Dengue Research Articles

A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil.

In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.

Newest “co-members” of the 1000s club: A case of severe transaminitis secondary to Epstein-Barr and dengue virus co-infection in a returning traveler

Background: Timely identification of the etiology of transaminitis is critical in informing subsequent management as strategies can vary from supportive care to urgent transplant assessment. This is especially important in returning travelers as there may be multiple causes of injury that need to be addressed. Case report: We present a case of severe transaminitis secondary to non-hepatitis viral co-infections. A 28-year-old south Asian male returning traveler presented with an acute liver injury (aspartate aminotransferase/alanine aminotransaminase levels of >4000 IU/l) and marked jaundice. A thorough and expanded work-up of acute hepatitis was negative aside from positive mononucleosis spot testing and positive dengue fever serologies. This atypical presentation of mononucleosis and dengue fever was managed conservatively, and the patient was discharged with outpatient follow-up after an eight-day admission. Conclusions: Usually, non-hepatitis viruses typically do not present with severe transaminitis or hyperbilirubinemia. These viruses, such as infectious mononucleosis and dengue fever, may work synergistically to cause an elevated inflammatory response, resulting in severe transaminitis in returning travelers. In the absence of a classic clinical presentation, clinicians should be aware of co-infections in returning travelers and test for them based on a thorough history and physical examination.

A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice

Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue virus (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity is poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions and higher neutralizing antibodies compared to circRNAs encoding monomeric or trimeric EDIII. Two doses of circRNAs encoding EDIII-Fc and ZIKV nonstructural protein NS1, another protective antigen, prevent lethal ZIKV infection in neonates born to immunized C57BL/6 mice and in interferon-α/β receptor knockout adult C57BL/6 mice. Importantly, a single-dose optimized circRNA vaccine with improved antigen expression confers potent and durable protection without inducing obvious DENV ADE in mice, laying the groundwork for developing flavivirus vaccines based on circRNAs encoding EDIII-Fc and NS1.

Empowering Communities through Citizen Science: Dengue Prevention in Córdoba.

Traditional mosquito vector control methods have proved ineffective in controlling the spread of dengue fever. This study aimed to assess the effectiveness of community engagement through student-led science in promoting dengue prevention and socioecological factors in the temperate urban city of Córdoba, Argentina. It assesses community perceptions, knowledge, attitudes, and preventive practices regarding dengue fever and its vector. Results showed a significant increase in knowledge about the vector and the disease and respondents' adoption of good preventive practices. Student-led science was identified as a valuable tool for reaching households and leading to behavior changes at home. Furthermore, the findings highlighted the need for school programs to address vector biology and vector-borne disease prevention all year round. This study provides invaluable insights into the effectiveness of community engagement through student-led science to promote dengue prevention and socioecological factors. The findings suggest that this approach could be used to control the spread in other regions affected by the disease.

Dengue fefer and mixed abortion among pregnant women: findgs of a comparative cross-sectional study

Background: Dengue situation in Bangladesh has escalated over the last few years causing significant mortality and morbidity. Pregnant women are highly vulnerable to dengue infection leading to various grave complications for both mother and foetus including missed abortion. Despite the severity of this condition, few studies have explored the association of dengue fever with missed abortion in Bangladesh. This study aimed to investigate the association between missed abortion and dengue fever. Methods: This comparative cross-sectional study enrolled 35 pregnant women having the history of missed abortion during the gestational age of less than 22 weeks and 35 pregnant women continuing their pregnancy with gestational age of more than 22 weeks receiving ante natal care. Both groups were selected conveniently. The study was conducted in a private facility from February to October, 2023. Data were collected from medical record review and analyzed with appropriate descriptive and analytical statistics. Cases of missed abortion attributed to dengue infection were compared with pregnant women receiving routine antenatal care if their pregnancies continued beyond 22 weeks’ gestation. Other predictive factors for missed abortion were also examined. Results: Dengue infection was detected among 14 (40%) of pregnant women with missed abortion in comparison to 3 (8.6%) pregnant women without missed abortion. Significant (p<0.05) association was found between dengue infection and missed abortion in pregnant women. Conclusion: Special preventive measures should be taken to protect pregnant mother against dengue infection. JOPSOM 2023; 42(1):62-67

Unraveling potential gene biomarkers for dengue infection through RNA sequencing.

Dengue virus hijacks host cell mechanisms and immune responses in order to replicate efficiently. The interaction between the host and the virus affects the host's gene expression, which remains largely unexplored. This pilot study aimed to profile the host transcriptome as a potential strategy for identifying specific biomarkers for dengue prediction and detection. High-throughput RNA sequencing (RNA-seq) was employed to generate host transcriptome profiles in 16 dengue patients and 10 healthy controls. Differentially expressed genes (DEGs) were identified in patients with severe dengue and those with dengue with warning signs compared to healthy individuals. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to elucidate the functions of upregulated and downregulated genes. Compared to healthy controls, 6466 genes were significantly differentially expressed (p < 0.05) in the dengue with warning signs group and 3082 genes in the severe dengue group, with over half being upregulated. The major KEGG pathways implicated included transport and catabolism (14.4%-16.3%), signal transduction (6.6%-7.3%), global and overview maps (6.7%-7.1%), viral diseases (4.6%-4.8%), and the immune system (4.4%-4.6%). Several genes exhibited consistent and significant upregulation across all dengue patients, regardless of severity: Interferon alpha inducible protein 27 (IFI27), Potassium Channel Tetramerization Domain Containing 14 (KCTD14), Syndecan 1 (SDC1), DCC netrin 1 receptor (DCC), Ubiquitin C-terminal hydrolase L1 (UCHL1), Marginal zone B and B1 cell-specific protein (MZB1), Nestin (NES), C-C motif chemokine ligand 2 (CCL2), TNF receptor superfamily member 17 (TNFSF17), and TNF receptor superfamily member 13B (TNFRSF13B). Further analysis revealed potential biomarkers for severe dengue prediction, including TNF superfamily member 15 (TNFSF15), Plasminogen Activator Inhibitor-2 (SERPINB2), motif chemokine ligand 7 (CCL7), aconitate decarboxylase 1 (ACOD1), Metallothionein 1G (MT1G), and Myosin Light Chain Kinase (MYLK2), which were expressed 3.5 times, 2.9 times, 2.3 times, 2.1 times, 1.7 times, and 1.4 times greater, respectively, than dengue patients exhibiting warning signs. The identification of these host biomarkers through RNA-sequencing holds promising implications and potential to augment existing dengue detection algorithms, contributing significantly to improved diagnostic and prognostic capabilities.

A Study of Clinical, Hematological and Biochemical Profiles of Patients with Pancytopenia

This study aimed to investigate patients’ clinical, hematologic, and biochemical profiles with pancytopenia. This prospective observational study was conducted at a tertiary care hospital from January 2019 to June 2020 on 80 patients, 39 (48.7%) were males and 41 (51.2%) were females, over the age of 18 presenting with pancytopenia. All the patients were subjected to thorough clinical and physical examinations. A complete blood count (CBC), peripheral smear examination, bone marrow aspiration, and reticulocyte count were performed. The data was analyzed using the IBM SPSS 20.0 software. Most of the cases had moderate (Hb&lt;7-9.9g/dl) anemia (63.7%, 51/80 cases), while severe anemia (&lt;7g/dl) was seen in 31.2% (25/80) cases, and 5% (04/80) cases showed mild anemia (Hb&lt;10-11.9g/dl). Most patients with severe anemia had vitamin B12 deficiency anemia (12/80), that is, 15%. Macrocytic anemia was noted in preponderance (50% cases, 40/80), whereas microcytic hypochromic and normocytic hypochromic anemia constituted 21.3% (17/80), and dimorphic anemia was seen in 7.5% (06/80) cases. Based on WBC counts, 56.3% of cases (45/80) showed counts between 2000 and 4000 cells/cu.mm, while counts between 1000 and 2000 cells/cu.mm were seen in 31.3% of cases (25/80), and 12.5% of cases (10/80) had counts of &lt;1000 cells/cu.mm. The study highlighted that 28.8% (23/80) had a platelet count between 50,000 and 1 lakh/cu.mm (mild thrombocytopenia), 36.3% (29/80) cases had a platelet count between 20,000 and 50,000/cu.mm (moderate thrombocytopenia), and 35% (28/80) cases had a platelet count less than 20,000/cu.mm (severe thrombocytopenia). The most common diagnosis of bone marrow aspiration was megaloblastic anemia, seen in 50.0% (6/12) cases. Megaloblasts were seen in 50.0% (6/12) cases of megaloblast anemia. The bone marrow aspirate of a patient with dengue fever and malaria showed macrophages containing engulfed red blood cells, lymphocytes, and platelets. Myeloblasts (&gt;20%) were seen in 1 (8.3%) case of AML, and decreased myelopoiesis was seen in 25% of cases (two cases of aplastic anemia and one case of MDS). This study concludes that vitamin B12 deficiency is the most common cause, which is more common in people who are strict vegetarians, with a predominance in the younger age group. The study also emphasized the vitality of the physical findings, detailed primary hematologic and biochemical investigations, and peripheral blood pictures, all of which provide precious information in the work-up of pancytopenia patients.

Malaria and dengue fever in febrile children entering healthcare facilities in Mwanza, Tanzania.

Plasmodium spp. infections and cases of malaria are a long-standing public health problem for children living in middle- and low-income countries. Dengue virus causes an emerging under-recognized disease burden. A cross sectional study was conducted between March 2020 and December 2021 to determine the status of malaria and dengue fever, and the associated factors in children living in Mwanza, Tanzania. Clinical features were recorded; blood samples were analyzed using dengue NS1 rapid diagnostics test (NS1-RDT), malaria rapid diagnostic test (MRDT) and PCR and microscopy for malaria parasites. Descriptive analysis was based on infection status; odds ratio and confidence interval were used to determine the factors associated with dengue fever and malaria. The prevalence of malaria in the 436 children included in the final analysis was 15.6%, 8.5%, and 12.1% as determined by MRDT, blood smear examination and PCR, respectively. The prevalence of dengue fever determined by the NS1-RDT was 7.8%. Body rash, muscle and joint/bone pain were associated with a positive rapid dengue test result. Retro-orbital pain characterized Plasmodium spp. and dengue virus co-infections. Clinical signs and symptoms could not readily differentiate between malaria and dengue fever patients or patients co-infected with both causative agents underscoring the urgent need for the accurate laboratory diagnostics. Additional large-scale studies are required to assess the epidemiological burden of acute febrile illness in developing countries and to produce data that will guide empirical treatment.

Dengue Fever in Urban Bangladesh: Atypical Presentations and Platelet Count Dynamics

Dengue fever, an arboviral infection transmitted by Aedes mosquitoes, remains a significant public health challenge in urban Bangladesh, especially in densely populated areas like Dhaka. This retrospective study investigates atypical clinical manifestations and platelet count dynamics among dengue patients, analyzing the association between thrombocytopenia and disease severity. Twenty patients treated in Dhaka were analyzed for clinical and hematological markers, with a specific focus on atypical presentations and platelet-hematocrit correlations. The findings highlight that while thrombocytopenia is a well-established indicator of dengue severity, several patients with critically low platelet counts did not exhibit typical warning signs, necessitating a more nuanced clinical approach.

Comprehending symmetry in epidemiology: A review of analytical methods and insights from models of COVID-19, Ebola, Dengue, and Monkeypox.

The challenge of developing comprehensive mathematical models for guiding public health initiatives in disease control is varied. Creating complex models is essential to understanding the mechanics of the spread of infectious diseases. We reviewed papers that synthesized various mathematical models and analytical methods applied in epidemiological studies with a focus on infectious diseases such as Severe Acute Respiratory Syndrome Coronavirus-2, Ebola, Dengue, and Monkeypox. We address past shortcomings, including difficulties in simulating population growth, treatment efficacy and data collection dependability. We recently came up with highly specific and cost-effective diagnostic techniques for early virus detection. This research includes stability analysis, geographical modeling, fractional calculus, new techniques, and validated solvers such as validating solver for parametric ordinary differential equation. The study examines the consequences of different models, equilibrium points, and stability through a thorough qualitative analysis, highlighting the reliability of fractional order derivatives in representing the dynamics of infectious diseases. Unlike standard integer-order approaches, fractional calculus captures the memory and hereditary aspects of disease processes, resulting in a more complex and realistic representation of disease dynamics. This study underlines the impact of public health measures and the critical importance of spatial modeling in detecting transmission zones and informing targeted interventions. The results highlight the need for ongoing financing for research, especially beyond the coronavirus, and address the difficulties in converting analytically complicated findings into practical public health recommendations. Overall, this review emphasizes that further research and innovation in these areas are crucial for addressing ongoing and future public health challenges.

Cerebellar Involvement in Dengue Fever

Abstract Dengue fever is a common and important arboviral infection prevalent in tropical countries, contributing to significant morbidity and mortality. The clinical spectrum of dengue fever ranges from simple febrile illness to life-threatening complications such as dengue hemorrhagic fever and dengue shock syndrome. Among the many unusual manifestations of this fever, a rare entity is its cerebellar involvement. This report aims to highlight this uncommon presentation.

Training on producing eucalyptus and betel leaf oil for dengue fever prevention

Dengue Hemorrhagic Fever (DHF) remains a significant public health issue in Indonesia and is endemic in nearly all provinces. The mortality rate from DHF continues to rise each year. To address this, health education on dengue fever prevention is essential. One preventive measure involves the use of natural ingredients. Betel leaves, in particular, can kill mosquito larvae due to the toxic substances they contain, which are especially harmful to mosquito larvae. Therefore, community service activities are necessary to raise awareness and provide practical solutions. This activity was conducted in Jetis Village, Sukoharjo, targeting 30 women in the Family Welfare Program (PKK) from the local community. The implementation included the preparation of pre-tests and post-tests, as well as training sessions. The questionnaire used in this activity assessed participants' skills through a pretest, followed by training in making eucalyptus and betel leaf oil, and concluded with a post-test. The results showed a significant improvement in the participants' skills, with most moving from "moderately competent" to "competent," as indicated by a P-value of 0.001. It can be concluded that the oil-making training effectively improved the skills of the PKK women.

Unlocking Hope: Paving the Way for a Cutting-Edge Multi-Epitope Dengue Virus Vaccine.

Dengue fever is a significant health issue in Pakistan, demanding a vaccine effective against all the viral strains. This study employs reverse vaccinology to develop potential dengue vaccine candidates (DVAX I-III). The study thoroughly examinedconserved areas of dengue virus serotypes 1-4's structural and non-structural proteins. Key viral proteins were analyzed to find antigenic peptides, which were incorporated into vaccine candidates and potentiated with adjuvants. Computational methods predicted peptide structures and evaluated their binding to immune receptors TLR 2, TLR 4, HLA *A1101, and DRB*401. A molecular dynamics simulation lasting 100ns of the DVAX II-TLR4 complex at different time intervals clearly indicated that the ligand is attached to the receptor. Normal mode analysis assessed the stability and flexibility of these interactions. Encouragingly, all three vaccine candidates demonstrated favorable interactions with these immune receptors and the potential to induce a robust immune response. These findings suggest their safety and warrant further in vivo studies to evaluate their efficacy for clinical development.

The Link between Dengue Fever and Kawasaki Disease in Children

The association between Kawasaki disease and dengue fever is uncommon and can be difficult to diagnose due to overlapping clinical symptoms. There have been few reported cases of children with confirmed dengue fever developing Kawasaki disease. A prior infection of dengue fever pronouncing a worse manifestation of Kawasaki disease is due to the very rare cases of this entity unknown. If a prior dengue fever associated with later Kawasaki disease leads to higher incidence of coronary dilatations in children are not clearly ruled out. The population of this concomitant entity is very small and therefore difficult to analyze incidentally due to high significant scientific standards. What is known is, that differentiating both diseases shows sometimes a clinical dilemma in children.

Dengue Envelope Protein as a Cytotoxic Factor Inducing Hemorrhage and Endothelial Cell Death in Mice

Dengue virus (DENV) infection, prevalent in tropical and subtropical regions, can progress to dengue hemorrhagic fever (DHF), which increases mortality during secondary infections. DHF is characterized by endothelial damage and vascular leakage. Despite its severity, no specific antiviral treatments exist, and the viral factors responsible for endothelial damage remain unclear. This study examines the role of the DENV envelope protein domain III (EIII) in inducing endothelial apoptosis using a mouse model. Additionally, we aim to explore whether cell death-inducing pathways could serve as drug targets to ameliorate EIII-induced endothelial injury and hemorrhage. In vitro experiments using human endothelial HMEC-1 cells demonstrated that both recombinant EIII (rEIII) and DENV markedly induced caspase-3-mediated endothelial cell death, an effect that was attenuated by co-treatment with chondroitin sulfate B (CSB), N-acetyl cysteine (NAC), and the caspase-3 inhibitor z-DEVD-FMK. In vivo, sequential injections of rEIII and anti-platelet immunoglobulin in mice, designed to mimic the clinical phase of DHF with peak viremia followed by an increase in DENV-induced Ig, including autoantibodies, revealed that these dual treatments markedly triggered caspase-3-dependent apoptosis in vascular endothelial cells at hemorrhage sites. Treatments with z-DEVD-FMK effectively reduced DHF-like symptoms such as thrombocytopenia, hemorrhage, inflammation, hypercoagulation, and endothelial damage. Additionally, CSB and NAC alleviated hemorrhagic symptoms in the mice. These results suggest that targeting EIII, reactive oxygen species, and caspase-3-mediated apoptosis could offer potential therapeutic strategies for addressing EIII-induced hemorrhagic pathogenesis.

Inhibitory peptides derived from Hepatitis C virus NS5A for reducing clinical symptoms of dengue virus infection

Lethal Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) caused by Dengue virus (DENV) infection necessitate the development of effective treatments. Peptides derived from the N-terminal amphipathic α-helix of hepatitis C virus (HCV) NS5A exhibit antiviral activity by disrupting liposomes with high curvatures, such as virus envelopes. This study engineered five peptides from HCV genotype 3a NS5A N-terminal α-helix and screened them for neutralizing efficacy against three DENV serotypes. Two peptides, 3a 3/20 and DS-05, showed superior therapeutic efficacy against DENV and were further evaluated in treating DHF/DSS induced by mouse-adapted DENV infection. Administration of 3a 3/20 and DS-05 post-infection significantly improved mortality and weight loss associated with DHF/DSS in AG6 mice. These peptides reduced viral load in internal organs and viremia to levels comparable with the positive control drug, JNJ-A07, a DENV NS3-NS4B inhibitor. Additionally, they attenuated the cytokine storm in the blood and expression of inflammatory cytokines in internal organ tissues, ameliorating liver and kidney dysfunction after DENV infection. Histopathological analysis revealed significant suppression of damages in internal organs. These findings suggest that the 3a 3/20 and DS-05 peptides improve clinical symptoms of DHF/DSS induced by DENV infection, indicating their potential for clinical application.

Genomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to Mosnodenvir

Dengue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. Here, by analyzing dengue virus (DENV) genomes from the 2023-2024 epidemic in the French Caribbean Islands, we show that they all exhibit mutation NS4B:V91A, previously associated with a marked decrease in sensitivity to mosnodenvir in vitro. Using antiviral activity tests on four clinical and reverse-genetic strains, we confirm a marked decrease in mosnodenvir sensitivity for DENV-2 ( > 1000 fold). Finally, combining phylogenetic analysis and experimental testing for resistance, we find that virus lineages with low sensitivity to mosnodenvir due to the V91A mutation likely emerged multiple times over the last 30 years in DENV-2 and DENV-3. These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains.

A mixed method evaluation of knowledge, attitude and practice on dengue fever among Lalitpur Metropolitan City residents: a cross-sectional investigation.

Dengue poses a significant global public health challenge, including in Nepal. Understanding community's knowledge, attitudes, and behaviors concerning dengue fever is imperative to developing effective prevention and control strategies. This study aimed to assess the knowledge, attitude, and practices related to dengue fever among residents of Lalitpur Metropolitan City. A descriptive cross-sectional household study was conducted using a mixed-method approach, which included quantitatively studying 636 individuals and conducting 20 qualitative interviews. The data was collected between April 2023 and June 2023. The multistage cluster sampling method was applied for household selection during the quantitative study and a purposive judgmental sampling method was used to identify participants for the qualitative interviews. Face-to-face interviews were conducted using a structured questionnaire for the quantitative study and an interview guide for the qualitative study. Quantitative data were analysed using logistic regression in STATA version 13, and thematic analysis was applied to the qualitative data. The findings were validated through triangulation of results from both the qualitative and quantitative study. Regarding knowledge, 64.94% (n = 413/636) reported being informed about dengue fever. In terms of attitude, a substantial majority, 91.51% (n = 582/636), expressed a positive attitudes toward dengue fever, indicating a favorable perception and knowledge of its significance. Concerning practice, 49.84% (n = 317/636) of respondents reported actively engaging in dengue fever prevention measures. The variables gender, previous history of dengue fever and residency were the determinants of dengue fever knowledge. Additionally, gender, residency, and attitude were predictors of preventive practices concerning dengue fever. Our study revealed that while the community demonstrated good knowledge of dengue fever and positive attitudes toward prevention, their preventive practices were inconsistent, indicating a gap between knowledge and action. A positive attitude was linked to better adherence to preventive measures. To address this gap, it is crucial to promote a positive attitude toward dengue prevention through initiatives like education efforts and social mobilization programs. Implementing Social and Behavior Change Communication (SBCC) programs focused on dengue prevention and control measures can help bridge this knowledge-action gap.

Glycerophospholipid remodeling is critical for orthoflavivirus infection.

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.

“Dengue fever is not just urban or rural: Reframing its spatial categorization.”

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.