A Review of the Changing Global Impact of Arthropod-Borne Virus Diseases and Recent Initiatives from the World Health Organization

Introduction

Arthropod-borne viruses (arboviruses) are RNA viruses that depend on transmission to humans and other vertebrates through the bites of infected mosquitoes, ticks, and sand flies [1,2]. Several arbovirus families include Flaviviridae, Togaviridae, and Bunyaviridae (Table 1) [1,2]. Arboviruses have a profound impact on human health due to their complex transmission cycles, which involve vectors and reservoir hosts [3]. In 2019, a Global Burden of Disease study estimated that the global burden of dengue was up to 390 million infections per year, driven by urbanization, travel, and climate change [4]. Other Aedes mosquito-borne viruses (Zika, chikungunya, and yellow fever), Culex mosquito-borne viruses (Japanese encephalitis, West Nile fever, Rift Valley fever), and tick-borne viruses (Tick-borne encephalitis, Crimean-Congo hemorrhagic fever) share a similar increase in incidence and range, and similar environmental driving factors (Table 1) [5,6].

Throughout most of human history, arthropod-borne virus (arbovirus) diseases, mainly transmitted by Aedes mosquitoes (Aedes aegypti and Aedes albopictus) were found in subtropical and tropical regions. Some arboviruses and their vectors are known to have spread worldwide during the 17th and 18th centuries, establishing local cycles of transmission wherever there were suitable environmental conditions [3]. However, arbovirus diseases are now rapidly spreading worldwide, even to the northern hemisphere, driven by climate change, population growth and density (urbanization), and the ease and frequency of international travel [2,3]. The global impact of arbovirus disease is significant and is increasing, contributing to approximately 700,000 annual deaths [7]. Currently, reports of dengue virus infection have demonstrated this disease to be of significant medical importance, with recent global estimates indicating 390 million annual cases worldwide, of which 96 million cases are symptomatic [8]. Other arbovirus diseases of concern include chikungunya, Zika, and yellow fever, as well as West Nile virus, Japanese encephalitis, and tick-borne encephalitis viruses [2,9].

This article aims to review the changing global distribution of arbovirus transmission, the increased risk to human health from arbovirus diseases, and the potential for both epidemics and future pandemics, which have led to recent recommendations from the World Health Organization (WHO) and warrant their inclusion as candidates for Disease X.

Climate Change and Arbovirus Disease

In 2023, the WHO identified climate change as the most significant global threat to human health [10]. Climate change is attributed to rising atmospheric concentrations of greenhouse gases resulting from the burning of fossil fuels by populations in both developed and developing countries [10,11]. In 2022, the world experienced the highest temperatures for more than 100,000 years, while global investment in fossil fuels continued to increase [11,12]. Important evolutionary factors in the transmission and pathogenesis of arboviruses include the capacity to undergo genetic mutations that increase the infectivity of vectors and hosts, promote evasion of immune responses, and increase their pathogenicity in new viral strains [13,14]. Also, mosquito and tick vectors can adapt to new habitats and hosts, a process now accelerated by climate change [14]. Other factors that drive transmission include inadequate prevention, control, and infection surveillance, limited access to healthcare resources, increased travel, and urbanization [15]. Rainfall, temperature, and humidity are essential for arthropod vectors to breed, and climate change is extending the geographic range and potential for arbovirus transmission [15,16]. Increasing urbanization, deforestation, and replacement of land for agricultural and livestock use have altered the habitats of mosquitoes and ticks, leading to an increase in human-vector contact and transmission of arboviruses from wildlife reservoirs [16,17]. Recent changes in wildlife populations of mammal and bird viral reservoirs have led to an increase in arboviruses in the natural world [16,18]. Also, population movement, conflict, and economic instability affect public health systems, sanitation, water supplies, and housing, which can facilitate arbovirus transmission [16,18].

The 2023 Lancet Commission reported a lack of progress in protecting individuals from the adverse health effects of climate change, with developing countries being disproportionately affected and unprepared for epidemics and potential pandemics [12]. Climate change continues to impact global health due to increasing temperatures, the effects of air pollution, extreme weather events, changes in the spread of infectious diseases and emerging pathogens and is also driving an increase in vector-borne disease, including arbovirus diseases [11,19]. In December 2023, the Intergovernmental Panel on Climate Change (IPCC) published its Sixth Assessment Report (AR6), providing a comprehensive summary of the current state of knowledge on the impacts and health risks associated with climate change, as well as recommendations for mitigation and adaptation to these effects [20]. During the past decade, the IPCC has reported an increase in the prevalence of vector-borne diseases and highlighted the importance of monitoring arbovirus diseases, including dengue and West Nile virus disease [20].

WHO 2025 Recommendations for Dengue, Chikungunya, Zika, and Yellow Fever

On March 31, 2022, the WHO Global Arbovirus Initiative identified the need for risk mapping as a required source of evidence for arbovirus disease surveillance and provided updated recommendations to improve current management [21,22]. The 2022 WHO Global Arbovirus Initiative was developed across the WHO Health Emergencies Programme, the Immunization, Vaccines and Biologicals Department, and the Department of Control of Neglected Tropical Diseases, with international partners [21,22]. The One Health approach was employed, which is a collaborative, interdisciplinary method that considers the interconnectedness of human, animal, and environmental health conditions to address global challenges related to infectious diseases and climate change [23]. The One Health approach to arbovirus disease connects human health, veterinary medicine, and wildlife agencies to monitor arboviruses, transmission risk, and implement targeted public health interventions [23].

The 2022 WHO Global Arbovirus Initiative aims to provide a framework for responding to emerging or re-emerging arbovirus diseases with epidemic and pandemic potential by monitoring risk, pandemic prevention and preparedness, disease detection and response, and developing international collaborations to mitigate the growing risk of outbreaks, epidemics, and potential pandemics due to arboviruses (Table 2) [21,22]. The six ‘pillars’ defined by the 2022 WHO Global Arbovirus Initiative included: monitoring and anticipating infection risk; reducing local epidemic risk; improving vector control; preventing and preparing for pandemics; fostering innovation; and building an international coalition of partners (Table 2) [21,22].

Following three years of negotiations that identified gaps and inequities in the global response to the COVID-19 pandemic, on May 20, 2025, the 78th World Health Assembly of the WHO adopted the Pandemic Agreement, hiughlighting the importance of pandemic preparedness [24,25]. The WHO Pandemic Agreement outlines approaches to enhance international coordination for pandemic prevention, preparedness, and response, as well as access to vaccines, diagnostics, and therapeutics [24,25].

The arbovirus diseases dengue, chikungunya, Zika, and yellow fever have been identified as an escalating global threat in urbanized areas, as indicated by new global risk maps for Aedes-borne arboviruses [26]. Lim and colleagues have recently described a multi-disease risk model that incorporates evaluation of the ecological niche combined with a nested surveillance model, which can address a large dataset of more than 20,000 occurrence points [26]. This model illustrates the convergence of a common global distribution with the recent spread of chikungunya and Zika, which closely aligns with areas suitable for dengue [26]. Lim and colleagues also estimated that 5.66 billion people now live in areas susceptible to dengue, chikungunya, and Zika, and 1.54 billion people in areas susceptible to yellow fever [26]. These modelling studies have also highlighted significant differences between developed and developing countries in their surveillance capabilities, with higher-income regions more likely to detect and report arbovirus diseases, potentially leading to an overestimation of risk from arbovirus diseases in the US and Europe [26].

On July 4, 2025, the World Health Organization (WHO) published its first global guidelines for managing infections caused by the four most significant arboviruses: dengue virus, chikungunya virus, Zika virus, and yellow fever virus [2]. Other arbovirus diseases include Japanese encephalitis, Rift Valley fever, and West Nile fever, which are caused by viruses transmitted by Culex mosquitoes. Tick-borne encephalitis and Crimean-Congo hemorrhagic fever, which have also shown a recent increase in range and incidence, share similar environmental driving factors [5,6].

Several factors have influenced the development of the new WHO guidelines [2]. First, previous WHO guidance documents have been developed primarily based on available evidence and expert clinical opinion, without applying the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology [2]. Second, there are increasing reports of the size and frequency of arbovirus epidemics that require healthcare resource planning and preparedness, including for disease outbreaks in regions where these arbovirus infections were previously uncommon, such as the northern hemisphere [2]. Currently, the WHO estimates that more than 5.6 billion people are at risk from four major arbovirus infections, including the dengue virus, chikungunya virus, Zika virus, and yellow fever virus [2].

Dengue

Worldwide, dengue (breakbone fever) is the most common mosquito-borne viral disease [27]. Dengue fever is a disease that can be traced back to first-century China, with possible epidemics in Africa, Asia, and North America during the 1780s [27,28]. In the past decade, an increase in reported dengue cases has been attributed to increased international travel, global warming, and a decline in vector control programs [29]. Humans are the primary hosts of the dengue virus, which is transmitted between humans by infected female Aedes aegypti and Aedes albopictus mosquitoes that breed in stagnant water [30,31]. Dengue has been a disease primarily found in Asia and tropical countries, but cases have been increasingly reported in southern Europe, with virus-infected mosquitoes detected in central and northern Europe [32,33].

During the past decade, there has been a northwest expansion of the mosquito vector and dengue virus due to climate change [29,30]. In October 2023, more than 4.2 million cases of dengue were reported, compared with half a million in 2000 [32]. According to the WHO Dengue Dashboard, as of October 27, 2025, the total number of reported dengue cases worldwide was 4,435,594, comprising 1,839,891 confirmed cases, 20,814 severe cases, and 3,178 total deaths attributed to the dengue virus [34].

Several factors make control of dengue virus infection difficult, beyond controlling the mosquito vector, which include the presence of several antigenic serotypes of the virus that challenge vaccine development, and a spectrum of clinical manifestations that range from mild (fever) to rapidly and potentially fatal (coagulopathy and shock) [8,31]. Several serotypes of the dengue virus exist, differing antigenically. Therefore, infection with one serotype of dengue virus does not confer immunity from other serotypes, which may explain why the production of effective vaccines has been challenging [35]. The dengue virus targets and replicates in the cytoplasm of mononuclear cells in the peripheral blood, tissues, and lymph nodes [31,35]. Following infection from a mosquito bite, dengue fever develops in an individual who is not immune [31]. However, some serotypes of the dengue virus can cause more severe illnesses, including dengue hemorrhagic fever and dengue shock syndrome, which can lead to shock and coagulopathy [8,31]. The incubation period for dengue virus infection can range from three days to more than one week [31]. The initial symptoms of dengue fever are nonspecific and similar to other viral infections, which means that cases of dengue may remain undiagnosed [31]. Dengue hemorrhagic fever is a more severe condition that occurs either following secondary infection or in infants with maternal transfer of antibodies to the dengue virus and can result in dengue shock syndrome and multiorgan failure [31]. The rapid change in the distribution of the vector and virus underscores the importance of improved vector control and the need to develop effective vaccine prevention and treatments for dengue [19,36].

Chikungunya

The chikungunya virus (genus Alphavirus) belongs to the family Togaviridae, which is an enveloped RNA virus that encodes four non-structural proteins (nsP1 to nsP4) and five structural proteins (C, E3, E2, 6K, and E1) [37]. Chikungunya is now known to have a single serotype and three major genotypes (West African, East Central South African, and Asian) [38,39].

The first reports of chikungunya virus outbreaks were from eastern Tanzania in 1952, and urban outbreaks were first recorded in Asia in the 1970s [38]. However, since 2004, outbreaks of chikungunya virus infection have been reported more frequently and more widely. By 2013, cases of mosquito-transmitted chikungunya were reported in the Americas [38]. Chikungunya virus disease has now been reported in Asia, Africa, the Americas, and Europe [39]. Between January and September 2025, there was a global increase in reported cases of chikungunya, particularly in the Americas region, where 155 deaths from the chikungunya virus were reported [40]. During this time, there were 181,679 confirmed cases, including in the African region (108 cases), Mediterranean region (67 cases), European region (56,456 cases), the Americas (100,329 cases), the South-East Asia region (3,420 cases), and the Pacific region (21,299 cases) [40].

Following a mosquito bite, the chikungunya virus targets and replicates in the cytoplasm of human epithelial cells, endothelial cells, fibroblasts, and macrophages found in connective tissue, joints, muscles, skin fibroblasts, and the central nervous system (CNS) [39]. There are two cycles of transmission for the chikungunya virus: urban transmission (human to mosquito to human) and sylvatic transmission (animal to mosquito to human) [39]. The incubation period ranges from one to 12 days, with an acute stage of infection lasting approximately 10 days [39]. The symptoms of acute chikungunya virus infection include fever, back pain, joint pain, and headache, with a typical clinical manifestation of swollen and painful joints of the hands [39]. The long-term effects of chikungunya virus infection include relapse of joint pain in the distal joints, tendinitis, and carpal or tarsal tunnel syndrome [39]. These clinical symptoms may be mistaken for those of a rheumatological disease, which may explain why many cases of chikungunya virus infection may be underdiagnosed.

Zika

The Zika virus is a flavivirus that replicates in the nucleus of infected cells [41]. However, much of the pathogenesis of this viral infection remains unknown [41]. In 1947, the Zika virus was first isolated in a rhesus monkey in Uganda [42]. The Zika virus was isolated the following year from the mosquito Aedes africanus, with the first human cases detected in Uganda and Tanzania [42]. Between 1969 and 1983, the geographical distribution of the Zika virus expanded to India, Pakistan, Malaysia, and Indonesia, with sporadic cases reported in humans and with only mild symptoms [42,43]. In 2007, the first large outbreak of Zika was reported in the Pacific Island of Yap (Micronesia) [42]. Low levels of infection were reported until 2013 [43]. By March 2015, Brazil notified the WHO of almost 7,000 cases [42]. In February 2016, the WHO declared that the recent association of Zika infection with microcephaly and other neurological disorders in newborn infants constituted a Public Health Emergency of International Concern (PHEIC) [42]. Currently, more than 90 countries and territories have reported evidence of mosquito-transmitted Zika virus infections, and in 2024, more than 30,000 Zika cases were reported, with most from the Americas, where there is active infection surveillance [43].

Symptoms of acute Zika virus infection typically begin with a mild headache, fever, and conjunctivitis, followed by a maculopapular rash of the upper body that spreads to the palms and soles [41,44]. Symptoms of acute infection are mild and usually last for no more than a week [41]. Although Aedes mosquitoes primarily transmit the Zika virus, it can also be transmitted sexually, as well as through the transfusion of blood and blood products, and organ transplantation [44]. In adults, the long-term effects of infection can include neurologic conditions, such as Guillain-Barré syndrome [41]. Vertical transmission from mother to fetus can occur and is associated with microcephaly in newborn babies [41,44,45]. Currently, no effective vaccines or antiviral agents are available for the prevention or treatment of Zika virus infection.

Yellow Fever

Yellow fever is an acute viral hemorrhagic fever caused by infection with the yellow fever virus, Orthoflavivirus flavi, which belongs to the family, Flaviviridae [46,47]. The yellow fever virus is transmitted to humans and non-human primates primarily by the Aedes, Haemagogus, and Sabethes mosquito species [46]. Transmission of the yellow fever virus occurs in three distinct cycles: the sylvatic (or jungle) cycle, the intermediate (or savannah) cycle, and the urban yellow fever cycle [46]. The urban yellow fever cycle involves the transmission of the virus between humans and Aedes aegypti mosquitoes in densely populated (urban) areas, which can result in large-scale epidemics when vaccine uptake is low [47].

Infection with the yellow fever virus can be asymptomatic or mild, with an incubation period of up to 3 days [46]. The most common symptoms are fever, backache, muscle pain, headache, loss of appetite, and nausea, which last for a few days [46]. However, in rare cases, patients develop a high fever with renal and liver involvement, jaundice, renal failure, and hemorrhage [46]. Therefore, the severe forms of yellow fever can be misdiagnosed as dengue, malaria, or viral hepatitis [46]. However, effective vaccines are available for yellow fever, and vaccination is the most effective preventive measure, providing lifelong immunity [46].

In 2017, the WHO established the long-term Eliminate Yellow fever Epidemics (EYE) strategy (2017–2026) in response to the increasing risk of urban yellow fever outbreaks, the risk of international spread, and the threat to global health security [48]. The EYE strategy has three main objectives: protecting at-risk populations by implementing mass vaccination campaigns and programs; preventing the global spread of yellow fever by improving outbreak preparedness and response; and rapidly identifying and containing outbreaks of yellow fever [48].

Of all the arbovirus diseases, yellow fever has made the most progress in control through vaccine development and global strategic epidemic preparedness. However, the increasing concern regarding the control of yellow fever has shown that when infection surveillance is poor, vaccine uptake is low, and social, environmental, and demographic factors favor arbovirus transmission, epidemics can still occur, which is why these concerns are warranted [2].

Vertical Transmission of Arboviruses

Vertical transmission (mother-to-child transmission) of viral infection is rare, as the placental maternal-fetal interface provides physical, molecular, and immunological mechanisms to protect the developing fetus [49]. Emerging arboviral pathogens that can be transmitted from mother to fetus via the placenta include Zika virus, West Nile virus, and Rift Valley fever virus [45]. However, mother-to-child transmission during breastfeeding has also been reported for the dengue virus and chikungunya virus [50].

Disease X

The term Disease X was first introduced by the WHO in 2018 as an identifier for a candidate disease, caused by Pathogen X, and likely to be a priority pathogen capable of causing a global pandemic [51]. In 2018, before the COVID-19 pandemic due to SARS-CoV-2, the WHO published its annual review of diseases with the potential to cause a public health emergency due to the absence of treatment or vaccines and prioritized 10 diseases under the Research and Development Blueprint, recommending accelerated research and development [52]. In 2018, the list included three arbovirus-related diseases: Crimean-Congo hemorrhagic fever, Rift Valley fever, and Zika [52]. The WHO included two coronavirus-associated diseases, Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS) [52]. Also, four diseases associated with high mortality in isolated outbreaks were included as priority diseases: Ebola virus disease, Marburg virus disease, Lassa fever, and Nipah [52]. Finally, the WHO identified the need to include Disease X in the 2018 Research and Development Blueprint to highlight the importance of unknown human pathogens with epidemic and pandemic potential [52]. In 2018, the WHO acknowledged that several diseases were outside the scope of the Research and Development Blueprint, including influenza, HIV/AIDS, dengue, yellow fever, malaria, tuberculosis, cholera, smallpox, plague, leishmaniasis, and West Nile virus [52]. The WHO recognized that these diseases posed significant public health problems and required surveillance and management through disease control, research, and development initiatives that were in place in 2018 [52].

Arbovirus Diseases and Disease X

In 2025, the WHO global management guidelines identified the four most significant arbovirus diseases as dengue, chikungunya, Zika, and yellow fever [2,26]. While these four Aedes mosquito-borne arbovirus diseases may seem to be the leading contenders for Disease X, other potential arbovirus diseases include those caused by Culex mosquito-borne viruses, as well as Japanese encephalitis, Rift Valley fever, and West Nile fever [5,6]. Additionally, tick-borne encephalitis and Crimean-Congo hemorrhagic fever are arbovirus diseases that have exhibited similar recent trends in spread [5,6].

West Nile fever is an arbovirus disease that has been overlooked as a potential candidate for Disease X, despite its rapidly increasing incidence in the US. The neurotropic arbovirus, West Nile virus, was first identified in 1937 in Uganda and is a member of the Japanese encephalitis serocomplex with a primary host in birds [53]. West Nile virus is transmitted to humans mainly by the Culex spp. mosquito [53]. Pigs are amplifying hosts, with humans and horses serving as incidental hosts for the virus [53]. The first case of West Nile virus was identified in the US in 1999 in New York City, and it is now reported to be the leading cause of mosquito-borne disease in the US, with millions of reported cases [54]. West Nile virus can be transmitted from infected humans in transfused blood and transplanted organs [53]. In 2020, modeling studies showed that an air temperature of 24°C or more results in a peak incidence of infection [55]. This finding explains why West Nile virus infections in Europe and North America are more common during the summer and early autumn [53,56]. Climate change has increased the incidence and geographical expansion of cases of West Nile virus infections in Mediterranean countries and northern European countries, as temperatures have risen [56].

Future Directions

Advances in arbovirus infection diagnosis have been made, including the development of molecular and serological techniques [57]. Emerging technologies include the development of point-of-care diagnostics and CRISPR-based assays [57]. Novel vector control measures include genetic modifications of mosquito populations and artificial intelligence (AI)-driven surveillance systems [57]. The WHO Global Arbovirus Initiative has identified risk mapping as a key evidence gap within the arbovirus disease surveillance pillar [2,22]. In April 2025, Brady and colleagues proposed that a new generation of risk mapping models should be developed to prepare for the global threat of mosquito-borne and tick-borne arbovirus diseases [58]. These authors highlighted the importance of using risk mapping models by arbovirus control programs at a time when difficult decisions must be made about investing in novel vector control tools, vaccines, and the development of therapeutic agents [4,58]. Advances in arbovirus infection diagnosis have been made, including the development of molecular and serological techniques [59]. Novel vector control measures include genetic modifications of mosquito populations and artificial intelligence (AI)-driven surveillance systems [59].

Conclusions

More integrated approaches to disease prevention and pandemic preparedness are likely to initially focus on Aedes-borne viruses (dengue, chikungunya, Zika, and yellow fever), with consideration of the level of threat by region [2,60]. The unified and multidisciplinary approaches to pandemic preparedness for arbovirus diseases include targeting multiple reservoirs and vectors to tackle threats to human health and ecosystems, maintaining clean water, air, energy, and food supplies [61]. Therefore, if an arbovirus is a contender for Pathogen X, implementation of the WHO Global Arbovirus Initiative may also control Crimean-Congo haemorrhagic fever, Rift Valley fever, and infection from West Nile virus, as well as lesser-known arboviruses [21].