Hemorrhagic Fever Research Articles

The Impact of Host Factors on the Spread of Dengue Hemorrhagic Fever

This study uses a survey of the affected human population to evaluate the impact of host variables on the spread of Dengue Hemorrhagic Fever (DHF) in Indonesia. The study investigated observable factors influencing DHF transmission by operationalizing important variables drawn from theoretical frameworks. The findings highlight the significance of host-related factors in understanding the dynamics of DHF, offering useful insights for the development of successful public health initiatives. The study's goal is to lessen the impact of DHF on communities, safeguard vulnerable groups, and reduce the frequency of serious health problems. The study recommends focused interventions to improve community resilience against DHF, emphasizing the importance of health practices and environmental effects. Finally, the study emphasizes the importance of continued public awareness and education measures in Indonesia to tackle this persistent health threat and prevent future epidemics.

Crimean-Congo hemorrhagic fever cases diagnosed during an outbreak of Sudan virus disease in Uganda, 2022-23.

In September 2022, Uganda experienced an outbreak of Sudan virus disease (SVD), mainly in central Uganda. As a result of enhanced surveillance activities for Ebola disease, samples from several patients with suspected viral hemorrhagic fever (VHF) were sent to the VHF Program at Uganda Virus Research Institute (UVRI), Entebbe, Uganda, and identified with infections caused by other viral etiologies. Herein, we report the epidemiologic and laboratory findings of Crimean-Congo hemorrhagic fever (CCHF) cases that were detected during the SVD outbreak response. Whole blood samples from VHF suspected cases were tested for Sudan virus (SUDV) by real-time reverse transcription-polymerase chain reaction (RT-PCR); and if negative, were tested for CCHF virus (CCHFV) by RT-PCR. CCHFV genomic sequences generated by metagenomic next generation sequencing were analyzed to ascertain strain relationships. Between September 2022 and January 2023, a total of 2,626 samples were submitted for VHF testing at UVRI. Overall, 13 CCHF cases (including 7 deaths; case fatality rate of 53.8%), aged 4 to 60 years, were identified from 10 districts, including several districts affected by the SVD outbreak. Four cases were identified within the Ebola Treatment Unit (ETU) at Mubende Hospital. Most CCHF cases were males engaged in livestock farming or had exposure to wildlife (n = 8; 61.5%). Among confirmed cases, the most common clinical symptoms were hemorrhage (n = 12; 92.3%), fever (n = 11; 84.6%), anorexia (n = 10; 76.9%), fatigue (n = 9; 69.2%), abdominal pain (n = 9; 69.2%) and vomiting (n = 9; 69.2%). Sequencing analysis showed that the majority of identified CCHFV strains belonged to the Africa II clade previously identified in Uganda. Two samples, however, were identified with greater similarity to a CCHFV strain that was last reported in Uganda in 1958, suggesting possible reemergence. Identifying CCHFV from individuals initially suspected to be infected with SUDV emphasizes the need for comprehensive VHF testing during filovirus outbreak responses in VHF endemic countries. Without expanded testing, CCHFV-infected patients would have posed a risk to health care workers and others while receiving treatment after a negative filovirus diagnosis, thereby complicating response dynamics. Additionally, CCHFV-infected cases could acquire an Ebola infection while in the ETU, and upon release because of a negative Ebola virus result, have the potential to spread these infections in the community.

Characterization of non-standard viral genomes during arenavirus infections identifies prominent S RNA intergenic region deletions.

Arenaviruses, a family of negative-sense RNA viruses spread by rodents, are a leading cause of severe hemorrhagic fever in humans. Due to a paucity of antivirals and vaccines for arenaviruses, there is a need to identify new mechanisms for interfering with arenavirus replication. In several negative-sense RNA viruses, natural viral interference results from the production of non-standard viral genomes (nsVGs) that activate the innate immune system and/or compete for essential viral products. Although it is well established that arenaviruses produce strong interfering activities, it is unknown if they produce interfering nsVGs. Here, we show that arenaviruses produce deletions within the intergenic region of their small (S) RNA genome, and these deletions inhibit viral glycoprotein production during minigenome replication. S RNA deletions are more abundant when arenaviruses are grown in high-interfering conditions and are associated with reduced viral replication. Overall, we found that arenaviruses produce internal deletions within the S RNA intergenic region that are capable of decreasing glycoprotein production. These natural arenavirus interfering molecules provide a new target for the generation of therapeutics against arenaviruses.IMPORTANCEArenaviruses are hemorrhagic fever-causing pathogens that infect millions of people a year. There are currently no approved antivirals that target arenaviruses, and understanding natural mechanisms that inhibit arenavirus replication is crucial for the development of effective therapeutics. Here, we identified multiple deletions within arenavirus genomes that remove major replicative elements of the viral genomes. We show that deletions that remove the intergenic region of the viral genome can prevent viral protein production. These deletions were found in all arenaviruses tested in this study representing a mechanism that could be harnessed for the development of antivirals that broadly target the arenavirus family.

Computational insights in design of Crimean-Congo hemorrhagic fever virus conserved immunogenic nucleoprotein peptides containing multiple epitopes.

Crimean-Congo hemorrhagic fever virus (CCHFV) belongs to Nairoviridae family and has tripartite RNA genome. It is endemic in various countries of Asia, Africa, and Europe and is primarily transmitted by Hyalomma ticks but nosocomial transmission also been reported. Vaccines for CCHF are in early phase of clinical trial; therefore, this work is centered on identification of potential immunogenic peptide as vaccine candidates with application of different immunoinformatics approaches. Eleven conserved (>90%) peptides of CCHFV nucleoprotein were selected for CD8+ T-cell (NetMHCpan 4.1b and NetCTLpan 1.1 server) and CD4+ T-cell (NetMHCIIpan-4.0 server and Tepitool) epitope prediction. Three peptides containing multiple CD8+ and CD4+ T-cell and B-cell epitopes were identified on basis of consensus prediction approach. Peptides displayed good antigenicity score of 0.45-0.68 and predicted to bind with diverse human leukocyte antigen (HLA) alleles. Molecular docking was performed with epitopes to HLA and HLA-epitopes complex to T-cell receptor (TCR). In most of the cases, docked complex of HLA-epitope and HLA-epitopes-TCR have the binding energy close to respective natural bound peptide complex with HLA and TCR. Molecular dynamic simulation also revealed that HLA-peptide complexes have minimum fluctuation and deviation than HLA-peptide-TCR docked over 50ns simulation run. Considering these findings, identified peptides can serve as potential vaccine candidates for CCHFV disease.

Replication Characteristics of African Swine Fever Virus (ASFV) Genotype I E70 and ASFV Genotype II Belgium 2018/1 in Perivenous Macrophages Using Established Vein Explant Model.

African Swine Fever Virus (ASFV), resulting in strain-dependent vascular pathology, leading to hemorrhagic fever, is an important pathogen in swine. The pathogenesis of ASFV is determined by the array and spatial distribution of susceptible cells within the host. In this study, the replication characteristics of ASFV genotype I E70 (G1-E70) and ASFV genotype II Belgium 2018/1 (G2-B18) in the environment of small veins were investigated in an established vein explant model. Immunofluorescence staining analysis revealed that perivenous macrophages (CD163+ cells) were widely distributed in the explant, with most of them (approximately 2-10 cells/0.03 mm2) being present close to the vein (within a radius of 0-348 µm). Upon inoculation with G1-E70 and G2-B18, we observed an increase in the quantity of cells testing positive for viral antigens over time. G1-E70 replicated more efficiently than G2-B18 in the vein explants (7.6-fold for the ear explant at 72 hpi). The majority of ASFV+ cells were CD163+, indicating that macrophages are the primary target cells. Additional identification of cells infected with ASFV revealed the presence of vimentin+, CD14+, and VWF+ cells, demonstrating the cellular diversity and complexity associated with ASFV infection. By the use of this new vein explant model, the susceptibility of vascular and perivascular cells to an ASFV infection was identified. With this model, it will be possible now to conduct more functional analyses to get better insights into the pathogenesis of ASFV-induced hemorrhages.

Enabling laboratory readiness and preparedness for the evaluation of suspected viral hemorrhagic fevers: development of a laboratory toolkit.

Viral hemorrhagic fevers (VHFs), such as Ebola virus disease, Marburg virus disease, and Lassa fever, are associated with significant morbidity and mortality and the potential for person-to-person transmission. While most individuals in whom VHF is suspected will ultimately be diagnosed with a non-VHF illness, such patients may present to any United States healthcare facility (HCF) for initial evaluation; therefore, all HCFs must be prepared to evaluate and initiate care for suspect VHF patients, especially if they are acutely ill. Included within this evaluation is the ability to perform basic routine laboratory testing before VHF-specific diagnostic test results are available, as well as rapid malaria testing to assess for a common, dangerous "VHF mimic." To improve laboratory preparedness and readiness in the initial care of suspect VHF patients who may present to acute care hospitals. Plan-Do-Study-Act quality improvement model. Frontline healthcare facilities and their clinical laboratories. We describe the development of a laboratory testing toolkit for a suspect VHF patient that can assist frontline HCFs in providing basic laboratory testing required for the care of these patients. The toolkit provides guidance on infection prevention and control, waste management, occupational health, laboratory test collection, processing, and resulting, in the context of suspect VHF patient evaluation. The toolkit is designed to be readily adapted by any frontline HCF in the US. With the guidance provided, facilities will be able to support safer initial evaluation of VHF suspects and ensure high-quality patient care.

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.

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.

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.

Assessment of the Prevalence of Leptospiroses and Hemorrhagic Fever with Renal Syndrome in the Leningrad Region

Assessment of the Prevalence of Leptospiroses and Hemorrhagic Fever with Renal Syndrome in the Leningrad Region

MicroRNA let-7a regulation of Hantaan virus replication by Targeting FAS Signaling Pathways

Hantaan virus (HTNV) infection in humans can cause hemorrhagic fever and renal syndrome (HFRS). Understanding host responses to HTNV infection is crucial for developing effective disease intervention strategies. Previous RNA-sequencing studies have investigated the role of microRNAs (miRNAs) in the post-transcriptional regulation of host genes in response to HTNV infection. In this study, we demonstrated that HTNV infection induces let-7a expression in human umbilical vein endothelial cells (HUVEC) and that HTNV G protein upregulates the expression of let-7a. miRNA let-7a mimics and inhibitors validated the predicted targets, including cell apoptosis genes (FAS, caspase-8, and caspase-3) and inflammatory factors (IL-6 and its related factors). Modulation of miRNA let-7a levels by miRNA mimics and inhibitors affected HTNV replication, indicating that HTNV modulates host miRNA expression to affect the outcome of the antiviral host response.

The hnRNP A2B1 is important for the replication of SFTSV and other RNA viruses.

The heterogeneous nuclear ribonucleoprotein (hnRNP A2B1) is a key component of the hnRNP complex involving RNA modulation in eukaryotic cells and it has also been reported to be involved in the replication of the hepatitis E virus, influenza A virus, and hepatitis B virus. However, it is not clear whether the role of the hnRNP A2B1 in viral replication is conserved among RNA viruses and what is the mechanism of hnRNP A2B1 in RNA virus replication. In this study, we first used severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne RNA virus that causes a severe viral hemorrhagic fever as well as other RNA viruses including VSV-GFP, SeV, EV71, and ZIKV to demonstrate that knockout hnRNPA2B1 gene inhibited viral RNA replication and overexpression of hnRNP A2B1 could restore the RNA levels of all tested RNA viruses. These results suggest that hnRNPA2B1 upregulation of viral replication is conserved among RNA viruses. Next, we demonstrated that hnRNP A2B1 was translocated from the nucleus to the cytoplasm under RNA virus infection including SFTSV, VSV-GFP, SeV, EV71, and ZIKV, suggesting translocation of hnRNP A2B1 from the nucleus to the cytoplasm is crucial for RNA virus replication. We then used SFTSV as a model to demonstrate the mechanism of hnRNP A2B1 in the promotion of RNA virus replication. We found that overexpression of SFTSV nucleoprotein can also cause hnRNP A2B1 translocation from the nucleus to the cytoplasm and that the SFTSV NP interacted with the RNA recognition motif 1 domain of hnRNP A2B1. We further demonstrated that the hnRNP A2B1 interacted with the 5' UTR of SFTSV RNA. In conclusion, we revealed that the hnRNP A2B1 upregulation of viral RNA replication is conserved among RNA viruses; the mechanism of hnRNP A2B1 in promotion of SFTSV viral RNA replication is that SFTSV NP interacted with the hnRNPA2B1 to retain it in the cytoplasm where the hnRNP A2B1 interacted with the 5' UTR of SFTSV RNA to promote the viral RNA replication.IMPORTANCESevere fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus with a high mortality rate of up to 30%. In this study, we first used SFTSV as a model to demonstrate that the role of hnRNPA2B1 in viral replication is conserved in SFTSV. Then we used other RNA viruses, including VSV-GFP, SeV, EV71, and ZIKV, to repeat the experiment and demonstrated the same results as SFTSV in all tested RNA viruses. By knocking out the hnRNPA2B1 gene, SFTSV RNA replication was inhibited, and overexpression of hnRNPA2B1 restored RNA levels of SFTSV and other tested RNA viruses. We revealed a novel mechanism where the SFTSV nucleoprotein interacts with hnRNPA2B1, retaining it in the cytoplasm. This interaction promotes viral RNA replication by binding to the 5' UTR of SFTSV RNA. The findings suggest that targeting hnRNPA2B1 could be a potential strategy for developing broad-spectrum antiviral therapies, given its conserved role across different RNA viruses. This research provides significant insights into the replication mechanisms of RNA viruses and highlights potential targets for antiviral interventions.

Immunogenicity of various variants of Ebola and Marburg virus glycoprotein genes in recombinant adenoviral vectors

INTRODUCTION. Marburg and Ebola viruses cause severe haemorrhagic fever in humans and primates. Currently, there are no licensed prophylactic vaccines that can simultaneously prevent the spread or reduce the severity of both diseases caused by these filoviruses. The development of effective prophylactic vaccines requires studies aimed at selecting the most immunogenic forms of protective antigens.AIM. This study aimed to evaluate humoral immune induction in animals after administration of recombinant adenoviral vectors expressing various forms of Ebola and Marburg virus glycoproteins (GPs).MATERIALS AND METHODS. Samples of recombinant human adenovirus type 5 (rAd5) were obtained using homologous recombination in Escherichia coli, growth in HEK293 cells, and purification by CsCl gradient ultracentrifugation. The resulting rAd5 samples were characterised in terms of their identity (PCR and whole-genome sequencing), the concentration of viral particles (fluorescence spectroscopy), and the concentration of infectious viral particles (TCID50 assay). Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the GP-specific IgG titres in the sera of immunised mice.RESULTS. The authors constructed rAd5 samples, and each construct contained an expression cassette with a GP gene form encoding a full-length GP, a GP without the mucin-like domain, or a GP without both the glycan cap and the mucin-like domain. Each of these forms was studied using the GPs of four filoviruses, including Zaire Ebola virus, Sudan Ebola virus, Bundibugyo Ebola virus, and Marburg virus. Neither of the forms had a critical effect on the rAd5 replicative capacity. Three weeks after immunisation, the highest GP-specific IgG production was induced by the rAd5 samples encoding either the full-length GP or the GP without the mucin-like domain. The GP without both the glycan cap and the mucin-like domain was the least immunogenic antigen regardless of the filovirus species.CONCLUSIONS. The most promising constructs for the development of filovirus vaccines based on recombinant adenoviral vectors are the constructs that include the genes encoding the fulllength GP or the GP without the mucin-like domain.

Assessment of the Influence of Climatic Factors on the Incidence of Crimean Hemorrhagic Fever: a Comprehensive Analysis of Data for Russia, Kazakhstan, Turkey and Iran between 1999 and 2022

Assessment of the Influence of Climatic Factors on the Incidence of Crimean Hemorrhagic Fever: a Comprehensive Analysis of Data for Russia, Kazakhstan, Turkey and Iran between 1999 and 2022

Replication kinetics of pathogenic Eurasian orthohantaviruses in human mesangial cells

BackgroundEurasian pathogenic orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury (AKI). The virulence of orthohantaviruses varies enormously and direct infection of different renal cell types contribute to pathogenesis. Glomerular mesangial cells play an essential role in the interplay between kidney cells and proper kidney function. Therefore, we analyzed the replication competence of different orthohantavirus species in primary mesangial cells and a mesangial cell line.MethodsWe tested the suitability of the mesangial cell line CIHGM-1 (conditionally immortalized human glomerular mesangial cells) as cell culture model for orthohantavirus kidney infection by comparison with primary human renal mesangial cells (HRMCs). We analyzed infection with high pathogenic Hantaan virus (HTNV), moderate pathogenic Puumala virus (PUUV) and non-/low-pathogenic Tula virus (TULV).ResultsEffective viral spread was observed for PUUV only, whereas infection with HTNV and TULV was abortive. However, in contrast to TULV, HTNV exhibits an initially high infection rate and declines afterwards. This replication pattern was observed in HRMCs and CIHGM-1 cells. Viability or adhesion was neither impaired for PUUV-infected CIHGM-1 nor HRMCs. A loss of migration capacity was observed in PUUV-infected CIHGM-1 cells, but not in HRMCs.ConclusionsThe identification of differences in the replication competence of pathogenic orthohantavirus strains in renal mesangial cells is of special interest and may provide useful insights in the virus-specific mechanisms of orthohantavirus induced AKI. The use of CIHGM-1 cells will facilitate the research in a relevant cell culture system.

Outcomes from a Zoonotic Disease Prioritization workshop using One Health approach in Mozambique, 2018 to 2023

IntroductionAround 75% of (re)emerging infections are of zoonotic origins. The risk of zoonotic transmission in Mozambique is high because approximately 81% of the country’s labor force is involved with agriculture, which represents a vulnerability for more frequent human-animal interaction and risk of spillover events. A One Health Zoonotic Disease Prioritization (OHZDP) workshop was conducted in Mozambique to facilitate coordination and collaboration within and across sectors to prevent, detect, and respond to zoonotic disease threats. Based on the success of this integrated workshop, the stakeholders developed actions whose results have a great impact on animal welfare, environment and improving public health.MethodsIn 2018, representatives from Mozambique’s human, animal, and environmental sectors from government, universities, research institutions and partners used US CDC’s OHZDP Process to prioritize endemic and emerging zoonotic diseases of greatest national concern and develop recommendations and key interventions needed to advance One Health in Mozambique. After the OHZDP workshop, the Mozambique One Health Secretariat used a theory of change methodology to identify activities for implementation from the recommendations of the OHZDP workshop. Since the OHZDP workshop, the Secretariat has monitored progress of activities annually.ResultsMozambique’s priority zoonotic diseases are rabies, zoonotic tuberculosis, salmonellosis, zoonotic avian influenza, trypanosomiasis, brucellosis, and Crimean-Congo hemorrhagic fever. One Health recommendations and interventions to address the priority zoonotic diseases focused on One Health collaboration, communication, and coordination; laboratory; surveillance; preparedness and response; prevention; workforce development; and research. After the OHZDP workshop, Mozambique established One Health coordination mechanisms, developed training courses for surveillance, laboratory diagnosis, outbreak investigation, and preparedness and response for the priority zoonotic diseases, conducted joint research, and developed plans.ConclusionPrioritization of zoonotic diseases is critical as it facilitated the key One Health players in Mozambique to optimize resources, gain a greater understanding of zoonotic diseases, and implement policies and activities that promote multisectoral, interdisciplinary, and transdisciplinary collaboration across human, animal, and environmental sectors to prevent, detect, and respond to public health threats. The success of these activities implemented by the local Government and One Health partners were built from the implementation and momentum from the Mozambique’s OHZDP workshop.

Early intervention of 5% albumin shown superior control of vascular integrity and function compared to ringer’s lactatein hospitalized adult with grade I & II Dengue hemorrhagic fever: a multicenter randomized controlled trial in Indonesia

BackgroundDengue virus remains a major public health problem with one of the hallmark pathologies is the vascular leakage caused by endothelial dysfunction which can lead to Dengue Hemorrhagic Fever (DHF) manifestation. In the status quo, no specific therapy has been discovered but rather heavily relies on judicious and frequent monitoring of intravenous fluids administration. The current guideline has discussed the roles of fluid therapy during the Dengue Shock Syndrome (DSS) stage, however, administration of early fluid intervention for DHF grade I and II remains uncharted territory. In addition, the choice and timing of colloid administration remains underexplored. As one of the widely available colloids, 5% albumin has known physiological properties that potentially minimize plasma leakage. Therefore, this study aimed to evaluate the benefit of early intervention of 5% albumin in adults with DHF in the hope of preventing the lethal progression to DSS and further, shorten the length of stay (LOS) for patients.MethodsWe conducted a multicenter, open-labeled, randomized controlled trial in Jakarta and Banten to compare the effect of early intervention with 5% albumin in adult patients with DHF compared to Ringer’s Lactate (RL). Statistical analyses were conducted using unpaired t-test and Mann-Whitney for normally and abnormally distributed data respectively.ResultsAdult patients with a diagnosis of DHF grade I and II that being hospitalized to receive the early intervention of 5% albumin had significantly lower levels of hemoconcentration 4, 12, and 24 h (p = 0.002, 0.001, 0.003, respectively), higher platelet counts 4 h (p = 0.036), higher serum albumin levels 48 h (p = 0.036), lower proteinuria 24 and 48 h post-albumin administration (p < 0.001, < 0.001, respectively), and shorter LOS (p < 0.001) when compared to the RL group.ConclusionEarly intervention of 5% albumin showed better control on vascular integrity and function compared to ringer lactate in hospitalized adults with grade I & II DHF, thus halting the progression of DHF into DSS and other related complications which leads to faster recovery and shorter length of stay.Trial registrationThe study was registered to www.clinicaltrial.gov with trial registration number NCT04076254, and registration date October 31st 2016.

THE RELATIONSHIP BETWEEN COMMUNITY BEHAVIOR AND SOWING OF ABATE POWDER IN PREVENTING AEDES LARVAE AT PASI PEUKAN BARO VILLAGE AND PASI RAWA VILLAGE SIGLI SUB DISTRICT, PIDIE REGENCY

Background: Dengue Hemorrhagic Fever (DHF) in Aceh Province in 2022 were recorded at 2,079 cases,, with 16 deaths. with the morbidity rate for Dengue Hemorrhagic Fever (DHF) in 2022 amounting to 38 per 100,000 population. Cases of dengue fever in Pidie Regency in 2022 were 318 cases. Research Objective: To determine community behavior towards sowing abate powder to prevent aedes larvae in Kota Sigli Subdistrict, Regency Pidie, Aceh Province, data collected in the form of larva surveys, distribution of research questionnaires and observation were conducted from 24 January to 28 February 2024 with the number of respondent involved 71 respondents in Pasi Peukan Baro village and 84 respondents in Pasi Rawa village, and total were 155 respondents. Research Method: Quantitative research with a cross-sectional study research design. Results: The results of Chi Square analysis in Pasi Peukan Baro village was showed a relationship between knowledge (p-value 0.000) and attitude (p-value 0.016) with community sowing behavior of abate powder in preventing aedes larvae.Meanwhile in Pasi Rawa village there is a relationship between education (p-value 0.028) and knowledge (p-value 0.000) with community sowing behavior of abate powder in preventing aedes larvae. Based on the results of the logistic regression test, the most dominant factors that were significantly related in Pasi Peukan Baro village are the age variable (p-value=0.074, CI 95%=0.032-1.170 OR=0.194) and the variable knowledge (p-value=0.001, CI 95%=3.305-95.053, OR=17.724) while in Pasi Rawa village the most dominant factor is knowledge variable (p-value=0.000, CI 95%=19.089-1831.905, OR=187.000). Conclusion:In Pasi Peukan Baro village there is a relationship between the knowledge variable and attitude variable with community sowing behavior of abate powder in preventing aedes larvae.There is a relationship between education variable and knowledge variable with community sowing behavior of abate powder in Pasi Rawa village.

Ocular and adnexal manifestations post dengue hemorrhagic fever.

This study aims to present a case series detailing sight-threatening ocular and adnexal manifestations following dengue fever. A retrospective observational study was conducted, analyzing records of patients presenting with ocular manifestations post dengue fever at a tertiary eye care institute in Uttar Pradesh from October 2023 to November 2023. Demographic details, systemic comorbidities, and detailed ophthalmic examinations were recorded. Fifteen eyes of 13 patients with dengue fever were studied. The mean age of presentation was 39.07 years, with a male predominance (84.61%). Systemic comorbidities were noted in 30.76% (diabetes mellitus) and 23.07% (hypertension) of patients. Thrombocytopenia was observed in 53.84% of patients, while 23.07% required blood transfusions, and 15.38% experienced systemic bleeding episodes. The majority of cases were unilateral (84.61%), with the best-corrected visual acuity of perception of light in 84.61% of cases. Diminution of vision was the most common presenting symptom (84.61%), followed by pain (53.84%), redness (38.46%), and watering (23.07%). Major ocular manifestations included panophthalmitis (26.07%), total ophthalmoplegia (26.07%), endogenous endophthalmitis (20%), central retinal artery occlusion (20%), retinal hemorrhage (20%), ischemic optic neuropathy (20%), orbital cellulitis (13.3%), proptosis (13.3%), retrobulbar hemorrhage (13.3%), retinal detachment (13.3%), and foveolitis (6.7%). The diverse array of ocular and adnexal manifestations in dengue hemorrhagic fever may result in permanent visual loss, emphasizing the need for adequate treatment and timely intervention. The risk of sight-threatening complications underscores the importance of early screening by ophthalmologists and increased public awareness.