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Infectious diseases exploit niches that are often spatially defined as urban and/or rural. Yet spatial research on infectious diseases often fails to define "urban" and "rural" and how these contexts might influence their epidemiology. We use dengue fever, thought to be mostly an urban disease with rural foci, as a device to explore local definitions of urban and rural spaces and the impact of these spaces on dengue risk in the provinfine urban and rural locales. Interviews conducted from 2019 to 2021 with 71 residents and 23 health personce of Esmeraldas, Ecuador. Ecuador, like many countries, only uses population size and administrative function to denel found that they identified the availability of basic services, extent of their control over their environment, and presence of underbrush and weeds (known in Ecuador as monte and maleza and conceptualized in this paper as natural disorder) as important links to their conceptions of space and dengue risk. This broader conceptualization of space articulated by local residents and professionals reflects a more sophisticated approach to characterizing dengue risk than using categories of urban and rural employed by the national census and government. Rather than this dichotomous category of space, dengue fever can be better framed for health interventions in terms of specific environmental features and assemblages of high-risk spaces. An understanding of how community members perceive risk enhances our ability to collaborate with them to develop optimal mitigation strategies.

Major dengue epidemics throughout Nicaraguas history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity.

The intention-to-treat (ITT) analysis of the Applying Wolbachia to Eliminate Dengue (AWED) trial estimated a protective efficacy of 77.1% for participants resident in areas randomised to receive releases of wMel-infected Aedes aegypti mosquitoes, an emerging dengue preventive intervention. The limiting assumptions of ITT analyses in cluster randomised trials and the mobility of mosquitoes and humans across cluster boundaries indicate the primary analysis is likely to underestimate the full public health benefit. Using spatiotemporally-resolved data on the distribution of Wolbachia mosquitoes and on the mobility of AWED participants (n = 6306), we perform complier-restricted and per-protocol re-examinations of the efficacy of the Wolbachia intervention. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis returned an estimated efficacy of 80.7% (95% CI 65.9, 89.0) and the per-protocol analysis estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimated wMel exposure of ≥ 80% compared to those with

Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.

Infectious diseases are a significant burden in global healthcare. Pathogens engage with different host defense mechanisms. However, it is currently unknown if there are disease-specific immune signatures and/or if different pathogens elicit common immune-associated molecular entities to common therapeutic interventions. We studied patients enrolled through the Human Immunology Project Consortium (HIPC), which focuses on immune responses to various infections. Blood samples were collected and analyzed from patients during infection and follow-up time points at the convalescent stage. The study included samples from patients with Lyme disease (LD), tuberculosis (TB), malaria (MLA), dengue virus (DENV), and West Nile virus (WNV), as well as kidney transplant patients with cytomegalovirus (CMV) and polyomavirus (BKV) infections. Using an antibody-based assay, we quantified ~ 350 cell surface markers, cytokines, and chemokines involved in inflammation and immunity. Unique protein signatures were identified specific to the acute phase of infection irrespective of the pathogen type, with significant changes during convalescence. In addition, tumor necrosis factor receptor superfamily member 6 (TNR6), C-C Motif Chemokine Receptor 7 (CCR7), and C-C motif chemokine ligand-1 (CCL1) were increased in the acute and convalescent phases across all viral, bacterial, and protozoan compared to blood from healthy donors. Furthermore, despite the differences between pathogens, proteins were enriched in common biological pathways such as cell surface receptor signaling pathway and response to external stimulus. In conclusion, we demonstrated that irrespective of the pathogen type, there are common immunoregulatory and proinflammatory signals.

Dengue viruses (DENV1-4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

The distribution and intensity of viral diseases transmitted by Aedes aegypti mosquitoes, including dengue, have rapidly increased over the last century. Here, we study dengue virus (DENV) transmission across the ecologically and demographically distinct regions or Ecuador. We analyzed province-level age-stratified dengue incidence data from 2000-2019 using catalytic models to estimate the force of infection of DENV over eight decades. We found that provinces established endemic DENV transmission at different time periods. Coastal provinces with the largest and most connected cities had the earliest and highest increase in DENV transmission, starting around 1980 and continuing to the present. In contrast, remote and rural areas with reduced access, like the northern coast and the Amazon regions, experienced a rise in DENV transmission and endemicity only in the last 10 to 20 years. The newly introduced chikungunya and Zika viruses have age-specific distributions of hospital-seeking cases consistent with recent emergence across all provinces. To evaluate factors associated with geographic differences in DENV transmission potential, we modeled DENV vector risk using 11,693 Aedes aegypti presence points to the resolution of 1 hectare. In total, 56% of the population of Ecuador, including in provinces identified as having increasing DENV transmission in our models, live in areas with high risk of Aedes aegypti, with population size, trash collection, elevation, and access to water as important determinants. Our investigation serves as a case study of the changes driving the expansion of DENV and other arboviruses globally and suggest that control efforts should be expanded to semi-urban and rural areas and to historically isolated regions to counteract increasing dengue outbreaks.

Dengue fever is a mosquito-borne illness that infects 390 million people annually. Dengue outbreaks in Guatemala have been occurring more often and at increased rates since the first dengue outbreak in Guatemala in the 1970s. This study will examine environmental and socioeconomic factors associated with dengue in Guatemala at the municipality (county) level. Socioeconomic factors included population density, Mayan population, economic activity, and attending school. Environmental factors included average minimum annual temperature and annual precipitation. The relationship between environmental and socioeconomic variables and dengue fever incidence was initially evaluated through univariate zero-inflated negative binomial models, and then again through three zero-inflated multivariate negative binomial regression models. For all three models, elevation was considered a predictor of zero-inflation. In the combined model, there was a positive relationship between minimum temperature, economic activity and dengue fever incidence, and a negative relationship between population density, Mayan population and dengue fever. Predicted rates of dengue fever incidence and adjusted confidence intervals were calculated after increasing minimum yearly temperature by 1°C and 2°C. The three municipalities with the highest minimum yearly temperature (El Estor, Iztapa, and Panzós) and the municipality of Guatemala, all had an increase in the magnitude of the risk of dengue fever incidence following 1°C and 2°C increase in temperature. This research suggests that these socioeconomic and environmental factors are associated with risk of dengue in Guatemala. The predicted rates of dengue fever also highlight the potential effect that climate change in the form of increasing temperature can have on dengue in Guatemala.

Dengue fever (DF) is one of the most rapidly spreading mosquito-borne viral diseases in the world. It can impose an enormous socioeconomic and disease burden on the world's population. The spatial and temporal distribution patterns of DF cases in China are heterogeneous. It is evident that further research is necessary to identify the high-risk areas of dengue occurrence and associated risk factors at a fine spatiotemporal scale. This will facilitate the prevention and control of DF transmission. With the rapid development of remote sensing (RS) and geographic information system (GIS) technology, RS and GIS technology have played an important role in monitoring, forecasting, and identifying influencing factors and formulating prevention and control strategies for DF. In China, the majority of dengue cases were clustered in Guangdong and Yunnan Provinces. In this study, Bayesian spatiotemporal models were fitted at the county level in order to quantify the relationships between environmental and socioeconomic factors and DF. Our findings indicate that both environmental and socioeconomic factors can affect the transmission of DF in Guangdong and Yunnan Provinces. However, the underlying drivers and the spatially clustered patterns observed in the two provinces appear to be different. The results indicate that elevated temperatures facilitate the transmission of DF, but it was found that the risk of DF begins to decrease when the temperature exceeds 27.6 oC in Guangdong Province. There was a positive correlation between temperature and the incidence of DF, although no statistical significance was found in Yunnan Province. In Guangdong Province, the amount of precipitation did not significantly affect the incidence of DF. In Yunnan Province, the relationship between precipitation and DF is nonlinear. As the amount of precipitation increases, the risk of DF epidemics increases. In addition, vegetation cover can significantly affect the DF transmission, but the nonlinear relationships between vegetation cover and DF are diverse and complex in these two provinces. The incidence of DF was found to be positively correlated with the level of urbanization at the county level. The findings may prove beneficial to the governments of both provinces in the development of targeted strategies for the control of DF outbreaks at the county level. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionDengue virus causes illnesses with or without warning indicators for severe complications. There are no clear prognostic signs linked to the disease outcomes.Clinical and laboratory parameters among 102 adult including 17 severe dengue (SD), 33 with warning and 52 without warning signs during early and critical phases were analyzed by statistical and machine learning (ML) models.In classical statistics, abnormal ultrasound findings, platelet count, and low lymphocytes were significantly linked with SD during the febrile phase, while low creatinine, high sodium, and elevated AST/ALT during the critical phase. ML models highlighted AST/ALT and lymphocytes as key markers for distinguishing SD from non-severe dengue, aiding clinical decisions.Parameters like liver enzymes, platelet counts and USG findings were linked with SD.USG testing at an earlier phase of dengue and a point-of-care system for the quantification of AST/ALT levels may lead to an early prediction of SD. [ABSTRACT FROM AUTHOR]

Background Dengue virus (DENV) nonstructural protein 1 (NS1) has multiple functions within infected cells, on the cell surface, and in secreted form, and is highly immunogenic. Immunity from previous DENV infections is known to exert both positive and negative effects on subsequent DENV infections, but the contribution of NS1-specific antibodies to these effects is incompletely understood. Methods We investigated the functions of NS1-specific antibodies and their significance in DENV infection. We analyzed plasma samples collected in a prospective cohort study prior to symptomatic or subclinical secondary DENV infection. We measured binding to purified recombinant NS1 protein and to NS1-expressing CEM cells, antibody-mediated natural killer (NK) cell activation by plate-bound NS1 protein, and antibody-dependent cellular cytotoxicity (ADCC) of NS1-expressing target cells. Results We found that antibody responses to NS1 were highly serotype cross-reactive and that subjects who experienced subclinical DENV infection had significantly higher antibody responses to NS1 in preinfection plasma than subjects who experienced symptomatic infection. We observed strong positive correlations between antibody binding and NK activation. Conclusions These findings demonstrate the involvement of NS1-specific antibodies in ADCC and provide evidence for a protective effect of NS1-specific antibodies in secondary DENV infection. [ABSTRACT FROM AUTHOR]

Ground water tanks are known to be preferred Aedes aegypti oviposition places providing opportunities for adult and larvae control. Therefore, a dual‐effect insecticidal coating (IC) (alphacypermethrin/ pyriproxyfen) with a slow‐release mechanism and safe for users could be applied within Aedes spp. breeding sites, representing a promising option. Bioassays were designed to determine the mortality and sterilizing effects on gravid mosquitoes exposed to IC. The effect of inhibition of emergence was evaluated in eggs, larvae and pupae exposed in different containers. For the water safety assessment concentrations of active ingredients were determined by reverse phase high performance liquid chromatography (RP‐HPLC) and the health risk was calculated. The IC applied to the interior walls of water‐holding containers showed efficacy against Ae. aegypti in terms of high gravid‐female mortality (81% at 24 h, p < 0.01), sterilizing effect (inhibition of oviposition by 63%, p < 0.01) and emergence inhibition (100% in eggs, L3 and L4; 97% in pupae). The offspring rate was reduced [only 0.15 (38/250) new adults emerged per exposed gravid females as against 11.90 per unexposed female (2976/250) at baseline]. Emergence inhibition was recorded up to 12 months and adult mortality >80% up to 6 months. The use of water stored in treated containers, either for washing or drinking, is not expected to pose a health risk to users. IC applied to domestic water containers has dual and complementary action that reduces Ae. aegypti densities (immature and adult stages). This represents baseline information for a cluster randomized efficacy trial in Colombia. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze the epidemiological and clinical characteristics of dengue fever (DF) in Fuzhou, the capital city of Fujian Province, southeast China. Methods: A retrospective analysis was performed on 251 cases of DF diagnosed at the fever clinic of the Second Affiliated Hospital of Fujian University of Chinese Medicine in Fuzhou City, Fujian Province. Epidemic characteristics, such as the number of cases, age distribution, sex distribution, seasonal distribution, and spatial distribution in each region, were analyzed. The patients' clinical manifestations, signs, auxiliary examinations, and prognoses were analyzed. Results: The age distribution of DF cases was mainly concentrated in 30–39 years (20.72%) and 50–59 years (21.12%). There were no sex differences among the patients. Of these cases, 60.16% were concentrated on the lower floors, with retirees having the highest proportion. The seasonal peak of DF in Fuzhou area was from September to November. The SDE plot showed that the cases were mainly concentrated in Jin'an and Gulou districts. Etiological tests revealed serum NS1 antigen (97.61%), serum IgM antibody (15.14%), and serum IgG antibody (0.40%). There were no significant differences in clinical manifestations between the children's and non-children's groups. Laboratory tests have shown that the disease is prone to multi-system dysfunction, including the blood system, digestive system, urinary system and internal environment. ROC curve analysis showed that WBC, N, LY, PLT, and CRP levels had specific diagnostic values for DF. Conclusions: The epidemiological situation and clinical characteristics of DF in Fuzhou City were analyzed to guide the formulation of reasonable prevention and treatment measures. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is a mosquito-borne virus that causes dengue fever, a significant public health concern in many tropical and subtropical regions. Dengue is endemic in more than 100 countries, primarily in tropical and subtropical regions of the world. Each year, up to 400 million people get infected with dengue. Approximately 100 million people get sick from infection, and 40,000 die from severe dengue. Unfortunately, dengue vaccine development is also marred with various complicating factors, as the forefront candidate vaccine performed unsatisfactorily. Moreover, the only licensed vaccine (Dengvaxia) for children 9 through 16 years of age is available in just a few countries. The treatment difficulties are compounded by the absence of an effective antiviral agent. Exploring plant-based therapeutics for dengue from the laboratory to clinical application involves a multi-stage process, encompassing various scientific disciplines. Individual investigators have screened a wide range of plant extracts or compounds for potential antiviral activity against DENV. In vitro studies help identify candidates that exhibit inhibitory effects on viral replication. Some of the most promising medicinal plants showing in vitro activity against DENV include Andrographis paniculate, Acorus calamus, and Cladogynos orientalis. Further laboratory studies, both in vitro and in animal models (in vivo), elucidate the mechanisms of action by which the identified compounds exert antiviral effects. Medicinal plants such as Carica papaya, Cissampelos pareira, and Ipomea batata exhibited potent platelet-enhancing activities while Azadirachta indica and Curcuma longa showed promising effects in both in vitro and in vivo studies. Based on positive preclinical results, researchers design clinical trials. This involves careful planning of trial phases, patient recruitment criteria, ethical considerations, and endpoints. The most important medicinal plants showing efficacy and safety in clinical trials include Carica papaya and Cissampelos pareira. This review suggests that several promising medicinal plants exist that have the potential to be turned into clinical drugs to treat dengue infection. However, in addition to developing synthetic and plant-based therapies against dengue infection, vector management strategies should be made robust, emphasizing the need to focus on reducing disease incidence. [ABSTRACT FROM AUTHOR]

Background: The 2023 dengue outbreak has proven that dengue is not only an endemic disease but also an emerging health threat in Bangladesh. Integrated studies on the epidemiology, clinical characteristics, seasonality, and genotype of dengue are limited. This study was conducted to determine recent trends in the molecular epidemiology, clinical features, and seasonality of dengue outbreaks. Methods: We analyzed data from 41 original studies, extracting epidemiological information from all 41 articles, clinical symptoms from 30 articles, and genotypic diversity from 11 articles. The study adhered to the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration guidelines. Results: A total of 565,438 dengue cases and 2,587 fatalities were documented from January 2000 to March 2024. Notably, 60% of cases during the 2019 and 2023 outbreaks were reported in regions previously considered non-endemic. Fatalities were more frequent among women (70%). The majority of the studies (95–100%) used the NS1Ag test, followed by IgG or IgM and RT-PCR tests. New hotspots of dengue transmission were identified in the southern (Khulna, 10.8% and Barishal, 11.8%) and southeastern (Chattogram, 13.8%) regions of Bangladesh. Serotyping was conducted on 92.4% (1,456 of 1,575) of isolates between 2012 and 2023. Of the four serotypes, DENV3 was the most prevalent (57%), followed by DENV2 (30%), DENV1 (11%), and DENV4 (<1%). Genotype DENV3-I (43 of 59 isolates) was the most prevalent, followed by DENV3-II (8 of 59). The highest frequency of dengue cases was observed in August (26.3%), followed by September (22.5%), October (20.2%), and November (13.08%). Fever (90.51, 95% CI 85–100%) was the most prevalent symptom, followed by headache (57.98, 95% CI 12–100%), vomiting (51.16, 95% CI 23–91%), abdominal pain (34.12, 95% CI 12–85%), and myalgia (25.53, 95% CI 13–85%), respectively. Conclusion: This study provides integrated insights into the molecular epidemiology, clinical features, seasonality, and transmission of dengue in Bangladesh and highlights research gaps for future studies. [ABSTRACT FROM AUTHOR]