembly of recombinant subviral particles (RSPs) that share antigenic features with virions. Mouse immunization with lineage 1 WNV RSPs induced a potent humoral response against WNV with production of neutralizing antibodies. A single inoculation of RSPs formulated with Al(OH)₃ as adjuvant protected mice against a lethal challenge with WNV strains from lineage 1 or 2. The cross-reactivity of the response elicited by these RSPs was analyzed against the related flavivirus Usutu virus (USUV), which shares multiple ecological and antigenic features with WNV. Immunization with WNV-RSPs increased specific, although low, antibody titers found upon subsequent USUV infection.     

The Complete Sequence of a West Nile Virus Lineage 2 Strain Detected in a Hyalomma marginatum marginatum Tick Collected from a Song Thrush (Turdus philomelos) in Eastern Romania in 2013 Revealed Closest Genetic Relationship to Strain Volgograd 2007

In this study the first complete sequence of the West Nile virus (WNV) lineage 2 strain currently circulating in Romania was determined. The virus was detected in a Hyalomma marginatum marginatum tick collected from a juvenile song thrush (Turdus philomelos) in the Romanian Danube Delta close to the city of Tulcea, end of August 2013. Our finding emphasizes the role of ticks in introduction and maintenance of WNV infections. Sequence analyses revealed close genetic relationship of the Romanian WNV strain to strain Reb_Volgograd_07_H, which was isolated from human brain tissue during an outbreak of West Nile neuroinvasive disease (WNND) in Russia in 2007. In 2010 the Eastern European lineage 2 WNV caused an outbreak of human WNND in Romania. Partial sequences from subsequent years demonstrated that this WNV strain became endemic in Eastern Europe and has been causing outbreaks of varying sizes in southern Russia since 2007 and in Romania since 2010.     

An Integrative Eco-Epidemiological Analysis of West Nile Virus Transmission

West Nile disease, caused by the West Nile virus (WNV), is a mosquito-borne zoonotic disease affecting humans and horses that involves wild birds as amplifying hosts. The mechanisms of WNV transmission remain unclear in Europe where the occurrence of outbreaks has dramatically increased in recent years. We used a dataset on the competence, distribution, abundance, diversity and dispersal of wild bird hosts and mosquito vectors to test alternative hypotheses concerning the transmission of WNV in Southern France. We modelled the successive processes of introduction, amplification, dispersal and spillover of WNV to incidental hosts based on host–vector contact rates on various land cover types and over four seasons. We evaluated the relative importance of the mechanisms tested using two independent serological datasets of WNV antibodies collected in wild birds and horses. We found that the same transmission processes (seasonal virus introduction by migratory birds, Culex modestus mosquitoes as amplifying vectors, heterogeneity in avian host competence, absence of ‘dilution effect’) best explain the spatial variations in WNV seroprevalence in the two serological datasets. Our results provide new insights on the pathways of WNV introduction, amplification and spillover and the contribution of bird and mosquito species to WNV transmission in Southern France.     

新疆伊犁地区马脑组织西尼罗病毒感染的调查

目的了解新疆伊犁地区草原放养马群中西尼罗病毒(W estN ile virus,WNV)中枢感染的流行状况。方法采用一步法实时荧光定量逆转录聚合酶链反应(Real Tim e RT-PCR)对采自新疆伊犁地区草原放养、未接种WNV疫苗的189例马脑组织进行WNV包膜蛋白(E)基因片段检测。结果被检马脑组织标本中未发现WNV E基因片段。结论目前尚没有证据表明我国新疆伊犁地区的放养马中存在WNV脑炎的感染,提示该地区出现WNV脑炎流行的可能性小。     

Economic conditions predict prevalence of West Nile virus

Understanding the conditions underlying the proliferation of infectious diseases is crucial for mitigating future outbreaks. Since its arrival in North America in 1999, West Nile virus (WNV) has led to population-wide declines of bird species, morbidity and mortality of humans, and expenditures of millions of dollars on treatment and control. To understand the environmental conditions that best explain and predict WNV prevalence, we employed recently developed spatial modeling techniques in a recognized WNV hotspot, Orange County, California. Our models explained 85-95% of the variation of WNV prevalence in mosquito vectors, and WNV presence in secondary human hosts. Prevalence in both vectors and humans was best explained by economic variables, specifically per capita income, and by anthropogenic characteristics of the environment, particularly human population and neglected swimming pool density. While previous studies have shown associations between anthropogenic change and pathogen presence, results show that poorer economic conditions may act as a direct surrogate for environmental characteristics related to WNV prevalence. Low-income areas may be associated with higher prevalence for a number of reasons, including variations in property upkeep, microhabitat conditions conducive to viral amplification in both vectors and hosts, host community composition, and human behavioral responses related to differences in education or political participation. Results emphasize the importance and utility of including economic variables in mapping spatial risk assessments of disease.     

A 20-year historical review of West Nile virus since its initial emergence in North America: Has West Nile virus become a neglected tropical disease?

After the unexpected arrival of West Nile virus (WNV) in the United States in 1999, the mosquito-borne virus quickly spread throughout North America. Over the past 20 years, WNV has become endemic, with sporadic epizootics. Concerns about the economic impact of infection in horses lead to the licensure of an equine vaccine as early as 2005, but few advances regarding human vaccines or treatments have since been made. There is a high level of virus transmission in hot/humid, subtropical climates, and high morbidity that may disproportionately affect vulnerable populations including the homeless, elderly, and those with underlying health conditions. Although WNV continues to cause significant morbidity and mortality at great cost, funding and research have declined in recent years. These factors, combined with neglect by policy makers and amenability of control measures, indicate that WNV has become a neglected tropical disease.     

Epidemiologic situation of West Nile fever in Russia in 2010

Problem of tropical arbovirus infection--West Nile fever (WNF)--spread in Russian Federation is discussed. Biology of WNF is discussed, WNF sources and reservoir are characterized. WNF outbreaks in Russia during the past 2 decades are presented in detail. Outbreaks of different years, possible causes and epidemiology are discussed. Features of WNF clinical course during various outbreaks and WNF diagnostic problems are presented.     

Infection of mouse neurones by West Nile virus is modulated by the interferon-inducible 2'-5' oligoadenylate synthetase 1b protein

Over the past 7 years, West Nile zoonosis has been an emerging concern for public health in Europe, Middle East and more recently in North America. West Nile virus causes epidemic outbreaks in humans and infected patients may exhibit severe neurological symptoms. Because susceptibility and sensitivity to West Nile virus infections may depend on host genetic factors, a mouse model has been established to investigate the genetic determinism of host susceptibility to West Nile virus. A nonsense mutation in gene encoding the 1b isoform of the 2'-5'oligoadenylate synthetase (OAS1b) was constantly associated with the susceptibility of mouse strains to experimental West Nile virus infection. Oligoadenylate synthetase are interferon-inducible proteins playing a role in the endogeneous antiviral pathway. It was of interest to establish whether interferon-alpha and OAS 1B were sufficient to mediate resistance to West Nile virus infection. In the present study, we showed that interferon-alpha had the ability to modulate West Nile virus infection in mouse. In vitro, interferon-alpha protected mouse neuroblastoma cells against West Nile virus infection if cells have been pretreated with the cytokine for several hours. As a consequence of the presence of a stop codon, the Oas1b gene of the susceptible mice encodes a truncated and presumably inactive form, while resistant mice have a normal copy of the gene. Stable mouse neuroblastoma cell clones overexpressing mutant or wild-type OAS 1B were established. Replication of West Nile virus was less efficient in cells that produce the normal copy of OAS 1B as compared to those expressing the truncated form. Our data illustrate the notion that interferon-alpha and Oas genes may be critical for West Nile virus pathogenesis.