West Nile Fever (WNF) is a mosquito-borne viral infection caused by the West Nile virus (WNV), a member of the Flaviviridae family. The virus primarily incubates in a bird-mosquito transmission cycle, with humans and other mammals serving as incidental hosts.

The West Nile virus was first identified in 1937 in the West Nile region of Uganda. It is primarily transmitted to humans through the bite of infected mosquitoes, which acquire the virus by feeding on infected birds. In urban environments, mosquitoes are often the primary vectors of WNV transmission. Additionally, WNV can be transmitted through blood transfusions, organ transplantation, and from mother to fetus during pregnancy or through breastfeeding, although these modes of transmission are less common. ^[1]

Most individuals infected with WNV remain asymptomatic, while approximately 20% develop West Nile fever, characterized by flu-like symptoms such as fever, headache, body aches, and fatigue. However, in a small percentage of cases (less than 1%), WNV infection can lead to severe neuroinvasive diseases such as West Nile encephalitis, meningitis, or acute flaccid paralysis. These neurological complications can result in long-term disabilities or, in severe cases, death. Elderly individuals and those with weakened immune systems are at higher risk of developing severe forms of WNV disease. ^[2]

West Nile virus is endemic in many parts of the world. The virus has demonstrated an ability to cause sporadic outbreaks and endemic transmission in previously unaffected regions. In recent decades, there has been a significant increase in the frequency and geographic distribution of WNV outbreaks globally. ^[3] This expansion is attributed to various factors, including climate change, globalization, increased human and bird populations, and the movement of infected birds and mosquitoes through trade and travel routes. The epidemiology of WNV varies regionally, with seasonal fluctuations in transmission intensity influenced by environmental factors such as temperature, rainfall, and mosquito population dynamics. Understanding the global distribution and epidemiology of WNV is essential for implementing effective surveillance, prevention, and control measures to mitigate the impact of the disease on public health.

The documented history of West Nile Virus (WNV) traces back to its initial identification in Camargue, France, during the 1960s.^[3] Subsequent to its discovery, the European Union (EU) witnessed the emergence of West Nile Fever outbreaks, notably in Algeria in 1994 and Romania in 1996, with the latter experiencing a significant toll of 393 hospitalized cases and 17 fatalities in Bucharest.^[2] In 1999, Volgograd, Astrakhan, and Rostov in Russia collectively reported 318 human cases and 40 deaths attributed to WNV.^[2] The virus further manifested in Italy in 1998 and southern France in 2000, where cases of encephalitis linked to WNV were reported in horses.^[2] By 2008, Italy documented human cases associated with neurological complications.^[2] The spread of WNV extended to Spain and Portugal in 2010, marking the first recorded instances of the virus affecting horses and humans in these regions, subsequently impacting horses, humans, and birds.^[2] In the United Kingdom, WNV was identified in birds beginning in 2003.^[2] Human epidemics were recorded in the Balkan region during 2011 and 2012, with Italy and Hungary also experiencing spread during the latter year.^[2] The most substantial human outbreak in the EU occurred in 2018, affecting 11 countries and resulting in 1548 individuals contracting the disease via mosquito bites, a phenomenon attributed to elevated regional temperatures.^[4] Additionally, in 2020, outbreaks of WNV were observed in the EU, including in Spain and the Netherlands.^[4]

During summer and early fall, the prevalence of West Nile Virus (WNV) infections peaks, constituting the primary period of transmission.^[3] The virus is more commonly found in tropical and temperate regions, where environmental conditions favor mosquito breeding and viral replication.^[3] Ambient temperature plays a crucial role in shaping the dynamics of WNV transmission, influencing mosquito reproduction rates and the duration of the virus within mosquito populations, thereby impacting its spread.^[4] Higher temperatures contribute to accelerated growth rates in mosquito populations, reduce the interval between blood meals, and enhance the rate of virus evolution.^[3] Additionally, elevated ambient temperatures expedite the replication cycle of the virus itself.^[3] The interplay between weather patterns and climate directly affects vector competence, determining the availability of suitable habitats for both vectors and hosts.

The phenomenon of climate change exacerbates the spread of WNV by raising ambient temperatures, facilitating its dissemination into new regions and expanding its geographical range.^[3] Furthermore, increased precipitation resulting from climate change creates more standing water, providing conducive breeding sites for mosquitoes and subsequently increasing mosquito populations.^[3] Conversely, decreased precipitation can also lead to higher mosquito populations and WNV transmission due to alterations in the food web and reduced predation pressure, leading to heightened vector-host interactions.^[3] Climate change-induced precipitation anomalies further contribute to the ease of WNV spread.^[3]

Outbreaks of WNV typically initiate in rural areas, particularly wetlands, where birds and mosquitoes establish an endemic cycle, before spreading to organic-rich water sources in urban areas.^[3] Additionally, higher vegetation opacity is positively correlated with increased mosquito activity, further influencing the dynamics of WNV transmission.^[3] These ecological and climatic factors collectively contribute to the complexity of WNV transmission dynamics and underscore the importance of comprehensive surveillance and mitigation strategies.

Ecological factors, encompassing the presence of hosts including both birds and mosquitoes, and the intricate interactions between the pathogen and its vector and environmental milieu, are pivotal in understanding the transmission dynamics of West Nile Virus (WNV).^[3] WNV outbreaks consistently coincide with the annual arrival of migratory birds in Europe, typically occurring during late summer and early fall. This temporal correlation strongly suggests a significant role for bird migration in the dissemination of the virus across regions.^[5] Moreover, investigations have revealed the presence of analogous viruses to WNV, such as Eastern and Western equine encephalomyelitis alphaviruses, within migrating bird populations.^[5] These findings underscore the importance of avian migration pathways in the global spread of arboviruses and highlight the potential for intercontinental transmission facilitated by migratory bird movements.

In 2020, significant hotspots of West Nile Virus (WNV) activity were identified across various regions, with southwest Spain, northern Italy, and northern Greece emerging as major focal points.^[4] Additionally, notable outbreaks occurred in Hungary, Romania, and Germany, contributing to the overall dissemination of the virus within Europe.^[4] These regions experienced heightened WNV transmission, leading to increased human infections and necessitating intensified surveillance and control measures. Furthermore, Italy, Greece, Russia, and Romania have consistently been recognized as hotspots for WNV activity, underscoring the persistent challenge posed by the virus in these areas.^[6] The recurrence of WNV outbreaks in these countries emphasizes the need for sustained efforts in monitoring and management to mitigate the public health impact of the disease.

The potential impact of the 2020 Covid-19 pandemic on West Nile Virus (WNV) surveillance cannot be overlooked, as attention and resources were redirected towards addressing the novel virus, possibly leading to decreased surveillance efforts in some nations.^[4] Within the European Union (EU), surveillance of WNV is conducted through the European Surveillance System operated by the European Center for Disease Prevention and Control (ECDC).^[7] The ECDC collaborates closely with organizations such as the World Organization for Animal Health and the European Food Safety Authority to enhance monitoring and response capabilities.^[7] Reports of WNV outbreaks in horses within the EU are channeled through the Animal Disease Notification System to the European Commission for further action.^[7] In countries like Austria, France, Greece, and Italy, surveillance efforts are specifically tailored towards the early detection of West Nile Fever.^[7] Serosurveys play a crucial role in identifying the presence of the virus in horses, while surveillance of birds and mosquitoes is conducted to enable early detection and response measures.^[7] Furthermore, in response to the 2018 outbreaks, countries like Slovenia, Italy, Serbia, and Greece implemented After Action Reviews and adopted a One Health approach to effectively address the challenges posed by WNV.^[8] These collaborative efforts underscore the importance of coordinated surveillance and response strategies in combating the spread of WNV within Europe.

West Nile virus (WNV) infection typically manifests with most individuals remaining asymptomatic, while approximately 20-40% of those infected develop symptoms ranging from mild flu-like illness to severe West Nile encephalitis.^[9] The incidence of severe neurologic disease is less than 1%.^[9] However, there are public health concerns regarding the prevalence of the disease in blood donors due to the potential for transmission through blood transfusions.^[10] Early detection of outbreaks is crucial as it can accelerate the public health response, aiding in containment and mitigation efforts.

In Europe, the disease burden of WNV fluctuates, with notable peaks and troughs in reported cases. The highest number of cases was recorded in 2018, with 1,548 human cases reported across European Union countries.^[11] In other years, the number of cases has been significantly lower but a notable increase has still been observed.^[11] This variability underscores the importance of robust surveillance and reporting mechanisms to accurately track the prevalence of WNV and implement timely interventions to prevent further transmission and mitigate clinical outcomes.

Diagnosis of West Nile Virus (WNV) primarily relies on detecting viral RNA in serum or cerebrospinal fluid.^[9] Although specific therapeutic treatments for WNV infections are lacking, severe cases, notably West Nile encephalitis, may necessitate intensive care unit interventions, life support therapy, and rehabilitation.^[9] Supportive care forms the cornerstone of management to alleviate symptoms and manage complications. Prevention strategies, including mosquito control measures and public health awareness campaigns, are vital in curbing virus transmission and minimizing its impact.

Severe illness tends to be more prevalent among the elderly population, particularly those over 50 years old, who face a tenfold higher risk of developing neurologic symptoms.^[12] This risk escalates dramatically for patients older than 80 years.^[12]

The IgM antibody test, especially the IgM-capture enzyme-linked immunosorbent assay, is commonly employed for diagnosis.^[13] This test exhibits high sensitivity (95-100%) in both serum and spinal fluid.^[13] However, WNV-specific IgM antibodies may not be detectable until around the fourth day of illness.^[13]

The incubation period in humans ranges from 3 to 15 days.^[13] Symptoms often commence with a mild febrile illness, including fever, headache, and myalgias. Some individuals may develop a roseolar or maculopapular rash.^[12]

Limited data suggest that immunocompromised patients may face an increased risk of severe disease.^[13] Transmission of WNV can also occur through blood transfusions, necessitating screening among blood donors.^[12]

While serious non-neurologic complications such as myocarditis, pancreatitis, and fulminant hepatitis are rare, they may occur.^[12] Patients with profound muscle weakness may require intubation and mechanical ventilation for support.^[12]

West Nile Virus (WNV) surveillance and recording mechanisms vary in quality between countries in Europe, leading to inconsistencies in data detection.^[9] Furthermore, there is a lack of surveillance systems and health policies in place to effectively manage outbreaks.^[9] To address these challenges, there is a critical need for precise definitions of viral circulation, standardized surveillance protocols, and coordinated efforts among public health agencies to enhance monitoring and response capabilities.^[9] Such measures are essential for early detection, containment, and mitigation of West Nile Virus outbreaks.

Surveillance efforts often focus on monitoring the avian population, as birds serve as primary hosts for the virus.^[13] The most common route of infection to humans is through the bite of infected Culicine mosquitoes.^[12] Mosquitoes become infected when they feed on infected birds that have high levels of WNV in their blood.^[12] Birds of the family Corvidae are particularly susceptible to WNV infection.^[12]

West Nile Virus is not transmitted from person to person by mosquitoes.^[12] However, transmission of WNV can occur via red blood cell, plasma, and platelet transfusions, highlighting the need for stringent screening measures among blood donors to prevent iatrogenic transmission.^[12] Coordinated surveillance efforts targeting both avian populations and mosquito vectors are crucial for early detection and containment of WNV transmission, thus mitigating the impact of outbreaks on human health.

Vector control measures are a primary strategy for preventing the spread of West Nile Virus (WNV). The virus, transmitted mainly by mosquitoes, can travel long distances through bird populations.^[14] Integrated Vector Management (IVM), endorsed by the World Health Organization, is a key approach that involves rational decision-making to optimize resources for vector control.^[14] Strategies include reducing vector density and human-vector contact.^[14] However, the complex transmission cycle of WNV presents challenges, requiring comprehensive surveillance and targeted interventions.^[14] Larval control, aimed at containing mosquito populations by managing immature stages, is a crucial aspect.^[14] Efforts focus on mapping breeding sites, eliminating standing water, and using larvicides.^[14] While specific larval population thresholds are lacking, methods such as bacterial larvicides have shown high efficacy. Additionally, personal protection measures, including repellents and window screens, play a role in minimizing human-mosquito contact and reducing the risk of infection.^[14]

As of the current date, there are no licensed vaccination options available for West Nile Virus (WNV).^[9] While some vaccine candidates are under evaluation, efforts to develop a licensed human vaccine have faced challenges and stalled progress.^[9] Despite ongoing research and clinical trials, the absence of a licensed vaccine underscores the need for continued investment and innovation in vaccine development to mitigate the impact of WNV on public health.

2010 Outbreak in Greece

In 2010, Greece experienced a significant outbreak of West Nile Virus, marking one of the earliest large-scale incidents in Europe. The outbreak primarily affected the region of Central Macedonia, with numerous cases reported in both humans and animals. According to the European Centre for Disease Prevention and Control (ECDC), Greece reported 262 confirmed human cases and 35 deaths during this outbreak, drawing attention to the emergence of WNV as a public health threat in Europe.^[15]

2018 Outbreak in Southern Europe

In 2018, Southern Europe faced another notable outbreak of West Nile Virus, with multiple countries reporting increased activity of the virus. Italy, in particular, experienced a surge in human cases, with regions like Lombardy and Veneto being heavily affected. According to the Italian Ministry of Health, there were 123 confirmed cases and 11 deaths related to WNV in Italy during 2018, highlighting the severity of the outbreak.^[16]

2019 Outbreak in Serbia

Serbia encountered a significant outbreak of West Nile Virus in 2019, with the virus spreading across various regions of the country. According to the Serbian Institute of Public Health, there were 356 confirmed cases of WNV infection and 35 fatalities reported during this outbreak. The outbreak raised concerns among public health authorities in Europe regarding the increasing geographical spread and impact of WNV in the continent.^[17]

2020 Outbreak in Spain

Spain witnessed a notable outbreak of West Nile Virus in 2020, particularly in the regions of Andalusia and Extremadura. The Spanish Ministry of Health confirmed a total of 77 human cases and 6 deaths attributed to WNV during this period. The outbreak prompted coordinated efforts by health authorities to implement mosquito control measures and raise awareness among the population about the risks of WNV transmission.^[18]

2021 Outbreak in Greece and Romania

In 2021, Greece and Romania experienced significant outbreaks of West Nile Virus, underscoring the continued threat posed by the virus in Europe. Greece reported 315 confirmed cases and 48 deaths, while Romania recorded 63 confirmed cases and 9 deaths during the outbreak. The outbreaks prompted enhanced surveillance and control measures in affected areas to mitigate further transmission of the virus.^[17]

1. Vector Control and Surveillance: Effective vector control measures and surveillance systems are fundamental for dengue prevention and control. Strategies such as larval source reduction, insecticide spraying, and biological control have shown efficacy in reducing mosquito populations and interrupting west nile transmission cycles. Surveillance systems for monitoring mosquito abundance and west nile cases enable early detection of outbreaks, facilitating timely intervention.^[19]

2. Integrated Vector Management (IVM): Integrated vector management, which integrates multiple control methods and emphasizes community participation, has emerged as a cornerstone of west nile control efforts. IVM approaches encompass environmental management, chemical control, biological control, and community mobilization, aiming to reduce mosquito breeding sites and limit west nile transmission. Studies have demonstrated the effectiveness of IVM in reducing dengue vector populations and disease incidence.^[19]

3. Early Detection and Diagnosis: Early detection and accurate diagnosis of dengue cases are crucial for timely outbreak response and patient management. Advances in diagnostic tools, including rapid diagnostic tests and molecular assays, have improved the capacity for early dengue detection. Enhanced surveillance systems, coupled with syndromic surveillance and outbreak investigations, enable public health authorities to identify and respond to dengue outbreaks promptly.^[20]

4. Community Engagement and Education: Engaging communities in west nile prevention and control efforts through education and community-based interventions is essential for sustainable disease control. Community participation in vector control activities, such as source reduction campaigns and clean-up drives, can effectively reduce mosquito breeding sites. Health education initiatives aimed at raising awareness about west nile transmission, symptoms, and preventive measures empower individuals to protect themselves and their communities from West Nile.^[21]

5. Climate Change and Urbanization: The impacts of climate change and urbanization influence the epidemiology of West Nile Virus, exacerbating disease transmission dynamics. Climate factors, such as temperature and precipitation patterns, influence mosquito breeding habitats and west nile vector distribution. Urbanization and population growth create conducive environments for mosquito proliferation, increasing the risk of west nile transmission in urban areas. Addressing the environmental and social determinants of dengue risk is critical for mitigating the impact of climate change and urbanization on dengue outbreaks.^[22]

California's vector control program has implemented a comprehensive strategy to monitor and control mosquito populations, reducing the incidence of WNF in the state. This includes targeted surveillance, larval habitat reduction, and community outreach efforts. Main efforts include reducing nonessential water, vegetation management, and public awareness measures.^[23]

Chicago's Public Health Response

Following an outbreak of WNF, Chicago implemented an aggressive public health response, including enhanced mosquito surveillance, community-based interventions, and public awareness campaigns. These efforts led to a significant reduction in WNV cases.^[24]

France developed a national plan for the prevention and control of vector-borne diseases, including WNF. This plan focuses on early detection, targeted control measures, and coordination among public health authorities to minimize the spread of WNV. Clinical surveillance of human non-neuroinvasive cases is also implemented.^[7]

Uganda implemented a community-based surveillance program to detect and respond to outbreaks of WNV. Through active involvement of local communities, this program has improved early detection of cases and facilitated rapid response interventions.^[25]

Within the European Union (EU), surveillance of West Nile Virus (WNV) is conducted through the European Surveillance System managed by the European Center for Disease Prevention and Control (ECDC).^[7] This system serves as a vital platform for monitoring and reporting WNV cases, facilitating early detection and response efforts across member states. In addition to its role in WNV surveillance, the ECDC collaborates closely with international organizations such as the World Organization for Animal Health and the European Food Safety Authority.^[7] These collaborations enhance the exchange of information and expertise, bolstering the EU's capacity to effectively address the public health challenges posed by WNV and other emerging infectious diseases. Such coordinated efforts underscore the importance of international cooperation in mitigating the spread of vector-borne diseases within Europe and beyond.

Intersectoral collaboration plays a crucial role in coordinating response plans to combat West Nile Virus (WNV) outbreaks.^[7] While efforts to mitigate the spread of WNV primarily occur at the national level, there is a growing recognition of the need for a more extensive collaborative response.^[26] Such collaboration facilitates the sharing of resources, expertise, and best practices among countries, thereby enhancing the effectiveness of response efforts. Moreover, coordination of methodologies across Europe would be advantageous in establishing standardized virus response protocols.^[26] By aligning methodologies, countries can streamline surveillance, diagnostic, and intervention strategies, fostering a more cohesive and efficient approach to WNV management across the continent. This emphasizes the importance of cross-border cooperation and harmonization in addressing the public health challenges posed by WNV within Europe.

Integrative surveillance efforts, coupled with economic and social disparities, pose challenges in establishing standardized data on the spread of West Nile Virus (WNV) across Europe.^[27] These factors contribute to variations in surveillance methodologies, data collection practices, and reporting systems among European countries, hindering efforts to compile comprehensive and uniform datasets on WNV transmission. Despite the recognition of the need for a coordinated response, the majority of mitigation efforts remain country-based, with limited collaboration on a larger scale.^[26] This fragmented approach underscores the complexity of addressing WNV within a diverse European landscape and highlights the importance of fostering cross-border cooperation to effectively combat the spread of the virus across the continent.

In combating the spread of West Nile Virus (WNV) in Europe, prioritizing research initiatives is essential for effective prevention and control strategies. A primary focus must be on the development of vaccines, given the severe long-term effects and health threats posed by WNV. Research efforts should aim to create vaccines that not only provide robust immunity against WNV but also address the unique challenges posed by the virus, such as its ability to cause neurological complications.^[1] To achieve this, it is crucial to investigate the most effective ways to target different cells based on factors like longevity, duration, and persistence of antibodies.^[1] Understanding these dynamics will inform the design of vaccines that offer durable protection against WNV infection.

Furthermore, research on the use of platforms for vaccine research and development is imperative. Exploring diverse technological approaches and methodologies can expedite the vaccine development process while ensuring safety and efficacy. Additionally, addressing safety issues associated with vaccine candidates is paramount to instill public confidence and facilitate widespread vaccination programs. Rigorous evaluation of vaccine safety profiles through preclinical and clinical studies is essential to mitigate potential risks and ensure the deployment of safe and effective vaccines against WNV, especially towards susceptible populations. Research efforts should focus on understanding the unique immune responses and vulnerabilities of these populations to tailor vaccination strategies accordingly.

Moreover, advancements in diagnostic testing methodologies are crucial for early detection and surveillance of WNV outbreaks. Improving testing accuracy and accessibility can facilitate prompt intervention and containment measures to curb the spread of the virus. Additionally, comprehensive mosquito control strategies are essential for reducing vector populations and interrupting WNV transmission cycles.^[1] Research should explore innovative approaches for mosquito control, considering environmental factors and social settings that influence mosquito habitats and human-mosquito interactions. Enhancing surveillance and risk assessment of mosquitoes in Europe is also critical for proactive disease management. Integrating social and environmental data into surveillance systems can enhance our understanding of WNV transmission dynamics and inform targeted interventions to mitigate the risk of outbreaks.

Surveillance

In confronting the spread of West Nile Virus (WNV) across Europe, bolstering public health infrastructure emerges as a critical imperative to effectively combat this emerging threat. While surveillance remains the cornerstone of WNV prevention, it is also recognized as being costly and time-consuming.^[28] However, it remains the most effective tool for early detection and intervention. Despite this, there is a concerning trend of increased demand coupled with reduced resources for the health sector. This disjuncture underscores the urgent need for governments and stakeholders to prioritize investment in public health infrastructure to fortify surveillance capabilities and response mechanisms.

One Health Perspective

The escalating healthcare costs associated with addressing WNV and other non-communicable diseases (NCDs) and vector-borne illnesses highlight the urgency of proactive measures to strengthen public health infrastructure. These diseases not only exact a toll on individual health but also exert significant economic burdens, affecting poverty levels and productivity within communities.^[29] Recognizing the multifaceted impact of human activity on disease incidence, it becomes evident that a comprehensive approach is required to mitigate the spread of WNV. This entails addressing risk factors for geographic expansion, including human mobility, population growth, trade, and climate change. Collaboration across different levels of governance – local, regional, national, and global – as well as across diverse disciplines such as veterinary medicine, public health, and technology, is paramount. This collaboration is a perspective commonly known as “One Health."^[29] By fostering these synergistic partnerships through the One Health perspective, Europe can effectively confront the challenges posed by WNV and safeguard the health and well-being of its populations for generations to come.

Implementing sound policy measures is paramount for effective prevention and control of West Nile Virus (WNV) transmission in Europe. Proper allocation of resources, collaboration within a One Health approach, and vaccination research would make great strides in tackling the issue of prevention and control first within Europe, then worldwide eradication.

Surveillance and control

In tackling the spread of WNV in Europe, policymakers must prioritize a comprehensive approach that integrates robust surveillance and proactive mosquito control measures. Governments should allocate resources towards strengthening surveillance systems, investing in advanced technologies for early detection and rapid response to outbreaks. Collaborative efforts between public health agencies, veterinary services, and research institutions are crucial for sharing information and coordinating efforts in disease surveillance and vector control. The importance of community engagement and reporting would play an extremely important role in surveillance, and promoting awareness would help decrease the spread of the virus through things like mosquito spray and vaccination.

One Health

Furthermore, policymakers should adopt a One Health approach to address the broader social determinants of WNV transmission. This approach recognizes the interconnectedness of human, animal, and environmental health and advocates for interdisciplinary collaboration. Integrating One Health principles into public health agendas can strengthen resilience against WNV and enhance overall health outcomes.^[30] Enhanced collaboration between health sectors, including human and veterinary medicine, environmental science, and agriculture, is essential for effective One Health implementation. Policymakers should facilitate interdisciplinary partnerships, data sharing, and joint surveillance efforts to identify and mitigate WNV risks at the human-animal-environment interface. By fostering collaboration across sectors and implementing evidence-based policies, policymakers can develop holistic solutions to prevent and control WNV transmission while addressing the underlying determinants of disease emergence and spread.

Vaccination

Finally, vaccination programs should be prioritized as a cornerstone of WNV prevention policies. Governments should work towards facilitating access to safe and effective vaccines, particularly for vulnerable populations such as the elderly and immunocompromised individuals. Implementing comprehensive vaccination campaigns, along with robust surveillance to monitor vaccine coverage and efficacy, can significantly reduce the burden of WNV-related morbidity and mortality.

• West Nile virus
• West Nile fever
• List of West Nile virus outbreaks
  • West Nile virus in the United States