Dengue fever, caused by the dengue virus (DENV), poses a significant global health challenge, particularly in tropical and subtropical regions. Recent increases in indigenous DENV cases in Europe are concerning, reflecting rising incidence linked to climate change and the spread of Aedes albopictus mosquitoes. These vectors thrive under environmental conditions like temperature and humidity, which are increasingly influenced by climate change. Additionally, global travel accelerates the cross-border spread of mosquito-borne diseases. DENV manifests clinically in a spectrum from asymptomatic cases to severe conditions like dengue hemorrhagic fever and dengue shock syndrome, influenced by viral serotype and host factors. In 2024, Brazil experienced a fourfold increase in dengue cases compared to 2023, accompanied by higher mortality. Conventional control measures, such as vector control, community engagement, and vaccination, proved insufficient as climate change exacerbated mosquito proliferation, challenging containment efforts. In this regard, our review analyzes prevention measures and therapeutic protocols during the outbreak while addressing DENV transmission dynamics, clinical presentations, and epidemiological shifts. It also evaluates diagnostic strategies combining clinical assessment with serological and molecular testing, providing information to improve diagnostic and preventive measures. The global expansion of dengue-endemic regions, including outbreaks in Europe, highlights the urgent need for enhanced surveillance, proactive interventions, and international collaboration to mitigate the growing threat of Dengue and other arboviruses like West Nile, Zika, Chikungunya, Oropouche, and Yellow Fever viruses.

Cyclic di-GMP (bis-(3′ → 5′) cyclic dimeric guanosine monophosphate) is a ubiquitous bacterial second messenger that regulates a wide range of cellular processes, including biofilm formation, motility, virulence, and environmental adaptation. Its intracellular levels are dynamically controlled by diguanylate cyclases (DGCs), which synthesize c-di-GMP from GTP, and phosphodiesterases (PDEs), which degrade it into linear pGpG or GMP. The functional effects of cytoplasmic c-di-GMP are mediated through diverse effector proteins, including PilZ domain-containing receptors, transcription factors, and riboswitches. In Leptospira interrogans, a major pathogenic species responsible for leptospirosis, the regulatory roles of c-di-GMP remain poorly understood. Here, we performed a comprehensive bioinformatics and structural analysis of all predicted c-di-GMP related proteins in L. interrogans serovar Copenhageni strain Fiocruz L1-130. Our analysis identified 17 proteins containing GGDEF domain, five proteins containing both GGDEF and EAL domains, four proteins containing EAL domain, five proteins containing HD-GYP domain, 12 proteins containing PilZ domain, and one protein containing an MshEN domain. Comparative analysis with well-characterized bacterial homologs suggests that L. interrogans possess a complex c-di-GMP network, likely involved in modulating biofilm formation, host-pathogen interactions, and environmental survival. These findings provide new insights into the c-di-GMP regulatory network and on signal transduction in Leptospira and lay the foundation for future functional studies aimed at understanding its role in physiology, virulence and persistence.

Dengue fever, caused by the dengue virus (DENV), presents a significant global health challenge, especially in tropical and subtropical regions. The exponential increase in native DENV cases in Europe is concerning, indicating a significant rise in incidence. As climate change intensifies, it is crucial to implement proactive measures to address the presence of Aedes albopictus (Asian tiger mosquito) in Europe to prevent dengue and other tropical diseases from becoming endemic in temperate regions. In 2024, Brazil experienced a dramatic surge in dengue cases, reporting an incidence rate four times higher than that of 2023, accompanied by a notable rise in mortality. This alarming trend underscores the urgent need for heightened surveillance and preventive measures, as it may signal the potential for new dengue outbreaks in non-tropical regions. Herein, we explored various aspects of DENV transmission, clinical manifestations, epidemiological trends, and management strategies. DENV transmission depends on Aedes mosquitoes as vectors and humans as hosts. The Aedes species is easily identified by its distinctive black-and-white striped legs. Factors such as temperature, humidity, and precipitation significantly influence mosquito proliferation, and these factors are increasingly affected by climate change. Additionally, the rise in global travel is facilitating the spread of viruses across borders, particularly arboviruses like DENV. Understanding these dynamics is crucial for effective public health interventions. DENV presents a spectrum of clinical manifestations, ranging from asymptomatic cases to severe conditions such as dengue hemorrhagic fever and dengue shock syndrome, influenced by viral serotype and host factors. We explored various diagnostic approaches that integrate clinical symptoms with serological and molecular testing. In Brazil, prevention strategies including vector control, community engagement, and vaccination programs have been implemented. However, these measures have proven insufficient to avert the outbreak in 2024. Climate change drives the geographical expansion of dengue-endemic areas, with recent outbreaks in Europe highlighting the evolving epidemiological landscape. Vigilant global collaboration is essential to mitigate the impact of dengue and other emerging arboviruses, including West Nile virus, Zika virus, Chikungunya virus, Oropouche virus, and Yellow Fever virus.

Cyclic di-GMP (bis-(3′→5′) cyclic dimeric guanosine monophosphate) is a ubiquitous bacterial second messenger that regulates a wide range of cellular processes, including biofilm formation, motility, virulence, and environmental adaptation. Its intracellular levels are dynamically controlled by diguanylate cyclases (DGCs), which synthesize c-di-GMP from GTP, and phosphodiesterases (PDEs), which degrade it into linear pGpG or GMP. The functional effects of cytoplasmic c-di-GMP are mediated through diverse effector proteins, including PilZ domain-containing receptors, transcription factors, and riboswitches. In Leptospira interrogans, a major pathogenic species responsible for leptospirosis, the regulatory roles of c-di-GMP remain poorly understood. Here, we performed a comprehensive bioinformatics and structural analysis of all predicted c-di-GMP related proteins in L. interrogans serovar Copenhageni strain Fiocruz L1-130, a serovar generally associated with severe manifestations of leptospirosis in humans. Our analysis identified seventeen proteins containing GGDEF domain, five proteins containing both GGDEF and EAL domains, four proteins containing EAL domain, five proteins containing HD-GYP domain, twelve proteins containing PilZ domain, and one protein containing an MshEN domain. Comparative analysis with well-characterized bacterial homologs suggests that L. interrogans possess a complex c-di-GMP signaling network, likely involved in modulating biofilm formation, host–pathogen interactions, and environmental survival. These findings provide new insights into the c-di-GMP regulatory network and on signal transduction in Leptospira and lay the foundation for future functional studies aimed at understanding its roles in physiology, virulence, and persistence.