Hemorrhagic Fever Research Articles

Serodiagnosis of Secondary Dengue Infection in a Tertiary Care Hospital, Mysuru

Dengue is one among the acute viral infections with the probability of fatal complications. In 2017; NVBDCP reported 157220 positive dengue cases with 250 deaths in India; 17018 cases and 5 deaths in Karnataka. Most primary infections are uneventful. The critical illness like Dengue Haemorrhagic Fever and Dengue Shock Syndrome are generally attributed to serotype cross-reactivity. Identification of secondary dengue infection in the early onset of illness is beneficial. Therefore, methods to discrepate primary and secondary dengue infection are of significant prognostic value. The current study is a hospital based prospective analytical evaluation and was aimed to discriminate secondary from primary dengue virus infection in clinically suspected dengue cases presenting with fever and thrombocytopenia. Patients of all age groups attending Krishna Rajendra Hospital on outpatient and inpatient basis with clinically suspected dengue fever of less than 5 days associated with thrombocytopenia were included in the study. The samples were tested in the VRDL of the Microbiology Department for dengue NS1 antigen and IgM antibodies, positive for both were further subjected to IgG antibodies. IgM /IgG ratio was used to differentiate primary and secondary dengue infections. Dengue infection was categorized based on WHO guidelines. A total of 17,841 samples were tested from May 2017 to December 2023; out of 17841 samples tested 2111 (60.74%) were positive for dengue NS1 and IgM. Of the 2111 dengue NS1 and IgM positive cases, 1700 (80.5%) were having secondary dengue infection, whereas 411 (19.46%) were having primary infection. Early detection of secondary infection helps the clinician in anticipating dengue related complications with appropriate therapeutic intervention, thereby reducing further complications and mortality.

The Dynamics of NS1 Antigen and Platelet Levels in the Acute Phase of Dengue Hemorrhagic Fever

Introduction: Dengue hemorrhagic fever (DHF) is a significant global health concern, particularly in tropical and subtropical regions. The early diagnosis and effective management of DHF are crucial to reduce morbidity and mortality. The NS1 antigen and platelet count are two key laboratory parameters used in the diagnosis and monitoring of DHF. This study aimed to investigate the dynamics of NS1 antigen and platelet levels during the acute phase of DHF and their correlation with disease severity. Methods: A prospective cohort study was conducted at a tertiary care hospital in Central Java, Indonesia. Patients presenting with suspected DHF were enrolled and followed up during their hospitalization. Blood samples were collected at admission and at regular intervals to measure NS1 antigen levels and platelet counts. Clinical and laboratory data were collected to assess disease severity. Results: A total of 150 patients were included in the study. The majority of patients were adults (median age, 32 years) with a female predominance (58%). The median duration of fever at presentation was 4 days. NS1 antigen levels were significantly higher in patients with DHF compared to those with dengue fever (DF) (p < 0.001). Platelet counts were significantly lower in patients with DHF compared to those with DF (p < 0.001). NS1 antigen levels showed a negative correlation with platelet counts (r = -0.62, p < 0.001). The levels of NS1 antigen and platelet count were also significantly associated with disease severity. Conclusion: The dynamics of NS1 antigen and platelet levels during the acute phase of DHF provide valuable insights into disease pathogenesis and can aid in the early diagnosis and prediction of disease severity. The negative correlation between NS1 antigen and platelet levels suggests a potential role of NS1 in the development of thrombocytopenia in DHF. Further studies are needed to elucidate the exact mechanisms underlying these observations.

Seroprevalence of Crimean-Congo Hemorrhagic Fever Among Cows and Their Owners in Nineveh Province, Iraq

Seroprevalence of Crimean-Congo Hemorrhagic Fever Among Cows and Their Owners in Nineveh Province, Iraq

Comparison of epidemiological characteristics between hemorrhagic fever with renal syndrome patients and severe fever with thrombocytopenia syndrome patients.

Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences.

A conformable mathematical model of Ebola Virus Disease and its stability analysis

Ebola Virus Disease (EVD) is a viral hemorrhagic fever that affects humans and other primates. It is characterized by rapid virus spread in a short period of time. The disease has the potential to spread to many different regions of the world. In this paper, we have developed a modified mathematical model of the Ebola virus, adding the quarantine population as a control strategy. The quarantine population F and parameters ρ3 represent the rate at which individuals enter the quarantine compartment, which is vital in controlling the virus spread within society. The conformable derivatives have been applied to the modified model to observe the behavior of individuals for fractional derivative values between 0.7 and 1. For a modified model, the threshold parameter (R0) has been determined using the Next-Generation Matrix (NGM) method. We have checked local and global stability at a disease-free equilibrium point using Routh-Herwitz (RH) criteria and Castillo-Chavez, respectively. Numerical results obtained through the Fourth-Order Runge Kutta Method (RK4) demonstrate, a decrease in the virus transmission rate after following the implementation of the quarantine strategy.

Cellular N-myristoyl transferases Are Required for Mammarenavirus Multiplication.

The mammarenavirus matrix Z protein plays critical roles in virus assembly and cell egress, whereas heterotrimer complexes of a stable signal peptide (SSP) together with glycoprotein subunits GP1 and GP2, generated via co-and post-translational processing of the surface glycoprotein precursor GPC, form the spikes that decorate the virion surface and mediate virus cell entry via receptor-mediated endocytosis. The Z protein and SSP undergo N-terminal myristoylation by host cell N-myristoyltransferases (NMT1 and NMT2), and G2A mutations that prevent myristoylation of Z or SSP have been shown to affect Z mediated virus budding and GP2 mediated fusion activity required to complete the virus cell entry process. In the present work, we present evidence that the validated on-target specific pan NMT inhibitor DDD85464 exerts a potent antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) that correlated with reduced Z budding activity and GP2 mediated fusion activity, as well as proteasome mediated degradation of the Z protein. The potent anti-mammarenaviral activity of DDD85646 was also observed with the hemorrhagic fever causing mammarenaviruses Junin (JUNV) and Lassa (LASV) viruses. Our results support exploration of NMT inhibition as a broad-spectrum antiviral against human pathogenic mammarenaviruses.

The 2016 Severe Floods and Incidence of Hemorrhagic Fever With Renal Syndrome in the Yangtze River Basin

Hemorrhagic fever with renal syndrome (HFRS), a neglected zoonotic disease, has received only short-term attention in postflood prevention and control initiatives, possibly because of a lack of evidence regarding the long-term association of flooding with HFRS. To quantify the association between severe floods and long-term incidence of HFRS in the Yangtze River basin and to examine the modifying role of geographical factors in this association. This cross-sectional study collected data on HFRS cases between July 1, 2013, and June 30, 2019, from 58 cities in 4 provinces (Anhui, Hubei, Hunan, and Jiangxi) in the Yangtze River basin of China, with a breakpoint of flooding in July 2016, generating monthly data. The 3 years after July 2016 were defined as the postflood period, while the 3 years before the breakpoint were defined as the control period. Statistical analysis was performed from October to December 2023. City-level monthly flooding, elevation, ruggedness index, and closest distance from each city to the Yangtze River and its tributaries. The primary outcomes were the number of city-level monthly HFRS cases and the number of type 1 (spring or summer) and type 2 (autumn or winter) HFRS cases. A total of 11 745 patients with HFRS were reported during the study period: 5216 patients (mean [SD] age, 47.1 [16.2] years; 3737 men [71.6%]) in the control period and 6529 patients (mean [SD] age, 49.8 [15.8] years; 4672 men [71.6%]) in the postflood period. The pooled effects of interrupted time series analysis indicated a long-term association between flooding and HFRS incidence (odds ratio, 1.38; 95% CI, 1.13-1.68), with type 1 cases being at highest risk (odds ratio, 1.71; 95% CI, 1.40-2.09). The metaregression results indicated that elevation and ruggedness index were negatively associated with the risk of HFRS, while the distance to rivers interacted with these associations. This cross-sectional study of the long-term association between flooding and HFRS incidence, as well as the modification effects of geographical factors, suggests that severe floods were associated with an increased risk of HFRS within 3 years. This study provides evidence for the development of HFRS prevention and control strategies after floods.

National burden of Ebola virus disease in Democratic Republic of the Congo: the urgency to act.

Ebola virus disease (EVD) has long been a major public health concern for Democratic Republic of the Congo (DR Congo). First identified in DR Congo in 1976, the country has witnessed more than 25 outbreaks of this deadly disease, which has a case fatality rate of nearly 90% and manifesting with symptoms such as diarrhoea, vomiting, stomachache and haemorrhagic fever. African fruit bats have been speculated to be the reservoir of this virus. DR Congo is currently facing another EVD outbreak simultaneously with other communicable diseases, rendering it vulnerable to a shortage of medical and paramedical staff along with distrust among remote communities towards local authorities due to armed conflict and political instability. Moreover, lack of ring vaccinations and inefficient surveillance of suspected individuals are some other significant hurdles in disease control. Despite the availability of rVSV-ZEBOV/Erbevo vaccine and many antibody-based vaccines, challenges including politicization, low access to remote communities, and illiteracy have limited their effectiveness. Recently, the Congolese govt. has put in efforts such as building local capacities at the health zone level, outbreak control intervention, community engagement and social mobilization to counter the rising EVD cases. Four successive Strategic Response Plans have been implemented to increase resource mobilization by DR Congo and her partners. The Spread of zoonotics such as EVD can be confronted by implementing the One Health approach, which involves medical staff, veterinarians and public health officials.

Investigation on the Epidemic Situation of Epidemic Hemorrhagic Fever in an Island Industrial Park in Zhoushan, China.

Objective: To investigate the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) and compare the S and M gene sequences of hantavirus (HV) between rodents and the infected cases. Methods: Detailed epidemiological investigations were conducted on the cases' working and living areas. Captured rodents were classified by night trapping method, and their lungs and blood were collected for virus carriage detection after aseptic dissection. Viral S and M fragments of HV RNA were amplified and sequenced from positive samples of cases and mice, and their homology was analyzed. Results: After reconstruction, the geographic and living environment changed significantly, altering rodent behaviors. The industrial park, characterized by high population density, poor living conditions, and frequent contact of rodent (feces) and humans, had a high rodent density and HV virus infection ratio. Four workers infected with HV were positive for anti-HV immunoglobulin G (IgG) and IgM. Among the positive samples, HV RNA was detected in all two cases, and four Rattus norvegicus specimens were Seoul type HV S3 subtype. The virus had the closest relationship with Rod/2012/QHD/4/Gc (Hebei, China) and RuianRn180 (Zhejiang, China), with the 100% homology of M gene segment. The homology of viral S gene segment exhibited the closest relationship with the Jiangxi isolated JiangxiXinjianRn-09-2011, ranging from 99.6% to 99.8%. Conclusion: The HV sequencing showed a strong epidemiological relationship between the cases and host rodents. Improving living environmental health conditions, administering HFRS vaccine, and reducing rodent density and human-rodent contact can mitigate the risk of HFRS.

Recent research advances in the development of Dabie Banda virus vaccines.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.

Crimean-Congo Hemorrhagic Fever Virus Kinetics in Serum, Saliva, and Urine, Iran, 2018.

Little is known about using noninvasive samples for diagnosing Crimean-Congo hemorrhagic fever (CCHF). We investigated detection of CCHF virus in serum, saliva, and urine samples. Our results indicate that serum is the best sample type for CCHF diagnosis; saliva can be used for noninvasive sampling.

Impact of Waste Management on Infectious Disease Control: Evaluating Strategies to Mitigate Dengue Transmission and Mosquito Breeding Sites – A Systematic Review

Background: Dengue, a mosquito-borne viral disease primarily transmitted by Aedes mosquitoes, is a significant global public health concern, particularly in tropical and subtropical regions. Severe cases, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), can be fatal. Recent outbreaks in Bangladesh highlight the disease's escalating threat, with inadequate waste management playing a critical role in mosquito breeding and disease transmission. Methods: This review aims to assess the effectiveness of various waste management techniques, such as gasification, pyrolysis, compaction, and incineration, in reducing the buildup of garbage and, therefore, the spread of mosquito breeding grounds. This review also assesses the waste-derived containers used for storing wastewater, which act as breeding grounds for dengue mosquitoes. This review identifies Aedes aegypti mosquito larvae density in ten dengue-endemic regions. Larval samples were collected from various outdoor containers using dipping methods and analyzed through the Container Index (CI). The CI represents the percentage of containers infested with larvae and indicates the potential for dengue transmission. Results: The review revealed that high CI values in locations such as Dire Dawa, Ethiopia (54%), and Tamil Nadu, India (32.2%) indicated significant risk for dengue transmission. In contrast, a low CI value of 0.15% was observed in Rawalpindi, Pakistan, corresponding with lower dengue incidence. Results showed that poorly managed waste sites, particularly those accumulating stagnant water, contributed to higher CI values. Conclusion: Effective waste management, including proper disposal and reduced breeding grounds, is crucial in mitigating dengue transmission. The review emphasizes the need for improved waste management infrastructure, community involvement, and government-led policy frameworks to control Aedes mosquito populations and reduce dengue outbreaks.

Knowledge and Attitudes Regarding Crimean-Congo Hemorrhagic Fever Among Slaughterhouse Workers in Sana'a and Dhamar Cities-Yemen: A Cross-Sectional Study.

Crimean-Congo Hemorrhagic Fever (CCHF) is a viral infection spread through tick bites or contact with secretions from infected animals or humans, posing a risk to slaughterhouse workers. This study aimed to evaluate the knowledge and attitudes of slaughterhouse workers in Yemen towards CCHF. A cross-sectional study conducted on 173 adults working at slaughterhouses in Sana'a and Dhamar cities, Yemen using a multi-stage sampling. The questionnaire used in the study was a reliable survey instrument (with a Cronbach's alpha coefficient of 0.71) employed for the purpose of data collection. The questionnaire encompassed three distinct sections: 1)- demographic inquiries pertaining to age, gender, marital status, level of education, and occupation; 2)- knowledge-based inquiries consisting of 27 items;3)- the attitude section consisted of 11 questions. After completing the questionnaire, the data were analyzed by SPSS version 24, using percentages, chi-square test, and Spearman correlation coefficient. The mean age of the participants was 30.6 years with a SD of 11.2 years, with 84.4% male and 15.6% female. Most slaughterhouse workers were butchers (78.6%) and some were shepherds (21.4%). The participants had poor knowledge (86.7%) and attitude (72.3%) towards CCHF. There exists a noteworthy association between the knowledge scores and the gender, education level, and occupation (P=0.035, P=0.039, P=0.001). A significant positive correlation was identified between knowledge and attitude scores (r = 0.715, P<0.001). The majority of respondents had poor knowledge of CCHF. Educational programs are essential for increasing community awareness, with involvement of technical experts crucial for disseminating information on preventing and managing CCHF.

Predicting immune response targets in orthoflaviviruses through sequence homology and computational analysis.

Flaviviruses cause severe encephalitic or hemorrhagic diseases in humans. Its members, Kyasanur forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (ALKV), cause hemorrhagic fever and are prevalent in India and Saudi Arabia, respectively, while the tick-borne encephalitis virus (TBEV) causes a dangerous encephalitic infection in Europe and Asia. However, little information is available about the targets of immune responses for these deadly viruses. Here, we predict potential antigenic peptide epitopes of viral envelope protein for inducing a cell-mediated and humoral immune response. Using the Immune Epitope Database and Analysis Resource (IEDB-AR), we identified 13 MHC-I and two MHC-II dominant conserved epitopes in KFDV and ALKV and six MHC-I and three MHC-II epitopes in TBEV envelope proteins. Parallelly, we also predicted B-cell linear and discontinuous envelope protein epitopes for these viruses. Interestingly, the epitopes are conserved in all three viral envelope proteins. Further, the discontinuous epitopes are structurally compared with the available DENV, ZIKV, WNV, TBEV, and LIV envelope protein antibody structures. Overall structural comparison analyses highlight (i) lateral ridge epitope in the ED-III domain of E protein, and (ii) envelope dimer epitope (EDE) could be targeted for developing potent vaccine candidates as well as therapeutic antibody production. Moreover, existing structural and biochemical functions of the same epitopes in homologous viruses are predicted to have a reduced antibody-dependent enhancement (ADE) effect on flaviviral infection.

Dengue virus infection: potential applications of "Omics" based approaches

Dengue, caused by the dengue virus (DENV), a member of the flavivirus family, continues to pose a significant threat to populations worldwide, despite advances in technology. Nearly half of the global population is at risk of contracting the disease, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). The precise mechanisms underlying the progression of DF to DHF and DSS remain unclear, and the presence of various DENV serotypes exacerbates this situation. Urbanization and climate change are expected to affect dengue epidemiology, potentially increasing the frequency and intensity of outbreaks. This review aims to consolidate the current knowledge on the biological characteristics, pathogenesis, and application of "Omics" based strategies for biomarker discovery for precision medicine. Although the precise mechanisms behind the progression from DF to DHF/DSS are not fully understood, hypotheses include immune over-activation, cytokine storms, and antibody-dependent enhancement. Studies of comorbid conditions have shown no significant association with the development of DHF/DSS in patients with diabetes, hypertension, or other chronic diseases. Despite the far-reaching and intricate nature of dengue, the inconsistencies found in clinical pathophysiological studies underscore the need for additional research aimed at elucidating the pathogenesis of DHF/DSS and devising effective preventive measures. Identifying the differentially expressed genes, proteins, and metabolites in DF, DHF, and DSS may enrich our understanding of the mechanisms underlying their pathogenesis. Moreover, these differentially regulated pathways may serve as novel therapeutic targets. These biomarkers may also be utilized for disease surveillance and the evaluation of the efficacy of therapeutic interventions for personalized treatment. Continuous research is essential to gain deeper insights into the mechanisms and progression of dengue fever and to formulate more effective prevention and control strategies. A multidisciplinary approach is vital for comprehending dengue virus pathogenesis, identifying risk factors, and creating targeted interventions, particularly through biomarker discovery using "Omics" approaches.

Proposed Neural Network Model to Estimate Hemorrhagic Fever Iraqi People Statistics

Proposed Neural Network Model to Estimate Hemorrhagic Fever Iraqi People Statistics

MODELING DHF IN CENTRAL JAVA USING HYBRID NONPARAMETRIC SPLINE TRUNCATED-FOURIER SERIES APPROACH

Regression analysis aims to determine the relationship and influence of predictor variables on response variables through regression curve. The problem with nonparametric regression research so far is that it only uses one approach, causing the estimation results to be biased, even though each data sub-pattern has its own suitability depending on the approach method used. Therefore, the hybrid method emerged as a development of nonparametric regression. Hybrid models are models that combine approach methods, with the hope of increasing accuracy in modeling analysis. This research was carried out using two non-parametric approaches, namely Spline Truncated and Fourier Series. Dengue Hemorrhagic Fever (DHF) is a disease caused by the dengue virus. DHF is endemic and occurs throughout the year, especially during the rainy season because mosquitoes reproduce optimally. The aim of this research is to estimate the Hybrid Nonparametric Spline Truncated -Fourier Series model and apply the estimation results to data on DHF cases in Central Java. The data used to apply the hybrid nonparametric Spline Truncated-Fourier series regression model is DHF in the city/districts of Central Java. Estimation smoothing parameters uses the GCV (Generalized Cross Validation) method. The best model is selected based on largest R-Square and the smallest MSE. Modeling the disease of DHF cases in Central Java using the Spline Truncated-Fourier Series hybrid estimator produced the best model from the Spline Truncated model with two knot points for each predictor and the Fourier Series model with value of 9. Based on the results obtained, it can be compared that the Truncated Spline-Fourier Series hybrid model is better than the Spline Truncated model, this can be seen from the largest R-square, namely 99.94% and the smallest MSE.

Understanding the delay in identifying Sudan Virus Disease: gaps in integrated disease surveillance and response and community-based surveillance to detect viral hemorrhagic fever outbreaks in Uganda, September 2022

BackgroundEarly detection of outbreaks requires robust surveillance and reporting at both community and health facility levels. Uganda implements Integrated Disease Surveillance and Response (IDSR) for priority diseases and uses the national District Health Information System (DHIS2) for reporting. However, investigations after the first case in the 2022 Uganda Sudan virus outbreak was confirmed on September 20, 2022 revealed many community deaths among persons with Ebola-like symptoms as far back as August. Most had sought care at private facilities. We explored possible gaps in surveillance that may have resulted in late detection of the Sudan virus disease (SVD) outbreak in Uganda.MethodsUsing a standardized tool, we evaluated core surveillance capacities at public and private health facilities at the hospital level and below in three sub-counties reporting the earliest SVD cases in the outbreak. Key informant interviews (KIIs) were conducted with 12 purposively-selected participants from the district local government. Focus group discussions (FGDs) were conducted with community members from six villages where early probable SVD cases were identified. KIIs and FGDs focused on experiences with SVD and Viral Hemorrhagic Fever (VHF) surveillance in the district. Thematic data analysis was used for qualitative data.ResultsForty-six (85%) of 54 health facilities surveyed were privately-owned, among which 42 (91%) did not report to DHIS2 and 39 (85%) had no health worker trained on IDSR; both metrics were 100% in the eight public facilities. Weak community-based surveillance, poor private facility engagement, low suspicion index for VHF among health workers, inability of facilities to analyze and utilize surveillance data, lack of knowledge about to whom to report, funding constraints for surveillance activities, lack of IDSR training, and lack of all-cause mortality surveillance were identified as gaps potentially contributing to delayed outbreak detection.ConclusionBoth systemic and knowledge-related gaps in IDSR surveillance in SVD-affected districts contributed to the delayed detection of the 2022 Uganda SVD outbreak. Targeted interventions to address these gaps in both public and private facilities across Uganda could help avert similar situations in the future.

Molecular insight into the neutralization mechanism of human-origin monoclonal antibody AH100 against Hantaan virus.

Both Old World and New World hantaviruses are transmitted through rodents and can lead to hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome in humans without the availability of specific therapeutics. The square-shaped surface spikes of hantaviruses consist of four Gn-Gc heterodimers that are pivotal for viral entry into host cells and serve as targets for the immune system. Previously, a human-derived neutralizing monoclonal antibody, AH100, demonstrated specific neutralization against the Old World hantavirus, Hantaan virus. However, the precise mode binding of this neutralizing monoclonal antibody remains unclear. In the present study, we determined the structure of the Hantaan virus Gn-AH100 antigen-binding fragment complex and identified its epitope. Crystallography revealed that AH100 targeted the epitopes on domain A and b-ribbon and E3-like domain. Epitope mapping onto a model of the higher order (Gn-Gc)4 spike revealed its localization between neighboring Gn protomers, distinguishing this epitope as a unique site compared to the previously reported monoclonal antibodies. This study provides crucial insights into the structural basis of hantavirus neutralizing antibody epitopes, thereby facilitating the development of therapeutic antibodies.IMPORTANCEHantaan virus (HTNV) poses a significant threat to humans by causing hemorrhagic fever with renal syndrome with high mortality rates. In the absence of FDA-approved drugs or vaccines, it is urgent to develop specific therapeutics. Here, we elucidated the epitope of a human-derived neutralizing antibody, AH100, by determining the HTNV glycoprotein Gn-AH100 antigen-binding fragment (Fab) complex structure. Our findings revealed that the epitopes situated on the domain A and b-ribbon and E3-like domain of the HTNV Gn head. By modeling the complex structure in the viral lattice, we propose that AH100 neutralizes the virus by impeding conformational changes of Gn protomer, which is crucial for viral entry. Additionally, sequence analysis of all reported natural isolates indicated the absence of mutations in epitope residues, suggesting the potential neutralization ability of AH100 in diverse isolates. Therefore, our results provide novel insights into the epitope and the molecular basis of AH100 neutralization.

Sosialisasi Pencegahan Demam Berdarah Dengue pada Anak Sekolah Dasar Dusun Setro Kecamatan Bergas Kabupaten Semarang

One way to raise awareness of love for the environment and prevent dengue hemorrhagic fever is through outreach to school children. Socialization is one way to increase knowledge about preventing dengue hemorrhagic fever. The outreach aims to control the increasing incidence of dengue hemorrhagic fever cases. The method used begins with observation and giving a questionnaire to be filled in regarding questions regarding dengue hemorrhagic fever. After the data is found, a nursing diagnosis is then formulated, followed by implementation activities in the form of edugames and community service. Pre post analysis of knowledge using the Wilcoxon test showed that the p value (0.000) showed that there was an increase in knowledge between before and after socialization.