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Spatial distribution of West Nile virus in humans and mosquitoes in Israel, 2000–2014

  • Author Footnotes
    1 Yaniv Lustig and Zalman Kaufman contributed equally.
    Yaniv Lustig
    Correspondence
    Corresponding author at: National Center for Zoonotic Viruses, Central Virology Laboratory, Ministry of Health, Sheba Medical Center, Ramat-Gan, Israel. Fax: +972 3 5302457.
    Footnotes
    1 Yaniv Lustig and Zalman Kaufman contributed equally.
    Affiliations
    Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel
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  • Author Footnotes
    1 Yaniv Lustig and Zalman Kaufman contributed equally.
    Zalman Kaufman
    Footnotes
    1 Yaniv Lustig and Zalman Kaufman contributed equally.
    Affiliations
    Israel Center for Disease Control, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel
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  • Ella Mendelson
    Affiliations
    Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Laor Orshan
    Affiliations
    Laboratory of Entomology, Ministry of Health, Jerusalem, Israel
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  • Emilia Anis
    Affiliations
    Division of Epidemiology, Ministry of Health, Jerusalem, Israel

    Braun School of Public Health, Hebrew University and Hadassah, Jerusalem, Israel
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  • Yael Glazer
    Affiliations
    Division of Epidemiology, Ministry of Health, Jerusalem, Israel

    Department of Public Health, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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  • Daniel Cohen
    Affiliations
    Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Tamy Shohat
    Affiliations
    Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Ravit Bassal
    Affiliations
    Israel Center for Disease Control, Ministry of Health, Chaim Sheba Medical Center, Tel-Hashomer, Israel
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  • Author Footnotes
    1 Yaniv Lustig and Zalman Kaufman contributed equally.
Open AccessPublished:September 04, 2017DOI:https://doi.org/10.1016/j.ijid.2017.08.011

      Abstract

      Objectives

      Israel has a long history of West Nile virus (WNV) morbidity, and the rate of detection of WNV in mosquitoes has been high since 2000. The aim of this study was to integrate several WNV datasets in order to gain an insight into the geographical distribution of WNV in Israel.

      Methods

      Three choropleth maps were generated showing WNV human morbidity, WNV prevalence in mosquitoes, and the results of a nationwide serological survey, based on the division of Israel into 15 sub-districts.

      Results

      The maps show a high endemicity of WNV in Israel. In respect to the morbidity map, the population residing in the central part of the country and in Arava Region is at higher risk of developing the disease than the population of the rest of Israel. Interestingly, high prevalence rates of both WNV serology and WNV-infected mosquitoes were detected in Arava Region, but lower prevalence rates were detected in most areas of the coastal region, suggesting that other factors might also be important in the development of symptomatic WNV infections.

      Conclusions

      These results underline the high prevalence of WNV in Israel and point to specific risk areas for WNV infections across the country.

      Keywords

      Introduction

      West Nile virus (WNV) is a vector-borne flavivirus whose reservoir includes many species of birds, and the virus is primarily transmitted by Culex mosquitoes (
      • Go Y.Y.
      • Balasuriya U.B.
      • Lee C.K.
      Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses.
      ). Approximately 80% of WNV infections in humans have no symptoms and 20% cause a mild febrile illness termed West Nile fever (WNF). However, approximately 1% of cases are much more severe, leading to West Nile neuroinvasive disease (WNND) (
      • Kramer L.D.
      • Styer L.M.
      • Ebel G.D.
      A global perspective on the epidemiology of West Nile virus.
      ). Several WNV outbreaks with high numbers of WNND cases have occurred in animals and humans in Europe, the Middle East, and North America since the 1990s (
      • Anis E.
      • Grotto I.
      • Mendelson E.
      • Bin H.
      • Orshan L.
      • Gandacu D.
      • et al.
      West Nile fever in Israel: the reemergence of an endemic disease.
      ,
      • Bin H.
      • Grossman Z.
      • Pokamunski S.
      • Malkinson M.
      • Weiss L.
      • Duvdevani P.
      • et al.
      West Nile fever in Israel 1999-2000: from geese to humans.
      ,
      • Calistri P.
      • Giovannini A.
      • Hubalek Z.
      • Ionescu A.
      • Monaco F.
      • Savini G.
      • et al.
      Epidemiology of west nile in europe and in the mediterranean basin.
      ,
      • Hernandez-Triana L.M.
      • Jeffries C.L.
      • Mansfield K.L.
      • Carnell G.
      • Fooks A.R.
      • Johnson N.
      Emergence of west nile virus lineage 2 in europe: a review on the introduction and spread of a mosquito-borne disease.
      ,
      • Murray K.O.
      • Mertens E.
      • Despres P.
      West Nile virus and its emergence in the United States of America.
      ).
      WNF has been known in Israel since the early 1950s. The virus was responsible for several outbreaks occurring in that decade and an additional outbreak in 1980 (
      • Anis E.
      • Grotto I.
      • Mendelson E.
      • Bin H.
      • Orshan L.
      • Gandacu D.
      • et al.
      West Nile fever in Israel: the reemergence of an endemic disease.
      ). Following a massive outbreak in geese in 1998–1999, a large-scale human outbreak occurred in 2000, with more than 400 confirmed cases and nearly 40 fatalities (
      • Anis E.
      • Grotto I.
      • Mendelson E.
      • Bin H.
      • Orshan L.
      • Gandacu D.
      • et al.
      West Nile fever in Israel: the reemergence of an endemic disease.
      ,
      • Bin H.
      • Grossman Z.
      • Pokamunski S.
      • Malkinson M.
      • Weiss L.
      • Duvdevani P.
      • et al.
      West Nile fever in Israel 1999-2000: from geese to humans.
      ,
      • Weinberger M.
      • Pitlik S.D.
      • Gandacu D.
      • Lang R.
      • Nassar F.
      • Ben David D.
      • et al.
      West Nile fever outbreak, Israel, 2000: epidemiologic aspects.
      ). Since then, outbreaks of varying magnitude have frequently been recorded, with nearly 1400 cases of WNF and WNND reported in Israel between 2000 and 2012 (
      • Anis E.
      • Grotto I.
      • Mendelson E.
      • Bin H.
      • Orshan L.
      • Gandacu D.
      • et al.
      West Nile fever in Israel: the reemergence of an endemic disease.
      ). Furthermore, several studies conducted on specific study populations have demonstrated high WNV IgG seroprevalence in Israel (
      • Bin H.
      • Grossman Z.
      • Pokamunski S.
      • Malkinson M.
      • Weiss L.
      • Duvdevani P.
      • et al.
      West Nile fever in Israel 1999-2000: from geese to humans.
      ,
      • Chowers M.Y.
      • Green M.S.
      • Bin H.
      • Weinberger M.
      • Schlaeffer F.
      • Pitlik S.
      • et al.
      Post-epidemic serosurvey of West Nile fever in Israel.
      ,
      • Cohen D.
      • Zaide Y.
      • Karasenty E.
      • Schwarz M.
      • LeDuc J.W.
      • Slepon R.
      • et al.
      Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.
      ). A nationwide cross-sectional serological survey recently conducted by the Central Virology Laboratory (CVL) and the Israel Center for Disease Control, found an overall WNV seroprevalence of 11.1% in Israel (
      • Bassal R.
      • Shohat T.
      • Kaufman Z.
      • Mannasse B.
      • Shinar E.
      • Amichay D.
      • et al.
      The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study.
      ). Importantly, despite the geographic diversity of the country, this previous study divided Israel into only seven regions, thus the differential WNV seroprevalence across Israel was only broadly characterized.
      Following the 2000 outbreak, a national mosquito surveillance system was established in Israel (
      • Orshan L.
      • Bin H.
      • Schnur H.
      • Kaufman A.
      • Valinsky A.
      • Shulman L.
      • et al.
      Mosquito vectors of West Nile Fever in Israel.
      ). This system detects WNV-positive mosquitoes and characterizes their WNV genotypes. Overall, 336 mosquito pools were positive for WNV infection from 2000 to 2014, demonstrating the high circulation of WNV in Israel (
      • Lustig Y.
      • Hindiyeh M.
      • Orshan L.
      • Weiss L.
      • Koren R.
      • Katz-Likvornik S.
      • et al.
      Fifteen years of mosquito surveillance reveals high genetic diversity of West Nile Virus in Israel.
      ); however the geographic distribution of WNV-infected mosquitoes was not assessed.
      The geographic position of Israel between three continents makes it an important transit zone for migratory birds. Therefore the analysis of WNV in mosquitoes and geographic information regarding acute WNV infection in Israel, as well as exposure of the general population, could provide valuable information on WNV circulation not only in Israel but also in the entire Mediterranean basin. This study was performed to characterize WNV morbidity, WNV seroprevalence, and WNV-infected mosquitoes in Israel geographically.

      Materials and methods

      Laboratory investigation and definition of West Nile disease (WND)

      The CVL performs diagnostics and also receives information for all WNV-infected patients diagnosed in the CVL and in other hospitals in Israel. This information is transferred to the relevant regional health districts, which then complete an epidemiological investigation of the patients and report the results through a nationwide surveillance system to the Division of Epidemiology of the Ministry of Health. Data collected in this manner are restricted to new cases of WNF with a severe illness that requires hospitalization.
      In this study, the place of infection was considered the patient’s residence, due to difficulty obtaining sufficient information on the suspected place of exposure for each patient from the case investigations. The detection of IgM and IgG antibodies against WNV in serum and cerebrospinal fluid (CSF) samples was performed by enzyme-linked immunosorbent assay (ELISA). Samples obtained during the years 2001–2007 were investigated using an assay developed in the CVL. Samples obtained during the years 2008–2013 were investigated using commercial IgM and IgG kits (West Nile Detect ELISA; InBios International, Inc., Seattle, WA, USA). Finally, samples obtained in 2014 were assessed by WNV IgM capture (DxSelect ELISA and IgG DxSelect ELISA kits; Focus Diagnostics Inc., Cypress, CA, USA).

      Mosquito surveillance

      Mosquito trapping and collections were carried out by the Pest Control Unit of the Ministry of Environmental Protection. Trapping sites varied according to the location of mosquito breeding sites and their relevance to control activities, as well as information on WNF cases, and was contingent on the personnel employed. It was not always possible to collect mosquitoes repeatedly from the same localities. Mosquito processing and WNV identification was performed exactly as described previously (
      • Lustig Y.
      • Hindiyeh M.
      • Orshan L.
      • Weiss L.
      • Koren R.
      • Katz-Likvornik S.
      • et al.
      Fifteen years of mosquito surveillance reveals high genetic diversity of West Nile Virus in Israel.
      ). During the period 2000 to 2014, 7135 pools containing a total of 277 186 mosquitoes arrived at CVL for the detection of WNV RNA. Using TaqMan RT-PCR for the envelope protein, WNV RNA was detected in 336 (4.71%) of the total pools analyzed.

      Choropleth maps

      ArcGIS 10.4.1 (ESRI, Redlands, CA, USA) was used to create choropleth maps to present WNV morbidity, seropositivity, and mosquitoes positive for WNV at the sub-district level in Israel. Officially, Israel is divided into 15 sub-districts. For the purposes of this study, the respective polygon of Be’er Sheva sub-district (the most southern sub-district of Israel) was split into two regions based on its sub-divisions (seven natural areas): (1) Arava Region, comprising the south-eastern part of Be’er-Sheva sub-district, and (2) the other six natural areas. This was done in order to represent the studied attributes of this specific region more accurately. The following aspects were considered when taking this action: (1) Arava Region lies along the Rift Valley (one of the main routes for bird migration during the spring and autumn seasons) and is known to be highly endemic for WNF, (2) Be’er-Sheva sub-district as a whole is sparsely populated (the population of Arava Region constitutes about 9% of the overall population of this sub-district), and (3) computing rates based on the overall population of Be’er-Sheva sub-district would dilute the effects characteristic of Arava Region.

      Results

      WNF has been a notifiable disease in Israel since 2001. During the years 2001–2014, 1233 patients were diagnosed with an acute WNV infection in Israel, with an overall annual infection rate of 1.29 per 100 000 across Israel. In order to determine whether certain areas of Israel are more prone to acute WNV infection, the geographical distribution of WNV morbidity in Israel was studied at the sub-district level in this study (see Materials and methods) in terms of annual average rates over this period, using the population data for the year 2006 as the denominator (Figure 1). High morbidity rates were found in Arava Region (5.4 cases per 100 000 per year), as well as in the central part of the country (from Rehovot sub-district to Haifa sub-district (range 1.27–2.43 cases per 100 000 per year)).
      Figure 1
      Figure 1Geographic distribution of acute West Nile virus (WNV)-infected cases in Israel (2001–2014 average). Residence locations (by address) of acute WNV infection patients diagnosed from 2001 to 2014 in Israel were overlaid on the geographical map of Israel at the sub-district level, and the annual average number of human cases per 100 000 inhabitants was calculated. Different colors show the prevalence range in each area. The names of sub-districts are indicated.
      Since WNV seroprevalence data reflect exposure of the general population to WNV, these have added value for assessing the spatial distribution of WNV in Israel. In order for the data to reflect long-term exposure and be less influenced by annual fluctuations in WNV infection dynamics, only seroprevalence data retrieved from adult persons should be included. Therefore, the results of the WNV seroprevalence survey (
      • Bassal R.
      • Shohat T.
      • Kaufman Z.
      • Mannasse B.
      • Shinar E.
      • Amichay D.
      • et al.
      The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study.
      ) were reanalyzed and presented as the percentages of seropositivity in persons aged 30 years and above at the sub-district level (Figure 2). Out of 1318 samples tested, 241 (18.3%) were IgG seropositive for WNV. Relatively high prevalence rates were identified in Arava Region in the south (25.3%) and in the sub-districts of Tel Aviv (25.3%), Petah Tiqwa (31.6%), Hadera (25%), Akko (23.2%), and Ashkelon (22.9%).
      Figure 2
      Figure 2Results of a cross-sectional seroprevalence study based on sera collected between 2011 and 2014. The percentage of West Nile virus (WNV) IgG-positive Israeli adults (≥30 years) out of the total population in each sub-district in Israel, based on residence locations (by address), is presented. Different colors show the prevalence range in each area. The names of sub-districts are indicated.
      As mosquitoes serve as the vector of the disease, Figure 3 presents the sub-district geographical distribution of mosquitoes carrying the virus as a percentage of the number of times the mosquito pools were found to be positive for WNV out of the total pools collected during the years 2000 to 2014. The results showed a high level of mosquito infestation with WNV in Arava Region (21.9%).
      Figure 3
      Figure 3Geographical distribution of mosquitoes carrying West Nile virus (WNV) (2000–2014 average). Trapping site locations of WNV-infected mosquito pools were overlaid on the sub-district geographical map of Israel and the percentage of positive mosquito pools out of the total mosquito pools trapped is indicated for each sub-district. Different colors show the percentage WNV-positive mosquito pools. The names of sub-districts are indicated.

      Discussion

      There are on average 70 ± 40 cases of symptomatic WNV infection in Israel per year (
      • Anis E.
      • Grotto I.
      • Mendelson E.
      • Bin H.
      • Orshan L.
      • Gandacu D.
      • et al.
      West Nile fever in Israel: the reemergence of an endemic disease.
      ), and a high prevalence of Culex mosquitoes (the primary vectors of WNV) has been observed in the country (
      • Orshan L.
      • Bin H.
      • Schnur H.
      • Kaufman A.
      • Valinsky A.
      • Shulman L.
      • et al.
      Mosquito vectors of West Nile Fever in Israel.
      ). Despite a substantial amount of data on WNV circulation in mosquitoes having been accumulated over the last 16 years (
      • Lustig Y.
      • Hindiyeh M.
      • Orshan L.
      • Weiss L.
      • Koren R.
      • Katz-Likvornik S.
      • et al.
      Fifteen years of mosquito surveillance reveals high genetic diversity of West Nile Virus in Israel.
      ), studies have not looked into risk areas for WNV disease and endemicity in Israel. In this study, data collected in Israel during the period 2000–2014 on patients with acute WNV infections, as well as the prevalence of WNV antibodies and WNV-infected mosquitoes, were analyzed. Using these datasets, the spatial distribution of WNV infections in Israel was investigated.
      The results showed high endemicity of WNV throughout Israel. WNV is endemic in many countries across the globe, and high levels of WNV infection, WNV seroprevalence, and WNV-infected mosquitoes are observed in several countries. A WNV infection rate of 0.45 per 100 000 persons per year was recently reported in the continental USA, with California having the highest infection rate detected in this country at 1.49 per 100 000 persons per year (
      • Krow-Lucal E.
      • Lindsey N.P.
      • Lehman J.
      • Fischer M.
      • Staples J.E.
      West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2015.
      ). WNV seroprevalence of 2.1%, 2.5%, 2.6%, 6.5%, 27.2%, and 55% has been reported from Greece, Turkey, New York, Spain, Gabon, and Egypt, respectively (
      • Biceroglu S.U.
      • Karatayli E.
      • Bayram A.
      • Turhan A.
      • Degirmenci A.
      • Aydinok Y.
      • et al.
      Investigation of West Nile virus among healthy blood donors in the western part of Turkey.
      ,
      • Hadjichristodoulou C.
      • Pournaras S.
      • Mavrouli M.
      • Marka A.
      • Tserkezou P.
      • Baka A.
      • et al.
      West Nile Virus Seroprevalence in the Greek Population in 2013: A Nationwide Cross-Sectional Survey.
      ,
      • Mostashari F.
      • Bunning M.L.
      • Kitsutani P.T.
      • Singer D.A.
      • Nash D.
      • Cooper M.J.
      • et al.
      Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey.
      ,
      • Piron M.
      • Plasencia A.
      • Fleta-Soriano E.
      • Martinez A.
      • Martinez J.P.
      • Torner N.
      • et al.
      Low Seroprevalence of West Nile Virus in Blood Donors from Catalonia, Spain.
      ,
      • Pourrut X.
      • Nkoghe D.
      • Paweska J.
      • Leroy E.
      First serological evidence of West Nile virus in human rural populations of Gabon.
      ,
      • Youssef S.R.
      • Eissa D.G.
      • Abo-Shady R.A.
      • Aly Fouad N.T.
      • Kattab D.K.
      • Fathey H.
      • et al.
      Seroprevalence of anti-WNV IgG antibodies and WNV-RNA in Egyptian blood donors.
      ), while rates of WNV-infected mosquitoes of 0.06% and 1.9% have been measured in Spain and Italy, respectively (
      • Calzolari M.
      • Pautasso A.
      • Montarsi F.
      • Albieri A.
      • Bellini R.
      • Bonilauri P.
      • et al.
      West Nile Virus Surveillance in 2013 via Mosquito Screening in Northern Italy and the Influence of Weather on Virus Circulation.
      ,
      • Engler O.
      • Savini G.
      • Papa A.
      • Figuerola J.
      • Groschup M.H.
      • Kampen H.
      • et al.
      European surveillance for West Nile virus in mosquito populations.
      ). In contrast, the present study points to much higher levels of WNV prevalence in Israel. The average seropositivity detected in Israel was 11%, with areas reaching 16% WNV seroprevalence (
      • Bassal R.
      • Shohat T.
      • Kaufman Z.
      • Mannasse B.
      • Shinar E.
      • Amichay D.
      • et al.
      The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study.
      ) for all ages and 18.3% for those aged 30 years and above. In accordance with the present study, a WNV seroprevalence study performed on samples obtained from healthy Israeli soldiers in 1982, 1987, and 1989 demonstrated seroprevalence of 18.6% (
      • Cohen D.
      • Zaide Y.
      • Karasenty E.
      • Schwarz M.
      • LeDuc J.W.
      • Slepon R.
      • et al.
      Prevalence of antibodies to West Nile fever, sandfly fever Sicilian, and sandfly fever Naples viruses in healthy adults in Israel.
      ). Mosquito infection rates were found to reach more than 20% in Arava Region, with an average of 11.1% across the country, while the annual average rate of acute WNV infection was found to be 1.29 cases per 100 000, reaching a maximum rate of 5.4 acute infections per 100 000 population per year in Arava Region. These data demonstrate the high endemicity of WNV in Israel on the one hand and the substantial geographical difference in WNV infection on the other. This interesting phenomenon highlights Israel as a universal model for WNV infection dynamics and distribution.
      The high incidence rate of WNV morbidity in Arava Region, which is part of the Great Rift Valley, is not surprising since 21.9% of all mosquito pools tested were infected with WNV in that area (Figure 3). This is also evident in the geographic WNV seroprevalence map (Figure 2), which shows that 27.9% of the adult population was previously infected with WNV. Interestingly, an extensive serological survey of WNV in horses demonstrated high WNV seroprevalence along the Great Rift Valley (
      • Aharonson-Raz K.
      • Lichter-Peled A.
      • Tal S.
      • Gelman B.
      • Cohen D.
      • Klement E.
      • et al.
      Spatial and temporal distribution of West Nile virus in horses in Israel (1997-2013)–from endemic to epidemics.
      ), demonstrating the high circulation of WNV in Arava Region. Although this area is sparsely populated, it has already been shown (
      • Leshem Y.
      • Yom-Tov Y.
      Routes of migrating soaring birds in Israel.
      ) that as a focal point between Asia and Africa, a major bird migration route passes from Sinai and crosses into Jordan exactly in this region. As an area with numerous plantations and low altitude, high numbers of WNV-infected mosquitoes, which infect the population, are likely to be present.
      As shown in Figure 1 high morbidity rates were found in the central part of the country. This phenomenon was not correlated with rates of WNV-positive mosquitoes and was only partly correlated with WNV seropositivity (in the districts of Petah Tiqwa, Hadera, and Tel Aviv). Since only a very small percentage (approximately 1%) of WNV-infected humans develop an acute infection requiring hospitalization, it is difficult to anticipate the level of correlation between WNV morbidity and WNV exposure parameters (as measured here by both WNV seroprevalence and WNV infection in mosquitoes).
      It is also important to keep in mind that the coastal central region of Israel comprises densely populated areas, and therefore it is also possible that fewer WNV-infected mosquitoes are required for human infection in the central region than in other less populated areas. Future studies will look at the temporal fluctuations in acute WNV infections in combination with locations of WNV-infected mosquitoes to analyze the spatio-temporal epidemiology of WNV. This, in combination with temperature and climatic, precipitation, and topographic data, will hopefully allow the prediction of WNV outbreaks and geographic locations of WNV infections in Israel.
      This study is subject to a few limitations. First, due to the long period of time encompassed by the study (14 years), several different assays were used to determine WNV infection; therefore some variations in WNV diagnosis might exist. Second, there might have been cross-reactions of other closely related flaviviruses such as Zika virus and dengue virus with the WNV IgM and IgG kits used, and although these viruses are currently not known to be circulating in Israel, the possibility that a few false-positive WNV infections were detected cannot be completely excluded. Since this study was based on 14 years of surveillance and showed the annual average infection rate of mosquitoes and morbidity data, it allowed more accurate analysis that was less influenced by single-year variations; this strengthens the validity of the study. It should, however, be kept in mind that the seroprevalence data are based on samples obtained between 2011 and 2014, therefore demonstrating the geographical distribution of long term exposure and, thus, it is not clear when exactly the exposure occurred. Previous data (
      • Bassal R.
      • Shohat T.
      • Kaufman Z.
      • Mannasse B.
      • Shinar E.
      • Amichay D.
      • et al.
      The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study.
      ) have shown that the number of years living in Israel is associated with higher WNV seroprevalence, suggesting that the seroprevalence rate will be lower in persons of a younger age. For this reason WNV seroprevalence in adults (≥30 years) was analyzed here, which will measure long-term seroprevalence and reduce fluctuations due to annual dynamics.
      In conclusion, this study examining 14 years of continuous WNV infections identified high endemicity of WNV throughout Israel. Specifically, both Arava Region and the central part of Israel were identified as areas with a higher prevalence of morbidity than the rest of the country. The implementation of similar programs in other countries and the analysis of data as performed in the present study could aid decision-makers in allocating resources for WNV disease prevention and the development of appropriate programs for mosquito surveillance schemes in Israel and across the globe.

      Formatting of funding sources

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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