Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor
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99 GENERAL AND MISCELLANEOUS↗
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Google Health Trends performance reflecting dengue incidence for the Brazilian states
Abstract Background Dengue fever is a mosquito-borne infection transmitted by Aedes aegypti and mainly found in tropical and subtropical regions worldwide. Since its re-introduction in 1986, Brazil has become a hotspot for dengue and has experienced yearly epidemics. As a notifiable infectious disease, Brazil uses a passive epidemiological surveillance system to collect and report cases; however, dengue burden is underestimated. Thus, Internet data streams may complement surveillance activities by providing real-time information in the face of reporting lags. Methods We analyzed 19 terms related to dengue using Google Health Trends (GHT), a free-Internet data-source, and compared it with weekly dengue incidence between 2011 to 2016. We correlated GHT data with dengue incidence at the national and state-level for Brazil while using the adjusted R squared statistic as primary outcome measure (0/1). We used survey data on Internet access and variables from the official census of 2010 to identify where GHT could be useful in tracking dengue dynamics. Finally, we used a standardized volatility index on dengue incidence and developed models with different variables with the same objective. Results From the 19 terms explored with GHT, only seven were able to consistently track dengue. From the 27 states, only 12 reported an adjusted R squared higher than 0.8; these states were distributed mainly in the Northeast, Southeast, and South of Brazil. The usefulness of GHT was explained by the logarithm of the number of Internet users in the last 3 months, the total population per state, and the standardized volatility index. Conclusions The potential contribution of GHT in complementing traditional established surveillance strategies should be analyzed in the context of geographical resolutions smaller than countries. For Brazil, GHT implementation should be analyzed in a case-by-case basis. State variables including total population, Internet usage in the last 3 months, and the standardized volatility index could serve as indicators determining when GHT could complement dengue state level surveillance in other countries.
59 BASIC BIOLOGICAL SCIENCES↗
Assessing Disparities of Dengue Virus Transmission Risk across the US-Mexican Border Using a Climate Driven Vector-Epidemiological Model
Dengue fever is a mosquito‐borne viral disease reemerging throughout much of the tropical Americas. Dengue virus transmission is explicitly influenced by climate and the environment through its primary vector, Aedes aegypti. Temperature regulates Ae. aegypti development, survival, and replication rates as well as the incubation period of the virus within the mosquito. Precipitation provides water for many of the preferred breeding habitats of the mosquito, including buckets, old tires, and other places water can collect. Although transmission regularly occurs along the border region in Mexico, dengue virus transmission in bordering Arizona has not occurred. Using NASA's TRMM (Tropical Rainfall Measuring Mission) satellite for precipitation input and Daymet for temperature and supplemental precipitation input, we modeled dengue transmission along a US‐Mexico transect using a dynamic dengue transmission model that includes interacting vector ecology and epidemiological components. Model runs were performed for 5 cities in Sonora, Mexico and southern Arizona. Employing a Monte Carlo approach, we performed ensembles of several thousands of model simulations in order to resolve the model uncertainty arising from using different combinations of parameter values that are not well known. For cities with reported dengue case data, the top model simulations that best reproduced dengue case numbers were retained and their parameter values were extracted for comparison. These parameter values were used to run simulations in areas where dengue virus transmission does not occur or where dengue fever case data was unavailable. Additional model runs were performed to reveal how changes in climate or parameter values could alter transmission risk along the transect. The relative influence of climate variability and model parameters on dengue virus transmission is assessed to help public health workers prepare location specific infection prevention strategies.
Morin, Cory↗
Variations in Modeled Dengue Transmission over Puerto Rico Using a Climate Driven Dynamic Model
Dengue fever is a mosquito‐borne viral disease reemerging throughout much of the tropical Americas. Dengue virus transmission is explicitly influenced by climate and the environment through its primary vector, Aedes aegypti. Temperature regulates Ae. aegypti development, survival, and replication rates as well as the incubation period of the virus within the mosquito. Precipitation provides water for many of the preferred breeding habitats of the mosquito, including buckets, old tires, and other places water can collect. Because of variations in topography, ocean influences and atmospheric processes, temperature and rainfall patterns vary across Puerto Rico and so do dengue virus transmission rates. Using NASA's TRMM (Tropical Rainfall Measuring Mission) satellite for precipitation input, ground‐based observations for temperature input, and laboratory confirmed dengue cases reported by the Centers for Disease Control and Prevention for parameter calibration, we modeled dengue transmission at the county level across Puerto Rico from 2010‐2013 using a dynamic dengue transmission model that includes interacting vector ecology and epidemiological components. Employing a Monte Carlo approach, we performed ensembles of several thousands of model simulations for each county in order to resolve the model uncertainty arising from using different combinations of parameter values that are not well known. The top 1% of model simulations that best reproduced the reported dengue case data were then analyzed to determine the most important parameters for dengue virus transmission in each county, as well as the relative influence of climate variability on transmission. These results can be used by public health workers to implement dengue control methods that are targeted for specific locations and climate conditions.
Morin, Cory↗
Changing temperature profiles and the risk of dengue outbreaks
As temperatures change worldwide, the pattern and competency of disease vectors will change, altering the global distribution of both the burden of infectious disease and the risk of the emergence of those diseases into new regions. To evaluate the risk of potential summer dengue outbreaks triggered by infected travelers under various climate scenarios, we develop an SEIR-type model, run numerical simulations, and conduct sensitivity analyses under a range of temperature profiles. Our model extends existing theoretical frameworks for studying dengue dynamics by introducing temperature dependence of two key parameters: the mosquito extrinsic incubation period and the lifespan of mosquitoes, which empirical data suggests are both highly temperature dependent. We find that changing temperature significantly alters dengue risk in an inverted U-shape, with temperatures in the range 27-31°C producing the highest risk. As temperatures increase beyond 31°C, the determinants of dengue risk begin to shift from mosquito biting rate and carrying capacity to the duration of the human infectious period, suggesting that changing temperatures not only alter dengue risk but also the potential efficacy of control measures. To illustrate the role of spatial and temporal temperature heterogeneity, we select five US cities where the primary dengue vector, the mosquito Aedes aegypti , has been observed, and which have had dengue cases in the past: Los Angeles, Houston, Miami, Brownsville, and Phoenix. Our analysis suggests that an increase of 3°C leads to an approximate doubling of the risk of dengue in Los Angeles and Houston, but a reduction of risk in Miami, Brownsville, and Phoenix due to extreme heat.
54 ENVIRONMENTAL SCIENCES↗
Simulated Transmission of the Dengue Virus Across the US-Mexico Border Using Remotely Sensed and Ground Based Weather Data
Incidence of dengue fever, caused by a mosquito transmitted virus, have increased in the Americas during recent decades. In the US, local transmission has been reported in southern Texas and Florida. However, despite its close proximity to dengue endemic areas in Mexico and the presence of a primary mosquito vector, there are no reports of local transmission in Arizona. Many studies have demonstrated that weather influences dengue virus transmission by regulating vector development rates, vector habitat availability, and the duration of the virus extrinsic incubation period (EIP). The EIP, the period between mosquito infection and the ability for it to retransmit the virus, is especially important given its high sensitivity to temperature and the short lifespan of mosquitoes. Other studies, however, have suggested that human related factors such as socioeconomic status and herd immunity may explain much of the disparity in dengue incidence in the US‐Mexico border region. Using a meteorologically driven model of vector population dynamics and virus transmission we compare simulations of dengue fever cases in southern Arizona and northern Mexico. A Monte Carlo approach is employed to select parameter values by evaluating simulations in Hermosillo Mexico with reported dengue fever case data. Simulations that replicate the case data best are retained and rerun using remotely sensed climate data from other Arizona and Mexico locations to determine the relative influence of weather on virus transmission. Although human and environmental factors undoubtedly influence dengue transmission in the US‐Mexico border regions, weather is a major facilitator of the transmission process.
Dengue↗
Age-specific case data reveal varying dengue transmission intensity in US states and territories
Dengue viruses (DENV) are endemic in the US territories of Puerto Rico, American Samoa, and the US Virgin Islands, with focal outbreaks also reported in the states of Florida and Hawaii. However, little is known about the intensity of dengue virus transmission over time and how dengue viruses have shaped the level of immunity in these populations, despite the importance of understanding how and why levels of immunity against dengue may change over time. These changes need to be considered when responding to future outbreaks and enacting dengue management strategies, such as guiding vaccine deployment. We used catalytic models fitted to case surveillance data stratified by age from the ArboNET national arboviral surveillance system to reconstruct the history of recent dengue virus transmission in Puerto Rico, American Samoa, US Virgin Islands, Florida, Hawaii, and Guam. We estimated average annual transmission intensity (i.e., force of infection) of DENV between 2010 and 2019 and the level of seroprevalence by age group in each population. We compared models and found that assuming all reported cases are secondary infections generally fit the surveillance data better than assuming all cases are primary infections. Using the secondary case model, we found that force of infection was highly heterogeneous between jurisdictions and over time within jurisdictions, ranging from 0.00008 (95% CrI: 0.00002–0.0004) in Florida to 0.08 (95% CrI: 0.044–0.14) in American Samoa during the 2010–2019 period. For early 2020, we estimated that seropositivity in 10 year-olds ranged from 0.09% (0.02%–0.54%) in Florida to 56.3% (43.7%–69.3%) in American Samoa. In the absence of serological data, age-specific case notification data collected through routine surveillance combined with mathematical modeling are powerful tools to monitor arbovirus circulation, estimate the level of population immunity, and design dengue management strategies.
60 APPLIED LIFE SCIENCES↗
Characterizing risk for Dengue in Brazil: a multi-dimensional approach
Dengue is the most common mosquito-borne infectious disease worldwide, primarily caused by the Aedes Aegypti mosquitoes. There are approximately 100-400 million cases annually, with roughly half of the global population at risk. In recent years, and particularly in 2024, there has been a major increase in Dengue cases in North and South America. One of the most heavily affected countries is Brazil, where there has been a 230% increase in cases in 2024 compared to 2023. In a report in June 2024, the CDC released a report indicating 3 risk groups for dengue: infants aged ≤1 year, pregnant women, and adults over 65 years old. Due to the spike in cases, it’s important to understand what factors contribute to Dengue risk and create a model to quantify it in order to inform decisions on how to respond. The main 2 parts of this project were a) exploring the spatial relationships between these 3 Dengue risk group populations and aedes aegypti mosquitoes in Brazil and b) creating an index to quantify risk for Dengue in Brazil. The 10 cities with the highest risk were identified, and it was found that the east coast and southern regions are at highest risk. The findings in this study provide insights into cities and areas of Brazil that should be focused on for targeting Dengue spread.
59 BASIC BIOLOGICAL SCIENCES↗
Modeled Forecasts of Dengue Fever in San Juan, PR Using NASA Satellite Enhanced Weather Forecasts
Dengue virus is transmitted between humans and mosquitoes of the genus Aedes and causes approximately 96 million cases of disease (dengue fever) each year (Bhatet al. 2013). Symptoms of dengue fever include fever, headache, nausea, vomiting, and eye, muscle and joint pain (CDC). More sever manifestations such as abdominal pain, bleeding from nose and gums, vomiting of blood, and clammy skin occur in rare cases of dengue hemorrhagic fever (CDC). Dengue fever occurs throughout tropical and sub-tropical regions worldwide, however, the geographical range and size of epidemics is increasing. Weather and climate are drivers of dengue virus transmission dynamics (Morin et al. 2013) by affecting mosquito proliferation and the virus extrinsic incubation period (i.e. required time for the virus to replicate and disseminate within the mosquito before it can retransmit the virus).
vector↗
Environmental and Socio-Demographic Determinants of Dengue Fever in Colombo City, Sri Lanka
Dengue fever has increased exponentially in Sri Lanka, from 24.4 cases per 100,000 in 2003 to 165.3 per 100,000 population in 2013. Although early warning systems using predictor models have been previously developed in other settings, it is important to develop such models in each local setting. Further, the ability of these models to be applicable at smaller geographic units will enhance current vector control and disease surveillance measures. The aim of this paper was to identify environmental and socio-economic status (SES) risk factors that may predict dengue fever at the Gram Niladhari Divisions (GND) level (smallest administrative unit) in Colombo city, Sri Lanka. These factors included landcover classes, amount of vegetation, population density, water access and neighborhood SES as determined by roof type. A geographically weighted regression (GWR) was used to develop the prediction model. A total 55 GND units covering an area of 37 sq km were investigated. We found that GND units with decreased vegetation, higher built-up area, higher population density and poor access to tap-water supply were associated with high risk of dengue; the pertinent GND units were concentrated in the center of the city. This is the first study in Sri Lanka to include both environmental and socio-demographic factors in prediction models for dengue fever. The methodology may be useful in enhancing ongoing dengue fever control measures in the country, and to be extended to other countries in the region that have an increasing incidence of dengue fever.
Tipre, Meghan↗
Municipality Level Simulations of Dengue Fever Incidence in Puerto Rico Using Ground Based and Remotely Sensed Climate Data
Dengue fever (DF) is caused by a virus transmitted between humans and Aedes genus mosquitoes through blood feeding. In recent decades incidence of the disease has drastically increased in the tropical Americas, culminating with the Pan American outbreak in 2010 which resulted in 1.7 million reported cases. In Puerto Rico dengue is endemic, however, there is significant inter‐annual, intraannual, and spatial variability in case loads. Variability in climate and the environment, herd immunity and virus genetics, and demographic characteristics may all contribute to differing patterns of transmission both spatially and temporally. Knowledge of climate influences on dengue incidence could facilitate development of early warning systems allowing public health workers to implement appropriate transmission intervention strategies. In this study, we simulate dengue incidence in several municipalities in Puerto Rico using population and meteorological data derived from ground based stations and remote sensing instruments. This data was used to drive a process based model of vector population development and virus transmission. Model parameter values for container composition, vector characteristics, and incubation period were chosen by employing a Monte Carlo approach. Multiple simulations were performed for each municipality and the results were compared with reported dengue cases. The best performing simulations were retained and their parameter values and meteorological input were compared between years and municipalities. Parameter values varied by municipality and year illustrating the complexity and sensitivity of the disease system. Local characteristics including the natural and built environment impact transmission dynamics and produce varying responses to meteorological conditions.
Remote Sensing↗
Using heterogeneous data to identify signatures of dengue outbreaks at fine spatio-temporal scales across Brazil
Dengue virus remains a significant public health challenge in Brazil, and seasonal preparation efforts are hindered by variable intra- and interseasonal dynamics. Here, we present a framework for characterizing weekly dengue activity at the Brazilian mesoregion level from 2010–2016 as time series properties that are relevant to forecasting efforts, focusing on outbreak shape, seasonal timing, and pairwise correlations in magnitude and onset. In addition, we use a combination of 18 satellite remote sensing imagery, weather, clinical, mobility, and census data streams and regression methods to identify a parsimonious set of covariates that explain each time series property. The models explained 54% of the variation in outbreak shape, 38% of seasonal onset, 34% of pairwise correlation in outbreak timing, and 11% of pairwise correlation in outbreak magnitude. Regions that have experienced longer periods of drought sensitivity, as captured by the “normalized burn ratio,” experienced less intense outbreaks, while regions with regular fluctuations in relative humidity had less regular seasonal outbreaks. Both the pairwise correlations in outbreak timing and outbreak trend between mesoresgions were best predicted by distance. Our analysis also revealed the presence of distinct geographic clusters where dengue properties tend to be spatially correlated. Forecasting models aimed at predicting the dynamics of dengue activity need to identify the most salient variables capable of contributing to accurate predictions. Our findings show that successful models may need to leverage distinct variables in different locations and be catered to a specific task, such as predicting outbreak magnitude or timing characteristics, to be useful. This advocates in favor of “adaptive models” rather than “one-size-fits-all” models. The results of this study can be applied to improving spatial hierarchical or target-focused forecasting models of dengue activity across Brazil.
59 BASIC BIOLOGICAL SCIENCES↗
Graph Representation Learning for Dengue Forecasting
In 2017, the largest recorded dengue outbreak in Sri Lanka’s history occurred. Since then, dengue has continued to threaten national health across Sri Lanka. The development of an effective Early Warning System (EWS) for dengue outbreaks is essential for Sri Lanka’s Ministry of Health to take preventative measures. We propose the use of Graph Neural Networks as EWS. Using earth observational data from NASAs global satellites and dengue incidence data from Sri Lanka s Ministry of Health, we developed a series of traditional and graph representation EWS to forecast Dengue cases across Sri Lanka’s 25 districts between 2013 and 2022. We demonstrate empirically that Graph Neural Networks which incorporate spatiotemporal relations significantly outperform traditional EWS such as Autoregressive Integrated Moving Average (ARIMA), Random Forest, and Long Short-Term Memory (LSTM). Our source code is available on GitHub and will be provided in the final submission.
Graph Neural Networks↗
Electropolymerized-molecularly imprinted polymers (E-MIPS) as sensing elements for the detection of dengue infection
Here, a straightforward in situ detection method for dengue infection was demonstrated through the molecular imprinting of a dengue nonstructural protein 1 (NS1) epitope into an electropolymerized molecularly imprinted polyterthiophene (E-MIP) film sensor. The key enabling step in the sensor fabrication is based on an epitope imprinting strategy, in which short peptide sequences derived from the original target molecules were employed as the main template for detection and analysis. The formation of the E-MIP sensor films was facilitated using cyclic voltammetry (CV) and monitored in situ by electrochemical quartz crystal microbalance (EC-QCM). Surface properties were analyzed using different techniques including atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and polarization modulation-infrared reflection-adsorption (PM-IRRAS). The standard calibration curve (R = 0.9830) was generated for the detection of the epitope, Ac-VHTWTEQYKFQ-NH 2 , with a linear range of 0.2 to 30 μg/mL and detection limit of 0.073 μg/mL. A separate calibration curve (R = 0.9786) was obtained using spiked buffered solutions of dengue NS1 protein, which resulted in a linear range of 0.2 to 10 μg/mL and a detection limit of 0.056 μg/mL. The fabricated E-MIP sensor exhibited long-term stability, high sensitivity, and good selectivity towards the targeted molecules. These results indicated that the formation of the exact and stable cavity imprints in terms of size, shape, and functionalities was successful. In our future work, we aim to use our E-MIP sensors for NS1 detection in real-life samples such as serum and blood.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Structure of the dengue virus RNA promoter
Dengue virus, a single-stranded positive sense RNA virus, is the most prevalent mosquito-borne pathogen in the world. Like all RNA viruses, it uses conserved structural elements within its genome to control essential replicative steps. A 70 nt stem–loop RNA structure (called SLA), found at the 5'-end of the genome of all flaviviruses, functions as the promoter for viral replication. This highly conserved structure interacts with the viral polymerase NS5 to initiate RNA synthesis. Here, we report the NMR structure of a monomeric SLA from dengue virus serotype 1, assembled to high-resolution from independently folded structural elements. The DENV1 SLA has an L-shaped structure, where the top and side helices are coaxially stacked, and the bottom helix is roughly perpendicular to them. Because the sequence is highly conserved among different flavivirus genomes, it is very likely that the three-dimensional fold and local structure of SLA are also conserved among flaviviruses and required for efficient replication. This work provides structural insight into the dengue promoter and provides the foundation for the discovery of new antiviral drugs that target this essential replicative step.
59 BASIC BIOLOGICAL SCIENCES↗
A Coupled Mathematical Model of the Intracellular Replication of Dengue Virus and the Host Cell Immune Response to Infection
Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, infecting globally 390 million individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter because of severe plasma leakage. Given that the outcome of infection is likely determined by the kinetics of viral replication and the antiviral host cell immune response (HIR) it is of importance to understand the interaction between these two parameters. In this study, we use mathematical modeling to characterize and understand the complex interplay between intracellular DV replication and the host cells' defense mechanisms. We first measured viral RNA, viral protein, and virus particle production in Huh7 cells, which exhibit a notoriously weak intrinsic antiviral response. Based on these measurements, we developed a detailed intracellular DV replication model. We then measured replication in IFN competent A549 cells and used this data to couple the replication model with a model describing IFN activation and production of IFN stimulated genes (ISGs), as well as their interplay with DV replication. By comparing the cell line specific DV replication, we found that host factors involved in replication complex formation and virus particle production are crucial for replication efficiency. Regarding possible modes of action of the HIR, our model fits suggest that the HIR mainly affects DV RNA translation initiation, cytosolic DV RNA degradation, and naïve cell infection. We further analyzed the potential of direct acting antiviral drugs targeting different processes of the DV lifecycle in silico and found that targeting RNA synthesis and virus assembly and release are the most promising anti-DV drug targets.
59 BASIC BIOLOGICAL SCIENCES↗
Envisioning urban environments resilient to vector-borne diseases: a protocol to study dengue in Vietnam
Transmitted primarily by Aedes aegypti (Ae. aegypti) and Aedes albopictus (Ae. albopictus), arboviral diseases pose a major global public health threat. Dengue, chikungunya, and zika are increasingly prevalent in Southeast Asia. Among other arboviruses, dengue and zika are becoming more common in Central and South America. Given human encroachment into previously uninhabited, often deforested areas, to provide new housing in regions of population expansion, conceptualizing built urban environments in a novel way is urgently needed to safeguard against the growing climate change-driven threat of vector-borne diseases. By understanding the spread from a One Health perspective, enhanced control and prevention can be achieved. This is particularly important considering that climate change is likely to significantly impact the persistence of ponded water where mosquitoes breed due to increasing temperature and shifting rainfall patterns with regard to magnitude, duration, frequency, and season. Models can incorporate aquatic mosquito stages and adult spatial dynamics when habitats are heterogeneously available, thereby including dispersal and susceptible-exposed-infected-recovered (SEIR) epidemiology. Coupled with human population distribution (density, locations), atmospheric conditions (air temperature, precipitation), and hydrological conditions (soil moisture distribution, ponding persistence in topographic depressions), modeling has improved predictive ability for infection rates. However, it has not informed interventional approaches from an urban environment perspective which considers the role of ponds/lakes that support green spaces, the density of population that enables rapid spread of disease, and varying micro-habitats for various mosquito stages under climate change. Here, for an example of dengue in Vietnam, a preventive and predictive approach to design resilient urban environments is proposed, which uses data from rapidly expanding metropolitan communities to learn continually. This protocol deploys computational approaches including simulation and machine learning/artificial intelligence, underpinned by surveillance and medical data for validation and adaptive learning. Its application may best inform urban planning in low-middle income countries in tropical zones where arboviral pathogens are prevalent.
60 APPLIED LIFE SCIENCES↗
Designed, highly expressing, thermostable dengue virus 2 envelope protein dimers elicit quaternary epitope antibodies
Dengue virus (DENV) is a worldwide health burden, and a safe vaccine is needed. Neutralizing antibodies bind to quaternary epitopes on DENV envelope (E) protein homodimers. However, recombinantly expressed soluble E proteins are monomers under vaccination conditions and do not present these quaternary epitopes, partly explaining their limited success as vaccine antigens. Using molecular modeling, we found DENV2 E protein mutations that induce dimerization at low concentrations (<100 pM) and enhance production yield by more than 50-fold. Cross-dimer epitope antibodies bind to the stabilized dimers, and a crystal structure resembles the wild-type (WT) E protein bound to a dimer epitope antibody. Mice immunized with the stabilized dimers developed antibodies that bind to E dimers and not monomers and elicited higher levels of DENV2-neutralizing antibodies compared to mice immunized with WT E antigen. Our findings demonstrate the feasibility of using structure-based design to produce subunit vaccines for dengue and other flaviviruses.
59 BASIC BIOLOGICAL SCIENCES↗