In Vitro Cleavage Assay to Characterize DENV NS2B3 Antagonism of cGAS.

cGAS is a key cytosolic dsDNA receptor that senses viral infection and elicits interferon production through the cGAS-cGAMP-STING axis. cGAS is activated by dsDNA from viral and bacterial origins as well as dsDNA leaked from damaged mitochondria and nucleus. Eventually, cGAS activation launches the cell into an antiviral state to restrict the replication of both DNA and RNA viruses. Throughout the long co-evolution, viruses devise many strategies to evade cGAS detection or suppress cGAS activation. We recently reported that the Dengue virus protease NS2B3 proteolytically cleaves human cGAS in its N-terminal region, effectively reducing cGAS binding to DNA and consequent production of the second messenger cGAMP. Several other RNA viruses likely adopt the cleavage strategy. Here, we describe a protocol for the purification of recombinant human cGAS and Dengue NS2B3 protease, as well as the in vitro cleavage assay.

Pre-vax metabolic clues: Cracking the code to a better dengue vaccine.

Multi-omic analysis deciphers the impact of cell-intrinsic and systemic metabolomes on dengue vaccination immunogenicity.

Estimating dengue disease and economic burden to inform municipal-level policymakers: Method for a pragmatic city-level observational cohort study.

Background: Recent trials have confirmed the effectiveness of promising dengue control technologies - two vaccines and Wolbachia. These would generally be applied at the municipal level. To help local officials decide which, if any, control strategy to implement, they need affordable, timely, and accurate data on dengue burden. Building on our previous work in Mexico, Indonesia, and Thailand, we developed a streamlined prospective method to estimate dengue burden at the municipal level quickly, accurately, and efficiently. Methods: The method entails enrolling and repeatedly interviewing 100 patients with laboratory-confirmed dengue. They will be selected after screening and testing about 1,000 patients with clinical dengue. The method will capture both acute and chronic effects relating to disease, economic burden, and psychological impacts (presenteeism). The total time requirements are 1.5 years, comprised of 0.25 years for planning and approvals, 1 year for data collection (a full dengue cycle), and 0 .25 years for data cleaning and analysis. A collaboration with municipal and academic colleagues in the city of Semarang, Central Java, Indonesia shows how the method could be readily applied in Indonesia's eighth largest city (population 1.8 million). Conclusions: Many surveillance studies gather only information on numbers of cases. This proposed method will provide a comprehensive picture of the dengue burden to the health system, payers, and households at the local level.

Effects of the oxoaporphine alkaloid hernandonine on dengue virus. Evidence for its mechanisms of action.

BACKGROUND: Dengue, caused by the dengue virus (Orthoflavivirus dengue, encompassing DENV types 1-4), is a member of the Flaviviridae family. The symptoms of dengue range from subclinical or mild manifestations to potentially fatal complications. The management of severe dengue is exceptionally challenging due to the absence of effective antiviral medications. In this context, natural products, whether in the form of pure compounds or standardized plant extracts, have emerged as a promising source for the development of novel antiviral therapeutics. Hernandonine, an oxoaporphine alkaloid found in Hernandia nymphaeifolia (C. Presl) Kubitzki. serves both as a metabolite and an inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase. PURPOSE: This study investigated the ability of hernandonine to inhibit DENV infection and explored its potential mechanisms. STUDY DESIGN: To assess the in vitro anti-DENV activity, cells or induced pluripotent stem cell (iPSC)-derived cerebral organoids were exposed to hernandonine before or after infection with DENV. Along with hernandonine, the endocytosis modulators, genistein, wortmannin, Methyl-ß-cyclodextrin (MßCD) and lovastatin, were used in the assays. METHODS: The DENV infectivity and virion production in cells or cerebral organoids treated with compounds were determined. Various methods, including cell and cerebral organoids imaging, protein and gene detection were conducted to explore their antiviral mechanisms. RESULTS: The results revealed notable antiviral properties of hernandonine, particularly in inhibiting DENV during the early stages of infection. Mechanistic analysis demonstrated that, akin to genistein, wortmannin, methyl-ß-cyclodextrin (MßCD), and lovastatin, hernandonine exerted an influence on cholesterol-rich lipid rafts. It also restrained the pseudopodial movement ability of cells, potentially through the downregulation of cytoskeleton and endocytosis regulatory genes or protein expression. Moreover, hernandonine's virucidal activity was demonstrated. Hernandonine's inhibition of DENV infection was further validated in a disease-relevant iPSC-derived cerebral organoids model, a novel DENV-2 infection system worthy of further application. CONCLUSION: This study evidenced the potential of hernandonine as a novel candidate in the fight against DENV infection.

Vector competence of Aedes albopictus field populations from Reunion Island exposed to local epidemic dengue viruses.

Dengue virus (DENV) is the most prevalent mosquito-borne Flavivirus that affects humans worldwide. Aedes albopictus, which is naturally infected with the bacteria Wolbachia, is considered to be a secondary vector of DENV. However, it was responsible for a recent DENV outbreak of unprecedented magnitude in Reunion Island, a French island in the South West Indian Ocean. Moreover, the distribution of the cases during this epidemic showed a spatially heterogeneous pattern across the island, leading to questions about the differential vector competence of mosquito populations from different geographic areas. The aim of this study was to gain a better understanding of the vector competence of the Ae. albopictus populations from Reunion Island for local DENV epidemic strains, while considering their infection by Wolbachia. Experimental infections were conducted using ten populations of Ae. albopictus sampled across Reunion Island and exposed to three DENV strains: one strain of DENV serotype 1 (DENV-1) and two strains of DENV serotype 2 (DENV-2). We analyzed three vector competence parameters including infection rate, dissemination efficiency and transmission efficiency, at different days post-exposition (dpe). We also assessed whether there was a correlation between the density of Wolbachia and viral load/vector competence parameters. Our results show that the Ae. albopictus populations tested were not able to transmit the two DENV-2 strains, while transmission efficiencies up to 40.79% were observed for the DENV-1 strain, probably due to difference in viral titres. Statistical analyses showed that the parameters mosquito population, generation, dpe and area of sampling significantly affect the transmission efficiencies of DENV-1. Although the density of Wolbachia varied according to mosquito population, no significant correlation was found between Wolbachia density and either viral load or vector competence parameters for DENV-1. Our results highlight the importance of using natural mosquito populations for a better understanding of transmission patterns of dengue.

Predictors of acute kidney injury in dengue patients: a systematic review and meta-analysis.

BACKGROUND: Dengue infection poses a significant global health challenge, particularly in tropical and subtropical regions. Among its severe complications, Acute kidney injury (AKI) stands out due to its association with increased morbidity, mortality, and healthcare burdens. This Meta-analysis aim to identify and evaluate the predictors of AKI among dengue patients, facilitating early detection and management strategies to mitigate AKI's impact. METHODS: We searched PubMed, EMBASE, and Web of Science databases, covering literature up to February 2024. We included human observational studies reporting on AKI predictors in confirmed dengue cases. Nested-Knowledge software was used for screening and data extraction. The Newcastle-Ottawa Scale was used for quality assessment. R software (V 4.3) was utilized to compute pooled odds ratios (ORs) and 95% confidence intervals (CIs) for each predictor. RESULTS: Our search yielded nine studies involving diverse geographic locations and patient demographics. A total of 9,198 patients were included in the studies, with 542 diagnosed with AKI. in which key predictors of AKI identified include severe forms of dengue (OR: 2.22, 95% CI: 1.02-3.42), male gender (OR: 3.13, 95% CI: 1.82-4.44), comorbidities such as diabetes mellitus (OR: 3.298, 95% CI: 0.274-6.322), and chronic kidney disease (OR: 2.2, 95% CI: 0.42-11.24), as well as co-infections and clinical manifestations like rhabdomyolysis and major bleeding. CONCLUSION: Our study identifies several predictors of AKI in dengue patients. These findings indicate the importance of early identification and intervention for high-risk individuals. Future research should focus on standardizing AKI diagnostic criteria within the dengue context and exploring the mechanisms underlying these associations to improve patient care and outcomes.

Metabolomic profiling of dengue infection: unraveling molecular signatures by LC-MS/MS and machine learning models.

BACKGROUND & OBJECTIVE: The progression of dengue fever to severe dengue (SD) is a major public health concern that impairs the capacity of the medical system to predict and treat dengue patients. Hence, the present study used a metabolomic approach integrated with machine models to identify differentially expressed metabolites in patients with SD compared to nonsevere patients and healthy controls. METHODS: Comprehensively, the plasma was collected at different clinical phases during dengue without warning signs (DWOW, N = 10), dengue with warning signs (DWW, N = 10), and SD (N = 10) at different stages [i.e., day of admission (DOA), day of defervescence (DOD), and day of convalescent (DOC)] in comparison to healthy control (HC). The samples were subjected to LC‒ESI‒MS/MS to identify metabolites. Statistical and machine learning analyses were performed using R and Python language. Further, biomarker, pathway and correlation analysis was performed to identify potential predictors of dengue. RESULTS & CONCLUSION: A total of 423 metabolites were identified in all the study groups. Paired and unpaired t-tests revealed 14 highly differentially expressed metabolites between and across the dengue groups, with four metabolites (shikimic acid, ureidosuccinic acid, propionyl carnitine, and alpha-tocopherol) showing significant differences compared to HC. Furthermore, biomarker (ROC) analysis revealed 11 potential molecules with a significant AUC value of 1 that could serve as potential biomarkers for identifying different dengue clinical stages that are beneficial for predicting dengue disease outcomes. The logistic regression model revealed that S-adenosylhomocysteine, hypotaurine, and shikimic acid metabolites could be beneficial indicators for predicting severe dengue, with an accuracy and AUC of 0.75. The data showed that dengue infection is related to lipid metabolism, oxidative stress, inflammation, metabolomic adaptation, and virus manipulation. Moreover, the biomarkers had a significant correlation with biochemical parameters like platelet count, and hematocrit. These results shed some light on host-derived small-molecule biomarkers that are associated with dengue severity and novel insights into metabolomics mechanisms interlinked with disease severity.

Dengue Infection During Pregnancy and Adverse Birth Outcomes: A Systematic Review and Meta-Analysis.

Dengue is a rapidly spreading mosquito-borne viral disease, posing significant public health challenges in tropical and subtropical regions. This systematic review and meta-analysis aimed to evaluate the relationship between maternal dengue virus infection and adverse birth outcomes. A literature search was conducted in PubMed, Embase, and web of science databases until April 2024. Observational studies examining the association between laboratory-confirmed maternal dengue infection and adverse birth outcomes such as preterm birth, low birth weight (LBW), small for gestational age (SGA), stillbirth, and postpartum haemorrhage were included. Data were extracted, and risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to pool data in R software (V 4.3). Twenty studies met the inclusion criteria. The pooled prevalence of preterm birth among dengue-affected pregnancies was 18.3% (95% CI: 12.6%-25.8%), with an OR of 1.21 (95% CI: 0.78-1.89). For LBW, the pooled prevalence was 17.1% (95% CI: 10.4%-26.6%), with an OR of 1.00 (95% CI: 0.69-1.41). SGA had a pooled prevalence of 11.2% (95% CI: 2.7%-36.9%) and an OR of 0.93 (95% CI: 0.41-2.14). The prevalence of stillbirth was 3.3% (95% CI: 1.6%-6.8%), with significant associations found in some studies (RR: 2.67; 95% CI: 1.09-6.57). Postpartum haemorrhage had an OR of 1.97 (95% CI: 0.53-2.69). While maternal dengue infection was associated with a higher prevalence of preterm birth and LBW, the associations were not statistically significant. Significant associations were observed for stillbirth in specific studies. Further research with standardized methodologies is needed to clarify these relationships and identify potential mechanisms.

Gut symbiont-derived sphingosine modulates vector competence in Aedes mosquitoes.

The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 µM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission.

Bayesian spatio-temporal analysis of dengue transmission in Lao PDR.

Dengue, a zoonotic viral disease transmitted by Aedes mosquitoes, poses a significant public health concern throughout the Lao People's Democratic Republic (Lao PDR). This study aimed to describe spatial-temporal patterns and quantify the effects of environmental and climate variables on dengue transmission at the district level. The dengue data from 2015 to 2020 across 148 districts of Lao PDR were obtained from the Lao PDR National Center for Laboratory and Epidemiology (NCLE). The association between monthly dengue occurrences and environmental and climate variations was investigated using a multivariable Zero-inflated Poisson regression model developed in a Bayesian framework. The study analyzed a total of 72,471 dengue cases with an incidence rate of 174 per 100,000 population. Each year, incidence peaked from June to September and a large spike was observed in 2019. The Bayesian spatio-temporal model revealed a 9.1% decrease (95% credible interval [CrI] 8.9%, 9.2%) in dengue incidence for a 0.1 unit increase in monthly normalized difference vegetation index at a 1-month lag and a 5.7% decrease (95% CrI 5.3%, 6.2%) for a 1 cm increase in monthly precipitation at a 6-month lag. Conversely, dengue incidence increased by 43% (95% CrI 41%, 45%) for a 1 °C increase in monthly mean temperature at a 3-month lag. After accounting for covariates, the most significant high-risk spatial clusters were detected in the southern regions of Lao PDR. Probability analysis highlighted elevated trends in 45 districts, emphasizing the importance of targeted control strategies in high-risk areas. This research underscores the impact of climate and environmental factors on dengue transmission, emphasizing the need for proactive public health interventions tailored to specific contexts in Lao PDR.

Determining dengue infection risk in the Colombo district of Sri Lanka by inferencing the genetic parameters of Aedes mosquitoes.

BACKGROUND: For decades, dengue has posed a significant threat as a viral infectious disease, affecting numerous human lives globally, particularly in tropical regions, yet no cure has been discovered. The genetic trait of vector competence in Aedes mosquitoes, which facilitates dengue transmission, is difficult to measure and highly sensitive to environmental changes. METHODS: In this study we attempt, for the first time in a non-laboratory setting, to quantify the vector competence of Aedes mosquitoes assuming its homogeneity across both species; aegypti and albopictus and across the four Dengue serotypes. Estimating vector competence in relation to varying rainfall patterns was focused in this study to showcase the changes in this vector trait with respect to environmental variables. We quantify it using an existing mathematical model originally developed for malaria in a Bayesian inferencing setup. We conducted this study in the Colombo district of Sri Lanka where the highest number of human populations are threatened with dengue. Colombo district experiences continuous favorable temperature and humidity levels throughout the year creating ideal conditions for Aedes mosquitoes to thrive and transmit the Dengue disease. Therefore we only used the highly variable and seasonal rainfall as the primary environmental variable as it significantly influences the number of breeding sites and thereby impacting the population dynamics of Aedes. RESULTS: Our research successfully deduced vector competence values for the four identified seasons based on Monsoon rainfalls experienced in Colombo within a year. We used dengue data from 2009 - 2022 to infer the estimates. These estimated values have been corroborated through experimental studies documented in the literature, thereby validating the malaria model to estimate vector competence for dengue disease. CONCLUSION: Our research findings conclude that environmental conditions can amplify vector competence within specific seasons, categorized by their environmental attributes. Additionally, the deduced vector competence offers compelling evidence that it impacts disease transmission, irrespective of geographical location, climate, or environmental factors.

The greatest Dengue epidemic in Brazil: Surveillance, Prevention, and Control.

In this review, we discuss dengue surveillance, prevention, and control measures in Brazil. Data on dengue epidemics between 2000 and 2024 indicates an increase in the number of dengue cases and deaths. Global climate change is a key driver of this growth. Over the past 25 years, nearly 18 million Brazilians have been infected with the dengue virus, and the highest number of dengue cases in Brazil's history is projected to reach 2024. Dengue mortality in Brazil increased geographically over time. As of June, there were approximately 6 million probable cases and 4,000 confirmed deaths in Brazil, which represents the greatest dengue epidemic to date. Several technologies have been developed to control Aedes aegypti, including the deployment of Wolbachia-infected mosquitoes, indoor residual spraying, sterile insect techniques, and mosquito-disseminated insecticides. The Ministry of Health recommends integrating these technologies into health services. Brazil is the first country to incorporate the Takeda vaccine into its public health system, and the Butantan vaccine is currently undergoing Phase 3 clinical trials. Increasing the vaccination coverage and implementing novel Ae. aegypti control technologies could reduce the number of dengue cases in Brazil in the coming years. Community activities such as home cleaning and elimination of potential mosquito breeding sites, facilitated by social media and health education initiatives, must continue to achieve this reduction. Ultimately, a multisectoral approach encompassing sanitary improvements, mosquito control, vaccination, and community mobilization is crucial in the fight against dengue epidemics.

Sequential label shift detection in classification data: An application to dengue fever.

Classifiers have been developed to help diagnose dengue fever in patients presenting with febrile symptoms. However, classifier predictions often rely on the assumption that new observations come from the same distribution as training data. If the population prevalence of dengue changes, as would happen with a dengue outbreak, it is important to raise an alarm as soon as possible, so that appropriate public health measures can be taken and also so that the classifier can be re-calibrated. In this paper, we consider the problem of detecting such a change in distribution in sequentially-observed, unlabeled classification data. We focus on label shift changes to the distribution, where the class priors shift but the class conditional distributions remain unchanged. We reduce this problem to the problem of detecting a change in the one-dimensional classifier scores, leading to simple nonparametric sequential changepoint detection procedures. Our procedures leverage classifier training data to estimate the detection statistic, and converge to their parametric counterparts in the size of the training data. In simulated outbreaks with real dengue data, we show that our method outperforms other detection procedures in this label shift setting.

Larval crowding enhances dengue virus loads in Aedes aegypti, a relationship that might increase transmission in urban environments.

BACKGROUND: Climate change and urbanization will alter the global distribution of disease vectors, changing the disease burden in yet unpredictable ways. Aedes aegypti is a mosquito responsible for transmitting dengue, Zika, chikungunya, and yellow fever viruses that breeds in containers associated with urban environments. We sought to understand how ambient temperature and larval densities in the immature aquatic phases determine adult life history traits and dengue virus loads post-infection. We predicted that larval crowding and high temperatures would both lead to smaller mosquitoes that might struggle to invest in an immune response and, hence, would exhibit high viral loads. METHODS: We first examined larval densities from urban and rural areas via a meta-analysis. We then used these data to inform a laboratory-based 2x2 design examining the interacting effects of temperature (21 vs. 26°C) and density (0.2 vs. 0.4 larvae/mL) on adult life history and dengue virus loads. RESULTS: We found that urban areas had an ~8-fold increase in larval densities compared to more rural sites. In the lab, we found that crowding had more impact on mosquito traits than temperature. Crowding led to slower development, smaller mosquitoes, less survival, lower fecundity, and higher viral loads, as predicted. The higher temperature led to faster development, reduced fecundity, and lower viral loads. The virus-reducing effect of higher temperature rearing was, however, overwhelmed by the impact of larval crowding when both factors were present. CONCLUSIONS: These data reveal complex interactions between the environmental effects experienced by immature mosquitoes and adult traits. They especially highlight the importance of crowding with respect to adult viral loads. Together, these data suggest that urban environments might enhance dengue virus loads and, therefore, possibly transmission, a concerning result given the increasing rates of urbanization globally.

The TIRS trial: Enrollment procedures and baseline characterization of a pediatric cohort to quantify the epidemiologic impact of targeted indoor residual spraying on Aedes-borne viruses in Merida, Mexico.

Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.

The Citizen as a Public Health Actor: Complaints as Public Engagement with Aedes Mosquito Control in Singapore, 1965-1985.

In 1986, the World Health Organization heralded Singapore as a model for the control of dengue fever, a viral disease spread by the Aedes aegypti mosquito. Between 1965 and 1985, public health officials successfully employed educational campaigns and mandatory home inspections to convince citizens to guard against mosquito breeding at home. Although this story appears to recapitulate standard narratives of top-down progress in Singapore, this paper argues that the significant role of the public in public health has been overlooked. Citizens complained frequently, sometimes publicly, to public health authorities and often compelled direct responses from them. Through these complaints, citizens modified official anti-mosquito measures and expanded the reach of public health. Public health in Singapore thus appears not simply as the imposition of an autonomous state's vision onto a docile or even resistant citizenry but as a coevolution of the state and the public.

Effects of the El Niño-Southern Oscillation and seasonal weather conditions on Aedes aegypti infestation in the State of São Paulo (Brazil): A Bayesian spatio-temporal study.

BACKGROUND: Seasonal fluctuations in weather are recognized as factors that affect both Aedes (Ae.) aegypti mosquitoes and the diseases they carry, such as dengue fever. The El Niño-Southern Oscillation (ENSO) is widely regarded as one of the most impactful atmospheric phenomena on Earth, characterized by the interplay of shifting ocean temperatures, trade wind intensity, and atmospheric pressure, resulting in extensive alterations in climate conditions. In this study, we investigate the influence of ENSO and local weather conditions on the spatio-temporal variability of Ae. aegypti infestation index. METHODS: We collected seasonal entomological survey data of immature forms of Ae. aegypti mosquitoes (Breteau index), as well as data on temperature, rainfall and the Oceanic Niño Index (ONI) for the period 2008-2018 over the 645 municipalities of the subtropical State of São Paulo (Brazil). We grounded our analytical approach on a Bayesian framework and we used a hierarchical spatio-temporal model to study the relationship between ENSO tracked by ONI, seasonal weather fluctuations and the larval index, while adjusting for population density and wealth inequalities. RESULTS: Our results showed a relevant positive effect for El Niño on the Ae. aegypti larval index. In particular, we found that the number of positive containers would be expected to increase by 1.30-unit (95% Credible Intervals (CI): 1.23 to 1.37) with El Niño events (i.e., ≥ 1°C, moderate to strong) respect to neutral (and weak) events. We also found that seasonal rainfall exceeding 153.12 mm appears to have a notable impact on vector index, leading potentially to the accumulation of ample water in outdoor discarded receptacles, supporting the aquatic phase of mosquito development. Additionally, seasonal temperature above 23.30°C was found positively associated to the larval index. Although the State of São Paulo as a whole has characteristics favourable to proliferation of the vector, there were specific areas with a greater tendency for mosquito infestation, since the most vulnerable areas are predominantly situated in the central and northern regions of the state, with hot spots of abundance in the south, especially during El Niño events. Our findings also indicate that social disparities present in the municipalities contributes to Ae. aegypti proliferation. CONCLUSIONS: Considering the anticipated rise in both the frequency and intensity of El Niño events in the forthcoming decades as a consequence of climate change, the urgency to enhance our ability to track and diminish arbovirus outbreaks is crucial.