Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection.

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

A perspective on the worst ever dengue outbreak 2023 in Bangladesh: What makes this old enemy so deadly, and how can we combat it?

Background and Aims: Bangladesh has been going through outbreaks of dengue fever cases every year since 2000. Yet this year's (2023) episode of dengue fever has crossed every line concerning fatality. Symptoms of the fever range from high fever, headaches, and muscle aches to deadly dengue hemorrhagic fever (DHF). The present review aims to assess the current pathogenicity and associated risk factors of recent dengue outbreaks in Bangladesh. Methods: To perform this review work, we extracted relevant information from published articles available in PubMed, Scopus, and Google Scholar. We used dengue virus, dengue fever, and dengue outbreaks as keywords while searching for information. Results: This Aedes mosquito-transmitted viral fever is more common in Bangladesh because of the tropical nature and immense burden of populations, resulting in convenient conditions for the reproduction of the vector. The rapid genetic transformation of this RNA virus and the resistance of its vector against insecticides have intensified the situation. The number of hospitalized patients has increased, and the case fatality rate has risen to 0.47%. Inadequate mosquito control measures, plenty of vector breeding sites, and a lack of public awareness have worsened the situation. Routine spraying of effective insecticides in high-risk zones, regular inspection of potential mosquito breeding sites, and public awareness campaigns are the keys to limiting the spread of this virus. Also, the availability of detection kits, improved hospital settings, and trained health professionals are mandatory to keep disease fatalities under control. Conclusion: Dengue fever is a preventable disease. The successful development of a competent vaccine is now a prime need for preventing any future upsurge of the disease. Also, we recommend public awareness, vector control activities, and global collaboration to prevent spread.

Comparison of the Sensitivity and Specificity of Commercial Anti-Dengue Virus IgG Tests to Identify Persons Eligible for Dengue Vaccination.

The Advisory Committee on Immunization Practices (ACIP) recommended that dengue pre-vaccination screening tests for Dengvaxia administration have at least 98% specificity and 75% sensitivity. This study evaluates the performance of commercial anti-DENV IgG tests to identify tests that could be used for pre-vaccination screening. First, for 7 tests, we evaluated sensitivity and specificity in early convalescent dengue virus (DENV) infection, using 44 samples collected 7-30 days after symptom onset and confirmed by RT-PCR. Next, for the 5 best performing tests and two additional tests (with and without an external test reader) that became available later, we evaluated performance to detect past dengue infection among a panel of 44 specimens collected in 2018-2019 from healthy 9-16-year-old children from Puerto Rico. Finally, a full-scale evaluation was done with the 4 best performing tests using 400 specimens from the same population. We used virus focus reduction neutralization test and an in-house DENV IgG ELISA as reference standards. Of seven tests, five showed ≥75% sensitivity detecting anti-DENV IgG in early convalescent specimens with low cross-reactivity to Zika virus. For the detection of previous DENV infections the tests with the highest performance were the Euroimmun NS1 IgG ELISA (sensitivity 84.5%, specificity 97.1%) and CTK Dengue IgG rapid test R0065C with the test reader (sensitivity 76.2% specificity 98.1%). There are IgG tests available that can be used to accurately classify individuals with previous DENV infection as eligible for dengue vaccination to support safe vaccine implementation.

Investigating the Clinico-Demographic Characteristics of Dengue Fever and Its Seroprevalence at a Tertiary Care Hospital in Northern India.

Background and objective Dengue virus (DENV) is a major global health threat, causing over 50,000 deaths annually. The state of Uttar Pradesh (UP) in India faces significant challenges due to the increasing number of dengue cases detected. This study aimed to assess DENV seropositivity in the Raebareli district of UP, to offer crucial insights into the region's effective control and management strategies. Materials and methods This study, after obtaining approval from the ethics committee, analyzed blood samples of individuals suspected of having dengue at a teaching hospital in rural UP between January and December 2022. To determine the disease's seroprevalence, both dengue NS1 antigen ELISA and dengue IgM Microlisa were conducted. Furthermore, RT-PCR was performed on NS1-positive samples to confirm the serotypes. The collected data were analyzed using Epi Info 7.0. Results Of the 589 suspected dengue cases, 86 (14.60%) tested positive for dengue NS1 and/or IgM. Our findings showed that males (n=330, 56.03%) and adolescents and young adults (n=301, 51.1%) from rural areas (n=523, 88.4%) were predominantly affected. Cases peaked post-monsoon, and platelet levels were notably low in NS1-positive cases. Dengue serotype 2 (DEN-2) was found in all RT-PCR-positive samples. Our results revealed a dengue seroprevalence of 14.60% (n=86), which peaked in post-monsoon months. The higher incidence among males and young adults from rural areas attending the outpatient department highlights the importance of targeted interventions and community surveillance. RT-PCR confirmed the circulation of a single serotype in the region. Conclusions This study contributes crucial insights into dengue's epidemiology and clinical profile and its findings are all the more significant now as India prepares for phase 3 trials of a quadrivalent dengue-virus vaccine in 2024. Adolescent and young adult males have an increased likelihood of acquiring the virus, and this demographic can be prioritized for vaccine trials.

Dengue virus serotypes and related factors in children with dengue hemorrhagic fever in Southern Vietnam.

INTRODUCTION: After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study aimed to determine the distribution of dengue virus serotypes and their correlation with demographic factors, disease severity, clinical manifestations, and laboratory findings. METHODOLOGY: This study employed a cross-sectional design. Ninety-six dengue-infected children admitted to Can Tho Children's Hospital between October 2022 and March 2023 were included. Confirmation of dengue infection was achieved through the real-time polymerase chain reaction (RT-PCR). RESULTS: Among the identified serotypes, DENV-2 accounted for the highest proportion (71.87%), followed by DENV-1 (23.96%), and DENV-4 (4.17%). DENV-3 was not detected. No significant demographic, disease severity, or laboratory differences were observed among the identified dengue serotypes. However, DENV-2 was associated with a higher occurrence of mucous membrane hemorrhages and gastrointestinal bleeding compared to other serotypes. CONCLUSIONS: Although DENV-2 was the most prevalent serotype responsible for dengue in children in southern Vietnam, it did not lead to more severe cases compared to other serotypes. This finding is crucial for evaluating the illness's prognosis.

The rising global economic costs of invasive Aedes mosquitoes and Aedes-borne diseases.

Invasive Aedes aegypti and Aedes albopictus mosquitoes transmit viruses such as dengue, chikungunya and Zika, posing a huge public health burden as well as having a less well understood economic impact. We present a comprehensive, global-scale synthesis of studies reporting these economic costs, spanning 166 countries and territories over 45 years. The minimum cumulative reported cost estimate expressed in 2022 US$ was 94.7 billion, although this figure reflects considerable underreporting and underestimation. The analysis suggests a 14-fold increase in costs, with an average annual expenditure of US$ 3.1 billion, and a maximum of US$ 20.3 billion in 2013. Damage and losses were an order of magnitude higher than investment in management, with only a modest portion allocated to prevention. Effective control measures are urgently needed to safeguard global health and well-being, and to reduce the economic burden on human societies. This study fills a critical gap by addressing the increasing economic costs of Aedes and Aedes-borne diseases and offers insights to inform evidence-based policy.

Spatiotemporal models of dengue epidemiology in the Philippines: Integrating remote sensing and interpretable machine learning.

Previous dengue epidemiological analyses have been limited in spatiotemporal extent or covariate dimensions, the latter neglecting the multifactorial nature of dengue. These constraints, caused by rigid and traditional statistical tools which collapse amidst 'Big Data', prompt interpretable machine-learning (iML) approaches. Predicting dengue incidence and mortality in the Philippines, a data-limited yet high-burden country, the mlr3 universe of R packages was used to build and optimize ML models based on remotely sensed provincial and dekadal 3 NDVI and 9 rainfall features from 2016 to 2020. Between two tasks, models differ across four random forest-based learners and two clustering strategies. Among 16 candidates, rfsrc-year-case and ranger-year-death significantly perform best for predicting dengue incidence and mortality, respectively. Therefore, temporal clustering yields the best models, reflective of dengue seasonality. The two best models were subjected to tripartite global exploratory model analyses, which encompass model-agnostic post-hoc methods such as Permutation Feature Importance (PFI) and Accumulated Local Effects (ALE). PFI reveals that the models differ in their important explanatory aspect, rainfall for rfsrc-year-case and NDVI for ranger-year-death, among which long-term average (lta) features are most relevant. Trend-wise, ALE reveals that average incidence predictions are positively associated with 'Rain.lta', reflective of dengue cases peaking during the wet season. In contrast, those for mortality are negatively associated with 'NDVI.lta', reflective of urban spaces driving dengue-related deaths. By technologically addressing the challenges of the human-animal-ecosystem interface, this study adheres to the One Digital Health paradigm operationalized under Sustainable Development Goals (SDGs). Leveraging data digitization and predictive modeling for epidemiological research paves SDG 3, which prioritizes holistic health and well-being.

3D-QSAR and molecular docking studies of peptide-hybrids as dengue virus NS2B/NS3 protease inhibitors.

Global warming and climate change have made dengue disease a global health issue. More than 50 % of the world's population is at danger of dengue virus (DENV) infection, according to the World Health Organization (WHO). Therefore, a clinically approved dengue fever vaccination and effective treatment are needed. Peptide medication development is new pharmaceutical research. Here we intend to recognize the structural features inhibiting the DENV NS2B/NS3 serine protease for a series of peptide-hybrid inhibitors (R1-R2-Lys-R3-NH2) by the 3D-QSAR technique. Comparative molecular field analysis (q2 = 0.613, r2 = 0.938, r2pred = 0.820) and comparative molecular similarity indices analysis (q2 = 0.640, r2 = 0.928, r2pred = 0.693) were established, revealing minor, electropositive, H-bond acceptor groups at the R1 position, minor, electropositive, H-bond donor groups at the R2 position, and bulky, hydrophobic groups at the R3 position for higher inhibitory activity. Docking studies revealed extensive H-bond and hydrophobic interactions in the binding of tripeptide analogues to the NS2B/NS3 protease. This study provides an insight into the key structural features for the design of peptide-based inhibitors of DENV NS2B/NS3 protease.

In-vitro assessment of cutaneous immune responses to aedes mosquito salivary gland extract and dengue virus in Cambodian individuals.

Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.

Hyperinsulinemic State and Hypokalemic Quadriparesis in Tropical Fever: Is There a Link?

It is rare for quadriparesis to manifest as a symptom of tropical illnesses. With a history of only one fever episode one week prior, our patient, a 48-year-old male with obesity and prediabetes, who was also known to have ankylosing spondylitis, presented with acute onset flaccid quadriparesis. He did not exhibit any additional symptoms of dengue, such as bleeding tendencies, petechial rashes, thrombocytopenia, or febrile episodes. Upon examination, it was discovered that he had extremely low serum potassium levels and was dengue non-specific antigen 1 (NS1) positive. His hyperinsulinemia, as seen by elevated C peptide levels, most likely caused a transcellular shift that was then triggered by the dengue infection, leading to hypokalemic paralysis.

A scoping literature review of global dengue age-stratified seroprevalence data: estimating dengue force of infection in endemic countries.

BACKGROUND: Dengue poses a significant burden worldwide, and a more comprehensive understanding of the heterogeneity in the intensity of dengue transmission within endemic countries is necessary to evaluate the potential impact of public health interventions. METHODS: This scoping literature review aimed to update a previous study of dengue transmission intensity by collating global age-stratified dengue seroprevalence data published in the Medline, Embase and Web of Science databases from 2014 to 2023. These data were then utilised to calibrate catalytic models and estimate the force of infection (FOI), which is the yearly per-capita risk of infection for a typical susceptible individual. FINDINGS: We found a total of 66 new publications containing 219 age-stratified seroprevalence datasets across 30 endemic countries. Together with the previously available average FOI estimates, there are now more than 250 dengue average FOI estimates obtained from seroprevalence studies from across the world. INTERPRETATION: The results show large heterogeneities in average dengue FOI both across and within countries. These new estimates can be used to inform ongoing modelling efforts to improve our understanding of the drivers of the heterogeneity in dengue transmission globally, which in turn can help inform the optimal implementation of public health interventions. FUNDING: UK Medical Research Council, Wellcome Trust, Community Jameel, Drugs for Neglected Disease initiative (DNDi) funded by the French Development Agency, Médecins Sans Frontières International; Swiss Agency for Development and Cooperation and UK aid.

Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation, and flight activity in the major arbovirus vector Aedes aegypti.

Aedes aegypti females are natural vectors of important arboviruses such as dengue, zika, and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on A. aegypti flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin A expression in fat bodies in a time-dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP-linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24 h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24 h. Importantly, rotenone-sensitive respiration and complex I-III activity were specifically reduced 24 h upon zymosan injection. Also, loss of complex I activity compromised ATP-linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.

Prevalence and mortality of haemophagocytic lymphohistiocytosis in dengue fever: a systematic review and meta-analysis.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare complication of dengue fever with potentially life-threatening consequences and high mortality. Therefore, this study aims to investigate the prevalence, management and outcome of HLH in dengue fever. METHODS: The major electronic databases, including PubMed, ScienceDirect and Ovid SP, were searched from inception until 31 January 2024 to identify relevant studies. Pooled prevalence and mortality were calculated using the random-effects generic inverse variance model with a 95% CI. All the statistical analysis was conducted using R programming. RESULTS: A total of nine studies with 157 patients with HLH, 576 patients with severe dengue and 5081 patients with dengue fever were included in this meta-analysis. The prevalence of HLH in severe dengue (22.1%, 95% CI 8.07 to 48.0%) was significantly higher than the prevalence in dengue fever (3.12%, 95% CI 0.37 to 21.9%). The prevalence of HLH in severe dengue was higher in the paediatric population (22.8%, 95% CI 3.9 to 68.4%) compared with the adult population (19.0%, 95% CI 3.0 to 63.9%). The overall mortality rate was 20.2% (95% CI 9.7 to 37.2%). CONCLUSION: The prevalence of dengue-associated HLH was low in patients with dengue fever but is significantly higher in patients with severe dengue and a high mortality rate.

Dengue: A review of laboratory diagnostics in the vaccine age.

Background. Dengue is an important arboviral infection of considerable public health significance. It occurs in a wide global belt within a variety of tropical regions. The timely laboratory diagnosis of Dengue infection is critical to inform both clinical management and an appropriate public health response. Vaccination against Dengue virus is being introduced in some areas.Discussion. Appropriate diagnostic strategies will vary between laboratories depending on the available resources and skills. Diagnostic methods available include viral culture, the serological detection of Dengue-specific antibodies in using enzyme immunoassays (EIAs), microsphere immunoassays, haemagglutination inhibition or in lateral flow point of care tests. The results of antibody tests may be influenced by prior vaccination and exposure to other flaviviruses. The detection of non-structural protein 1 in serum (NS1) has improved the early diagnosis of Dengue and is available in point-of-care assays in addition to EIAs. Direct detection of viral RNA from blood by PCR is more sensitive than NS1 antigen detection but requires molecular skills and resources. An increasing variety of isothermal nucleic acid detection methods are in development. Timing of specimen collection and choice of test is critical to optimize diagnostic accuracy. Metagenomics and the direct detection by sequencing of viral RNA from blood offers the ability to rapidly type isolates for epidemiologic purposes.Conclusion. The impact of vaccination on immune response must be recognized as it will impact test interpretation and diagnostic algorithms.

The alteration of NK cells phenotypes related to the functions and dengue disease outcomes.

Natural killer cells (NK cells) are the front line of immune cells to combat pathogens and able to influence the subsequent adaptive immune responses. One of the factors contributing to pathogenesis in dengue hemorrhagic fever (DHF) disease is aberrant immune activation during early phase of infection. This study explored the profile of NK cells in dengue infected pediatric patients with different degrees of disease severity. DHF patients contained higher frequency of activated NK cells but lower ratio of CD56dim:CD56bright NK subsets. Activated NK cells exhibited alterations in several NK receptors. Interestingly, the frequencies of NKp30 expressing activated NK cells were more pronounced in dengue fever (DF) than in DHF pediatric patients. In vitro functional analysis indicated that degranulation of NK cells in responding to dengue infected dendritic cells (DCs) required cell-cell contact and type I IFNs. Meanwhile, Interferon gamma (IFN-γ) production initially required cell-cell contact and type I IFNs followed by Interleukin-12 (IL-12), Interleukin-15 (IL-15) and Interleukin-18 (IL-18) resulting in the amplification of IFN-γ producing NK cells over time. This study highlighted the complexity and the factors influencing NK cells responses to dengue virus. Degree of activation, phenotypes of activated cells and the crosstalk between NK cells and other immune cells, could modulate the outcome of NK cells function in the dengue disease.

Diagnostic performance of the bioline dengue duo rapid test on symptomatic patients assisted at Armed Forces Hospital (Hfa) in Brasília, Brazil.

Dengue necessitates accurate diagnosis. Rapid tests such as Bioline™ DENGUE DUO have gained traction, but validation in specific populations is essential. This study aimed to evaluate the performance of the Bioline™ test, alongside assessing the socio-epidemiological profile of symptomatic patients in a Brasília Military Hospital. The serum of 404 symptomatic patients was analyzed by the Bioline™ DENGUE DUO test, followed by Dengue virus detection and discrimination of the four serotypes by RT-qPCR. Accuracy was assessed using parameters including sensitivity (S), specificity (E), positive and negative predictive values (PPV and NPV), and positive (RV +) and negative (RV-) likelihood ratios. The NS1 component exhibited a sensitivity of 70.37%, a specificity of 97.30%, and an overall efficiency of 90.10% when compared to RT-qPCR as the gold standard. The IgM component demonstrated a sensitivity of 26.85%, a specificity of 89.53%, and an overall efficiency of 72.77% when compared to RT-qPCR as the gold standard. The IgG component demonstrated a sensitivity of 23.15%, a specificity of 68.92%, and an overall efficiency of 56.68% when compared to RT-qPCR as the gold standard. Several rapid tests are commercially available. However, considering variations across regions and demographic groups, it is important to question their accuracy in specific populations. Rapid tests are important screening tools, but they can have limitations for the certainty of diagnosis. Bioline™ DENGUE DUO displayed good specificity, but sensitivity was slightly below optimal levels. While helpful for confirming dengue, improvements are needed to effectively rule out the disease.

Neuroinvasion of emerging and re-emerging arboviruses: A scoping review.

Background: Arboviruses are RNA viruses and some have the potential to cause neuroinvasive disease and are a growing threat to global health. Objectives: Our objective is to identify and map all aspects of arbovirus neuroinvasive disease, clarify key concepts, and identify gaps within our knowledge with appropriate future directions related to the improvement of global health. Methods: Sources of Evidence: A scoping review of the literature was conducted using PubMed, Scopus, ScienceDirect, and Hinari. Eligibility Criteria: Original data including epidemiology, risk factors, neurological manifestations, neuro-diagnostics, management, and preventive measures related to neuroinvasive arbovirus infections was obtained. Sources of evidence not reporting on original data, non-English, and not in peer-reviewed journals were removed. Charting Methods: An initial pilot sample of 30 abstracts were reviewed by all authors and a Cohen's kappa of κ = 0.81 (near-perfect agreement) was obtained. Records were manually reviewed by two authors using the Rayyan QCRI software. Results: A total of 171 records were included. A wide array of neurological manifestations can occur most frequently, including parkinsonism, encephalitis/encephalopathy, meningitis, flaccid myelitis, and Guillain-Barré syndrome. Magnetic resonance imaging of the brain often reveals subcortical lesions, sometimes with diffusion restriction consistent with acute ischemia. Vertical transmission of arbovirus is most often secondary to the Zika virus. Neurological manifestations of congenital Zika syndrome, include microcephaly, failure to thrive, intellectual disability, and seizures. Cerebrospinal fluid analysis often shows lymphocytic pleocytosis, elevated albumin, and protein consistent with blood-brain barrier dysfunction. Conclusions: Arbovirus infection with neurological manifestations leads to increased morbidity and mortality. Risk factors for disease include living and traveling in an arbovirus endemic zone, age, pregnancy, and immunosuppressed status. The management of neuroinvasive arbovirus disease is largely supportive and focuses on specific neurological complications. There is a need for therapeutics and currently, management is based on disease prevention and limiting zoonosis.

The influence of gender and temephos exposure on community participation in dengue prevention: a compartmental mathematical model.

BACKGROUND: The use of temephos, the most common intervention for the chemical control of Aedes aegypti over the last half century, has disappointing results in control of the infection. The footprint of Aedes and the diseases it carries have spread relentlessly despite massive volumes of temephos. Recent advances in community participation show this might be more effective and sustainable for the control of the dengue vector. METHODS: Using data from the Camino Verde cluster randomized controlled trial, a compartmental mathematical model examines the dynamics of dengue infection with different levels of community participation, taking account of gender of respondent and exposure to temephos. RESULTS: Simulation of dengue endemicity showed community participation affected the basic reproductive number of infected people. The greatest short-term effect, in terms of people infected with the virus, was the combination of temephos intervention and community participation. There was no evidence of a protective effect of temephos 220 days after the onset of the spread of dengue. CONCLUSIONS: Male responses about community participation did not significantly affect modelled numbers of infected people and infectious mosquitoes. Our model suggests that, in the long term, community participation alone may have the best results. Adding temephos to community participation does not improve the effect of community participation alone.

Unilateral lateral rectus palsy following dengue: a case report.

Introduction and importance: Dengue fever is a mosquito-borne viral infection presenting with high-grade fever and other constitutional symptoms. Case presentation: This case report details a rare occurrence of lateral rectus palsy in an 18-year-old male subsequent to dengue infection. The patient initially presented with fever, a generalized tonic-clonic seizure (GTCS), and symptomatic hypoglycemia, leading to multiple organ dysfunction syndrome (MODS) necessitating intensive care. Remarkably, no haemorrhagic manifestations were observed. The MODS gradually resolved by the 12th day of admission, coinciding with the emergence of complaints about uniocular diplopia and right esotropia. Systemic examination, including a normal computed tomography (CT) head scan, did not reveal any abnormalities. Additionally, potential causes contributing to esotropia and diplopia were ruled out. The patient was subsequently managed expectantly for lateral rectus palsy following severe dengue. Follow-up assessments indicated a gradual improvement in esotropia and diplopia, and the patient was advised to continue the prescribed medications. Conclusion: This is the first documented case report of paralytic squint post-severe dengue in Nepal, emphasizing the importance of considering it as a differential diagnosis in tropical regions with endemic dengue infections. The case report advocates early identification and treatment of ophthalmic issues, notably with prednisolone, to achieve favourable outcomes, as evidenced by improvements in visual acuity, esotropia, and diplopia during follow-ups. Further research is essential to determine optimal treatment strategies for such neurological complications associated with dengue fever.