Dengue Antibodies Research Articles

A-261 Outcome of a survey on dengue lateral flow immunoassay test kit reading and interpretation by medical laboratory staff in a hospital laboratory

Abstract Background Lateral flow immunoassay (LFIA) tests, first introduced in 1959, are now the mainstay of clinical laboratories. Khoo Teck Puat Hospital (KTPH) is a 795-bed acute care general hospital located in the north of Singapore. The Department of Laboratory Medicine has been using dengue LFIA test kits for the detection of dengue NS1 antigen, IgM antibodies and IgG antibodies. While kits are cost-effective, user-friendly and provide rapid results, there is subjectivity in reading and interpretation of results. Methods We conducted a survey to assess test reading and interpretation by medical laboratory staff. Six serum and plasma specimens were analysed using Bioline™ Dengue IgG/IgM WB test device. Test kits at the end-point of sample incubation were photographed in both well-lit and dim conditions. A survey questionnaire was prepared using an online form builder tool using the photographs. Staff were invited to participate in the survey. They were allowed to report the result as ‘Positive’, ‘Negative’ or ‘Equivocal’. Results A total of sixteen responses were received. Results were 100% concordant for all 6 specimens in both well-lit and dim conditions. For one case, under a well-lit condition, 15 staff reported the result as ‘Positive’ while one staff reported ‘Equivocal’. Most of the reported results for samples with no consensus is split between ‘Positive’ and ‘Equivocal’. Conclusions Dengue viruses of all 4 known serotypes are endemic in Singapore. Positive results are tracked on a national level to identify areas of high dengue infection for intensive environmental and vector control measures. Hence, accurate reporting and identification of patients with dengue infection is important. Our survey shows that lighting conditions do not affect the interpretation of LFIA results. Reading and interpretation of dengue LFIA test kits however, remain dependent on user interpretation and newer test kits with optical readers may be useful in mitigating this.

Evaluation of three alternative methods to the plaque reduction neutralizing assay for measuring neutralizing antibodies to dengue virus serotype 2

BackgroundDengue is a global public health challenge which requires accurate diagnostic methods for surveillance and control. The gold standard for detecting dengue neutralizing antibodies (nAbs) is the plaque reduction neutralization test (PRNT), which is both labor-intensive and time-consuming. This study aims to evaluate three alternative approaches, namely, the MTT-based (or (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) microneutralization assay, the xCELLigence real-time cell analysis (RTCA), and the immuno-plaque assay-focus reduction neutralization test (iPA-FRNT).MethodsTwenty-two residual serum samples were tested for DENV-2 nAbs using all four assays at three neutralization endpoints of 50%, 70% and 90% inhibition in virus growth. For each neutralization endpoint, results were compared using linear regression and correlation analyses. Test performance characteristics were further obtained for iPA-FRNT using 38 additional serum samples.ResultsPositive correlation of DENV-2 neutralization titers for the MTT-based microneutralization assay and the PRNT assay was only observed at the neutralization endpoint of 50% (r = 0.690). In contrast, at all three neutralization end points, a linear trend and positive correlation of DENV-2 neutralization titers for the xCELLigence RTCA and the PRNT assays were observed, yielding strong or very strong correlation (r = 0.829 to 0.967). This was similarly observed for the iPA-FRNT assay (r = 0.821 to 0.916), which also offered the added advantage of measuring neutralizing titers to non-plaque forming viruses.ConclusionThe xCELLigence RTCA and iPA-FRNT assays could serve as suitable alternatives to PRNT for dengue serological testing. The decision to adopt these methods may depend on the laboratory setting, and the utility of additional applications offered by these technologies.

Dengue Seroprevalence in Different Geographic Zones of India: A Systematic Review and Meta-Analysis of Cross-Sectional Studies

Dengue is a highly prevalent mosquito-borne disease that is endemic in over 100 countries. It has a wider impact in terms of severity of illness and mortality risk in the absence of an effective vaccine as yet. The purpose of this study was to use meta-analysis to find out how common the dengue virus (DENV) is in India based on public data and to figure out how much of a problem. We searched, read, and reviewed about DENV in India that were available online. Forty-four cross-sectional studies were selected from the 178 records. There were reports of dengue cases in 14 out of the 28 states. Out of the patients presenting with symptoms of Dengue 27% of people were confirmed to have DENV infection with 82.29% (95% CI. 81-84%), having dengue IgM, 41.67% (95% CI: 40.16-43.43), having dengue IgG, and 23.97% (95% C.I. 14-43%), having both IgG and IgM from positive sample n=27156. Hospital-based cross-sectional studies on suspected Dengue-like illness (DLI) found that 99.48% of people had confirmed dengue out of the patients with features of DLI, and community-based studies found that 0.52% of DLI cases had dengue. The seroprevalence rates for East, South, North, and Western regions were 35.38% (95% C.I.14-31%), 11.57% (95% C.I. 2-69%), 38.10% (95% C.I. 9-61%), and 14.87% (95% C.I. 6-38%) correspondingly. DENV is interestingly spreading across the whole country, and the disease’s frequency varies a lot from place to place and from 2010-2023. However this review does not find appropriate published literature from 50% of the Indian states. The identification of IgG-class antibodies to dengue virus is indicative of prior exposure to this pathogen. Almost all immunocompetent individuals should have developed IgG antibodies against the dengue virus within three weeks of exposure. The presence of dengue virus IgM-class antibodies is indicative of an acute phase of infection. National Vector borne Disease Control Programme (NVBDCP) has some surveillance information, appropriate designed research into prevalence and risk factors for DENV infection would be required to provide adequate information for public health intervention.

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.

IgG, IgM, and Nonstructural Protein 1 Response Profiles after Receipt of Tetravalent Dengue Vaccine TAK-003 in a Phase 2 Randomized Controlled Trial.

The profiles of vaccine-induced dengue antibodies may differ from those produced following natural infection and could potentially interfere with the interpretation of diagnostic tests. We assessed anti-dengue IgG and IgM antibodies, and nonstructural protein 1 antigen profiles in the serum of adults who received a single dose of the tetravalent dengue vaccine TAK-003 as either an initially developed high-dose formulation or the standard approved formulation in a phase 2 study in Singapore (#NCT02425098). Immunoglobulin G and IgM profiles during the first 30 days postvaccination varied by baseline serostatus (microneutralization assay). Nonstructural protein 1 antigen was not detected in the serum of any participants. Vaccine-induced IgG and IgM antibodies can affect serological confirmation of subsequent dengue infection in vaccinees. These results highlight the limitations of using serological tests for dengue diagnosis, particularly in a postvaccination setting, and emphasize the need for more sensitive antigen- and molecular-based testing for accurate dengue diagnosis.

Dengue NS1 antibodies are associated with clearance of viral NS1.

Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Comparison between COVID-19 and DHF co-disease with COVID-19 alone in two pediatric sibling patients

We report herein the difference between Corona virus disease-19 (COVID-19) and dengue hemorrhagic fever (DHF) co-infection compared with COVID-19 alone in two pediatric sibling patients. This case report highlights a 10-year-old boy with both COVID-19 and DHF who had less severe coagulation disorder than his sister with COVID-19 alone. In a patient with a dual infection, the presence of dengue antibodies may induce immunological protection against COVID-19. We found reports of milder symptoms in patients who had dengue prior to SARS- CoV-2 infection; however, the opposite occured when SARS-CoV-2 infection precedes dengue.

Significance of Serological Markers in Diagnosis of Acute Dengue Infection: 2021 Outbreak

Objective: To highlight the significance of Dengue anti-IgM and Dengue NS1 antigen in diagnosing Acute Dengue infection. Study Design: Cross-sectional study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Sep to Nov 2021. Methodology: One hundred and fifty Dengue NS1-positive patients of either gender with age≥5 years were included. ELISA tested patients for detection of Dengue anti-IgM antibody. A questionnaire was used to collect demographic and personal data of each patient. Results: Out of 150 dengue NS1 positive samples, 26(17%) were positive for dengue anti-IgM. In collected samples, Dengue serological markers (NS1 and anti-IgM) positivity was observed based on ‘the day of onset of symptoms. On days 1 and 2, 54 and 44 NS1 positive samples were collected, respectively, but no one was found positive for anti-IgM. Anti-IgM was detected on day-3 and onwards. 27% Dengue anti-IgM positivity was found on day-3, which increased gradually as the time of infection increased. On day four, it was 53%; on day 5, it was 55%; on day-6, it was 60%; on day 7, it was 75%; and on day 8, it was 100%. Conclusions: The findings of present study suggested that anti-Dengue IgM antibodies are less significant than the Dengue NS1 antigen in diagnosing acute dengue infection.

The Value of Warning Signs From the WHO 2009 Dengue Classification in Detecting Severe Dengue in Children.

World Health Organization proposed 7 warning signs to identify the risk of severe dengue in 2009. This study aimed to evaluate the value of these warning signs in detecting severe dengue in children. A cross-sectional study was conducted utilizing data of children with clinical dengue infection obtained from medical records between January 2009 and December 2018 in Jakarta. Children with confirmed dengue were analyzed and stratified into 3 age groups: infants less than 1 year old, children 1-14 years and adolescents 15-18 years of age. Positive predictive value, negative predictive value (NPV), sensitivity and specificity of each warning sign present or absent on admission in detecting severe dengue were computed. Six hundred ninety-nine children with clinical dengue infection were enrolled, among whom 614 (87.8%) had confirmed dengue infection, either by antigen or antibody serological tests. Severe dengue occurred in 211/614 (34.4%) cases. In infants, important warning signs on admission to detect or exclude severe dengue were liver enlargement (NPV 80.8%) and clinical fluid accumulation (NPV 75%). In children and adolescents, warning sign with highest NPV (in children 76.6% and in adolescents 91.9%) was increase in hematocrit concurrent with a rapid decrease in platelet count. Other warning signs with high NPV values in children were abdominal pain (72%), vomiting (70%), clinical fluid accumulation (69.3%), and in adolescents' abdominal pain (80.7%), vomiting (75.7%), clinical fluid accumulation (82.7%). NPVs increase with more than 1 warning sign in all age groups. In infants, liver enlargement or clinical fluid accumulation are important warning signs for severe dengue, when both are absent, severe dengue is unlikely. In older children and adolescents, an increase in hematocrit with the concurrent rapid decrease in platelet count is most discriminative; followed by the absence of abdominal pain, vomiting or fluid accumulation are unlikely severe dengue.

Retrospective Study of Various Factors In Pediatric To Severe Dengue Infection

Introduction: Dengue epidemics are known to have occurred over the last three centuries in tropical, subtropical and temperate areas of the world. Annually a 100 million cases of Dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur in the world with a case fatality in Asian countries of 0.5%–3.5%. Objective: To assess the various factors in pediatric to severe dengue infection. Methods: A hospital-based Retrospective study was conducted at Department Of Paediatric, Mugda Medical College Hospital, Dhaka, Bangladesh from October to December 2023. Number of patients included in the study was 50. In children with high degree clinical suspicion of Dengue infection NS 1 antigen (who came within first 48 hours of fever) and/or Dengue antibody IgM, IgG (who came after five days of fever) were performed. Positive Dengue cases were taken written informed consent & interviewed on the risk factors of Dengue infection. Data related to patients demography, risk factors, clinical presentation, pattern of Dengue infection and outcome were documented on the pre-structured questionnaire. Results: The study was enrolled 100 patients of suspected dengue fever of whom 50 (50.0%) were serologically confirmed to have dengue infection. 30 (60%) patients were males and 20 (40%) were females. 38 (76%) patients had classic dengue fever while 12 (24%) fulfilled the criteria of dengue hemorrhagic fever. Of those patients with dengue hemorrhagic fever, 6 patients had developed dengue shock syndrome. Among the study 44 (88%) from urban and 6 (12%) rural area patients. All cases and is the most common symptom followed by headache, myalgia, vomiting etc. Hemorrhagic manifestations were seen that included petechiae, ecchymosis, gum bleeding, hematuria, malena, hematemesis and epistaxis. Most common complicationswere hepatic dysfunction, renal failure, multi organ failure, encephalopathy and ARDS. Among 50 suspected dengue cases 38 (76.0%) cases were serologically dengue positive. Among the 38 serologically dengue positive patients 17 (44.7%) were NS1 antigen positive, 13 (34.2%) IgM antibodies and 8(21.0%) both IgM and IgG antibodies positive. The distribution of the serologically dengue positive patients out of 50 clinically suspected cases. Conclusion: Dengue is one amongst the key causes of dedifferentiated fever. It presents as an extremely broad wellness and is hardly recognized as a clinical entity by primary health care physicians. This study highlights the practician the importance of break bone fever to clinicians within the areas of medical specialty, manifestations, complications and outcome of the wellness

Urinary dengue NS1 detection on Au-decorated ZnO nanowire platform

Biodetection for non-invasive diagnostics of fluids, especially urine, remains a challenge to scientists due to low target concentrations. And biological complexes of the detection target may contain contaminants that also interfere with any assay. Dengue non-structural 1 protein (Dengue NS1) is an important biomarker for dengue hemorrhagic fever and dengue shock syndrome. Here, we developed an Au-decorated nanowire platform and applied it with a sandwich fluorophore-linked immunosorbent well plate assay (FLISA) to detect Dengue NS1 in urine. For the platform, we fabricated zinc oxide (ZnO) nanowires to provide a high surface area and then coated them with gold nanoparticles (ZnO/Au nanowires) to simply modify the Dengue NS1 antibody and enhance the fluorescence intensity. Our platform employs a sandwich FLISA that exhibits high sensitivity, specifically detecting Dengue NS1 with a limit of detection (LOD) of 1.35 pg/mL. This LOD was 4500-fold lower than the LOD of a commercially available kit for Dengue NS1 enzyme-linked immunosorbent assay. We believe that our ZnO/Au nanowire platform has the potential to revolutionize the field of non-invasive diagnostics for dengue.

Exploring the Therapeutic Potential of Glycyrrhizic Acid in Liver Implication in Dengue Infection: A Case Report

Dengue is one of the most common infectious diseases affecting humans. The virus is transmitted between humans by the Aedes mosquito. It occurs hyperendemically in tropical and subtropical climates worldwide. Dengue infection can affect numerous organs, with the liver being the most frequently affected organ. The clinical spectrum of liver disorders ranges from mild elevation of transaminase enzymes to severe conditions such as acute liver failure. Several mechanisms have been proposed to describe hepatic dysfunction observed in dengue fever and dengue hemorrhagic fever, such as immunological injury, hypoxic injury, and direct viral damage due to reduced hepatic perfusion during shock. Glycyrrhizic acid, extracted in the form of glycyrrhizin from the root of the licorice plant Glycyrrhiza glabra, is referred to as Stronger Neo-Minophagen-C (SNMC®). It has shown effectiveness in reducing serum aminotransferase and bilirubin levels, attenuating hepatocyte apoptosis, and producing endogenous interferon. The following is a case report of a 23-year-old woman with dengue fever and elevated liver enzyme level. The patient’s vital signs were stable. A physical examination revealed no abnormalities. A complete blood count test showed thrombocytopenia without an elevation of the hematocrit. AST level was 901 U/L after admission. Causes of other hepatitis infections, such as hepatitis A, B, and C, were excluded. The dengue IgM and IgG antibody levels were reactive. After several days of hospitalization, the patient experienced clinical improvement after supportive therapy and the administration of glicyrrhizic acid or SNMC®.

An observer-blind, randomised, placebo-controlled, phase 1, single ascending dose study of dengue monoclonal antibody in healthy adults in Australia

Dengue is highly prevalent in Asia and Latin America and has no specific dengue antiviral treatment. A recombinant monoclonal antibody (VIS513) that neutralises all four serotypes of the dengue virus has been developed in India. After confirmation of safety and efficacy in preclinical studies, it was tested in a first-in-human study to assess the safety and pharmacokinetics. This was a partially blind (observer-blind), randomised, placebo-controlled, phase 1, single ascending dose study in Australia. Participants were dengue naive, healthy adults (aged 18-45 years) with no clinically significant disorders or immunosuppressive conditions. Four dose levels of dengue monoclonal antibody (ie, 1 mg/kg, 3 mg/kg, 7 mg/kg, and 12 mg/kg; n=4 for 1 mg/kg and n=10 each for 3 mg/kg, 7 mg/kg, and 12 mg/kg doses) were assessed in a dose-ascending way with a placebo control (n=2 for each dose cohort, total n=6) for each cohort except for 1 mg/kg. Within each cohort, participants were first randomly assigned (1:1) in a sentinel sub-cohort and then randomly assigned (9:1) in an expansion sub-cohort to dengue monoclonal antibody or placebo except for the 1 mg/kg cohort. Participants, investigators, and outcome assessors were masked and treatment administrators were not masked. 40 participants received a single intravenous injection or infusion of either dengue monoclonal antibody or placebo over a period of 3 min to 2 h and were followed up until day 85. The primary outcomes were proportion of participants with adverse events and serious adverse events (SAEs) up to 84 days after dosing whereas the secondary outcomes were to assess the pharmacokinetic profile of dengue monoclonal antibody and to assess the presence of anti-drug antibody (ADA) to dengue monoclonal antibody. All participants were included in the safety analysis and the pharmacokinetic population involved participants receiving dengue monoclonal antibody. This study is registered with ClinicalTrials.gov, NCT03883620. Between March 22 and Dec 23, 2019, 40 healthy adults were randomly assigned and all completed the study. There were no SAEs reported. None of the placebo recipients (n=6) reported any adverse events. 31 (91%) of 34 participants receiving dengue monoclonal antibody reported 143 adverse events (1 mg/kg: four [100%] of four participants; 3 mg/kg: ten [100%] of ten participants; 7 mg/kg: seven [70%] of ten participants; 12 mg/kg: ten [100%] of ten participants). Of these 143 adverse events, 80 were treatment-related adverse events in 28 (82%) of 34 participants. Headache (16 [47%] of 34), infusion reaction (11 [32%] of 34), lymphopenia (seven [21%] of 34), fatigue (five [15%] of 34), and pyrexia (four [12%] of 34) were the most common reactions. Infusion reactions were reduced in the 7 mg/kg (two [20%] of ten participants) and 12 mg/kg (three [30%] of ten) cohorts with paracetamol premedication compared with the 3 mg/kg cohort (five [50%] of ten). The majority of adverse events were grade 1 or grade 2 in severity, and resolved completely. Median maximum serum concentrations ranged from 28 μg/mL (1 mg/kg) to 525 μg/mL (12 mg/kg). The median elimination half-life ranged from 775 h (1 mg/kg) to 878 h (12 mg/kg). No ADA against dengue monoclonal antibody was detected. Dengue monoclonal antibody was safe and well tolerated. It showed a dose-proportionate increase in pharmacokinetic exposure. These data support further evaluation of dengue monoclonal antibody in patients with dengue for safety and efficacy. Serum Institute of India.

Comparative Diagnostic Value of Dengue Infection Using ELFA and Two Commercial Immuno-Chromatography Tests

Dengue Virus (DEN-V) can lead to a broad spectrum of clinical presentations, from mild symptoms to mortality. Based on the presence of antibodies, dengue infection is categorized into primary and secondary dengue. Early diagnosis is crucial for effective treatment of DEN-V infection. Non-Structural Antigen 1 (NS1) and dengue antibodies like immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-dengue are standard assays used for dengue diagnosis. Various immunoassay methods, including Enzyme-Linked Fluorescent Assay (ELFA) and Immuno-Chromatographic Tests (ICT), are employed to detect these antigens and antibodies. This study aimed to compare the diagnostic value between ELFA and two commercial ICTs for detecting NS1 antigen, IgM/IgG anti-dengue. Seventy suspected dengue patients with fever lasting two to seven days at Premier Hospital, Surabaya were enrolled in this study. Blood serum samples from the individuals were tested for NS1 antigen and IgM/IgG anti-dengue using VIDAS® and two commercial ICTs (Boson and SD Bioline). The sensitivity of NS1 antigen assays using ELFA and two ICTs was calculated, as well as the agreement rate between ELFA and both ICTs. ELFA demonstrated high sensitivity (77.97%) for NS1 antigen detection in diagnosing dengue infection compared to two ICTs (76.27% and 45.45%). Using an automated system in ELFA can offer more excellent diagnostic value and objective results and determine the cut-off ratio of IgM/IgG antibodies. All of this comes at a cost comparable to ICT.

Severe disease during both primary and secondary dengue virus infections in pediatric populations.

Dengue is a global epidemic causing over 100 million cases annually. The clinical symptoms range from mild fever to severe hemorrhage and shock, including some fatalities. The current paradigm is that these severe dengue cases occur mostly during secondary infections due to antibody-dependent enhancement after infection with a different dengue virus serotype. India has the highest dengue burden worldwide, but little is known about disease severity and its association with primary and secondary dengue infections. To address this issue, we examined 619 children with febrile dengue-confirmed infection from three hospitals in different regions of India. We classified primary and secondary infections based on IgM:IgG ratios using a dengue-specific enzyme-linked immunosorbent assay according to the World Health Organization guidelines. We found that primary dengue infections accounted for more than half of total clinical cases (344 of 619), severe dengue cases (112 of 202) and fatalities (5 of 7). Consistent with the classification based on binding antibody data, dengue neutralizing antibody titers were also significantly lower in primary infections compared to secondary infections (P ≤ 0.0001). Our findings question the currently widely held belief that severe dengue is associated predominantly with secondary infections and emphasizes the importance of developing vaccines or treatments to protect dengue-naive populations.

Is a therapeutic dengue monoclonal antibody on the way?

Is a therapeutic dengue monoclonal antibody on the way?

The dengue-specific immune response and antibody identification with machine learning

Dengue virus poses a serious threat to global health and there is no specific therapeutic for it. Broadly neutralizing antibodies recognizing all serotypes may be an effective treatment. High-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) and bioinformatic analysis enable in-depth understanding of the B-cell immune response. Here, we investigate the dengue antibody response with these technologies and apply machine learning to identify rare and underrepresented broadly neutralizing antibody sequences. Dengue immunization elicited the following signatures on the antibody repertoire: (i) an increase of CDR3 and germline gene diversity; (ii) a change in the antibody repertoire architecture by eliciting power-law network distributions and CDR3 enrichment in polar amino acids; (iii) an increase in the expression of JNK/Fos transcription factors and ribosomal proteins. Furthermore, we demonstrate the applicability of computational methods and machine learning to AIRR-seq datasets for neutralizing antibody candidate sequence identification. Antibody expression and functional assays have validated the obtained results.

Correlation of Serological Markers with Haematological Parameters in Diagnosis of Dengue: A Single Centre Study at a Tertiary Care Hospital of Pakistan

Objective: To correlate the serological markers with hematological parameters in the diagnosis of dengue fever. Background: Dengue is a viral disease spread by Aedes Aegypti mosquitoes. It is most common in Southeast Asia. In recent times yearly epidemics of dengue fever has put a great burden on our health care system. The World Health Organization (WHO) has classified symptomatic dengue as dengue fever with or without warning signs and severe dengue. Early diagnosis of the disease and management can save countless lives in this curable infectious disease. Methodology: It is a prospective observational study from HBS General Hospital, Islamabad. 102 patients who presented with fever and tested positive for NS1 antigen and/or IgM dengue antibodies and fulfilled the inclusion criteria over a period of one year were included. The demographic data along with serological and hematological results were recorded. Conclusion: The most common serological test in dengue infection is NS- 1. Thrombocytopenia, leucopenia, monocytosis and reversed neutrophil lymphocyte ratio are important hematological clues in diagnosis of dengue fever. Thrombocytopenia is most severe in NS- 1 postive group as compared to antibody positive groups.

First report of dengue virus among febrile malaria positive and negative patients in Nyala city, Western Sudan

Background: The mosquito borne dengue fever and malaria -; are major public health concerns in tropical settings. They are highly prevalent and considered one of the main etiology of febrile illnesses in Sudan. Aim: This study aimed to determine seroprevalence of dengue virus among febrile malaria positive and negative patients in Nyala city, Western Sudan by using Enzyme linked immuno sorbent assay (ELISA) to detect dengue virus IgM and IgG antibodies. It also aimed to study possible risk factors that may be associated with dengue virus and malaria infections. Methods: This cross sectional study, which was undertaken in different Hospitals in Nyala city, South Darfur state Sudan during June to December 2021. A total of 93 blood samples from febrile patients were collected in EDTA containers. Plasma was obtained by centrifugation and tested by ELISA (EUROIMMUN, Germany) according to manufactures instructions for dengue virus IgG and IgM antibodies. Malaria parasites were detected using microscopy of stained blood smears. Generated data was analyzed using the statistical package (SPSS) version 21. Results: Forty six (49.5%) out of 93 febrile patients were found infected with malaria parasites using blood smear microscopy. Among these malaria infected patients, the prevalence of dengue anti-virus IgG (49 .5%) was higher than that of IgM (16.1%) but was statistically insignificant (p>0.05). In the present study dengue infection was higher in males than in females but was statistically insignificant (P> 0.05) and the Age group 21-40 years was the most affected with dengue virus infection. Conclusion: The present study showed higher prevalance rate of dengue IgG among the participants of study more than IgM but was statistically insignificant There was no association between age and gender with seroplevance of dengue virus among febrile patients with and without malaria. The frequent existence of infections of DENV requires improved surveillance and control measures to combat this disease in Nyala, Sudan.

The burden of dengue in children and risk factors of transmission in nine districts in Sri Lanka

AbstractWe sought to understand the differences in age‐stratified seroprevalence rates in different regions in Sri Lanka to plan dengue vaccination programs, especially as the WHO has given guidance to vaccinate in high transmission settings. Age stratified seroprevalence rates were assessed in children, aged 10−20 years, in nine districts representing the nine provinces in Sri Lanka, from September 2022 to March 2023. A stratified multistage cluster was used to select 146 schools representing each district. Of the 5207 children recruited, the overall dengue seroprevalence rates in children was 24.8%, with the highest rates reported from Trincomalee (54.3%) and the lowest rates from Badulla (14.2%), which is a high‐altitude estate area. While the age‐stratified seroprevalence rates increased in some districts such as Trincomalee, Jaffna, Gampaha, and Ratnapura, which reported the highest seropositivity rates, there was no such increase with age in the other districts. There was a weak correlation between the dengue antibody positivity rates and age in most districts which had seroprevalence rates of >25%, while there was no increase in antibody titers with age in the other districts. The seroprevalence rates was significantly higher in urban areas (35.8%) compared to rural (23.2%) and estate areas (9.4%), although there was no association with seropositivity rates with population density (Spearman's r = −0.01, p = 0.98), in each district. The seroprevalence rates in many districts were very different to those reported from Colombo, with many districts reporting low transmission rates. These data would be important to consider when rolling out dengue vaccines in Sri Lanka.