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Open Access

Review

West Nile virus eco-epidemiology and climate change

  • Julian Heidecke ,

    Contributed equally to this work with: Julian Heidecke, Andrea Lavarello Schettini

    Roles Investigation, Writing – original draft, Writing – review & editing

    julian.heidecke@iwr.uni-heidelberg.de

    Affiliation Interdisciplinary Center for Scientific Computing and Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany

    ⨯
  • Andrea Lavarello Schettini ,

    Contributed equally to this work with: Julian Heidecke, Andrea Lavarello Schettini

    Roles Conceptualization, Investigation, Writing – original draft, Writing – review & editing

    Affiliation Interdisciplinary Center for Scientific Computing and Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany

    ⨯
  • Joacim Rocklöv

    Roles Conceptualization, Writing – original draft, Writing – review & editing

    Affiliations Interdisciplinary Center for Scientific Computing and Heidelberg Institute of Global Health, Heidelberg University, Heidelberg, Germany, Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden

    ⨯

Abstract

West Nile virus (WNV) is an arbovirus with a wide geographical distribution. It is maintained in an enzootic bird-mosquito cycle and exhibits regular zoonotic transmission to humans, to whom it can cause West Nile fever and neuroinvasive disease. Over the last decades, WNV has emerged as a serious health threat with profound impacts on animal and human health. It is broadly accepted that climate change impacts the transmission of WNV through multiple pathways via its impacts on vectors, the pathogen, hosts, and the environment. Although some clarity has been established, the outcomes of these climate-driven processes are yet to be better understood before they can fully benefit tailored prevention and control measures. This review focuses on the eco-epidemiology of WNV and how it is impacted by climate change through an integrative lens. We discuss the role of eco-epidemiological modeling in knowledge generation and highlight the importance of adopting an interdisciplinary and transdisciplinary One Health approach for improved surveillance, data collection, modeling, and translation of outcomes into actionable policy and control.

Citation: Heidecke J, Lavarello Schettini A, Rocklöv J (2023) West Nile virus eco-epidemiology and climate change. PLOS Clim 2(5): e0000129. https://doi.org/10.1371/journal.pclm.0000129

Editor: Shlomit Paz, University of Haifa, ISRAEL

Published: May 1, 2023

Copyright: © 2023 Heidecke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The study was supported by funding from the IDAlert project (http://idalertproject.eu) funded by the European Commission (no. 101057554). JR received support from the Alexander von Humboldt foundation through the funding instrument of an Alexander von Humboldt Professorship endowed by the Federal Ministry of Education and Research in Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

West Nile virus (WNV) is a zoonotic arthropod-borne flavivirus from the Japanese encephalitis serogroup complex. The ecology of WNV is complex involving several virus reservoirs, arthropod vectors, and incidental or final hosts. Virus transmission to vertebrate hosts primarily occurs through bites of infected mosquitoes, which in turn can become infected when they feed on infected hosts. Wild birds have been identified as the main reservoir of WNV [1]. In endemic areas the enzootic cycle is maintained between ornithophilic mosquitoes and birds, although direct transmission between birds has been documented in laboratory and farm settings [2]. Many wild bird species that act as WNV reservoirs do not show clinical signs of infection. However, some species are highly susceptible to developing disease and significant bird population declines due to WNV outbreaks have been observed, particularly in North American species [3]. Humans, equids, and other mammals act as final or dead-end hosts of WNV as they do not produce sufficient levels of viraemia to transmit the pathogen back to the vectors. However, even though infections cannot be sustained between mammal hosts, WNV can have detrimental consequences on their health and severe economic impacts. Most humans that become infected with WNV do not present any signs of illness. However, about 25% of infections develop into West Nile fever (WNF) greatly varying in severity and less than 1% develop into neuroinvasive disease. Among the latter, approximately 10% result in death [1]. Around 20% of infected horses present clinical signs [4] and approximately 8% will develop severe WNV disease with neurological symptoms. Within diseased animals, fatality rate has been observed between 22 and 44% [5]. Upon infection with WNV, both humans and horses generate a humoral response characterized by the production of WNV-specific antibodies [6–8]. However, the duration of protection from reinfection or severe disease is not yet fully understood. Given the burden of WNV in these species, great efforts have been made to prevent the disease, including the development of prophylactic and therapeutic drugs. At present, there are six licensed vaccines to use in horses, contributing greatly to reducing the incidence of the disease [9]. However, human vaccines are currently still not available, mainly due to the lack of clinically advanced product candidates and concerns about cross-immunity challenges [10].

WNV was first isolated from a human in the West Nile district in Uganda in 1937 [11]. Until the early 1990s, WNV was associated with sporadic cases and outbreaks in Africa, Eurasia, Australia, and the Middle East [12]. In 1996, there was an apparent shift in its epidemiology, when human outbreaks became more frequent and the incidence of cases presenting severe disease increased throughout the Middle East and Europe [13]. Since then, Europe has witnessed a continued expansion in the areas affected by WNV and an upsurging trend in cases marked by major outbreaks in 2010 and 2018 [14, 15]. In 1999, WNV was reported in North America for the first time and rapidly spread across the continent, eventually reaching Central and South America [16]. Now, the virus is considered endemic in many parts of the world and regularly leads to outbreaks in these areas. In the USA alone, since the first incursion of WNV into the country, more than 51,000 human clinical cases have been reported, including over 2,300 deaths. Based on these numbers, it is estimated that 7 million people have been infected [17]. Although WNV is primarily vector-borne in the zoonotic cycle, transmission through infected blood or organ donation has been documented [18], as well as a case of transplacental contamination [19]. Despite its relatively low virulence in human hosts, WNV is now considered to have the widest geographic distribution and the largest range of vector and host species among all vector-borne flaviviruses, representing an ongoing risk to global health [20].

Mean global temperature has risen 1.2°C above pre-industrial levels resulting in impacts on human, animal, and environmental health that include changes in infectious disease epidemiology [21]. It has become evident that the recent variations in climatic conditions have contributed to the endemization and suitability of WNV in various locations around the world [22, 23]. The relation between climate and WNV transmission has been excellently reviewed in a series of previous articles [14, 22, 23]. Here we review important aspects of WNV epidemiology at the vector and host level and major known effects of climatic conditions on both levels complementing these studies with a wider holistic One Health perspective. We focus specifically on the understanding and knowledge needs in relation to WNV and climate change and the role of eco-epidemiological modeling in this knowledge generation for improved policy and decision-making.

Vectors and climate

WNV can be transmitted by a wide range of mosquito vectors. However, only a few mosquito species from the genus Culex (Cx.) are considered the primary vector and are accepted to sustain transmission of the virus globally (Table 1) [2, 24, 25]. Females of some mosquito species need to take a vertebrate blood meal to produce eggs [25]. This is when mosquitoes can become infected and transmit pathogens. The role of individual vector species in WNV transmission and amplification is determined by various factors including their vector competence, biting behavior, and abundance. Vector competence describes the inherent ability of mosquito vectors to be infected by, replicate, and transmit the virus, which is highly variable among and within species [16, 26]. The time it takes from a vector’s exposure to the onset of its infectiousness is known as the extrinsic incubation period (EIP). Both the EIP and vector competence may depend on the viral variant the vector is exposed to [27–29].

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Table 1. Important vectors of WNV within the Cx. genus per world region.

https://doi.org/10.1371/journal.pclm.0000129.t001

Although some Cx. mosquitoes have been classified historically as ornithophilic, being able to maintain the enzootic cycle of WNV, they are now recognized as important bridge vectors, driving spillover to humans [30–32]. An overlap of Cx. pipiens and Cx. restuans, for example, seems to represent a high risk for spillover from birds to humans. This was observed in the northeastern United States due to high WNV prevalence and abundance of this species-pair, compensating for their predominantly bird-biting behavior [33]. By influencing host-vector contact rates mosquito feeding behavior plays a critical role in WNV transmission. Usually, mosquitoes have a preference to feed upon certain hosts, but their feeding patterns also result from host abundance and behavior such that vectors may feed upon certain species opportunistically when preferred ones are unavailable [34, 35]. It has been observed that mosquito biting behavior varies within the Cx. genus, geographically, and seasonally [30, 34, 36–40]. For example, an American study reported a particular shift of Cx. pipiens and Cx. tarsalis to feed on humans during late summer synchronized with dispersion and migration of their preferred host (American robins) and associated with amplification of human outbreaks [38]. Although observed at multiple sites this pattern seems not to be universal as indicated by studies in other regions of the USA that didn’t find a late summer feeding shift to humans. In such regions human infection risk might still intensify during late summer simply related to a high amplification of virus during this period [30] or it might diminish when mosquitoes shift to feed on less competent avian hosts [39].

Cx. vectors breed in standing-water and are considered quite ubiquitous as they are observed in both urban and rural settings. Some species are abundant outside of cities, like Cx. modestus which mainly breed in brackish marshes and flooded rice-fields [41] or Cx. tarsalis which prefer sunlit standing water, like in savannas or grasslands [42]. Mosquitoes from the Cx. pipiens complex thrive in aquatic habitats rich in organic content. Such habitat is often generated near human settlements or farms (e.g., in containers, storm sewers, ditches). High human population density near these “man-made” mosquito habitats indicates an increased risk for spillover of WNV. The predominantly mammal biting Cx. pipiens form molestus even develops in highly polluted water environments and mates in confined spaces, making it a perfect “domestic” mosquito [31]. In Northern temperate regions this form has adapted to anthropogenic below-ground environments where it remains viable and active year-round [43]. Where closely related vectors co-occur, they can give rise to hybrid populations which may present their very own characteristics [40, 43, 44].

The recent environmental changes impact species’ populations of vectors which manifests in altered abundance, range, and biting season. Despite their already broad distribution, Cx. mosquitoes have increased their geographical range and are projected to keep expanding to higher latitudes, also lengthening their activity season, and increasing their abundance in some regions [45–48]. In areas where temperatures will reach higher points than those ideal for mosquitoes, mortality is expected to increase, lowering vector abundance, especially during hot summers. Altitude is closely tied to environmental conditions like temperature, creating distinct ecological niches along altitudinal gradients. For example, in some regions of sub-Saharan Africa, Cx. pipiens seems to be confined to higher elevations, while Cx. quinquefasciatus is found at low to moderate elevations [49]. Therefore, as global temperatures continue to rise, mosquitoes may also shift to higher altitudes, and thus move into new ecosystems [50].

These shifts occur because of the vectors’ direct dependence on suitable climatic conditions for breeding and development. WNV transmitting mosquitoes are ectotherms, which means that their life cycle and phenology is influenced by ambient temperature, modulating their fecundity, development rates, activity (biting rate), and survival. These dependencies can be derived experimentally or from field observations and generally show to be unimodal and species-specific [51, 52]. They explain why episodes of extensive WNV transmission are seasonal in temperate regions where many mosquitoes enter dormancy when winter approaches and why temperatures well above thermal optima reduce the potential for transmission. Additionally, warmer temperatures have been shown to lead to faster replication of the virus within its vector and, thus, to a shorter EIP [53]. Moreover, WNV seems to have higher infection and transmission efficiency at higher temperatures as seen in increases in the vector competence with temperature across a variety of vector species [53–55]–albeit the response of these parameters to temperature is again expected to be unimodal [51, 52].

Furthermore, mosquito vectors rely on water availability to lay eggs and complete their reproduction cycle. Therefore, increased precipitation is believed to elevate vector abundance by increasing the number of potential breeding sites. On the other hand, during drought humans store water which provides artificial water pools preferred by some Cx. mosquitoes. Drought conditions can also benefit larval mosquito populations by disrupting food-web structures and leading to higher concentration of nutrients in available water sources [56, 57]. Additionally, some research has suggested that heavy rainfall can lead to flushing of eggs, larvae, and pupae of mosquitoes breeding in drains and ditches [58, 59]. Therefore, there is not a strictly positive or negative association between precipitation and beneficial conditions across all WNV vectors and precipitation regimes. Nevertheless, overall increased precipitation and both a more frequent occurrence of extreme rainfall and droughts, which is expected in climate change scenarios, has significant direct effects on vector population dynamics.

Avian hosts and climate

Several animal species are susceptible to WNV infection [60], however, it is primarily bird species that develop high enough viraemia to infect arthropod vectors and thus sustain the enzootic cycle of WNV via bird-mosquito-bird transmission [61]. Hundreds of bird species have been identified as susceptible to WNV infection and are considered the natural reservoir of the virus [1]. This diversity allows WNV to spread in both sylvatic and synanthropic transmission scenarios, in rural and urban areas wherever susceptible hosts and competent vectors co-occur [62].

Despite this ubiquity, bird species greatly differ in their susceptibility to WNV. While some species develop high viraemia (particularly passerine birds), others are more resistant to infection [61]. In addition, many bird species that act as WNV reservoirs do not present clinical signs of infection, yet certain bird species have shown to frequently develop disease and suffer high mortality rates [63]. In fact, mortality upon wild birds, especially corvids, has been used as an early surveillance signal of WNV activity [64]. Although factors influencing susceptibility to infection and disease are complex and still poorly understood, some that have been studied include age, life history, genetics, immunocompetency and behavioral ecology [25], in addition to the different viral strains that the birds are exposed to [65–67]. As described for other diseases in wildlife, closely related bird species may present similar degrees of susceptibility to WNV [68]. Young birds with less developed immune systems are more likely to develop high viraemia [61], and there is evidence that hatch-year birds are key amplifying hosts due to their lack of prior exposure to the virus and because they might be more prone to mosquito bites [69]. Bird immune systems thus play a central role in the susceptibility of the species and therefore the opportunity of the virus to replicate widely [70]. A first exposure to the virus triggers adaptive immune responses such as the production of neutralising antibodies that can remain present and protective against future WNV infections [71]. This is an important point to consider when evaluating prevalence of infection in bird populations through serosurveillance. There is evidence of WNV humoral response in birds being protective against St. Louis encephalitis virus (tough, interestingly, not the other way around) [72], suggesting some level of cross-protection against other flaviviruses [73].

For identifying host species contributing most to amplification of WNV, host competence is an important concept which describes the ability to acquire, maintain and transmit the virus. Studies in the lab on American species involving virus inoculation concluded that blue jays, common grackles, house finches, American crows, and house sparrows are the most competent out of 25 tested species [63]. Here, a host competence index was calculated from each species’ viraemia profile and a generalized viraemia-infectiousness relationship. While this can provide a preliminary indication of the relative host competence of different species (see also [74]), it is important to consider that lab studies may not reflect real-world conditions and are usually restricted to a limited number of species [75]. Moreover, Vaughan et al. [76] recently demonstrated that viraemia-infectiousness relationships can significantly depend on the source of the viremic blood. The authors found American robins to be significantly more infectious than common grackles at similar or even lower levels of viraemia, which highlights the risk of misclassifying host competence based on viraemia profiles alone. Overall knowledge on WNV host competence seems to be far from complete.

Clearly, bird species’ relative role in viral amplification is not only determined by their physiological ability to transmit WNV. The abundance of bird species and their attractiveness to mosquitoes are at least as decisive. Studies in North America incorporating Cx. pipiens’ feeding preference with host competence (as derived from the species’ typical viraemia profile) and abundance demonstrated that American robins are the main amplifying host in the considered regions. They were shown to be significantly overused as blood meal source when compared to their relative abundance in the avian community which let them act like super spreaders [30, 38, 77]. Other competent species were found to be less important because they were either significantly avoided by mosquitoes or were relatively rare in the study area. Later studies showed that the relative importance of bird species may vary between regions [64], season, and even on fine-spatial scales influenced by the host community composition [39]. For example, in Atlanta it was observed that Cx. mosquitoes significantly bite on moderately to poorly competent species (as suspected by their typical viraemia profiles), like northern cardinals or mimids, especially during peak transmission months and in certain urban microhabitats, where these species may slow down amplification and reduce the risk of spillover to humans [39]. A study from northern Italy combining blood-meal analysis and host abundance indicated that blackbirds and Eurasian magpies (as preferred blood meal sources), as well as house sparrows and collared doves (as abundant species that mosquitoes opportunistically feed upon), may be the main amplifiers in a European avian community [34]. The fact that amplification and spillover potential of WNV seem to depend on avian community composition and certain key species can act as sources or sinks of transmission by attracting a large part of mosquito bites, may explain why associations of avian diversity per se to WNV risk have led to ambiguous results [78–81].

Avian serosurveys may elucidate further factors determining which species are regularly exposed to WNV. Previous studies suggest a positive correlation between seroprevalence and the animals’ body size which can be attributed to the birds’ longevity, and higher attraction of vectors towards larger hosts [82, 83]. In addition, exposure to the virus seems to be modulated by migratory behavior. While some of the European studies do not support significant differences in seroprevalence between migratory and non-migratory species [83, 84], others found greater seroprevalence in migratory than resident birds, suggesting that the migratory birds spend part of their lives in southern areas with greater circulation of the virus than in the sample areas [82, 85–87]. In contrast, studies from California showed that migratory birds entering this state from southern wintering sites are rarely found antibody positive, more likely acquiring infection after entering the state, and that resident birds tend to be more often seropositive than migratory birds [88, 89]. Similarly, migratory birds sampled along eastern and midwestern flyways in the USA more frequently showed seropositivity when sampled during fall migration compared to spring migration [90].

These observations indicate that host distribution and mobility is an important factor to consider in WNV ecology. The ability of birds to travel long-distances particularly manifests during migration but even resident birds can move significant distances during dispersal episodes. How bird movements relate to the spatial spread of WNV is not understood in depth but currently it is thought that (i) migratory birds play an important role in introducing viral strains to new regions, (ii) dispersing resident birds and short-distance migratory birds contribute to the virus movement locally and are important for establishing and maintaining WNV in a specific region.

Twice a year, driven by seasonality, bird migration rearranges the global distribution of the avian community in response to biological needs. This provides a mechanism through which pathogens can be spread along migration routes harboring the potential to establish new endemic foci at great distance [91]. Migratory birds have long been suspected to play a significant role in dispersing WNV from Africa to Europe. Birds infected on their southern wintering grounds could carry the virus northward during spring migration where it reaches European wetlands and urban areas, potentially initiating virus circulation [92, 93]. In fact, there is evidence that migrating birds may have been responsible for several movements of WNV strains via migratory routes connecting Africa, the Middle East, and Europe [94–98] and the location under migratory routes was shown to be a significant risk predictor for European areas to be affected by human WNF [99]. With the ongoing expansion of WNV in Europe, there is now substantial risk of dispersion not only from southern areas in spring but also from Central and North-Eastern European countries during fall migration [100].

The introduction of WNV to the USA in 1999 gave the opportunity to study how WNV moves in a completely naïve but conducive environment with large populations of susceptible hosts and vectors. In fact, the virus spread from coast to coast within four years. It is now believed that several agents, including infected migratory and dispersing resident birds contributed to this rapid expansion [16, 93, 101]. This is based on phylogenetic studies, correlating the pattern of WNV circulation with migration pathways [102, 103], lab investigations presenting evidence that birds infected with WNV maintain their migratory disposition during the infectious period [104], modeling studies coming to different conclusions either suggesting the movement pattern of WNV is well explained by dispersing resident birds [105] or showing an involvement of rapid, long-distance movements [106, 107], and the already discussed evidence from seroprevalence studies.

The American seroprevalence studies also suggest a limited role of migrating birds in regularly transporting the virus south to north and support the absence of an extensive source of year-round WNV transmission in the Neotropics [108]. Additionally, while there is apparent gene flow between different geographic regions, likely mediated by bird movements [94, 109–111], phylogenetic analyses across the USA and Europe support local persistence, often presenting genetic similarity between strains detected in the same locations across subsequent transmission seasons [96, 109–117]. This suggests that, although WNV shows sporadic long-range movement, seasonal transmission of the virus in temperate regions where cool winter temperatures slow down or interrupt horizontal transmission does not depend on continued reintroduction but is supported by a combination of overwintering mechanisms such as low-level horizontal transmission, vertical transmission in dormant vectors, bird-to-bird transmission, and persistent bird infection [15, 70, 108].

As a result of species-specific evolutionary processes, many biological and life history traits in birds are shaped by the environmental conditions of their habitats. Some species are particularly sensitive to shifts in climatic conditions. In the recent past changes have been observed in species’ migration timing, migration routes, distribution, as well as the species richness, abundance, and composition of avian assemblages, likely caused by many factors including climate change [118–123]. For example, increasing spring temperatures have been linked to changes in the proportion of migratory species in European bird communities [124]. Moreover, there is a trend for earlier spring arrival of long-distance migratory birds to temperate regions triggered by complex effects of multiple climate indices at their breeding and non-breeding grounds [125]. A recent study estimated that at least half of the magnitude of long-term changes in egg laying date, body condition, and number of offspring in European birds are driven by warming temperatures [126], demonstrating the impact that global warming is having on natural populations’ physiology. Therefore, climate change should be expected to bring significant alterations to avian populations and the migration system, directly or indirectly through ecosystem change, that will have carry over effects on the emergence and distribution of WNV.

Eco-epidemiological models of WNV

To understand how the complex and often nonlinear impacts of climate and environment on the vector-host-pathogen nexus (Fig 1) propagate to the risk of WNV transmission, eco-epidemiological models of WNV spread provide a powerful tool. Broadly speaking, these are divided into two types of methodological approaches that have distinct benefits and limitations. While data-driven models are typically used to associate WNV circulation with certain climatic, ecological, and other relevant conditions [127, 128], process-based models explicitly describe the dynamic interactions between vectors, hosts and the environment that lead to disease transmission [129, 130] (see Box 1 for more details). Process-based models often involve substantial simplifications of reality and require calibration to observed data. On the other hand, data-driven models may incorporate process-based elements, such as using temperature-dependent R0 as a covariate instead of temperature directly [131]. Therefore, a strict separation of data-driven and process-based approaches is not always possible or desirable.

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Fig 1. Illustration of the WNV transmission cycle and major known climate sensitive factors affecting transmission through the vector-host-pathogen nexus.

https://doi.org/10.1371/journal.pclm.0000129.g001

Box 1. Techniques used in WNV eco-epidemiological risk modeling

Data-driven models use statistical and machine learning techniques to estimate prevailing associations between a set of selected covariates and disease occurrence, aiming to infer the most influential drivers of transmission and/or predict high-risk areas. Data-driven models can beparticularly useful for short-term predictions and early warnings of WNV risk as they can consider a large set of covariates and extrapolate from data collected under present/past conditions, without an imperative need to make hypotheses about the underlying mechanisms. This, however, also limits their ability to predict WNV risk when entering unprecedented data regimes like in climate change scenarios. Insights derived from these models are in most cases of correlative nature generating limited knowledge on causality.

Process-based models aim to capture the biological mechanisms underlying transmission of pathogens in their dynamic equations and provide a tool to simulate transmission dynamics. Deterministic population-level models are often used as an analytically tractable, but highly simplified, method to reveal mechanisms behind general patterns of disease spread. In addition, at this level of complexity it is often possible to derive a representation of the basic reproduction number R0 –the expected number of hosts to be infected by a single infected host in a susceptible population–in terms of parameters of the model. Process-based models can be made increasingly complex, up to stochastic individual-based models, which in principle allow to model arbitrary heterogeneity in the system. If all relevant aspects of transmission are translated to mathematical equations, process-based models are a powerful tool to extrapolate beyond known conditions. In practice their derivation, validation, and parameterization are challenging and require high-quality data.

Improved availability of climatic and environmental data, combined with advancements in affordable computational power, have led to an increasing use of machine learning models (such as tree-based methods, maximum entropy methods, and ensemble approaches) [128, 132–135] and Bayesian spatiotemporal models [127] to predict WNV. These methods tend to trade their flexibility and higher predictive capabilities for lower interpretability. Less complex models, like non-spatial logistic regression [99] or linear mixed effect models [136], can offer a straightforward solution to infer associations between drivers and disease occurrence. In a recent study, Marini et al. [137] presented a highly interpretable approach by modeling the WNV force of infection through normal distributions. They related the peak timing, variance, and overall intensity of predicted cases to covariates, demonstrating that such simple models can offer a reliable approach for infering drivers when eco-epidemiological data is scarce. There is a growing interest in developing explainable artificial intelligence frameworks to improve interpretability in complex models, which have already been used to identify important drivers of WNV risk [128]. Both highly predictive models, for forecasts and risk assessments, and explainable models, for better understanding of drivers and identification of intervention and control targets, play an important role in WNV research.

Process-based models are inherently explainable but the complexity of the WNV transmission cycle and limited availability of data on vector-host ecology and disease occurrence often challenge their usefulness in accurately describing WNV spread. A wide variety of models with different degrees of complexity have been proposed in the literature, ranging from relatively simple dynamical system that offer analytically tractable insights into WNV control strategies [138] to more recently developed models that explicitly account for bird movements [139], mosquito host preference [130], or avian host heterogeneity [78]. In addition, climatic drivers of WNV are increasingly incorporated in process-based models to account for their impact on transmission dynamics [129, 130, 140] or to derive climatically dependent expressions of R0 or related transmission suitability indices [51, 141, 142]. These approaches mainly consider mosquito-pathogen trait variations due to temperature [51, 129, 140, 142]. Some models also account for the influence of rainfall on the availability of suitable mosquito breeding habitat [143], the effect of humidity on vector biting and mortality [142], or the impact of photoperiod on mosquito diapausing [129, 143].

Climate and land cover drivers of WNV

Several modeling studies have provided valuable insights on the role of climatic conditions and land cover features in shaping the spatial-temporal heterogeneity in WNV risk, which is usually measured by some metric assessing the disease incidence or infection rates in humans, mosquitoes, birds, or equids.

A positive association has been repeatedly found between increased WNV risk and high temperatures [99, 127, 128, 136, 137, 144–150]. Mechanistically it is understood that part of this sensitivity results from the impact of temperature on the vectors and the pathogen described earlier. In a recent study the thermal response of vector-pathogen traits measured at constant temperature for several Cx. species and WNV has been incorporated into a process-based relative R0 model [51]. Evidence from this approach shows a unimodal response of R0 to temperature with transmission potential peaking between 23°C and 26°C with thermal limits and optima for transmission varying between vector species (Fig 2). Although focusing only on specific aspects of WNV transmission, this relative risk measure was shown to be consistent with human case data mapped out by mean summer temperatures in North America further supporting a unimodal (instead of a strictly positive) response of WNV risk to temperature. Similar indices were also shown to be compatible with patterns of WNV circulation in Europe [141, 142].

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Fig 2. Unimodal thermal response of relative R0 for WNV in four vector species adapted from [51].

WNV in Cx. pipiens (dark grey), Cx. tarsalis (blue), Cx. quinquefasciatus (red), and Cx. univitattus (orange).

https://doi.org/10.1371/journal.pclm.0000129.g002

For precipitation the picture seems less clear. Some studies found a negative correlation between high precipitation and WNV risk [127, 128, 148, 151], while others found a positive correlation [136], indicate that it depends on the region considered [145, 146, 152], or did not find any significant relationship [137]. More direct measures of land surface wetness, that might be more relevant to mosquito dynamics, have also been considered including remotely sensed indices of water availability [99, 128, 136], or measures of soil moisture from hydrological models [131, 153, 154]. It is thought that drought-like conditions can impact transmission dynamics directly by increasing vector-host contact due to aggregation of both around remaining water sources [153], adding to the complex and conflicting mechanisms with which water availability influences vector population dynamics.

A recent Europe-wide study found that a considerable part of the WNV risk may be explained by the preceding year’s climate trends, in particular by the mean summer temperature [128]. Other climatic predictors have been identified such as a mild winter [145, 147], low winter precipitation [128] and total annual precipitation from the preceding year, the later one presenting conflicting evidence [151, 152]. The impact of winter conditions might be due to influences on the overwintering success of WNV and the intensity and start of early transmission in temperate regions. In addition, the sequence of conditions leading into the summer appears to be a decisive precursor for the intensity of the transmission season. The study by Farooq et al. [128] indicates that low water availability throughout the first half of the year and high spring temperatures are correlated with WNV outbreaks. The latter is also supported by the findings of Marini et al. [137]. A recent review suggests that the severe WNV outbreak in Europe in 2018 might have been driven by a wet spring that offered suitable conditions for vector populations to expand while the following summer drought could have led to exacerbated transmission [15]. This sequence of events was also observed to be positively correlated with WNF in an analysis of earlier outbreaks in Europe [136] and linked to human WNV cases in eastern Colorado [154]. Similarly–but somewhat flipped–a study looking at WNV transmission to humans and sentinel chickens in Florida found that drought conditions in spring followed by a wet summer are positively correlated with WNV outbreaks [153]. Within the summer months high temperature again shows up as a consistent predictor of transmission [99, 150] and seems to unfold its impact with a time lag of 0–4 weeks [127, 146]. The inclusion of temperature-forcing and precipitation dependence has also shown to improve the outbreak forecast potential of process-based transmission models [140, 143].

Various land cover and geographical features have been linked to WNV transmission. For example, the study by Myer and Johnston [127] concluded that suburban and peri-urban areas where mosquito and bird populations may experience high contact intensity might be at highest risk of infection in mosquitoes. Both a high NDVI (a remotely sensed measure of greenness), indicating suitable habitat for birds but not necessarily for the considered container-breeding Cx. species, and high intensity urban development, frequently inhabited by the mosquitoes but not birds, were shown to be negatively correlated to the incidence of WNV in trapped mosquitoes in Nassau County, New York. Interestingly, a similar work on the neighboring Suffolk County [155] did not find any influence of developed areas on WNV incidence, underlining the importance of deriving these associations for individual areas. Zoonotic transmission has been linked to both rural and urban areas. In the USA, for example, human cases of WNV infection have been positively associated with urban land covers in North-eastern regions but with agricultural land covers in the Western United states, which has been explained by the habitat preferences of the respective dominant WNV vector species, i.e., the Cx. pipiens complex in the Northeast and Cx. tarsalis in the West [42]. In Europe WNV circulation is predominantly associated with natural and anthropized semi-natural areas [137], although it should be noted that several large human outbreaks have been documented in urban areas [14]. A recent study looking at phylogeographic patterns indicates that areas with high agricultural activities may accelerate and attract the spread of WNV in Europe and that WNV also tends to spread towards areas with a high level of urbanisation and a high coverage of wetland [156]. WNV occurrence in mosquitoes, birds, and equines has been linked to low altitude, presence of wetlands, heterogeneous agricultural areas, and various other land use types in Europe and the Mediterranean [135, 149, 150]. Similarly, various geographical covariates have been associated with the incidence of human WNV cases or outbreaks in Europe, including the presence of wetlands, the location of preceding years’ outbreaks [99], the presence of rain-fed agriculture, rivers, and low altitude [144], and the percentage of area covered by irrigated croplands and populated forests [136].

Paz [22, 23] additionally reviewed the potential impact of relative humidity and wind on WNV epidemiology and found only very limited research. Besides effects of humidity on vector population dynamics, correlations to hospital admission dates and morbidity in humans is reported for some regions although air temperature consistently seems to be the better predictor. Wind was reported as a potential mechanism impacting WNV through wind-blown mosquitos and by affecting bird migration via storm tracks. We also want to highlight a recent systematic review giving a detailed overview of studies relating environmental factors to WNV circulation in European and Mediterranean countries [157]. This article also demonstrated that most studies are currently focused on WNV vectors or mammal hosts while studies looking at environmental drivers of WNV in birds or the complete transmission cycle are underrepresented.

Trends in WNV risk and projections under climate change scenarios

Given the established relationships between biotic and abiotic conditions and WNV risk, projecting these factors forward is of invaluable importance to understand which areas will be potential future hotspots of transmission or will be at risk of introduction. Since most of the USA is currently experiencing average summer temperatures (based on 2001–2016 data) below the optimal temperature for transmission indicated by their temperature dependent R0 model, Shocket et al. [51] expect a net increase in WNV transmission in response to global warming if all other factors would remain constant. Additionally, they anticipate that warming may extend the transmission season and increase risk in higher latitudes and altitudes, while some areas may experience summer temperatures above the thermal optima that may lead to a reduced overall transmission or a bimodal transmission season. The 2022 Lancet countdown Europe report [158] includes a trend prediction from 1951 to 2020 on WNV risk in Europe driven by climate factors. Based on the machine learning model by Farooq et al. [128], an accelerating trend for increased WNV risk is reported with the largest increases in risk in northern and western Europe but with absolute risk remaining highest in southern, central, and eastern Europe. Recently, the authors also applied this model to different combined shared socioeconomic pathways and representative concentration pathways (RCPs), standing for a range of future climate change and socioeconomic scenarios [159]. This analysis indicated that the land areas at WNV risk in Europe could increase from currently (baseline 2000–20) 15% to 23–30% with an additional population at risk of 161–244 million mid 21st century, depending on the considered scenario, and with most notable increases in Western Europe.

So far, few other studies explicitly projected WNV risk under climate change scenarios. Based on a statistical model that identified drought and immunity as the primary drivers of interannual variation in WNV across the USA, Paull et al. [131] found that projections of drought severity under (RCP) 8.5, which can be seen as a worst-case scenario, could double the annual WNV cases by the mid-twenty-first century. Ewing et al. [129] assessed the risk of WNV introduction to the UK using temperature projections under RCP 8.5. Their process-based model accounts for the temperature-dependent seasonality in vector abundance, the temperature dependence of pathogen development rates and a seasonal-forcing in host birth rates. They also test different timings within the year for WNV introduction by migratory birds. Their findings indicate that the current climate in the UK is insufficient for WNV introduction, but the risk of transient outbreaks might extensively increase in the latter half of the 21st century. Some more projections using data-driven or process-based models have been generated [62, 132, 147, 148, 160, 161] generally showing the potential for an overall increase in transmission intensity and area under climate change but also predicting possible decreases for certain areas.

Further research needs

As of today, there is a consensus that climate change is having multifaceted effects on the transmission of WNV. There is still however a need for more data integration and holistic systems approaches to deepen the understanding further. Predicting WNV risk has proven exceptionally difficult, and while some relationships between drivers and disease occurrence have been established, eco-epidemiological models can, so far, only explain parts of the extreme spatial-temporal variability at which WNV infections occur. Additionally, in most cases, they seem only applicable on limited spatial scales, also narrowing the scope of current WNV climate change projections.

To some degree our limitations to predict and project WNV risk are due to knowledge gaps in the transmission cycle of WNV. There is a need to characterise in more depth the interplay of vector and host distribution, abundance, competence, and vector feeding preferences which has so far been studied only for a few species and study sites. These factors, which vary spatially and seasonally, have shown, however, to be important interrelated determinants of transmission and spillover, and that some species may play key roles in this complex system. Ideally, models would incorporate all components of the transmission cycle including the force of infection between all relevant species pairs in the system while accounting for mosquito biting preferences, species’ movement, habitat and phenology, land use and climatic conditions on a fine spatial scale similar to the framework envisioned by Kain et al. [78].

So far, however, many studies are limited by the lack of high-quality granular biological, ecological, and epidemiological observational data. Studies that integrate avian host distribution to estimate WNV risk, for example, often have to extrapolate from limited host competence experimental data [78, 162], are facing sparse distribution data on the considered spatial scale [128] or lack vector population data, thus carrying substantial uncertainty on an integral part of the transmission cycle [78, 83]. Better characterization of avian species’ role in the WNV cycle would not only help to map risk, but if certain key species could be identified (like it was the case with the American robin in regions of North America), further studies could investigate species-specific data and examine the influence of their behavior (e.g., their foraging, nesting, roosting, and migration) on transmission dynamics. Such efforts could, for example, shed further light on the role of avian movements as a mechanism influencing local dynamics (by shaping host availability for mosquito bites and dispersing infection locally), and the long-distance spread of WNV strains via migratory birds.

Strengthening data collection and sharing is therefore an important step to understand WNV dynamics in general, and ultimately how it is impacted by climate change. While major investments in data collection and technology have led to a wealth of robust (observed and simulated) climate and meteorological data, the data on biological and ecological processes and disease occurrence is often more resource-exhaustive, tend to be scarce, delayed and often biased [163–165]. However, there are promising developments in data collection, management, and analysis that are likely going to increase the availability of more complete and high-quality data sets in the future. These include, for example, the advent of technological advancements such as remote sensing, mosquito smart traps, and improved animal tracking devices as well as an increasing implementation of citizen science approaches [166–169].

Eco-epidemiological models that integrate improved and novel data streams with climatic and environmental data should not only increase our ability to predict WNV but also our understanding of climate-driven effects on transmission. To achieve this goal, it will be important to build explainable models that complement highly predictive approaches, as this will help to disentagle drivers’ individual effects and lead to a better assessment of intervention and control strategies. Though temperature is arguably the best described predictor, effort needs to be invested to quantify and integrate its (long-term) impact on every layer of WNV transmission in more detail beyond vector-pathogen traits, including hosts, habitats, and vector-host interaction. Consideration of other drivers like precipitation and land cover has led to ambiguous results that appear to be very region-specific and scale dependent. With an improved understanding of the transmission cycle and better region-specific data, it could be feasible to link these differences to local vector-host populations, habitat suitability including hydrological conditions, as well as potential human influences including land use and control measures that lead to unique dynamics. Simultaneously to building this fine scale understanding, effort should be put towards identifying more broad scale patterns that make large-scale predictions feasible. For example, it might be valuable to shed more light on which sequences of climatic conditions are precursors for an exacerbated transmission season.

Thus, many climate-driven impacts on WNV have been identified and many more are yet to be better understood and quantified. Projections of WNV risk, though agreeing on an overall trend of increasing risk, are still scarce and highly uncertain. They are limited in spatial scale and often extrapolate from associations derived from past/current conditions [62, 147, 148, 159–161] and/or confine to projecting only one aspect of climate-driven impacts on WNV, e.g., by focusing on temperature and/or vector-pathogen traits [62, 129, 161]. Thus, while these approaches are sophisticated and highly valuable, they could be complemented by projecting indicators that consider more drivers and by integrating process-based relationships in these models wherever feasible. Integrating a deeper mechanistic understanding would increase their ability to extrapolate beyond present-day conditions [170, 171], resulting in more reliable projections.

While improved projections up to the mid-21st century will be important to inform climate risk assessment and adaptation and where investments in surveillance and control systems are needed, long-term projections beyond mid-century are also needed to estimate the role of climate change mitigation and illustrate the impact of high emission high warming scenarios. We could imagine, for example, an approach that combines projections of avian species’ distribution integrated with projections for mosquitoes and combined with a spatialized R0-model that accounts for both host density and distribution to account for host community composition [78] and vector density and distribution to account for species-specific temperature-dependent vector-pathogen traits [51, 172].

To maintain a systems perspective, we further need holistic assessments that consider the impacts of climate change on WNV in context of various other factors that will undergo changes in the future. The predicted increase in urbanization, deforestation, and agriculture would additionally influence directly or indirectly the ecology of WNV as the distribution and abundance of both hosts [173] and vector [31] species is affected. Heightened loss and fragmentation of habitat could lead to bottlenecks exacerbating WNV sharing in wildlife and the fact that human WNV cases already mainly occur in human-modified areas is echoing that encroachments into wild habitats have to be seen as a risk factor for increased zoonotic transmission [174]. Various other relevant determinants of WNV transmission will undergo changes in the future like immunity patterns [131], socio-economic development [175–177], and human behavior, including potential mitigation and adaptation strategies, travel, and trade. In addition, our understanding of the mechanisms driving WNV transmission under climate change is suspect to the uncertainty of possible adaptive (co-)evolution of virus, vectors, and hosts (e.g., it is very well possible that future temperature response curves of mosquito-pathogen traits could show adaptation to new environmental conditions). More frequent and intense outbreaks due to climate change, including faster viral replication at high temperature, would offer more opportunities for viral evolution, potentially accelerating the adaptation of the pathogen to novel conditions as well as benefiting the emergence of high-fitness strains. Moreover, alterations to the avian migration system and species distribution shifts could open new routes of viral sharing between specific geographical areas and species. Models and projections accounting for these processes would further increase our ability to foresee the range of possible future scenarios.

Fostering transdisciplinary thinking

The case of WNV underlines once again that the health of animals, humans, and the environment is deeply intertwined and highlights the urgency to maintain a systemic and global perspective about the health threats emerging at that interface, particularly in the context of climate change.

A collaborative approach is needed to understand all the components of infectious disease dynamics and how these are impacted by ongoing environmental change. This goes beyond modeling studies, from the collection of data under an integrated surveillance system framework, to its analysis, to informing the implementation of policies and interventions, also beyond the health sector. The One Health concept stands out for fostering this kind of joint work highlighting collaborative efforts across multiple disciplines and sectors at local, national, regional, and global levels with the goal of achieving optimal health outcomes for people, animals, and our shared environment [178]. Clearly, addressing the research needs discussed in the previous section will require adopting this transdisciplinary thinking to prevent siloed approaches and increase communication and information sharing between experts from different fields. In this context, knowledge, technology, and financial resources need to be directed towards integrated surveillance and monitoring systems that cover disease surveillance across populations (including humans and other animal hosts). To leverage their full potential for research and monitoring such efforts should be harmonized and standardized across national borders, developing a culture of transnational data sharing [15]. Ultimately, improved and coordinated data collection–including reservoir, vector, host, and environmental information–will allow the development of functional early warning systems which can be implemented in preparedness plans. In some Italian regions, for example, the detection of WNV by their systematically shared entomological surveillance system informs the posterior screening of human blood donations and organs, allowing early case detection and control, as well as more efficient resource allocation [179].

Studying the dynamics of WNV through a One Health lens will enable us to craft policies and interventions aiming at containing risks earlier (e.g., at the animal reservoir source). These studies could help focus surveillance geographically and temporally, allowing for a more targeted resource allocation and informing on the need of control plans to reduce the risk of spillover and spread of outbreaks if it occurs. Additionally, partnerships resulting from collaborations (both in research and policy) not only allow to better understand and address complex phenomena, but also to overcome inefficiencies and work overlap [180]. To achieve this, improving advocacy and communication at government level is vital to promote the interdisciplinary One Health approach beyond the health sector.

It is important to implement a One Health approach considering multifaceted issues and solutions beyond the direct impact of zoonotic pathogens and spillover events at the human-animal interface. Other aspects such as social, economic, and environmental issues must be factored in. For example, the incursion of WNV into domestic bird populations, and what this means for poultry production, food security and the local economies, or the combined impact of land use and climate change on local biodiversity, and how this can ultimately affect ecosystem health and dynamics including ecosystem services on which we depend.

Conclusion

Climate-driven impacts on multi-host, multi-vector viruses like WNV are complex, involving a range of interactions across ecological processes, biological mechanisms, and social determinants. Environmental changes alter the geographical extent and intensity of transmission by affecting vector breeding and pathogen replication. In addition, impacts on host populations and host movement, land use changes and evolutionary processes are bringing changes to the dynamics of WNV that may alter its burden on animal and human health. Appropriate prevention and control will rely on our ability to understand the WNV transmission cycle, its dependence on environmental conditions and to improve our ability to predict and project WNV risk. In this knowledge generation eco-epidemiological models play an important role by providing quantitative evidence for attribution, and potential future scenarios which can guide monitoring and resource allocation. A bottleneck in carrying out this research, however, is the lack of true interdisciplinary and trans-sectoral approaches. Understanding and containing infectious diseases, especially those at the interface of human, animal and environmental health requires adopting a One Health approach in data collection, modeling and policy that involves coordination, collaboration, and communication between experts and stakeholders in several fields and sectors at local, national, regional, and global levels. Recognizing that the health of humans, animals and ecosystems are inextricably linked provides a conceptual framework to develop solutions to today’s most pressing health and environmental challenges.

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