The need for active and integrated involvement of the community and health professionals in the prevention and control of dengue hemorrhagic fever in Indonesia.

Successful control and prevention of dengue fever requires active involvement from all parties. For this reason, three innovative programs are needed, namely: i) increasing knowledge, attitude and practice (KAP) of the community and health professionals as capital in controlling dengue fever in a sustainable manner; ii) application of "3M Plus" to suppress vector breeding in household settings; iii) promotion of the "Jumantik" program as an effective community empowerment approach to prevent and control dengue fever based on community independence. It was concluded that successful control of dengue fever requires integration of the community and health workers through various innovative programs.

Rare Instances of Culture-Positive Dengue-Related Panophthalmitis: A Case Series.

Panophthalmitis is an exceptionally rare but severe ocular complication of dengue fever, which is currently a significant health concern in parts of India. It is a purulent inflammation encompassing all structures of the globe (choroid, retina, vitreous fluid, aqueous fluid, cornea, sclera, and conjunctiva) along with surrounding orbital and periorbital structures. This case series highlights the occurrence of panophthalmitis in three patients diagnosed with dengue, who were aged 35, 50, and 75 years. Despite aggressive medical management, including intravenous antibiotics, the patients were ultimately scheduled for evisceration surgery due to the extreme severity of the condition. Healthcare providers must be aware of the potential ocular complications in dengue cases and diagnose them promptly. While ocular involvement in dengue is rare, this case series emphasizes the importance of recognizing ocular manifestations in dengue patients, as early diagnosis and prompt intervention can prevent severe complications.

Beyond the norm: a rare presentation of dengue fever resulting in combined rhabdomyolysis and TMA-induced AKI-a case report.

Dengue is the most prevalent arthropod-transmitted infection worldwide. Its clinical presentation ranges from subclinical illness to multi-organ failure. Acute kidney injury (AKI) is one of its complications, having a number of different pathogeneses. The patient herein described presented with thrombotic microangiopathy (TMA) and rhabdomyolysis, a combination never previously reported in the literature. He was diagnosed with dengue at a primary care hospital, after which he was referred to us with fever and oliguria. His blood workup and kidney biopsy revealed a picture of combined TMA and rhabdomyolysis-induced AKI. He developed sepsis after his first session of plasmapheresis, that had to be discontinued and he was further managed with dialysis and supportive care. The patient showed remarkable recovery, regaining kidney function after one month.

Dynamics and Efficacy: A Comprehensive Evaluation of the Advanced Dengue Fever Surveillance and Early Warning System in Ningbo City, 2023.

Objective: To conduct a comprehensive evaluation of the Dengue Fever Surveillance and Early Warning System deployed in Ningbo City during 2023, focusing on its capacity for timely identification and reporting of dengue fever cases, particularly imported cases from endemic regions. Methods: A detailed data of patient clinical features and blood profile trends was collected from clinical records and surveillance reports, focusing on the rapid diagnostic processes and surveillance rigor. This study assessed the effectiveness of the system in identifying and reporting dengue cases and identified the limitations of the existing framework through a basic statistical approach. Results: The system demonstrated timely identification and reporting of dengue fever cases, with a particular emphasis on imported cases. However, several limitations were identified, including the need for more precise monitoring criteria and improved coordination with medical entities. Conclusion: The study underscores the critical role of public health bodies in managing disease outbreaks and advocates for enhanced methodologies to refine epidemic control efforts. The findings contribute to the advancement of early warning mechanisms and the improvement of proactive infectious disease monitoring in metropolitan environments, providing valuable insights for fortifying the Dengue Fever Surveillance and Early Warning System in Ningbo City.

Spatial mapping of dengue fever prevalence and its association with geo-climatic factors in Lahore, Pakistan.

A vector-borne disease of concern for global public health, dengue fever has been spreading its endemicity and several cases in recent years, particularly in Lahore Pakistan. Dengue transmission is influenced by geo-climatic conditions. This study aimed to map the spatial prevalence of dengue fever in Lahore and its association with geo-climatic factors during the epidemic of the year 2021. In this study, geo-climatic factors that could potentially encourage the growth of the virus are chosen for this study, and their temporal and spatial changeability relate to dengue cases. The objective of this study is to use meteorological, satellite data and Geographic Information System (GIS) techniques to map dengue outbreaks and identify the risk-prone areas by relating geo-climatic factors with dengue outbreaks. The dengue patients and their locations data were collected from the Directorate General of Health Services (DGHS) Lahore. This study uses Google Earth and Landsat-8 OLI/TIRs images to extract geo-climatic and land use parameters. The dot density maps technique was used to represent the spatiotemporal distribution of dengue cases. The hotspot analysis was applied to show the hotspots of dengue cases in district Lahore at the Union Council (UC) level. The Normalised Difference Vegetation Index (NDVI), Normalised Difference Water Index (NDWI), built-up area, population density, precipitation, and Land Surface Temperature (LST) are the factors employed. In this study, correlation was performed to test the significance between precipitation and the prevalence of dengue fever in Lahore. The results show that the incidence and prevalence of dengue fever month-wise at the UC level in Lahore. The distribution pattern of dengue outbreaks in the Lahore area and its demographic factors were found to be associated. It concludes that the increase in the spread of dengue fever is associated with the monsoon rains. The prevalence of dengue is associated with water bodies and high land surface temperature, but it does not represent any significant relation with vegetation cover and land use in Lahore during the year 2021. The study pinpointed the locations that are most susceptible and require care to prevent such outbreaks in the future.

Complete Blood Count Values Over Time in Young Children During the Dengue Virus Epidemic in the Dominican Republic From 2018 to 2020.

Background: Dengue fever (DF) is a mosquito-borne illness with substantial economic and societal impact. Understanding laboratory trends of hospitalized Dominican Republic (DR) pediatric patients could help develop screening procedures in low-resourced settings. We sought to describe laboratory findings over time in DR children with DF and DF severity from 2018 to 2020. Methods: Clinical information was obtained prospectively from recruited children with DF. Complete blood count (CBC) laboratory measures were assessed across Days 1-10 of fever. Participants were classified as DF-negative and DF-positive and grouped by severity. We assessed associations of DF severity with demographics, clinical characteristics, and peripheral blood studies. Using linear mixed-models, we assessed if hematologic values/trajectories differed by DF status/severity. Results: A total of 597 of 1101 with a DF clinical diagnosis were serologically evaluated, and 574 (471 DF-positive) met inclusion criteria. In DF, platelet count and hemoglobin were higher on earlier days of fever (p < = 0.0017). Eighty had severe DF. Severe DF risk was associated with thrombocytopenia, intraillness anemia, and leukocytosis, differing by fever day (p < = 0.001). Conclusions: In a pediatric hospitalized DR cohort, we found marked anemia in late stages of severe DF, unlike the typically seen hemoconcentration. These findings, paired with clinical symptom changes over time, may help guide risk-stratified screenings for resource-limited settings.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.

Dengue and leptospirosis coinfection: a case series.

BACKGROUND: Both dengue and Leptospira infections are endemic to tropical and subtropical regions, with their prevalence increasing in recent decades. Coinfection with these pathogens presents significant diagnostic challenges for clinicians due to overlapping clinical manifestations and laboratory findings. This case report aims to elucidate two clinical scenarios where the coinfection of dengue and leptospirosis complicates the disease course, creating a diagnostic conundrum. CASE PRESENTATION: We present the clinical scenarios of two Bangladeshi males, aged 25 and 35 years, who were admitted to our hospital with acute febrile illness. The first patient exhibited hepatic and renal involvement, while the second presented with symptoms initially suggestive of meningoencephalitis. Both cases were initially managed under the presumption of dengue infection based on positive serology. However, further evaluation revealed coinfection with Leptospira, complicating the disease course. Both patients received appropriate treatment for dengue and antibacterial therapy for leptospirosis, ultimately resulting in their recovery. CONCLUSION: These case scenarios underscore the critical importance for clinicians in regions where dengue and Leptospira are endemic to consider both diseases when evaluating patients presenting with acute febrile illness.

Integrated Approach to Severe Dengue Complicated by Guillain-Barré Syndrome and Multi-organ Failure.

This report details the case of a female patient who was admitted with severe dengue, which was further complicated by bilateral pneumonia and multiple organ involvement. The patient also developed quadriparesis, a neurological complication, and had a recent history of vaccination with the COVISHIELD COVID-19 vaccine. A nerve conduction study later determined the condition to be acute motor axonal neuropathy, a variant of Guillain-Barré syndrome (GBS). While neurological complications, such as GBS, are rare in dengue cases, they can significantly affect patient outcomes. Treatment with intravenous immunoglobulin (IVIG) has proven to be an effective disease-modifying therapy for GBS. IVIG therapy is recognized for its anti-inflammatory and immunomodulatory effects, making it beneficial in certain autoimmune conditions, including those involving the nervous system. However, its use in severe infections or sepsis remains controversial. In this case, IVIG therapy was administered alongside broad-spectrum antibiotics. The patient's favorable response to IVIG therapy and subsequent clinical improvement highlight the importance of early recognition and targeted intervention for neurological complications in dengue cases.

Integrated serum proteomic and N-glycoproteomic characterization of dengue patients.

Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.

Forecasting and mapping dengue fever epidemics in China: a spatiotemporal analysis.

BACKGROUND: Dengue fever (DF) has emerged as a significant public health concern in China. The spatiotemporal patterns and underlying influencing its spread, however, remain elusive. This study aims to identify the factors driving these variations and to assess the city-level risk of DF epidemics in China. METHODS: We analyzed the frequency, intensity, and distribution of DF cases in China from 2003 to 2022 and evaluated 11 natural and socioeconomic factors as potential drivers. Using the random forest (RF) model, we assessed the contributions of these factors to local DF epidemics and predicted the corresponding city-level risk. RESULTS: Between 2003 and 2022, there was a notable correlation between local and imported DF epidemics in case numbers (r = 0.41, P < 0.01) and affected cities (r = 0.79, P < 0.01). With the increase in the frequency and intensity of imported epidemics, local epidemics have become more severe. Their occurrence has increased from five to eight months per year, with case numbers spanning from 14 to 6641 per month. The spatial distribution of city-level DF epidemics aligns with the geographical divisions defined by the Huhuanyong Line (Hu Line) and Qin Mountain-Huai River Line (Q-H Line) and matched well with the city-level time windows for either mosquito vector activity (83.59%) or DF transmission (95.74%). The RF models achieved a high performance (AUC = 0.92) when considering the time windows. Importantly, they identified imported cases as the primary influencing factor, contributing significantly (24.82%) to local DF epidemics at the city level in the eastern region of the Hu Line (E-H region). Moreover, imported cases were found to have a linear promoting impact on local epidemics, while five climatic and six socioeconomic factors exhibited nonlinear effects (promoting or inhibiting) with varying inflection values. Additionally, this model demonstrated outstanding accuracy (hitting ratio = 95.56%) in predicting the city-level risks of local epidemics in China. CONCLUSIONS: China is experiencing an increasing occurrence of sporadic local DF epidemics driven by an unavoidably higher frequency and intensity of imported DF epidemics. This research offers valuable insights for health authorities to strengthen their intervention capabilities against this disease.

The Efficacy of Montelukast in Reducing the Risk of Warning Signs and Subsequent Dengue Shock Syndrome in Adult Dengue Fever Patients.

BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS). OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients. METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality. RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03). CONCLUSION: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.

Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever.

BACKGROUND: Dengue fever, an acute insect-borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear. METHODS: We used single-cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results. RESULTS: Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF-ß signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice. CONCLUSIONS: In this study, single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

A Study on the Clinical Profile of Patients Presenting With Dengue Fever and the Precision Prediction of Dengue Severity Using Platelet Count at Presentation.

Background The most prevalent arbovirus infection in the world, dengue, has become a serious public health issue. This study aims to examine the clinical characteristics of individuals who present with dengue fever and use platelet count prediction to estimate the severity of dengue. Materials and methods This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from February 2022 to May 2024. A total of 100 patients older than 12 years old who had dengue fever (presenting within three days of the first symptom) and were dengue NS1 antigen-positive in the laboratory were included. Patients under 12 years of age and pregnant women were excluded. Also excluded were patients with a history of prior dengue infection and patients on medications causing thrombocytopenia, such as antiplatelets (aspirin). Written informed consent was obtained from each patient. For adolescent boys and girls aged 13-18, consent was obtained from a parent or legal guardian along with the adolescent's assent. Data were collected through physical examinations and laboratory investigations. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York), with descriptive statistics and tests for nonparametric data, setting the significance at p<0.05. Results The average age of the study participants was 29.48 ± 10.62 years, with 24% in the 0-20 year age group, 36% in the 21-30 age group, 24% in the 31-40 age group, 12% in the 41-50 age group, 3% in the 51-60 age group, and 1% in the 61-70 age group. Men comprised 65% of the population, with 35% being women. Weakness was the most prevalent symptom, followed by nausea and fever with chills. Patients with dengue fever without warning indications had a median platelet count of 114,000/µL upon admission; those with dengue fever with warning signs had a median count of 35,500/µL; and those with severe dengue had a median count of 25,000/µL. These distinctions attained statistical significance, underscored by p-values of <0.001. The predictive model for severe dengue using platelet count on presentation demonstrated a robust capacity to anticipate severe dengue with a noteworthy association (p<0.04), indicating an increased risk of severe dengue with a lower platelet count (<25,000/µL, odds ratio (OR) 7.5). Conclusion Dengue was more common in the young population, with a predominance of male patients. Weakness was the most common symptom. Patients with a platelet count less than 25,000/µL had 7.5 times more odds of developing severe dengue.

Retrospective study on the dengue fever outbreak in Puntland State, Somalia.

BACKGROUND: Dengue infection is a mosquito-borne, endemic viral disease, particularly in developing countries. Here, we report the results of the clinicodemographic, serologic profile and the monthly occurrence of a recent dengue fever outbreak in Puntland State (Somalia). METHODOLOGY: We analyzed the data of 956 dengue-suspected patients who were investigated using the rapid diagnostic testing (RDT) method for detecting NS1 (dengue virus non-structural protein) and IgM antibodies employing the SD Biosensor Dengue Dou NS Ag and IgM test kit (Germany) at the Puntland Public Health Referral Laboratory from November 21, 2022, to May 27, 2023. RESULTS: We found that 118 cases were positive for dengue among the suspected patients enrolled in the present study. Of these cases, 76.2% were dengue NSI positive, 13.6% were dengue IgM positive, and 10.2% were both NSI and IgM positive. The number of females and males in the confirmed cases was equal, and most (48.3%) were aged 20 years or less. 43.1% of them lived in the Nugal region, particularly in Garowe. Clinically, fever was the most frequent symptom (88.9%). The cases peaked in December 2022 but dropped from January to March, with a slight rise in February, and then increased in April and May 2023. CONCLUSION: This study highlights the clinicodemographic characteristics, seroprevalence, and monthly occurrence of dengue in Puntland. We recommend improving vector control measures, enhancing case management, strengthening dengue surveillance, developing an early warning system, and conducting future studies to characterize the circulating strains.

Atypical Hemorrhages Secondary to Dengue Infection and Cardiopulmonary Resuscitation: Subcutaneous Thrombin Injection as a Salvage Technique for Refractory Femoral Artery Hemorrhage.

Dengue fever is a viral infection transmitted by the bites of female Aedes mosquitoes. Repeat infections with different viral serotypes are possible, with an increased risk of severe dengue. Dengue hemorrhagic fever is one of the most severe presentations of dengue, with thrombocytopenia, increased capillary permeability with resultant rash, and an increased risk of spontaneous bleeding. The management of severe dengue is done through supportive care and symptomatic management only, as there are no specific treatments available. We describe a case of severe dengue hemorrhagic fever presenting with atypical hemorrhage from both the psoas muscle and the femoral arterial puncture sites. These were successfully treated with large calibrated Gelfoam particle embolization for the psoas hemorrhage and regional thrombin injection for the femoral arterial puncture sites.

Immunogenicity, Safety and Efficacy of the Dengue Vaccine TAK-003: A Meta-Analysis.

The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003's immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries.

Unraveling the Genomic Evolution of Dengue Virus Serotype 1: A Case Study from Yantai, China.

In August 2023, we identified a case of dengue fever in Yantai City, which was imported from Xishuangbanna, China. To investigate its evolutionary history and population dynamics, we utilized the metatranscriptomic method to obtain the virus' whole genome sequence. Together with 367 selected dengue virus whole genome sequences from the NCBI database, we constructed a time-scaled Maximum Clade Credibility (MCC) tree. We found that our sequence exhibited a high homology with a sequence of DENV1 (OR418422.1) uploaded by the Guangzhou Center for Disease Control and Prevention in 2023, with an estimated divergence time around 2019 (95% HPD: 2017-2023), coinciding with the emergence of SARS-CoV-2. The DENV strain obtained in this study belongs to genotype I of DENV1. Its ancestors experienced a global epidemic around 2005 (95% HPD: 2002-2010), and its progeny strains have spread extensively in Southeast Asia and China since around 2007 (95% HPD: 2006-2011). The Bayesian skyline plot indicates that the current population of DENV1 has not been affected by SARS-CoV-2 and is expected to maintain stable transmission. Hence, it is imperative to track and monitor its epidemiological trends and genomic variations to prevent potential large-scale outbreaks in the post-SARS-CoV-2 era.