ABSTRACT

Dengue is an arbovirus infection whose etiologic agent is transmitted by the Aedes aegypti mosquito. Since the early 1980s, when the circulation of the dengue virus (DENV) was confirmed in Brazil, the disease has become a growing multifactorial public health problem. This article presented the main factors that have contributed to the frequent dengue epidemics in recent years, such as the behavior of the vector, climate change, and social, political, and economic aspects. The intersection between these different factors in the dynamics of the disease is highlighted, including the increase in the mosquito population due to higher temperatures and rainy periods, as well as the influence of socioeconomic conditions on the incidence of dengue. Some mosquito control strategies are also addressed, including the use of innovative technologies such as drones and the Wolbachia bacterium, as well as the hope represented by the dengue vaccine. Nevertheless, the need for integrated and effective public policies to reduce social inequalities and the impacts of climate change on the spread of dengue is emphasized.

Keywords:
Arbovirus infections; Vectors; Climate change; Public policies; Control

INTRODUCTION

The term “arbovirus” is derived from Arthropod-borne virus and refers to a diverse group of viruses, typically spherical in shape, with RNA as their genetic material¹1. Davis LE, Beckham JD, Tyler KL. North American encephalitic arboviruses. Neurol Clin 2008; 26(3): 727-57. https://doi.org/10.1016/j.ncl.2008.03.012
https://doi.org/10.1016/j.ncl.2008.03.01... . Arboviruses primarily circulate in enzootic cycles within tropical or temperate regions, where they are transmitted to wild vertebrate animals through the bites of infected hematophagous arthropods, particularly mosquitoes and ticks²2. Lopes N, Nozawa C, Linhares REC. Características gerais e epidemiologia dos arbovírus emergentes no Brasil. Rev Pan-Amaz Saúde 2014; 5(3): 55-64. https://doi.org/10.5123/s2176-62232014000300007
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However, due to human activities, some arboviruses have adapted to environmental changes and initiated an urban transmission cycle, with humans as the vertebrate hosts and urban mosquitoes as vectors³3. Donalísio MR, Freitas ARR, Von Zuben APB. Arboviruses emerging in Brazil: challenges for clinic and implications for public health. Rev Saude Publica 2017; 51: 30. https://10.1590/S1518-8787.2017051006889
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https://doi.org/10.1016/j.jcv.2012.07.00... . While significant arboviruses such as Zika (ZIKV) and chikungunya (CHIKV) are transmitted to humans in urban settings, the dengue virus (DENV), a member of the Flaviviridae family and Orthoflavivirus genus, has the most significant impact on public health due to its high morbidity and mortality⁵5. Lima-Camara TN. Emerging arboviruses and public health challenges in Brazil. Rev Saúde Púlica 2016; 50: 36. https://doi.org/10.1590/S1518-8787.2016050006791
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The dengue virus has four antigenically distinct serotypes, known as DENV-1, DENV-2, DENV-3, and DENV-4⁶6. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol 2010; 8(12 Suppl): S7-16. https://doi.org/10.1038/nrmicro2460
https://doi.org/10.1038/nrmicro2460... . Globally, dengue is considered endemic in over 100 tropical and subtropical countries across the Americas, Africa, Asia, the Middle East, the Pacific Islands, and the Western Pacific Region, with approximately 4 billion people living in these at-risk areas⁷7. Center for Disease Control and Prevention. Areas with risk of dengue [Internet]. 2024 [cited on Apr 24, 2024]. Available at: https://www.cdc.gov/dengue/areas-with-risk/index.html
https://www.cdc.gov/dengue/areas-with-ri... . In 2013, a study estimated that there were roughly 390 million annual DENV infections worldwide, encompassing both symptomatic and asymptomatic cases⁸8. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature 2013; 496(7446): 504-7. https://doi.org/10.1038/nature12060
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In Brazil, although there were some reports of dengue cases in São Paulo and Rio de Janeiro at the beginning of the 20^th century, it was only in 1981/1982, following an epidemic in the city of Boa Vista, in the state of Roraima, that the clinical and laboratory diagnosis of the disease was confirmed, including the isolation of serotypes 1 and 4 of the virus⁹9. Osanai CH, Rosa AP, Tang AT, Amaral RS, Passos AD, Tauil PL. Surto de dengue em Boa Vista, Roraima. Relatório preliminar. Rev Inst Med Trop São Paulo 1983; 25(1): 53-4.. However, the epidemic in Boa Vista was successfully controlled⁹9. Osanai CH, Rosa AP, Tang AT, Amaral RS, Passos AD, Tauil PL. Surto de dengue em Boa Vista, Roraima. Relatório preliminar. Rev Inst Med Trop São Paulo 1983; 25(1): 53-4., and the DENV-1 and DENV-4 serotypes did not spread to other areas of the country.

After a few years of epidemiological silence, the DENV-1 serotype was isolated again in 1986, this time in the municipality of Nova Iguaçu, Rio de Janeiro, and it quickly spread to nearby cities and states¹⁰10. Schatzmayr HG, Nogueira RM, Travassos da Rosa AP. An outbreak of dengue virus at Rio de Janeiro--1986. Mem Inst Oswaldo Cruz 1986; 81(2): 245-6. https://doi.org/10.1590/s0074-02761986000200019
https://doi.org/10.1590/s0074-0276198600... ,¹¹11. Nogueira RM, Miagostovich MP, de Filippis AM, Pereira MA, Schatzmayr HG. Dengue virus type 3 in Rio de Janeiro, Brazil. Mem Inst Oswaldo Cruz 2001; 96(7): 925-6. https://doi.org/10.1590/S0074-02762001000700007
https://doi.org/10.1590/S0074-0276200100... . Four years later, in 1990, the DENV-2 serotype was isolated for the first time in the country, also in Rio de Janeiro, in the municipality of Niterói¹²12. Nogueira RM, Miagostovich MP, Lampe E, Schatzmayr HG. Isolation of dengue virus type 2 in Rio de Janeiro. Mem Inst Oswaldo Cruz 1990; 85(2): 253. https://doi.org/10.1590/S0074-02761990000200022
https://doi.org/10.1590/S0074-0276199000... . At that time, there was a significant increase in severe cases of the disease, along with the first recorded deaths related to previous infections¹³13. Nogueira RMR, Araújo JMG, Schatzmayr HG. Dengue viruses in Brazil, 1986-2006. Rev Panam Salud Publica 2007; 22(5): 358-63. https://doi.org/10.1590/S1020-49892007001000009
https://doi.org/10.1590/S1020-4989200700... . The circulation of DENV-3 in Brazil was first detected in late 2000, once again in Nova Iguaçu, Rio de Janeiro¹²12. Nogueira RM, Miagostovich MP, Lampe E, Schatzmayr HG. Isolation of dengue virus type 2 in Rio de Janeiro. Mem Inst Oswaldo Cruz 1990; 85(2): 253. https://doi.org/10.1590/S0074-02761990000200022
https://doi.org/10.1590/S0074-0276199000... ,¹⁴14. Nogueira RMR, Schatzmayr HG, de Filippis AMB, Santos FB, Cunha RV, Coelho JO, et al. Dengue virus type 3, Brazil, 2002. Emerg Infect Dis 2005; 11(9): 1376-81. https://doi.org/10.3201/eid1109.041043
https://doi.org/10.3201/eid1109.041043... . In 2010, the DENV-4 serotype was reintroduced in northern Brazil, detected initially in the state of Roraima¹⁵15. Temporão JG, Penna GO, Carmo EH, Coelho GE, Azevedo RSS, Nunes MRT, et al. Dengue virus serotype 4, Roraima State, Brazil. Emerg Infect Dis 2011; 17(5): 938-40. https://doi.org/10.3201/eid1705.101681
https://doi.org/10.3201/eid1705.101681... , and later isolated in Rio de Janeiro¹⁶16. Nogueira RMR, Eppinghaus ALF. Dengue virus type 4 arrives in the state of Rio de Janeiro: a challenge for epidemiological surveillance and control. Mem Inst Oswaldo Cruz 2011; 106(3): 255-6. https://doi.org/10.1590/S0074-02762011000300001
https://doi.org/10.1590/S0074-0276201100... . Since then, all four dengue virus serotypes have been circulating in the country.

By the end of May 2024, Brazil had recorded over 5 million probable cases of dengue and more than 3,000 confirmed deaths from the disease¹⁷17. Centro de Operações de Emergência (COE). Informe semanal. Edição o 16, SE 01 a 21/2024. Indicadores de dengue (2024) [Internet]. 2024 [cited on Jun 07, 2024]. Available at: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/a/arboviroses/informe-semanal/informe-semanal-no-16.pdf
https://www.gov.br/saude/pt-br/assuntos/... . Out of the 27 Federative Units, 10 declared a state of emergency: Amapá, Federal District, Espírito Santo, Goiás, Minas Gerais, Paraná, Rio de Janeiro, Rio Grande do Sul, Santa Catarina, and São Paulo¹⁷17. Centro de Operações de Emergência (COE). Informe semanal. Edição o 16, SE 01 a 21/2024. Indicadores de dengue (2024) [Internet]. 2024 [cited on Jun 07, 2024]. Available at: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/a/arboviroses/informe-semanal/informe-semanal-no-16.pdf
https://www.gov.br/saude/pt-br/assuntos/... . This was undoubtedly the worst dengue epidemic in the country’s history, surpassing the more than 1.6 million cases recorded in 2015 and 2023¹⁸18. GOV.BR. Série histórica de casos prováveis de dengue (2000-2023) [Internet]. 2024 [cited on Apr 25, 2024]. Available at: https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/d/dengue/situacao-epidemiologica/serie-historica-casos-provaveis-de-dengue-2000-2023
https://www.gov.br/saude/pt-br/assuntos/... .

As a multifactorial disease, various factors related to the key elements of virus transmission may explain the significant surge in dengue cases observed in the country. Thus, a comprehensive approach that considers the interaction between humans, vectors, pathogens, and the environment is crucial for evaluating the epidemiology of this disease.

Aedes aegypti as a public health concern

Transmission of all dengue virus serotypes to humans occurs through the bite of infected female mosquitoes of the main vector: Aedes (Stegomyia) aegypti (Linnaeus, 1762), which is prevalent in Brazil and worldwide. This species is also associated with the transmission of ZIKV and CHIKV in several countries, including Brazil⁶6. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, et al. Dengue: a continuing global threat. Nat Rev Microbiol 2010; 8(12 Suppl): S7-16. https://doi.org/10.1038/nrmicro2460
https://doi.org/10.1038/nrmicro2460... .

Aedes aegypti is a mosquito native to the African continent. Originally, populations of this mosquito were generalists, utilizing a wide variety of containers as breeding sites and feeding on the blood of various animals, both human and non-human¹⁹19. MBride CS, Baier F, Omondi AB, Spitzer SA, Lutomiah J, Sang R, et al. Evolution of mosquito preference for humans linked to an odorant receptor. Nature 2014; 515(7526): 222-7. https://doi.org/10.1038/nature13964
https://doi.org/10.1038/nature13964... ,²⁰20. Xia S, Dweck HKM, Lutomiah J, Sang R, McBride CS, Rose NH, et al. Larval sites of the mosquito Aedes aegypti formosus in forest and domestic habitats in Africa and the potential association with oviposition evolution. Ecol Evol 2021; 11(22): 16327-43. https://doi.org/10.1002/ece3.8332
https://doi.org/10.1002/ece3.8332... . However, recent studies indicate that in the Sahel region of West Africa, some populations of this species have evolved to feed more frequently on human blood and use artificial containers for egg-laying²¹21. Rose NH, Badolo A, Sylla M, Akorli J, Otoo S, Gloria-Soria A, et al. Dating the origin and spread of specialization on human hosts in Aedes aegypti mosquitoes. Elife 2023; 12: e83524. https://doi.org/10.7554/eLife.83524
https://doi.org/10.7554/eLife.83524... . This domesticated form of the Aedes aegypti mosquito has since spread worldwide, particularly in tropical and subtropical regions²²22. Powell JR, Tabachnick WJ. History of domestication and spread of Aedes aegypti – a review. Mem Inst Oswaldo Cruz 2013;108 Suppl 1(Suppl 1): 11-7. https://doi.org/10.1590/0074-0276130395
https://doi.org/10.1590/0074-0276130395... . The spread across continents was facilitated by the mosquito eggs’ high resistance to desiccation, allowing them to remain quiescent for up to a year, which supports the passive dispersal of the species²³23. Reiter P, Sprenger D. The used tire trade: a mechanism for the worldwide dispersal of container breeding mosquitoes. J Am Mosq Control Assoc 1987; 3(3): 494-501. PMID: 2904963.,²⁴24. Reiter P. Aedes albopictus and the world trade in used tires, 1988-1995: the shape of things to come? J Am Mosq Control Assoc 1998; 14(1): 83-94..

In Brazil, the arrival of Aedes aegypti likely occurred during the colonial period, when people were brought from the African continent to be enslaved²⁵25. Consoli RAGB, Lourenço-De-Oliveira R. 1994. Principais mosquitos de importância sanitária no Brasil. Rio de Janeiro: Fiocruz; 1994.. By the early 20^th century, this mosquito had already become a significant concern for Brazilian public health, as it served as the primary vector in the urban transmission cycle of the yellow fever virus. During this time, the country was experiencing severe yellow fever epidemics, particularly in the state of Rio de Janeiro. In response, President Rodrigues Alves (1903–1906) appointed Oswaldo Cruz as head of the General Directorate of Public Health, tasking him with leading the first public campaign against urban yellow fever and Aedes aegypti²⁶26. Benchimol JL. Febre amarela e epidemias: configurações do problema ao longo do tempo. Revista NUPEM 2021; 13(29): 36-71. https://doi.org/10.33871/nupem.2021.13.29.36.71
https://doi.org/10.33871/nupem.2021.13.2... . Through a policy that included eliminating breeding sites, using larvicides and insecticides, and isolating patients, Oswaldo Cruz succeeded in reducing yellow fever cases in the state. However, the complete eradication of the mosquito was not achieved until 1958²⁶26. Benchimol JL. Febre amarela e epidemias: configurações do problema ao longo do tempo. Revista NUPEM 2021; 13(29): 36-71. https://doi.org/10.33871/nupem.2021.13.29.36.71
https://doi.org/10.33871/nupem.2021.13.2... .

Currently, the eradication of Aedes aegypti is highly unlikely, so efforts to mitigate dengue cases are focused on controlling the mosquito population, primarily by eliminating or properly managing containers that can hold water.

Dengue and Aedes aegypti

The occurrence of dengue epidemics in Brazil is linked to various factors, including high population density, uncontrolled urban growth, social inequality, and the competence and adaptability of the mosquito vector, among others²⁷27. Teixeira MG, Costa MCN, Barreto ML, Mota E. Dengue and dengue hemorrhagic fever epidemics in Brazil: what research is needed based on trends, surveillance, and control experiences? Cad Saude Publica 2005; 21(5): 1307-15. https://doi.org/10.1590/S0102-311X2005000500002
https://doi.org/10.1590/S0102-311X200500... . The near-constant presence of Aedes aegypti in urban environments poses a significant challenge for public health.

The development cycle of Aedes aegypti is holometabolous, encompassing aquatic stages of egg, larva, and pupa, followed by the terrestrial adult stage. Female Aedes aegypti typically lay their eggs in artificial containers with stagnant water, such as tires, plant pots, water tanks, cans, bottles, etc.²⁵25. Consoli RAGB, Lourenço-De-Oliveira R. 1994. Principais mosquitos de importância sanitária no Brasil. Rio de Janeiro: Fiocruz; 1994.,²⁸28. Tauil PL. Urbanização e ecologia do dengue. Cad Saúde Pública 2001; 17(suppl): S99-S102. https://doi.org/10.1590/S0102-311X2001000700018
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https://doi.org/10.1590/S0036-4665200200... . However, even in urbanized areas, immature forms of Aedes aegypti have been found in natural breeding sites like bromeliads, bamboo internodes, and tree holes³⁰30. Varejão JBM, Santos CB, Rezende HR, Bevilacqua LC, Falqueto A. Criadouros de Aedes (Stegomyia) aegypti (Linnaeus, 1762) em bromélias nativas na Cidade de Vitória, ES. Rev Soc Bras Med Trop 2005; 38(3): 238-40. https://doi.org/10.1590/S0037-86822005000300006
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31. Ceretti-Júnior W, Medeiros-Sousa AR, Multini LC, Urbinatti PR, Vendrami DP, Natal D, et al. Immature mosquitoes in bamboo internodes in municipal parks, city of São Paulo, Brazil. J Am Mosq Control Assoc 2014; 30(4): 268-74. https://10.2987/14-6403R.1
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https://doi.org/10.1590/S1518-8787.20160... , demonstrating the species’ plasticity and dominance in human-occupied environments.

The development time from egg to adult Aedes aegypti shortens as temperature increases³³33. Couret J, Dotson E, Benedict MQ. Temperature, larval diet, and density effects on development rate and survival of Aedes aegypti (Diptera: Culicidae). PLoS One 2014; 9(2): e87468. https://10.1371/journal.pone.0087468
https://doi.org/10.1371/journal.pone.008... . In the laboratory, it was observed that at 25°C, the average development time from egg to adult for this species was 8.86 days. However, a temperature increase of just two degrees to 27°C reduced this development time to 7.30 days³⁴34. Rueda LM, Patel KJ, Axtell RC, Stinner RE. Temperature-dependent development and survival rates of Culex quinquefasciatus and Aedes aegypti (Diptera: Culicidae). J Med Entomol 1990; 27(5): 892-8. https://doi.org/10.1093/jmedent/27.5.892
https://doi.org/10.1093/jmedent/27.5.892... . Temperature can also influence the Extrinsic Incubation Period (EIP) of the virus, which is the time between a female mosquito taking a blood meal and the arrival of the virus in her salivary glands³⁵35. Chaves LF. Climate change and the biology of insect vectors of human pathogens. In: Johnson SN, Jones TH, eds. Global climate change and terrestrial invertebrates. Chichester: Wiley Online Library; 2017. p. 126-47. https://doi.org/10.1002/9781119070894
https://doi.org/10.1002/9781119070894... . Laboratory studies have shown that the EIP for the DENV-2 serotype is shorter in Aedes aegypti females at temperatures between 32°C and 35°C³⁶36. Watts DM, Burke DS, Harrison BA, Whitmire RE, Nisalak A. Effect of temperature on the vector efficiency of Aedes aegypti for dengue 2 virus. Am J Trop Med Hyg 1987; 36(1): 143-52. https://doi.org/10.4269/ajtmh.1987.36.143
https://doi.org/10.4269/ajtmh.1987.36.14... , allowing the virus to reach the mosquito’s salivary glands more quickly. In another laboratory study, it was demonstrated that a 2°C increase in temperature could reduce the EIP for both DENV-2 and DENV-4 serotypes in Aedes aegypti females³⁷37. Rohani A, Wong YC, Zamre I, Lee HL, Zurainee MN. The effect of extrinsic incubation temperature on development of dengue serotype 2 and 4 viruses in Aedes aegypti (L.). Southeast Asian J Trop Med Public Health 2009; 40(5): 942-50. PMID: 19842378.. At 28°C, both serotypes were detectable in the females’ salivary glands nine days after the blood meal, but this EIP dropped to five days when the temperature was raised to 30°C³⁷37. Rohani A, Wong YC, Zamre I, Lee HL, Zurainee MN. The effect of extrinsic incubation temperature on development of dengue serotype 2 and 4 viruses in Aedes aegypti (L.). Southeast Asian J Trop Med Public Health 2009; 40(5): 942-50. PMID: 19842378..

Furthermore, the pronounced anthropophilia exhibited by this mosquito is intensified by gonotrophic discordance, which leads the female to feed multiple times within the same oviposition cycle. This behavior increases the likelihood of the mosquito becoming infected and subsequently transmitting the virus to humans³⁸38. Lima-Camara TN, Honório NA, Lourenço-de-Oliveira R. Parity and ovarian development of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in metropolitan Rio de Janeiro. J Vector Ecol 2007; 32(1): 34-40. https://doi.org/10.3376/1081-1710(2007)32[34:paodoa]2.0.co;2
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https://doi.org/10.1111/jvec.12354... . These bioecological traits of Aedes aegypti offer partial insights into the challenges faced in controlling this mosquito and, consequently, in reducing dengue cases in Brazil.

Climate change and other factors

It is undeniable that the world is experiencing climate change, particularly global warming, driven by human activities over the centuries. According to the Intergovernmental Panel on Climate Change (IPCC), the global surface temperature is now approximately 1.1°C higher than in pre-industrial times, and this warming is expected to reach 1.5°C between 2030 and 2052 if the current rate of temperature increase continues⁴⁰40. Painel Intergovernamental sobre Mudanças Climáticas (IPCC). AR6 Synthesis Report. Climate Change 2023 [Internet]. [cited on Apr 25, 2024]. Available at: https://www.ipcc.ch/report/ar6/syr/
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https://doi.org/10.1016/j.actatropica.20... and periods of rainfall⁴¹41. Miyazaki RD, Ribeiro ALM, Pignatti MG, Campelo Júnior JH, Pignati M. Monitoramento do mosquito Aedes aegypti (Linnaeus, 1762) (Diptera: Culicidae), por meio de ovitrampas no Campus da Universidade Federal de Mato Grosso, Cuiabá, Estado de Mato Grosso. Rev Soc Bras Med Trop 2009; 42(4): 392-97. https://doi.org/10.1590/S0037-86822009000400007
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https://doi.org/10.1016/j.actatropica.20... . Similarly, the incidence of dengue cases is higher during the hottest and rainiest months⁴³43. Heinisch MRS, Diaz-Quijano FA, Chiaravalloti-Neto F, Pancetti FGM, Coelho RR, Andrade PS, et al. Seasonal and spatial distribution of Aedes aegypti and Aedes albopictus in a municipal urban park in São Paulo, SP, Brazil. Acta Trop 2019; 189: 104-13. https://doi.org/10.1016/j.actatropica.2018.09.011
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https://doi.org/10.1093/trstmh/traa030... . Since temperature and rainfall influence the dynamics of the Aedes aegypti vector, and dengue is a disease closely tied to these climatic variables, it is expected that climate change, particularly global warming, is impacting the epidemiology of this disease both in Brazil and globally⁴⁸48. McMichael AJ, Woodruff RE. Climate change and infectious diseases. In: Mayer KH, Pizer HF, eds. The social ecology of infectious diseases. London: Elsevier Science & Technology Academic Press; 2008. p.378-407.,⁴⁹49. Viana DV, Ignotti E. A ocorrência da dengue e variações meteorológicas no Brasil: revisão sistemática. Rev Bras Epidemiol 2013; 16(2): 240-56. https://doi.org/10.1590/S1415-790X2013000200002
https://doi.org/10.1590/S1415-790X201300... .

Many studies suggest that climate change will impact the geographic distribution of mosquito vectors and the diseases they transmit⁵⁰50. Kraemer MUG, Reiner Jr RC, Brady OJ, Messina JP, Gilbert M, Pigott DM, et al. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus. Nat Microbiol 2019; 4(5): 854-63. https://doi.org/10.1038/s41564-019-0376-y
https://doi.org/10.1038/s41564-019-0376-...

51. Liu-Helmersson J, Rocklöv J, Sewe M, Brännström Å. Climate change may enable Aedes aegypti infestation in major European cities by 2100. Environ Res 2019; 172: 693-9. https://doi.org/10.1016/j.envres.2019.02.026
https://doi.org/10.1016/j.envres.2019.02... -⁵²52. Iwamura T, Guzman-Holst A, Murray KA. Accelerating invasion potential of disease vector Aedes aegypti under climate change. Nat Commun 2020; 11(1): 2130. https://doi.org/10.1038/s41467-020-16010-4
https://doi.org/10.1038/s41467-020-16010... . Some models predict that with global warming, the distribution of Aedes aegypti could expand, and by 2080, this species may be present in approximately 159 countries worldwide, with its presence reported for the first time in at least three of them⁵⁰50. Kraemer MUG, Reiner Jr RC, Brady OJ, Messina JP, Gilbert M, Pigott DM, et al. Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus. Nat Microbiol 2019; 4(5): 854-63. https://doi.org/10.1038/s41564-019-0376-y
https://doi.org/10.1038/s41564-019-0376-... . The introduction of diseases into countries where the population has had little or no previous exposure to these pathogens can lead to significant epidemics, as seen with Zika and chikungunya⁵³53. Nunes MRT, Faria NR, Vasconcelos JM, Golding N, Kraemer MUG, Oliveira LF, et al. Emergence and potential for spread of Chikungunya virus in Brazil. BMC Med 2015; 13: 102. https://doi.org/10.1186/s12916-015-0348-x
https://doi.org/10.1186/s12916-015-0348-... ,⁵⁴54. Faria NR, Azevedo RSS, Kraemer MUG, Souza R, Cunha MS, Hill SC, et al. Zika virus in the Americas: early epidemiological and genetic findings. Science 2016; 352(6283): 345-9. https://doi.org/10.1126/science.aaf5036
https://doi.org/10.1126/science.aaf5036... .

A recent study evaluated climatic and demographic indicators in Brazil between 2000 and 2020 to explain the expansion of dengue fever and the increase in the number of cases nationwide⁵⁵55. Barcellos C, Matos V, Lana RM, Lowe R. Climate change, thermal anomalies, and the recent progression of dengue in Brazil. Sci Rep 2024; 14(1): 5948. https://doi.org/10.1038/s41598-024-56044-y
https://doi.org/10.1038/s41598-024-56044... . The study revealed that the number of microregions with incidence rates exceeding 300 per 100,000 inhabitants has been rising over the years, particularly in the western and southern parts of the Southeast and Central-West regions, respectively. Additionally, in the Central-West and South regions, an increase in the number of excessively hot days was observed between 2014 and 2020 compared to 2007 to 2013⁵⁵55. Barcellos C, Matos V, Lana RM, Lowe R. Climate change, thermal anomalies, and the recent progression of dengue in Brazil. Sci Rep 2024; 14(1): 5948. https://doi.org/10.1038/s41598-024-56044-y
https://doi.org/10.1038/s41598-024-56044... . The rise in the number of hot days, with temperatures above the regional norm, is one of the consequences of climate change that may help explain the observed increase in dengue incidence across the country⁵⁵55. Barcellos C, Matos V, Lana RM, Lowe R. Climate change, thermal anomalies, and the recent progression of dengue in Brazil. Sci Rep 2024; 14(1): 5948. https://doi.org/10.1038/s41598-024-56044-y
https://doi.org/10.1038/s41598-024-56044... .

A review study highlighted the effects that climate change, along with human behavior, can have on vector-associated diseases like dengue fever⁵⁶56. Souza WM, Weaver SC. Effects of climate change and human activities on vector-borne diseases. Nat Rev Microbiol 2024; 22(8): 476-91. https://doi.org/10.1038/s41579-024-01026-0
https://doi.org/10.1038/s41579-024-01026... . Periods of heavy rain, whether they cause flooding or not, as well as periods of drought, can influence the dynamics of pathogen transmission by vectors⁵⁶56. Souza WM, Weaver SC. Effects of climate change and human activities on vector-borne diseases. Nat Rev Microbiol 2024; 22(8): 476-91. https://doi.org/10.1038/s41579-024-01026-0
https://doi.org/10.1038/s41579-024-01026... . Increased rainfall can fill artificial containers left exposed in the environment, turning them into breeding sites for Aedes aegypti⁴⁹49. Viana DV, Ignotti E. A ocorrência da dengue e variações meteorológicas no Brasil: revisão sistemática. Rev Bras Epidemiol 2013; 16(2): 240-56. https://doi.org/10.1590/S1415-790X2013000200002
https://doi.org/10.1590/S1415-790X201300... ,⁵⁷57. Roiz D, Boussès P, Simard F, Paupy C, Fontenille D. Autochthonous chikungunya transmission and extreme climate events in southern France. PLoS Negl Trop Dis 2015; 9(6): e0003854. https://doi.org/10.1371/journal.pntd.0003854
https://doi.org/10.1371/journal.pntd.000... . Conversely, during droughts, people may store water in urban areas with irregular supply⁵⁸58. Lowe R, Lee SA, O’Reilly KM, Brady OJ, Bastos L, Carrasco-Escobar G, et al. Combined effects of hydrometeorological hazards and urbanisation on dengue risk in Brazil: a spatiotemporal modelling study. Lancet Planet Health 2021; 5(4): e209-e219. https://doi.org/10.1016/S2542-5196(20)30292-8
https://doi.org/10.1016/S2542-5196(20)30... . This water storage often occurs in improvised containers, such as buckets, barrels, and tanks, which are frequently not properly sealed, attracting Aedes aegypti females to lay their eggs⁵⁶56. Souza WM, Weaver SC. Effects of climate change and human activities on vector-borne diseases. Nat Rev Microbiol 2024; 22(8): 476-91. https://doi.org/10.1038/s41579-024-01026-0
https://doi.org/10.1038/s41579-024-01026... .

However, it is important to emphasize that, in addition to climate change, social, political, and economic factors can also facilitate the DENV transmission cycle. Rapid and unplanned urbanization, coupled with inadequate sanitary conditions, insufficient public health infrastructure, limited access to healthcare, and inadequate efforts to control the mosquito vector, also contribute to the occurrence of dengue epidemics⁵⁹59. San Martín JL, Brathwaite O, Zambrano B, Solórzano JO, Bouckenooghe A, Dayan GH, et al. The epidemiology of dengue in the Americas over the last three decades: a worrisome reality. Am J Trop Med Hyg 2010; 82(1): 128-35. https://doi.org/10.4269/ajtmh.2010.09-0346
https://doi.org/10.4269/ajtmh.2010.09-03... .

A study evaluated the spatio-temporal evolution of dengue cases in Brazil between 2001 and 2012, analyzing the relationship between reported records and sociodemographic factors⁶⁰60. Rodrigues NCP, Lino VTS, Daumas RP, Andrade MKN, O’Dwyer G, Monteiro DLM, et al. Temporal and spatial evolution of dengue incidence in Brazil, 2001-2012. PLoS One 2016; 11(11): e0165945. https://doi.org/10.1371/journal.pone.0165945
https://doi.org/10.1371/journal.pone.016... . The occurrence of dengue cases in Brazil between 2001 and 2012 was inversely associated with the proportion of people living in rural areas, that is, the greater the human population in cities, the greater the risk of dengue fever⁶⁰60. Rodrigues NCP, Lino VTS, Daumas RP, Andrade MKN, O’Dwyer G, Monteiro DLM, et al. Temporal and spatial evolution of dengue incidence in Brazil, 2001-2012. PLoS One 2016; 11(11): e0165945. https://doi.org/10.1371/journal.pone.0165945
https://doi.org/10.1371/journal.pone.016... . A direct and inverse association, respectively, was also observed between the Gini index and the presence of a sewage system with the risk of dengue fever⁶⁰60. Rodrigues NCP, Lino VTS, Daumas RP, Andrade MKN, O’Dwyer G, Monteiro DLM, et al. Temporal and spatial evolution of dengue incidence in Brazil, 2001-2012. PLoS One 2016; 11(11): e0165945. https://doi.org/10.1371/journal.pone.0165945
https://doi.org/10.1371/journal.pone.016... . In another study, it was demonstrated that the incidence of dengue presented a heterogeneous pattern in the Northeast of Brazil between 2014 and 2017, with social indicators such as human population density, education and social vulnerability showing a positive correlation with the disease⁶¹61. Carmo RF, Silva Júnior JVJ, Pastor AF, Souza CDF. Spatiotemporal dynamics, risk areas and social determinants of dengue in Northeastern Brazil, 2014–2017: an ecological study. Infect Dis Poverty 2020; 9(1): 153. https://doi.org/10.1186/s40249-020-00772-6
https://doi.org/10.1186/s40249-020-00772... . For example, access to piped water had a negative correlation with the incidence of dengue fever⁶¹61. Carmo RF, Silva Júnior JVJ, Pastor AF, Souza CDF. Spatiotemporal dynamics, risk areas and social determinants of dengue in Northeastern Brazil, 2014–2017: an ecological study. Infect Dis Poverty 2020; 9(1): 153. https://doi.org/10.1186/s40249-020-00772-6
https://doi.org/10.1186/s40249-020-00772... .

Human behavior plays a crucial role in the occurrence of dengue epidemics in Brazil, particularly in the elimination of Aedes aegypti breeding sites within homes, which relies heavily on societal mobilization. For example, a study conducted in a neighborhood in São José do Rio Preto, São Paulo, demonstrated that despite extensive educational efforts, including distributing leaflets to households, posting posters in public and commercial areas, holding meetings with mothers in daycare centers, and giving lectures in schools, there was no reduction in the number of breeding sites found in homes before and after the awareness program⁶²62. Chiaravalloti Neto F, Moraes MS, Fernandes MA. Avaliação dos resultados de atividades de incentivo à participação da comunidade no controle da dengue em um bairro periférico do Município de São José do Rio Preto, São Paulo, e da relação entre conhecimentos e práticas desta população. Cad Saúde Pública 1998; 14(Suppl 2): S101-S109. https://doi.org/10.1590/S0102-311X1998000600009
https://doi.org/10.1590/S0102-311X199800... .

In contrast, preventive actions against dengue in Catanduva, São Paulo, yielded positive results⁶³63. Chiaravalloti Neto F, Fiorin AM, Conversani DT, Cesarino MB, Barbosa AAC, Dibo MR, et al. Controle do vetor do dengue e participação da comunidade em Catanduva, São Paulo, Brasil. Cad Saúde Pública 2003; 19(6): 1739-49. https://doi.org/10.1590/S0102-311X2003000600018
https://doi.org/10.1590/S0102-311X200300... . Between 1999 and 2001, two areas on the outskirts of Catanduva were evaluated: one as a study area and the other as a control area. In the study area, vector control agents implemented preventive measures without applying larvicides or eliminating mosquito breeding sites. Educational materials were used to explain the Aedes aegypti life cycle, and recreational activities, such as theater and scavenger hunts, were conducted⁶³63. Chiaravalloti Neto F, Fiorin AM, Conversani DT, Cesarino MB, Barbosa AAC, Dibo MR, et al. Controle do vetor do dengue e participação da comunidade em Catanduva, São Paulo, Brasil. Cad Saúde Pública 2003; 19(6): 1739-49. https://doi.org/10.1590/S0102-311X2003000600018
https://doi.org/10.1590/S0102-311X200300... . As a result, the study area experienced a significant reduction in the proportion of households with potential containers or standing water compared to the control area. Additionally, there was a notable decrease in the average number of potential containers with stagnant water in households within the study area⁶³63. Chiaravalloti Neto F, Fiorin AM, Conversani DT, Cesarino MB, Barbosa AAC, Dibo MR, et al. Controle do vetor do dengue e participação da comunidade em Catanduva, São Paulo, Brasil. Cad Saúde Pública 2003; 19(6): 1739-49. https://doi.org/10.1590/S0102-311X2003000600018
https://doi.org/10.1590/S0102-311X200300... .

It is essential for society to feel a sense of responsibility in mosquito control efforts to successfully reduce breeding sites within homes. However, information and education must be complemented by coordinated public policies across all levels of government, focusing on effective basic sanitation measures, such as regular solid waste collection⁶⁴64. Faria MTS, Ribeiro NRS, Dias AP, Gomes UAF, Moura PM. Saúde e saneamento: uma avaliação das políticas públicas de prevenção, controle e contingência das arboviroses no Brasil. Ciênc Saúde Coletiva 2023; 28(6): 1767-76. https://doi.org/10.1590/1413-81232023286.07622022
https://doi.org/10.1590/1413-81232023286... . The link between dengue and social determinants underscores the need for specific public policies aimed at addressing inequalities to reduce the incidence of the disease in the most vulnerable regions.

The multisectoral nature of dengue highlights the challenges in controlling the disease within the country. The dominant tropical climate, characterized by hot and rainy months, naturally supports the establishment, expansion, and proliferation of Aedes aegypti. Additionally, this mosquito species possesses ecological and behavioral traits that enhance its vector capacity.

The current control methods appear to be insufficient in reducing vector density. For chemical control, the development of resistance in mosquito populations to certain classes of insecticides and larvicides poses a significant challenge⁶⁵65. Zara ALSA, Santos SM, Fernandes-Oliveira ES, Carvalho RG, Coelho GE. Estratégias de controle do Aedes aegypti: uma revisão. Epidemiol Serv Saúde 2016; 25(2): 391-404. https://doi.org/10.5123/S1679-49742016000200017
https://doi.org/10.5123/S1679-4974201600... . In mechanical control, the elimination and proper management of potential Aedes aegypti breeding sites can be difficult, particularly in hard-to-reach areas. As an alternative, drones have been identified as a valuable tool to address this limitation, as they can provide high-resolution images for identifying Aedes aegypti breeding sites in areas inaccessible to entomological surveillance agents⁶⁶66. Valdez-Delgado KM, Moo-Llanes DA, Danis-Lozano R, Cisneros-Vázquez LA, Flores-Suarez AE, Ponce-García G, et al. Field effectiveness of drones to identify potential Aedes aegypti breeding sites in household environments from Tapachula, a dengue-endemic city in southern Mexico. Insects 2021; 12(8): 663. https://doi.org/10.3390/insects12080663
https://doi.org/10.3390/insects12080663... ,⁶⁷67. Carrasco-Escobar G, Moreno M, Fornace K, Herrera-Varela M, Manrique E, Conn JE. The use of drones for mosquito surveillance and control. Parasit Vectors 2022; 15(1): 473. https://doi.org/10.1186/s13071-022-05580-5
https://doi.org/10.1186/s13071-022-05580... .

Wolbachia is an endosymbiotic bacterium found in various insect species, including Aedes (Stegomyia) albopictus⁶⁸68. Albuquerque AL, Magalhães T, Ayres CFJ. High prevalence and lack of diversity of Wolbachia pipientis in Aedes albopictus populations from Northeast Brazil. Mem Inst Oswaldo Cruz 2011; 106(6): 773-6. https://doi.org/10.1590/S0074-02762011000600021
https://doi.org/10.1590/S0074-0276201100... , a mosquito species considered a potential vector for DENV, ZIKV, and CHIKV in Brazil⁶⁹69. Ferreira-de-Lima VH, Andrade PS, Thomazelli LM, Marrelli MT, Urbinatti PR, Almeida RMMS, et al. Silent circulation of dengue virus in Aedes albopictus (Diptera: Culicidae) resulting from natural vertical transmission. Sci Rep 2020; 10(1): 3855. https://doi.org/10.1038/s41598-020-60870-1
https://doi.org/10.1038/s41598-020-60870... . Wolbachia is not naturally present in Aedes aegypti, and its introduction into this mosquito species reduces its competence to transmit dengue, Zika, and chikungunya viruses, potentially helping to decrease cases of these arboviruses in the country⁷⁰70. Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM, et al. A Wolbachia symbiont in Aedes aegypti limits infection with dengue, chikungunya, and Plasmodium. Cell 2009; 139(7): 1268-78. https://doi.org/10.1016/j.cell.2009.11.042
https://doi.org/10.1016/j.cell.2009.11.0... ,⁷¹71. Aliota MT, Peinado SA, Velez ID, Osorio JE. The wMel strain of Wolbachia Reduces Transmission of Zika virus by Aedes aegypti. Sci Rep 2016; 6: 28792. https://doi.org/10.1038/srep28792
https://doi.org/10.1038/srep28792... . Additionally, the bacteria are transmitted to subsequent generations through eggs⁷²72. Pinto SB, Riback TIS, Sylvestre G, Costa G, Peixoto J, Dias FBS, et al. Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: a quasi-experimental study. PLoS Negl Trop Dis 2021; 15(7): e0009556. https://doi.org/10.1371/journal.pntd.0009556
https://doi.org/10.1371/journal.pntd.000... . This control method involves releasing adult mosquitoes infected with the bacteria into target areas over several months. In Niterói, Rio de Janeiro, the release of these adult mosquitoes has demonstrated positive results⁷²72. Pinto SB, Riback TIS, Sylvestre G, Costa G, Peixoto J, Dias FBS, et al. Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: a quasi-experimental study. PLoS Negl Trop Dis 2021; 15(7): e0009556. https://doi.org/10.1371/journal.pntd.0009556
https://doi.org/10.1371/journal.pntd.000... . However, when implementing this biological control method, it is crucial to consider the genetic diversity of Brazilian Aedes aegypti populations and the country’s varying ecological and epidemiological contexts⁷³73. Pavan MG, Garcia GA, David MR, Maciel-de-Freitas R. The double-edged sword effect of expanding Wolbachia deployment in dengue endemic settings. Lancet Reg Health Am 2023; 27: 100610. https://doi.org/10.1016/j.lana.2023.100610
https://doi.org/10.1016/j.lana.2023.1006... .

The QDENGA^® vaccine represents a promising advancement in reducing dengue cases and mortality, particularly following the recent epidemic in Brazil, notably that of 2024. The vaccination regimen consists of two doses, and after 18 months, the overall effectiveness of QDENGA^® is 76.1% in seropositive individuals — those who have had previous exposure to the dengue virus — and 66.2% in seronegative individuals, who have not been exposed to the virus⁷⁴74. Torres-Flores JM, Reyes-Sandoval A, Salazar MI. Dengue vaccines: an update. BioDrugs 2022; 36(3): 325-36. https://doi.org/10.1007/s40259-022-00531-z
https://doi.org/10.1007/s40259-022-00531... . The vaccine’s overall efficacy against different DENV serotypes ranges from 95.1% (DENV-2) to 48.9% (DENV-3)⁷⁴74. Torres-Flores JM, Reyes-Sandoval A, Salazar MI. Dengue vaccines: an update. BioDrugs 2022; 36(3): 325-36. https://doi.org/10.1007/s40259-022-00531-z
https://doi.org/10.1007/s40259-022-00531... . Previously, the Dengvaxia^® vaccine was approved and introduced in Brazil in 2015 for individuals aged 9 to 44 years. However, this vaccine proved beneficial only for seropositive individuals⁷⁵75. Diaz-Quijano FA, Carvalho DS, Raboni SM, Shimakura SE, Mello AM, Costa-Ribeiro MCV, et al. Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs. Lancet Reg Health Am 2024; 35: 100777. https://doi.org/10.1016/j.lana.2024.100777
https://doi.org/10.1016/j.lana.2024.1007... . Since QDENGA^® was only introduced in 2024 and a limited number of doses have been administered, its full protective impact on the Brazilian population remains to be determined.

Even with the introduction of vaccination, political-social, and climatic factors must be addressed, as they present significant challenges for controlling both the mosquito vector and the disease. Implementing public policies for regular garbage collection and ensuring equitable access to piped water across the Brazilian population can substantially aid in reducing mosquito infestation and cases of arboviruses associated with Aedes aegypti. Additionally, effective measures to mitigate the impacts of climate change are essential to prevent increases in periods of drought and major flooding, which can affect the transmission dynamics of arboviruses and other infectious diseases impacting public health in Brazil.

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