Global Dengue Menace: Association with Climate Change

Abstract

Dengue, a viral disease, is transmitted by vectors such as Aedes aegypti and Aedes albopictus mosquitoes. A dramatic rise in dengue cases, exacerbated by climate change and urbanization in recent years, has caused public health challenge. Global warming, associated rise in sea level, and unpredictable rainfall accelerate the survival, development, and dispersal of Aedes mosquitoes significantly influencing dengue disease dynamics. Coupled with increased global trade and travel, dengue has spread to previously unaffected areas. Poor urban planning, overcrowding, inadequate sanitation, and improper water storage are important for favorable breeding environment of mosquitoes. Climate change triggers genetic adaptations in both vectors and virus, mostly enhancing their survival and transmissibility and influencing their virulence and epidemic potential. Effective outbreak control requires timely detection and reporting through integrated disease surveillance systems, and sustainable vector control through breeding site elimination and application of insecticides. Despite there is significant progress in vaccine and antiviral development, its implementation needs further research including community involvement and awareness campaigns. Dengue prevention is possible by understanding the interactions of climate, mosquito ecology, and disease transmission and by successful implementation of appropriate interventions. Therefore, integrated approach of public health agencies, policymakers, and communities is crucial to control and mitigate climate-driven dengue transmission.

1. Introduction

Dengue has been emerging as a major public health threat, with increasing outbreaks of acute febrile illness (AFI) endemic to tropical and subtropical regions globally. It is an arthropod-transmitted-mosquito-borne viral etiology AFI known alternatively as ‘breakdown fever’ coined by Benjamin Rush in 1787 because of its clinical presentations of myalgia and arthralgia [1]. Dengue fever has potentially affected one-half of the world’s population, with its first epidemic presentation in Asia, Africa, and North America in the 1780s [2]. Although its effect on low- and middle-income countries have been studied for years now, it has slowly invaded the high-income countries (HICs) following the path of other vector-borne diseases like malaria, chikungunya, scrub typhus, Japanese encephalitis, leptospirosis, and influenza A [3, 4]. Dengue is endemic in a few HICs or states, including Puerto Rico, Singapore, Aruba, and Brunei Darussalam. Other nations reporting frequent dengue outbreaks include French Polynesia, Queensland in Australia, Taiwan, The Bahamas, and New Caledonia. Smaller epidemics occur in other places, like France, Japan, Bermuda, and the US state of Florida [5, 6].

2. Etiology

The causative agent of dengue is a flavivirus named dengue virus (DENV), which is transmitted by the bite of adult female Aedes mosquitoes (Aedes aegypti and the Aedes albopictus species) and is responsible for widespread epidemics and endemic infections in populations that are not immune, especially in tropical and subtropical nations that are economically challenged. There are four independents but antigen-related serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) without any cross-immunity among the serotypes of the dengue virus.

3. Clinical presentation

Dengue fever (DF) severity ranges from moderate to undifferentiated fever illness to severe dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF). Although the 1997 World Health Organization (WHO) classification divided DF into undifferentiated fever, DF, and DHF and is still used, the 2009 WHO revision reviewed and classified DF disease into simple DF and severe DF for case treatment. Each category would primarily present with a high fever persistent for 2–7 days, hemorrhage (clinically presented in the form of petechiae, epistaxis, positive tourniquet test results, or thrombocytopenia), and shocks from plasma leakage (represented by hemoconcentration, or a hematocrit of 20% or higher), pleural effusion, and ascites [7, 8, 9].

4. Epidemiology

Each year, more than 100 countries are affected by the Dengue virus, risking life of roughly 3.6 billion people worldwide [6]. Ensuing malaria, the second most important vector-borne disease, is dengue infection in terms of its incidence and mortality rate. Dengue incidence has increased to 30-fold during the last 50 years [10]. Jakarta, Indonesia, and Cairo in Egypt were the pioneers of the dengue outbreak, which was reported in 1779; later, the incidence of dengue outbreaks was found in Asia, Africa, Australia, and America [11]. Of the total global dengue burden, India occupies the third position by contributing 33 million clinically apparent dengue cases each year [12]. In India, the high dengue burden states are West Bengal, Uttar Pradesh, Punjab, Haryana, Delhi, Gujarat, Kerala, Karnataka, and Tamil Nadu [13]. The high dengue infections in India due to elements like urbanization, higher population density, and favorable vector growth environments. With massive urbanization after World War II, dengue outbreaks became a burden in Southeast Asian countries. However, the Philippines was the first to face two consecutive outbreaks of dengue hemorrhagic fever in 1953 and 1956, respectively. Every year, throughout India, more than 100,000 infections and 200–400 deaths occur (NVBDCP 2021) [14]. Dengue coinfections with all four serotypes have been reported in different regions of India.

The highest number of dengue cases was reported in 2023, according to the World Health Organization, affecting almost over 80 countries, which resulted in a significant over 6.5 million cases and 7300 dengue-related death cases. Endemicity of the disease has been seen in more than 100 countries, with Asia representing 70% of the global burden of the disease [15]. Seasonality of the disease varies from May to October in Thailand and Myanmar, June to December in Malaysia and Vietnam, February to May in Brazil, and June to November in India [10].

Any age group of the population is susceptible to the disease, with approximately 30–60% of them manifesting symptoms of the disease. In non-endemic regions, young adults are more infected, whereas in endemic regions, children show the highest incidence rate [15]. Eighty-five percent of cases of child incidence are seen in Thailand, which includes the age group of 8–9 years, whereas in China, all age groups, from young adults to aged persons, are equally affected. There is no gender or occupation biasness in terms of infection rate [10]. Further dengue hemorrhagic fever (DHF), a result of secondary dengue infection, is the main reason for hospitalization and death cases.

In 2019, dengue cases reached unprecedented growth, with 129 countries falling into the domain [16]. COVID-19 pandemic (2020–2022). Along with the occurrence of El Nino, several reports of climate change showed a reduction in the number of DF cases, majorly due to a lower reporting rate and a slight decline in dengue cases. During 2023, an unexpected spike in dengue cases has led to nearly a historic high, with over 5 million cases and more than 5000 dengue-related deaths reported across more than 80 countries and territories in five WHO regions: Africa, Southeast Asia, the Americas, the Western Pacific, and the Eastern Mediterranean. Nearly 4.1 million (80%) have been reported in the Region of the Americas.

The World Health Organization (WHO) estimated a tenfold increase in reported cases globally between 2000 and 2019, going from 500,000 to 5.2 million (Table 1).

Type of fever	Case definition	Laboratory confirmation
Dengue	An acute viral illness caused by RNA virus (having any of the four DENV-1, DENV-2, DENV-3 and DENV-4 serotypes) belonging to the Flaviviridae family; transmitted through Aedes mosquitoes. It can be both clinically symptomatic and asymptomatic.
Dengue Fever	A case compatible with the clinical description of DF inclusive of at least one of the following: Isolation of the dengue virus from serum, plasma, and leucocytes. Detection of IgM antibody titer by ELISA in a single serum sample Detection of dengue virus antigen in serum by NS1-ELISA IgG seroconversion in paired sera after 2 weeks with fourfold rise of IgG titer. Detection of viral nucleic acid by PCR OR; Acute febrile illness requiring medical attention and presenting with at least two of the following: Headache Retro-orbital pain (pain behind the eyes) Myalgia (muscle pain) Arthralgia (joint pain) Rash Leukopenia (low white blood cell count) Nausea and Vomiting Swollen glands Single positive anti-dengue IgM test or Significantly elevated anti-dengue IgG antibody titer	In the viremic stage, NS1 ELISA antigen assay can be used.; Molecular diagnosis based on reverse transcription (RT-PCR), or real-time RT-PCR.
Dengue Negative	Clinical symptoms and EITHER: Single positive anti-dengue IgM test or Significantly elevated anti-dengue IgG antibody titer	Confirms absence of current dengue infection
Dengue Hemorrhagic Fever (DHF)	Confirmation of dengue virus infection and all of the following: Plasma Leakage: Hematocrit increase (>20% above average); Hematocrit drop (>20% after treatment) Pleural effusion (fluid in lungs) or ascites (fluid in abdomen) Low protein or albumin levels (adjusted for age) Hemorrhagic Manifestations: Positive tourniquet test; Petechiae (tiny red spots on skin) Ecchymoses (large bruises) Purpura (rash caused by bleeding) Mucosal bleeding (bleeding from gums, nose, etc.) Internal bleeding (vomiting blood, black stools, blood in urine) Thrombocytopenia: Platelet count less than 100,000/mm^3	Requires confirmation of dengue virus infection alongside evidence of plasma leakage, bleeding, and low platelets
Dengue Shock Syndrome (DSS)	Meets ALL criteria for DHF and evidence of circulatory failure: Rapid and weak pulse Narrow pulse pressure (<20 mmHg) or Age-specific hypotension Cold, clammy skin and altered mental status	Most severe form of dengue, requires immediate medical attention

Table 1.

Dengue fever presentations, case definitions and confirmations.

Adapted from Ref. [17].

5. Transmission of dengue virus

Primarily Aedes aegypti and meagrely Aedes albopictus are the major mosquito vectors responsible for the transmission of DENV from one person to another through a blood meal from a viremic person. Humans are the primary amplifying host. With a probability that >50% of the infected persons may enter an asymptomatic phase of infection. The ratio of asymptomatic to symptomatic infection is 2.2:1, and asymptomatic infection has a significant role in viral spread. Transmission of the DENV virus is maintained in two cycles: one is sylvatic between Monkey-Aedes-Monkey in jungle epidemic regions of Southeast Asia where Chimpanzee, Gibbon, and Macaque are the important natural reservoirs of the virus, whereas in village and city areas, the transmission pattern of the virus is Aedes-Human-Aedes that is the human cycle [18]. The incubation period of the virus within the mosquito body is 8–12 days; after that, the mosquito becomes infected with the virus for the rest of its 1-month life span. Infection with DENV results in high-titer viremia of about 7 days approximately, and transmission of the virus is mainly blood-borne through infected blood, organs, or other tissues but not through respiratory droplets, saliva, or sexual contact (Figure 1).

Figure 1.

Transmission of dengue virus from an infected person to Aedes mosquito.

A higher incidence of susceptibility to DENV infections is observed in adults, and this lasts for several years. Immunity against heterologous serotypes typically lasts from 2 months to 2 years. One of the main causes of DHF/DSS is multiple DENV infections or secondary dengue infections, where Antibody-Dependent Enhancement (ADE) may play a crucial role. Patients with comorbidities like asthma, sickle cell anemia, and diabetes are more likely to experience severe dengue complications. Numerous factors such as ethnicity, inheritance, blood type, and human leukocyte antigen (HLA) are related to disease vulnerability. For instance, individuals with AB blood type are at greater risk than those with A, B, or O blood types.

A higher incidence of susceptibility to DENV infections is seen in adults. Antibodies specific to the serotype are generated after infection in the serum against the same serotype, which lasts for several years or a lifetime, where 2 months to 2 years of immunity is generated against heterogeneous serotypes [19]. One of the main causes of DHF/DSS is due to multiple DENV infections or secondary dengue infections where antibody-dependent enhancement (ADE) may play a crucial role [20]. Additionally, infants who received maternal antibodies are more susceptible to DHF/DSS than those who have not received maternal antibodies upon infection. Patients with comorbidities like asthma, sickle cell anemia, and diabetes are more likely to have the risk of complications due to severe dengue [21]. Inheritance, ethnicity, blood type, and human leucocyte antigen (HLA) are various factors that are associated with disease susceptibility. For instance, individuals with A, B, and O blood types are less susceptible than AB blood type [22].

6. Role of Aedes mosquito as vector in dengue infection

Aedes aegypti and to a lesser extent Aedes albopictus are the two prime vectors which are responsible for spread of dengue virus infection. The distinct morphological features of Aedes ageypti are white scales on the dorsal surface following the thorax region and a single, thick white stripe on the body’s dorsum. It has a holometabolous life cycle, which consists of four stages: the egg, larva, pupa, and adult, having a life span of 2–5 weeks. They typically bite in the morning or evening during the day [23].

The mosquito picks up the virus while having a blood meal from an infected person; the virus then infects its midgut cells. The viral incubation period is 7–14 days within the mosquito body the it reaches its salivary glands so that it could infect the next person it bites. The saliva of mosquitoes contains several anti-hemostatic molecules that have anticoagulant and vasodilatory properties. Apoptosis and the inhibition of the generation of proinflammatory cytokines are two ways that salivary components regulate the proliferation of antigen-specific CD4+ T cells [24].

7. Impact of climate variables on vector ecology and dengue epidemiology

Climatic changes due to global warming, like increases in temperature, altered rainfall patterns, and heightened humidity, including the El Nino phenomenon in 2023 significantly influence dengue fever dynamics. Temperature variation accelerates mosquito development and mortality rates, thereby affecting the distribution, abundance, seasonal length, behavior of the Aedes mosquitoes and the virus incubation period in vectors [25], which facilitates the search for new hosts [26]. Shifts in mosquito behavior, such as increased daytime biting in warmer temperatures, challenge traditional nighttime vector control strategies like mosquito nets. Coupled with increased global trade and travel, allows dengue fever to spread to previously unaffected areas [27]. The complex interplay between climatic factors and mosquito ecology directly impacts the transmission dynamics of dengue fever [28]. These are compounded by a weakened health system, post-COVID-19, and high population movement, which have enhanced the dengue cases [29].

Humidity plays a vital role in the survival and dispersal of Aedes mosquitoes. Elevated humidity levels extend the lifespan of adult mosquitoes and enhance their ability to locate hosts through olfactory cues. Warmer temperatures and altered precipitation patterns prolong the mosquito active season leading to extended dengue season [30]. Furthermore, the expansion of Aedes mosquito populations into cooler or previously unsuitable habitats exposes new populations to the virus.

Poorly planned urbanization with inadequate sanitation, water storage practices, and waste management create favorable environments for dengue vector proliferation [27, 31]. Alterations in precipitation patterns such as intensified or untimely rainfall, create additional breeding grounds for vectors, prolonging dengue seasonal presence in endemic areas [26]. Additionally, the proliferation of Aedes mosquitoes in densely populated areas in urban environments exacerbates the risk of dengue outbreaks [32].

These climatic changes exert selection pressure on vectors and pathogens, triggering genetic adaptations that enhance survival and transmission capabilities, leading to alterations in their geographical distribution and the emergence of novel strains [33]. Studies employing machine learning-based models have predicted current and future mosquito abundances based on climatic factors (Figure 2) [34].

Figure 2.

Impact of climatic variables in vector dynamics and disease transmission.

8. Assessment of the association of climatic variables with dengue transmission dynamics

Researchers have extensively gathered data on dengue cases, climatic factors, and other relevant parameters from reliable sources such as public health databases, meteorological stations, satellite data, and local health departments to understand the relationship between climatic variables and dengue transmission. This data has facilitated the development of numerous statistical analyses and models over the past few years [31]. In addition to climatic conditions, factors such as vector abundance, human behavior, and socioeconomic conditions influence dengue transmission dynamics. Still, critical research gaps are hindering the development of predictive models and early warning systems for change in dengue dynamics. Addressing these gaps requires a deeper understanding of the complex interactions between climate variables and the integration of non-climatic drivers like urbanization, human mobility, and the evolutionary responses of vectors and pathogens. Bridging these gaps is crucial for enhancing the accuracy of predictive models and improving preparedness for changing disease transmission dynamics in a rapidly evolving climate [33].

Lei Xu et al. in a study developed an ecologically based model to predict dengue outbreaks in Guangzhou, China. They used data from the first 8 years (2005–2012) to build the model and tested its predictive capabilities during extensive outbreaks in 2013–2015. Structural equation modeling (SEM) was utilized to predict direct and indirect effects of variables such as rainfall and temperature, which influence mosquito abundance and dengue transmission rates [35]. A predictive link between climate and seasonal dengue was established by utilizing the generalized additive model of mosquito dynamics with mosquito surveillance records from 2005 to 2015 and a susceptible-infected-recovered (SIR) model in China [36]. Predictive models indicate that climate change will expand the areas with ideal temperatures for Aedes mosquitoes, increasing the number of regions at risk for dengue in the future [37]. Environmental factors such as altitude, temperature and rainfall are critical determinants of mosquito habitats, affecting reproduction and virus replication within mosquitoes [38, 39]. Studies have shown a positive correlation between high temperatures and lower dengue risk, while severe rainfall can increase dengue incidence [40, 41].

Xu Z et al. reviewed various modeling approaches, differentiating between mechanistic and correlative models. Based on detailed biological and ecological processes mechanistic models, simulate how dengue spreads in response to climate changes. Correlative models, which rely on statistical relationships between environmental variables and dengue incidence, identify associations without capturing the biological processes. Understanding the strengths and limitations of each approach is essential for accurate predictions of dengue’s future burden [42]. A study in southern Taiwan utilized a distributed lag nonlinear model and Markov random fields to identify the significant relationship between climatic variables like minimum temperature and extreme daily rainfall with dengue incidence. Including spatial information, the model predicted the spatiotemporal patterns of dengue fever [43]. Identifying the links between climatic, non-climatic, and socioeconomic factors with dengue incidence has allowed researchers to understand the spatial distribution of dengue and identify high-risk populations [44, 45].

9. Impact of environmental factors on dengue viral genome

Understanding how evolutionary responses within pathogen populations such as heightened resistance, opportunistic reactions, and the development of dominant variations from highly diverse genetic backgrounds and their subsequent worldwide dispersal are impacted by climate change is crucial. It is necessary to specifically describe how climatic change may affect the evolutionary drivers of certain strains or clonal groups [46]. Understanding how the mutual interaction of disease transmission and viral evolutionary dynamics impacts dengue epidemiology is crucial [47]. The co-circulation of four distinct DENV serotypes in the ecological setting of globalization, travel, climate change, urbanization, and growing the geographical distribution of the Ae. aegypti and Ae. albopictus vectors are contributing to the significant morbidity and mortality burden caused by dengue virus (DENV), which is seeing an increase around the globe [48].

Variations in genotypes, serotypes, and lineages’ genetic makeup have a significant role in determining the virulence, epidemic potential, and differences in viral fitness. Similar diversity variations, such as significant interepidemic reductions in dengue genetic diversity consistent with population bottlenecks that could significantly affect DENV evolutionary dynamics, are connected with epidemiologic dynamics [49]. The natural switch between invertebrate and vertebrate hosts, which places distinct selective pressures on the virus population, is a major contributor to DENV genetic variation [50]. Despite the severe purifying selection present in their genomes, DENV can adapt to different habitats. Their evolution and genetic diversity have been influenced by diverse groups of mosquito vector species in sylvatic cycles in Africa and Asia [51]. They have mostly been brought by humans through global transportation networks to different regions of the world. Their interactions with new mosquito hosts over the years have played a major role in their evolution in new regions having different environments.

The degree of intra-species variety is dynamic and subject to change over time in response to selective factors that may cause population bottlenecks in the viral population. This ultimately led to a loss of neurotropism and pathogenicity by limiting the virus’s capacity to adapt to new environments. Research has indicated that strains with quasispecies diversity that is either much higher or lower than wildtype are generally less fit. Arbovirus genome diversity is particularly intriguing since these viruses must adapt to exist in at least two very distinct environments: vertebrate hosts and arthropod vectors. Widespread vertebrate hosts and mosquito vectors are susceptible to infection by arboviruses, necessitating a flexible evolutionary approach that would profit from a high mutation rate [52]. In addition, this work discovered 112 mosquito genes displaying significant indications of local environmental adaptation linked to several topo-climate parameters using different landscape genomics techniques, all of which eliminate the confounding effects of shared ancestry on relationships between genetic and environmental variation. Certain genomic areas are subject to selective sweep and recent positive selection, as seen by the impacts of heat-shock proteins, which are known to aid in climate adaptation [53]. Thus, it is evident that Aedes’s genomic adaptability and evolution are linked to environmental conditions, which in turn exert selective pressure on the dengue genome, leading to variations in dengue genomes with differing propensity for epidemics. A study suggested that the path of adaptation is shaped by an ongoing influx of a high burden of deleterious mutations, which balances the impact of uncommon, host-specific beneficial mutations. Advantageous mutations cluster to certain areas of the genome and preferentially map to intrinsically disordered domains in the viral proteome. These adaptive alleles with redundant phenotypes could help DENV adapt to a particular host. This evolutionary constraint replicates patterns found in both DENV and Zika strains, suggesting that it encapsulates the fundamental biological and physicochemical limitations influencing the long-term evolution of viruses [54].

The increased risk of the introduction of novel viruses will arise from changes in international transportation brought about by the growth of human and animal trade across various locations. Global climate change, including global warming, either directly or indirectly, will have an impact on the epidemiology and evolution of DENVs. Genetic diversity will be impacted by changes in the ecology of the viruses that come with climate change-related environmental changes, such as exposure to novel vertebrates and mosquito hosts [55]. These changes will also have an impact on purifying selection of viral genome.

10. Public health measures to be practiced for combating dengue in the context of climate change

As Dengue fever is one of the major causes of public health concern, the World Health Organization (WHO) along with many countries program managers and regions has developed and published “Global Strategies for Dengue Prevention and Control” in 2012. They have also worked in collaboration with many dengue-endemic countries for dengue prevention and control [56]. The strategies published were built upon five key technical components:

1. Diagnosis and case management: Early Diagnosis and timely reporting are vital for activating outbreak control measures and clinical management practices such as effective supportive care (such as fluid replacement). Training of all clinical staff involved and well-organized management protocols across primary and secondary care facilities, which can reduce the mortality due to dengue [56]. Dengue fever is usually managed with supportive care, focuses on relieving symptoms and maintaining fluid balance to prevent dehydration. Patients with mild dengue fever may be managed at home, while those with more severe signs and symptoms require hospitalization. Dengue fever can cause plasma leakage and fluid loss, leading to dehydration and leading to life-threatening complications such as dengue shock syndrome. Monitoring fluid balance and hematocrit levels (a measure of blood concentration) is essential for assessing the severity of dengue illness and guiding fluid management [57, 58]. Point of care diagnosis would help in early diagnosis and

2. Integrated surveillance and outbreak preparedness: Epidemic response, risk assessment, program guidance and program evaluation rely on the information obtained from surveillance. A sustained integrated surveillance system encompasses both epidemiological and entomological aspects and it is essential for regular monitoring of endemic areas during interepidemic periods. These surveillance systems should be integrated into our national information systems and risk stratification maps developed by Member States can aid in this endeavor [59]. The Dengue Integrated Surveillance System is active in numerous countries affected by dengue fever. These countries actively monitor and collect data to implement guided control measures and evaluate the effectiveness of dengue prevention and control programs.

3. Sustainable vector control: Sustainable vector control is crucial for preventing and controlling dengue cases and outbreaks. Effective measures within an integrated vector management framework are necessary, addressing urban complexity, sanitation, water supply, solid waste management, and community participation. Desired disease reduction can only be achieved if public health threats are early detected, coupled with rapid and effective responses. This involves eliminating breeding sites by modifying environments to remove potential breeding grounds and ensuring proper drainage to prevent water accumulation. Biological control methods, such as introducing larvivorous fish like Gambusia affinis or Poecilia reticulata [60]. Other eco-friendly approaches include using Bacillus thuringiensis israelensis (BTI) bacterial larvicide [61], genetically modified mosquitoes, Wolbachia-infected Aedes, [59, 62, 63] and lethal Ovitrap units [64]. While chemical insecticides can be applied through fogging or residual spraying, careful management is necessary to prevent resistance. Public awareness campaigns are also vital, educating communities on preventive measures and encouraging participation in source reduction activities and personal protective measures like insect repellents and long-sleeved clothing.

4. Future vaccine implementation: The availability of a safe, efficacious, and cost-effective vaccine is of utmost need for dengue prevention. Significant progress has been made in vaccine development, with three tetravalent live-attenuated vaccines undergoing phase II and phase III clinical trials and three other vaccine candidates at earlier stages of clinical development [65, 66]. The first dengue vaccine to be licensed is Dengvaxia® CYD-TDV. CYD-TDV is a live recombinant tetravalent dengue vaccine created by Sanofi Pasteur. The vaccine efficacy was different in seropositive and seronegative individuals, and an increased risk of hospitalization was observed in seronegative vaccine [67, 68]. Further studies are required in search of effective vaccine candidates. Vaccination strategies may prioritize high-risk populations, such as individuals living in dengue-endemic areas or those at increased risk of severe disease. After the introduction of vaccination, surveillance systems are established to monitor vaccine coverage, adverse events following immunization (AEFI), and the impact of vaccination on dengue transmission and disease burden. This data helps to understand the success of the introduction of vaccination in the schedule.

5. Basic, operational, and implementation research: Priority should be given to surveillance research on insecticide resistance, integrating vector control and vaccination, through mathematical models and field studies. Research should aim to improve the efficacy, cost-effectiveness, sustainability, and scalability of existing and promising new control methods. This includes the development of new diagnostic tools, optimizing vector control strategies and basic research into dengue infections to identify drug targets and develop patient management strategies (Figure 3).

Figure 3.

Planned strategies for controlling Dengue vectors for implementation.

Advocacy, Resource Mobilization, Partnership, Coordination, and Collaboration, these factors are essential for the successful implementation of the global strategy. The impact of climate change on dengue vector ecology and dynamics underscores the urgent need for proactive public health interventions and climate adaptation strategies. By understanding the complex interactions between climate variables, mosquito ecology, and disease transmission, stakeholders can develop targeted interventions to mitigate the spread of dengue fever and protect vulnerable populations from its devastating effects. Collaboration between public health agencies, policymakers, and communities is essential to combating the emerging threat of climate-driven dengue transmission in the face of a changing climate.

11. Evaluation of adaptive measures for communities vulnerable to dengue transmission under changing climate conditions

Firstly, an assessment of current and future climatic conditions in the region is required which includes temperature, precipitation patterns, and other climatic variables that influence mosquito habitat suitability and dengue transmission. Then comes the identification of vulnerable populations based on population density, urbanization levels, mosquito breeding sites, socioeconomic conditions, access to healthcare facilities, and efficiency of existing vector control measures [69].

Successful implementation of adaptive strategies relies on community involvement and participation. Assessments should evaluate the awareness and involvement of local populations, as well as understand the perspectives, concerns, and priorities of stakeholders and relevant authorities regarding dengue prevention and climate change. Collaboration with community leaders, health officials, educators, and local organizations is necessary to redesign or implement existing preventive measures effectively. The effectiveness of preventive measures can only be seen if community-based initiatives raise awareness and promote behavior change such as promoting sustainable water management practices, solid waste management, and urban planning initiatives that reduce mosquito breeding habitats.

Partnership for Dengue Control (PDC) is a collaborative initiative that includes a diverse group of experts who work on the global issue of dengue prevention and control [70]. An active surveillance system in place monitoring dengue cases, mosquito populations, and environmental conditions can make early warnings about future outbreaks. This can help prevent and prepare for future outbreaks efficiently. It can also help improve healthcare infrastructure such as healthcare facilities, laboratory services, access to essential medicines and supplies, and capacity-building for healthcare workers to manage dengue cases effectively [71]. Evaluations should examine the informed decision-making for the development and implementation of adaptive plans based on the available resources. Ensure that adaptation strategies are integrated into broader climate change variation and public health planning processes at the local, national, and regional levels [72].

The effectiveness of the adaptive measures can be judged based on indicators such as dengue incidence rates, mosquito abundance, healthcare utilization rates, community participation levels, and changes in socioeconomic conditions over time. Regularly upgradation of adaptation plans and strategies in response to changing climate conditions, new scientific advances, and evolving communities is needed.

12. Future research directions and policy interventions to curb the dengue menace in the context with global warming

After reviewing the strengths and weaknesses of current research, many knowledge gaps have been identified, which require extensive future research and studies. These include exploring microclimatic parameters such as incorporating demographic, travel, and socioeconomic aspects, investigating climatic conditions in different geographical locations, identifying the locally important climatic factor that affects dengue outbreak, utilizing vector density data, and integrating vaccination drives into predictive models. In the context of climate change, forecasting the future incidence of dengue fever can help public health professionals and governments in the timely implementation of preventive measures to mitigate its impact [42].

Though some of the vaccine candidates are under clinical trial, only one vaccine, dengvaxia got FDA approval. The World Health Organization Strategic Advisory Group of Experts on Immunization (SAGE) recommended the use of dengvaxia in already dengue-infected individuals, restricting mass immunization. Hence, there is a need for a competent vaccine against dengue, which could be a potential area of research [73]. In the absence of a vaccine, the search for antiviral drugs continues to be important. Though a substantial number of compounds have been identified as having antiviral activity against dengue in vitro conditions, detailed studies of these compounds in animal models and humans are missing. Most of the antiviral for dengue virus target E protein, C protein, NS2B/NS3 protease, NS5 RNA-dependent RNA polymerase (RdRp), NS5 methyltransferase (MTase), NS4A, and NS4B [68]. Some of the antivirals are under clinical trials like celgosivir (causes misfolding and accumulation of E and NS1 protein in ER) [74, 75], lovastatin (effect on viral assembly) [76], and AT-752 (guanosine analog prodrug, inhibits NS5-RNA-dependent RNA polymerase activity) [77, 78], detailed research and clinical trials are required for clinical translation of these compounds as antiviral therapy. More efforts are required to understand the efficacy and long-term safety of the antivirals. By understanding the pathophysiology of dengue-associated hemophagocytic lymphohistiocytosis (HLH) and identifying novel therapeutic interventions and biomarkers, healthcare providers can adapt treatment strategies more effectively, leading to improved outcomes and better management of this potentially life-threatening complication [79].

Policy interventions that need to be incorporated into our system are “Public Awareness Campaigns” to educate communities about the risks of dengue and its prevention measures and encourage them to engage in early health-seeking behavior to avoid complications. The strengthening of “Vector Control Programs” is very important, which restricts the mosquito populations and prevents dengue outbreaks. Mosquito breeding grounds can be reduced by updating policies on waste management and urban planning. Thirdly, governments and international organizations should encourage research on dengue treatments, vaccines, and control strategies by providing support and funding. By prioritizing these research and policy initiatives, governments and health organizations can effectively combat the dengue menace in the face of global warming.