Rising Dengue Fever Cases Carry One Health Implications

During the past 2 decades, dengue fever cases have increased 10-fold, with more than 5 million total cases worldwide in 2023.¹ Cases are being reported in a wider geographic range, forcing regions with little to no experience in combating dengue to contend with outbreaks. The rise in dengue cases and escalating public health burden have drawn broad attention to a disease that may no longer be considered “tropical,” due to climate change.

Globally, dengue is the most widespread vector-borne disease, and the World Health Organization estimates that 3.9 billion people are at risk of infection.² In addition to being widespread, dengue can cause severe health outcomes. Most people who contract dengue do not have symptoms; for those who do, the most common are headaches, body aches, high fever, rash, and nausea.² About 5% of patients go on to develop what is known as severe dengue or dengue hemorrhagic fever, which causes bleeding and endothelial leak.³ This is more likely to occur in patients who have previously been infected with one dengue serotype and are then reinfected with another. The overall case fatality rate for dengue is difficult to assess due to variation in case definitions and reporting, but generally is less than 1% with treatment.¹ In 2023, there were over 5000 dengue-related deaths.¹

This alarming rise in one of the most concerning vector-borne diseases is attributable to a few key factors, several of which are interconnected. It is easiest to understand these trends through the lens of One Health, a framework that considers environmental, ecological, and human health as an integrated whole.⁴ In other words, the health of the planet and all living systems directly influences threats to human health, and vice versa. The One Health framework is especially pertinent when considering vectorborne diseases, as insect behavior and evolution add an additional layer of complexity to disease dynamics and ecology.

WEATHER AND CLIMATE CHANGE

Mosquito eggs are laid and hatch in standing water, so rainfall is a major determinant of when and where mosquitoes breed. Part of the spike in dengue fever cases in 2023, particularly in parts of South America, can be attributed to the El Niño phenomenon, which brings longer rainy seasons to some regions, allowing mosquitoes to breed for longer periods.⁵ The National Oceanic and Atmospheric Administration declared the arrival of El Niño in June 2023.⁶ However, experts believe that this is just 1 of several factors contributing to the increase in cases. A much broader trend is responsible for a large part of the uptick: our warming climate. As temperatures rise, the mosquitoes that spread dengue (mainly Aedes aegypti and Aedes albopictus) are expanding into new geographic ranges and can breed for longer periods in regions where they already exist. The current outbreak of dengue in Bangladesh is a clear case study of this phenomenon. In 2023, 1705 dengue-related deaths were recorded, more than triple the number for 2022.⁷ Unusually high rainfall and hot temperatures have increased the mosquito population in Bangladesh and led to an earlier arrival of dengue cases. This outbreak has pushed Bangladesh’s health systems to their limits, as a disease typically concentrated in the city of Dhaka has spread countrywide. Although climate change is leading to a surge of dengue cases in places like Bangladesh and Peru, its impact on mosquito habitat range is complex—some regions can expect fewer dengue cases.

Extremely high temperatures are detrimental to mosquito survival; the optimal temperature range for development of Aedes mosquitoes is 25 to 30 °C (77 to 86 °F), and optimal temperatures for dengue transmission are 20 to 26 °C (68 to 78.8 °F).⁸ Where temperatures are commonly above this level, and where rainfall is projected to decrease, it will be harder for Aedes mosquitoes to survive and transmit the virus. This means the regions in which dengue is common will change—current habitats may contract, whereas previously unsuitable habitats (eg, parts of Europe) will become warm and rainy enough to support Aedes mosquitoes.⁹ It is also essential to take stock of the knock-on effects of climate change; extreme weather events and changing patterns are leading to socioeconomic challenges and stressed health systems, whichlikely will impact the number of people affected by dengue and their access to care. Land use change and population movement also can increase the risk of dengue. Although dengue traditionally has been considered a primarily urban disease, recent research has suggested that rural cases may be growing. Proposed explanations include increased travel to urban areas, population growth, changing agricultural practices, and improved case reporting.10 Dengue cases also appear to rise in transitional environments where construction is occurring, as these environments often produce open mosquito breeding habitats.¹¹

INSECTICIDES & INTERVENTIONS

On top of climate and land use change, a major issue is that the insecticides that once controlled mosquito populations are now much less effective.¹² Mosquito populations have evolved resistance to many common pesticides, hindering one of the most historically reliable prevention strategies. Even if new pesticides are developed, it is impossible to outrun evolution forever—mosquitos have a short generation time, meaning populations can evolve rapidly. As such, it is essential to utilize pesticides sparingly to avoid resistance. Through an approach called integrated mosquito management, mosquito populations can be effectively curbed through removing habitats, using structural barriers, educating communities on safe practices, and using larvicides and insecticides where necessary.¹³

This more holistic method is widely employed and there is strong evidence for its effectiveness. However, just as mosquitoes can evolve resistance to pesticides, there is evidence that they have been adapting to evade structural and behavioral interventions as well—for instance, by biting during the day when bed nets do not provide protection.¹² Some researchers are now testing innovative strategies that harness advances in genetic engineering to reduce vector-borne illnesses. One of these approaches involves releasing genetically modified mosquitoes whose female offspring die and whose male offspring carry the same engineered gene. The male offspring will still be able to mate with females, in turn ensuring their female offspring also die. In this way, the trait is passed on to future generations, and the population of females declines.¹⁴

To combat malaria, efforts are underway to engineer and release mosquitoes that secrete antimicrobials that kill the malaria parasite—a similar approach with antivirals potentially could be developed for dengue.¹⁵ Another strategy is to release mosquitoes that are infected with Wolbachia, a harmless bacteria that competes with dengue and other viruses to make insects less likely to carry these harmful pathogens—this strategy has shown promising results in Colombia and other test locations.¹⁶ Of course, these strategies are unlikely to solve the issue forever, as pathogens could potentially adapt to infect genetically modified mosquitoes or outcompete Wolbachia. It is important to consider mosquitoes, and even the pathogens they carry, as intrinsic parts of their ecosystems. Vectors and diseases are not “separate” from their environments; treating them as such will only lead to ineffective interventions. Although there are no perfect solutions from the prevention perspective, a more holistic outlook is better than one that treats vectorborne diseases as a discrete problem with no ecological or evolutionary context.

PREPAREDNESS AND TREATMENTS
Given the severe threat posed by dengue, identifying and treating cases is critically important. Unfortunately, weak surveillance systems have led to delayed reporting and missed cases, which have contributed to more severe dengue outcomes.¹ Dengue is difficult to track, as most primary infections are asymptomatic and unlikely to be reported. This means it can be hard to detect an uptick in cases in a region and direct resources there until the outbreak is well underway. As such, building sustainable support for surveillance and intervention programs in resource-limited areas will be essential to improving health outcomes. Although catching cases early is important, there are no specialized antivirals for dengue fever; rather, symptoms are treated.¹⁷ Vaccines for dengue historically have been challenging to develop, given that the dengue virus attaches to immune cells.

There are 2 vaccines for dengue, but neither is as effective as would be ideal. Dengvaxia has a 60% efficacy rate against symptomatic dengue, but is only safe for people who have contracted dengue before. Qdenga has a 73% efficacy rate and is safe for people who have not had dengue before, but it has lower efficacy against some serotypes.¹⁸ These challenges in vaccination and treatment further highlight the gravity of the threat posed by dengue. Given the alarming spike in dengue fever cases and our relative lack of medical countermeasures, innovative prevention and mitigation strategies are more important than ever.

References

1. Dengue—global situation. World Health Organization. December 21, 2023. Accessed January 15, 2024. https://www.who.int/emergencies/disease-outbreak-news/item/2023-DON498
2. Dengue and severe dengue. World Health Organization. March 17, 2023. Accessed January 15, 2024. https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue
3. Smith DS. Dengue. Medscape. November 16, 2022. Accessed January 15, 2024. https://emedicine.medscape.com/article/215840-overview?form=fpf
4. One Health. World Health Organization. September 21, 2017. Accessed January 15, 2024. https://www.who.int/news-room/questions-and-answers/item/one-health
5. Aquino M. El Nino rains intensify record dengue outbreak in Peru. Reuters.June 18, 2023. https://www.reuters.com/world/americas/el-nino-rains-intensify-record-dengue-outbreak-peru-2023-06-08/
6. NOAA declares the arrival of El Nino. National Weather Service. June 8, 2023. Accessed January 15, 2024. https://www.weather.gov/news/230706-ElNino
7. Begum T. ‘Deadliest outbreak ever seen’: climate crisis fuels Bangladesh’s worst dengue epidemic. The Guardian. January 18, 2024. Accessed January 21, 2024. https://www.theguardian.com/global-development/2024/jan/18/bangladesh-deadliest-dengue-outbreak-climate-crisis-fuels-virus-global-spread
8. Liu Z, Zhang Q, Li L, et al. The effect of temperature on dengue virus transmission by Aedes mosquitoes. Front Cell Infect Microbiol. 2023;13:1242173. doi:10.3389/fcimb.2023.1242173
9. Khormi HM, Kumar L. Climate change and the potential global distribution of Aedes aegypti: spatial modelling using GIS and CLIMEX. Geospat Health. 2014;8(2):405-415. doi:10.4081/gh.2014.29
10. Man O, Kraay A, Thomas R, et al. Characterizing dengue transmission in rural areas: a systematic review. PLoS Negl Trop Dis. 2023;17(6):e0011333. doi:10.1371/journal.pntd.0011333
11. Gibb R, Colón-González FJ, Lan PT, et al. Interactions between climate change, urban infrastructure and mobility are driving dengue emergence in Vietnam. Nat Commun. 2023;14(1):8179. doi:10.1038/s41467-023-43954-0
12. Nolen S. Mosquitoes are a growing public health threat, reversing years of progress. New York Times. September 29, 2023. Accessed January 21, 2024 https://www.nytimes.com/2023/09/29/health/mosquitoes-malaria-disease-climate-change.html
13. Integrated mosquito management. CDC. Updated October 27, 2023. Accessed January 20, 2024. https://www.cdc.gov/mosquitoes/mosquito-control/professionals/integrated-mosquito-management.html
14. Waltz E. First genetically modified mosquitoes released in the United States. Nature. May 3, 2021. Accessed January 21, 2024. https://www.nature.com/articles/d41586-021-01186-6
15. Jones S. How genetically modified mosquitoes could eradicate malaria. Nature. June 28, 2023. Accessed January 21, 2024. https://www.nature.com/articles/d41586-023-02051-4
16. Lenharo M. Dengue rates drop after release of modified mosquitoes in Colombia. Nature. October 27, 2023. Accessed January 21, 2024. https://www.nature.com/articles/d41586-023-03346-2
17. Dengue treatment. CDC. Updated May 3, 2019. Accessed January 21, 2024. https://www.cdc.gov/dengue/healthcare-providers/treatment.html
18. Lenharo M. Dengue is spreading. Can new vaccines and antivirals halt its rise? Nature. November 7, 2023. Accessed January 21, 2024 https://www.nature.com/articles/d41586-023-03453-0