Age, gender, and infectious status-wise assessments of hematological parameters among patients with dengue infection.

Background: The aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. Methods: The recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. Results: The findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. Conclusion: In conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.

Early-phase factors associated with pediatric severe dengue in the Thai-Myanmar cross-border region.

BACKGROUND: Dengue disease is caused by dengue virus, which is transmitted by Aedes mosquitoes in tropical and subtropical regions worldwide. Although most infected individuals have benign febrile illness or no apparent symptoms, a small percentage develop severe dengue, a potentially fatal condition that occurs after a febrile stage. Many studies have identified factors predicting dengue severity among different populations and time courses. To help find practical approaches applicable in remote settings, we focused on the investigation of early factors associated with severe dengue in Thai-Myanmar cross-border region. METHODS: This retrospective case-control study was performed to determine factors contributing to severe dengue in the pediatric population. We reviewed the hospital records of patients with dengue infection aged 0-19 years who were admitted to Maesot General Hospital, situated near the Thai-Myanmar cross-border region, between 2017 and 2022. Medical data during the first 5 days of illness and outcomes were collected and analyzed. RESULTS: This study included 144 patients with a serologically confirmed diagnosis of dengue infection, with 43 severe and 101 non-severe cases. Among biological factors, being an infant and belonging to an ethnic group in Myanmar showed a significant association with severe dengue in the univariable analysis. Multivariable logistic regression revealed that the presence of mucosal bleeding (adjusted OR 5.39, 95% CI 1.06-27.52, P = 0.043), a change in hematocrit ≥ 10% (adjusted OR 3.68, 95% CI 1.15-11.74, P = 0.028), and serum albumin < 35 g/L (adjusted OR 8.10, 95% CI 2.55-25.72, P < 0.001) during the first 5 days of illness were significantly associated with developing severe dengue. CONCLUSIONS: This study supports the use of certain WHO warning signs and hematocrit change during febrile phase to predict pediatric severe dengue in low-resource settings. Potential factors such as very young age and ethnic groups warrant further exploration to identify risks contributing to severe dengue infection.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue.

Super epitope dengue vaccine instigated serotype independent immune protection in-silico.

Dengue becomes the most common life-threatening infectious arbovirus disease globally, with prevalence in the tropical and subtropical areas. The major clinical features include dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), a condition of hypovolemic shock. Four different serotypes of the dengue virus, known as dengue virus serotype (DENV)- 1, 2, 3 and 4 can infect humans. Only one vaccine is available in the market, named Dengvaxia by Sanofi Pasteur, but there is no desired outcome of this treatment due the antibody dependent enhancement (ADE) of the multiple dengue serotypes. As of now, there is no cure against dengue disease. Our goal in this work was to create a subunit vaccine based on several epitopes that would be effective against every serotype of the dengue virus. Here, computational methods like- immunoinformatics and bioinformatics were implemented to find out possible dominant epitopes. A total of 21 epitopes were chosen using various in-silico techniques from the expected 133 major histocompatibility complex (MHC)- I and major histocompatibility complex (MHC)- II epitopes, along with 95 B-cell epitopes which were greatly conserved. Immune stimulant, non-allergenic and non-toxic immunodominant epitopes (super epitopes) with a suitable adjuvant (Heparin-Binding Hemagglutinin Adhesin, HBHA) were used to construct the vaccine. Following the physicochemical analysis, vaccine construct was docked with Toll-like receptors (TLRs) to predict the immune stimulation. Consequently, the optimal docked complex that demonstrated the least amount of ligand-receptor complex deformability was used to conduct the molecular dynamics analysis. By following the codon optimization, the final vaccine molecule was administered into an expressing vector to perform in-silico cloning. The robust immune responses were generated in the in-silico immune simulation analysis. Hence, this study provides a hope to control the dengue infections. For validation of the immune outcomes, in-vitro as well as in-vivo investigations are essential.

Parents' Level of Knowledge, Attitudes, and Practices and Associated Sociodemographic Factors Regarding Dengue Infection in Children.

Background Dengue infection (DI) continues to rise in the Caribbean. Children are primarily affected by severe infection in this region. Parents thus play an essential role in identifying symptoms, seeking medical care, and preventing DI in their children. Grenada has been endemic to DI since 1956, and to date, no study has assessed the level of knowledge, attitude, and practices (KAP) among parents regarding DI. Objective To determine the level of parents' KAP and associated sociodemographic factors regarding DI in children in Grenada. Methods A quantitative cross-sectional study of 360 randomly selected parents attending postnatal and child-health clinics was conducted in Grenada. Parents completed a validated survey on demographic information and KAP regarding DI from September to December 2019. KAP scores were calculated and categorized as adequate or inadequate based on the percentage of correctly answered questions on the survey. Chi-square and logistic regression analyses were used to determine the level of KAP and associated sociodemographic factors among parents. Results Only 33.9% of parents had adequate knowledge regarding DI, which was independently associated with gender (p-value: 0.001, CI: 1.688-7.411), age (p-value: 0.001, CI: 0.037-0.443), occupation, education, and marital status. Nevertheless, most parents had a positive attitude toward DI prevention (56.4%) and practiced adequate prevention (73%) against DI. Higher education was independently associated with a positive attitude toward DI prevention (p-value: 0.013, CI: 0.190-0.825). However, no sociodemographic factors were associated with the prevention practices of DI. Conclusion This study revealed a low level of knowledge among parents, despite an adequate attitude and level of prevention against DI in Grenada. It identified specific groups, such as young, single parents of low educational status, as potential targets for educational campaigns to reduce DI-associated morbidity and mortality among Grenadian children.

Dual RNA-Seq reveals transcriptionally active microbes (TAMs) dynamics in the serum of dengue patients associated with disease severity.

Introduction: Dengue virus (DENV) is a flavivirus that has emerged as a global health threat, characterized by either asymptomatic or mild self-limiting febrile illness, but a subset of DENV outbreaks have been associated with severe disease. Studies have looked into the host immune response and dengue viral load during infection. However, it remains unknown how the active microbial isolates modulate the dengue viral infection. In this study, we demonstrate the significance of in-depth analysis of microbiota composition in the serum samples of dengue-infected patients. Materials and methods: RNA was extracted from the serum samples collected from 24 dengue positive patients. The human mapped reads generated through RNA-Sequencing (RNA-Seq) were removed, while the unmapped (non-human) reads were employed for microbial taxonomic classification using Kraken2 and Bracken2. Further, we assessed the initial blood parameters analyzing the complete blood count (CBC) profile of the patients. Results: Findings revealed differential abundance of commensals and pathogenic microbes in the early febrile period of hospitalized dengue patients, segregated into, High Viral Reads (HVR) and Low Viral Reads (LVR). The Campylobacter genus was abundant in the HVR whereas Lactobacillus dominated the LVR patients. At species level, the microbiota of HVR exhibited higher abundance of unique potential opportunistic microbes, compared to the commensal microbes' enrichment in the LVR patients'. We hypothesize that the DENV might alter the microbiota composition as observed by the increase in preponderance of opportunistic pathogens and an absence of commensals in the HVR. The presence of commensals in the LVR might explain, i) overall lower dengue viral reads compared to the HVR, and ii) shift in lymphocytes (high) and neutrophils (low) counts; resulting in a comparatively milder clinical manifestation in this group. Our findings may help in understanding the co-infection aspect that will be important to develop dengue therapeutics and vaccines. Discussion: This study highlights the potential of the unexplored roles of the TAMs in modulating the dengue disease severity using the metatranscriptomic sequencing. This study serves to enhance our understanding of the distinctive microbial and hematologic signatures in the early infection stage that differentiate patients with high viral reads patients from those with low dengue viral reads.

Dengue havoc: overview and eco-friendly strategies to forestall the current epidemic.

Dengue fever is a mosquito-borne viral illness that affects over 100 nations around the world, including Africa, America, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Those who get infected by virus for the second time are at greater risk of having persistent dengue symptoms. Dengue fever has yet to be treated with a long-lasting vaccination or medication. Because of their ease of use, mosquito repellents have become popular as a dengue prevention technique. However, this has resulted in environmental degradation and harm, as well as bioaccumulation and biomagnification of hazardous residues in the ecosystem. Synthetic pesticides have caused a plethora of serious problems that were not foreseen when they were originally introduced. The harm caused by the allopathic medications/synthetic pesticides/chemical mosquito repellents has paved the door to employment of eco-friendly/green approaches in order to reduce dengue cases while protecting the integrity of the nearby environment too. Since the cases of dengue have become rampant these days, hence, starting the medication obtained from green approaches as soon as the disease is detected is advisable. In the present paper, we recommend environmentally friendly dengue management strategies, which, when combined with a reasonable number of vector control approaches, may help to avoid the dengue havoc as well as help in maintaining the integrity of the ecosystem.

Impact of apoptotic biomarkers for prognosis of dengue disease severity among eastern Indian patients.

Dengue virus (DENV) induced severe manifestations is a precursor for fatality among infected patients. Previous autopsy examinations of severe dengue (SD) patients reported presence of apoptotic cells in liver, brain, intestinal and lung tissues. Thus, serum-level of major apoptotic proteins of dengue patients was evaluated in the current study, along with their biochemical parameters. Patients were categorized according to World Health Organization (WHO)-defined classification. DENV-infection was screened among 165 symptomatic patients by quantitative reverse transcription polymerase chain reaction, antidengue IgM, and IgG ELISA. Serum levels of apoptotic (Capase-3,7,8, Bcl-2 and FasL) and hepatic-markers, lipid profile, hematological parameters of 78 dengue-positive patients were determined by sandwich-ELISA/immunoturbidimetry/auto-analyzer. Significantly higher levels of caspase-3,7,8 and FasL was detected among SD patients compared to those without warning (WOW) signs. Amongst biochemical parameters, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase serum concentrations significantly increased among severe patients. Principal component analysis followed by hierarchical clustering differentiated severe and with warning dengue patient groups from those WOW using caspase-3,7,8 and FasL biomarkers-thus clearly distinguishing severe-dengue group. Correlation analyses also established strong positive correlation between caspase-3,7,8 and FasL. Thus, serum level of caspase-3,7,8 and FasL during early stage of infection could be used as biomarkers for WHO-defined dengue disease severity.

Nanomedicine as a potential novel therapeutic approach against the dengue virus.

Dengue is an arbovirus infection which is transmitted by Aedes mosquitoes. Its prompt detection and effective treatment is a global health challenge. Various nanoparticle-based vaccines have been formulated to present immunogen (antigens) to instigate an immune response or prevent virus spread, but no specific treatment has been devised. This review explores the role of nanomedicine-based therapeutic agents against dengue virus, taking into consideration the applicable dengue virus assays that are sensitive, specific, have a short turnaround time and are inexpensive. Various kinds of metallic, polymeric and lipid nanoparticles with safe and effective profiles present an alternative strategy that could provide a better remedy for eradicating the dengue virus.

Serotype-associated immune response and network immunoclusters in children and adults during acute Dengue virus infection.

The present study was designed as an exploratory investigation to characterize the overall profile of chemokines, growth factors, and pro-inflammatory/regulatory cytokines during acute DENV infection according to DENV-1, DENV-2, DENV-4 serotypes and age: children: <1-10-year-old (yo); adolescents:11-20 yo; adults 21-40 yo; and older adults: 41-75 yo. The levels of soluble immunemediators were measured in serum by high-throughput microbeads array in 636 subjects including 317 DENV-infected and 319 age-matching non-infected control (NI). Overall, most soluble mediators were increased in DENV-infected patients as compared to NI group regardless of age and DENV serotype, with high magnitude order of increase for CCL2, CXCL10, IL-1ß, IFN-γ, IL1-Ra (fold change >3x), except PDGF in which no fold change was observed. Moreover, despite the age ranges, DENV-1 and DENV-4 presented increased levels of VEGF, IL-6, and TNF-α in serum but decreased levels of PDGF, while DENV-2 exhibited increased levels of CXCL8, CCL4, and IL-12. Noteworthy was that DENV-2 showed increased levels of IL-12, IL-15, IL-17, IL-4, IL-9, and IL-13, and maintained an unaltered levels of PDGF at younger ages (<1-10 yo and 11-20 yo), whereas in older ages (21-40 yo and 41-75 yo), the results showed increased levels of CCL2, IL-6, and TNF-α, but lower levels of PDGF. In general, DENV infection at younger age groups exhibited more complex network immunoclusters as compared to older age groups. Multivariate analysis revealed a clustering of DENV cases according to age for a set of soluble mediators especially in subjects infected with DENV-2 serotype. Altogether, our findings demonstrate that the profile of circulating soluble mediators differs substantially in acute DENV according to age and DENV serotypes suggesting the participation of serotype-associated immune response, which may represent a potential target for development of therapeutics and could be used to assist medical directive for precise clinical management of severe cases.

A stochastic B cell affinity maturation model to characterize mechanisms of protection for tetravalent dengue vaccine constructs.

Dengue annually infects millions of people from a regionally and seasonally varying dengue virus population circulating as four distinct serotypes. Effective protection against dengue infection and disease requires tetravalent vaccine formulations to stimulate a balanced protective immune response to all four serotypes. However, this has been a challenge to achieve, and several clinical trials with different leading vaccine candidates have demonstrated unbalanced replication and interference of interindividual serotype components, leading to low efficacy and enhanced disease severity for dengue-naïve populations. Production of serotype-specific neutralizing antibodies is largely viewed as a correlate of protection against severe dengue disease. However, the underlying mechanisms that lead to these protective immune responses are not clearly elucidated. In this work, using a stochastic model of B cell affinity maturation, we tested different live-attenuated vaccine constructs with varied viral replication rates and contrasted the initiation and progress of adaptive immune responses during tetravalent vaccination and after dengue virus challenge. Comparison of our model simulations across different disease-severity levels suggested that individual production of high levels of serotype-specific antibodies together with a lower cross-reactive antibody are better correlates for protection. Furthermore, evolution of these serotype-specific antibodies was dependent on the percent of viral attenuation in the vaccine, and production of initial B cell and T cell populations pre- and post-secondary dengue infection was crucial in providing protective immunity for dengue-naïve populations. Furthermore, contrasting disease severity with respect to different dengue serotypes, our model simulations showed that tetravalent vaccines fare better against DENV-4 serotype when compared to other serotypes.

Abdominal and Chest Ultrasonography: A predictor for disease progression in nonsevere dengue.

Background: Dengue is one of the most rapidly spreading arboviral infections in the world. Ultrasound is well established in abdomino-thoracic evaluation of patients with dengue infection. The aim of this study was to explore the role of ultrasound in predicting occurrence of severe infection in dengue patients and in predicting deterioration in patients with nonsevere dengue. Methods: The serologically proven dengue patients who reported to hospital during the study period were divided into three categories based on the dengue infection severity score. Ultrasound findings of abdomen and chest in these patients were noted in the initial, as well as follow-up scans and inferences drawn. Results: 61% belonged to the category of Dengue Fever, 35% were in Dengue Hemorrhagic Fever category, and 4% had Dengue Shock Syndrome. Positive ultrasound findings were seen to be significantly higher in patients with severe dengue. Logistic regression analysis revealed the presence of pericholecystic fluid to be significantly associated with the severe disease, while the presence of gall bladder wall edema, ascites, and any ultrasound finding were significantly associated with the disease progression. The odds of a patient with severe dengue having gall bladder wall edema, ascites, or any ultrasound finding were 2.74, 2.04, and 2.619 times, respectively. Conclusion: Our study indicates that positive findings on ultrasound are significantly higher in severe dengue and also that ultrasound can be reliably used to identify the patients with nonsevere dengue who are likely to progress to severe dengue.

Advanced Age and Increased Risk for Severe Outcomes of Dengue Infection, Taiwan, 2014-2015.

Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age.

Heart failure after dengue infection- a population-based self-controlled case-series study.

BACKGROUND: Major cardiovascular events (MACEs) have been described with dengue infection. Among these MACEs, heart failure (HF) is the most common but has not been thoroughly assessed. This study aimed to evaluate the association between dengue and HF. METHODS: Under the self-controlled case-series study design, we used the Notifiable Infectious Disease dataset linkage with the National Health Insurance claims data to obtain the study subjects. All laboratory-confirmed dengue cases who were hospitalized for HF after dengue infection within one year between 2009 and 2015 in Taiwan were included. We identified the first 7 and 14 days after dengue infection as the risk intervals. The incidence rate ratio (IRR) and 95% confidence interval (CI) for HF were estimated by conditional Poisson regression. RESULTS: Among the 65,906 dengue patients, 230 had admission for HF after dengue infection within one year. The IRR of HF admission within the first week after dengue infection was 56.50 (95% C.I. 43.88-72.75). This risk was highest in >60 years (IRR = 59.32, 95% C.I. 45.43-77.43) and lower in 0-40 years (IRR = 25.82, 95% C.I. 2.89-231.02). The risk was nearly nine times higher among admission (for dengue infection) than among nonadmission cases (IRR 75.35 vs. 8.61, p < 0.0001). The risks increased slightly in the second week 8.55 and became less obvious after the third and fourth week. CONCLUSIONS: Patients with dengue infection have a risk of developing acute heart failure within one week, especially in >60 years, men, and dengue admission subjects. The findings emphasize the awareness of diagnosis and further appropriate treatment of HF.

Spontaneous coronary hematoma concomitant with myocarditis: the first report of double cardiac complication of dengue.

We reported the case of a 33-year-old male who presented a dengue infection complicated by spontaneous coronary artery intramural hematoma associated with acute myocarditis. The initial presentation was a typical acute coronary syndrome with ST-segment elevation. Coronary angiography and endocoronary optical coherence tomography confirmed the diagnosis of left anterior descending artery intramural hematoma. Cardiac magnetic resonance imaging revealed not only typical ischaemic injury but also lesions of acute myocarditis confirmed by native T1- and T2-mapping, sub-epicardial late gadolinium enhancement and pericardial effusion. This case highlights the multiple cardiac damages caused by dengue virus, their possible association (coincidental or linked?), and the impact of multimodal imaging on diagnosis and management.

Why are children highly vulnerable to dengue infection

@#The prevalence of dengue infection poses a great public health concern among people living in tropical and subtropical countries like the Philippines. Just recently in 2019, the Philippines had a dengue virus (DENV) outbreak where nearly half of the mortalities were children between 5 and 9 years of age, and around 73% of confirmed DENV cases were under the age of 19. Children are disproportionately affected and are considered to be highly vulnerable to severe dengue infection compared to adults due to several factors. These include: immunological differences--poorly developed immune systems, making them more susceptible to the virus; smaller body sizes and weight means that they are more likely to experience severe symptoms; and their tendency to play outdoors, make them more exposed to mosquito bites. Hence, this article provides an overview of the current understanding for the vulnerability of children to severe dengue infection compared to adults

KIR2DL2, KIR2DL5A and KIR2DL5B Genes Induce Susceptibility to Dengue Virus Infection, while KIR3DL3 and KIR2DS5 Confer Protection.

Background and Objectives: Dengue fever (DF), an emerging and re-emerging viral disease, is a major public health problem. The aim of this study was to investigate the influence of KIRs genes polymorphism and KIRs genotypes in susceptibility to dengue virus infection and disease severity in a population from Burkina Faso through a case-control study. Methods: KIRs genes determination was performed using PCR-SSP in 50 patients infected by dengue virus (DENV) and 54 Healthy controls (HC) subjects who had never been infected. Results: Data analysis showed significant association between frequencies of three KIR genes and dengue virus infection (DF): KIR2DL2 (OR: 7.32; IC: 2.87-18.65; P < 0.001); KIR2DL5A (OR: 15.00, IC: 5.68-39.59; P < 0.001) and KIR2DL5B (OR: 11.43; IC: 4.42-29; P < 0.001). While, KIR3DL3 (OR: 0.13, IC: 0.052-0.32; P < 0.001) and KIR2DS5 (OR: 0.12; IC: 0.04-0.30; P < 0.001) were associated with protection against DF. KIR2DL4 (OR: 9.75; IC95%: 1.33-70.97; p: 0.03) and KIRD3DL1 (OR: 12.00; IC95%: 1.60-90.13; p: 0.02) were associated with an increased risk in the development of secondary dengue infection (SDI). Conclusion: The results suggest a contribution of KIR2DL2, KIR2DL5A, and KIR2DL5B genes in the susceptibility of DF development. In contrast, KIR3DL3 and KIR2DS5 were associated with protection against DF development by enhancing both innate and acquired immune responses.

Efficacy of Dengue Vaccines in the Prevention of Severe Dengue in Children: A Systematic Review.

Dengue is a vector-borne disease caused by the dengue virus (DENV) and is a major health concern worldwide, particularly in regions of endemic disease. Dengue usually presents as a self-limited febrile illness. In some cases, more severe forms with hemorrhage and shock can occur, and children are especially prone to develop it. These forms can be lethal without appropriate management, and no antiviral treatment exists today. In the absence of a curative treatment for dengue, its clinical prevention remains essential. One vaccine - the chimeric yellow fever-dengue-tetravalent dengue vaccine (CYD-TDV) - has been approved for use in some populations, and several others are currently in development, including Takeda's tetravalent dengue vaccine candidate (TAK-003). This study is a systematic review of the current literature realized to evaluate the efficacy of the dengue vaccines in preventing severe dengue in children. This review focuses on the vaccines CYD-TDV and TAK-003. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, and Google Scholar were the databases used to find the relevant data. The articles were selected using specific inclusion and exclusion criteria, and quality appraisal was realized with standardized quality assessment tools. Overall, our study shows that the dengue vaccines CYD-TDV and TAK-003 confer protection against severe dengue in children. Some distinctions exist depending on the vaccine type, the age, and the dengue serostatus of patients. While demonstrating encouraging results, this review also emphasizes the need for more in-depth studies about the safety and efficacy of dengue vaccines.

Plasmablast Expansion Following the Tetravalent, Live-Attenuated Dengue Vaccine Butantan-DV in DENV-Naïve and DENV-Exposed Individuals in a Brazilian Cohort.

An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naïve and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naïve and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naïve vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naïve and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses.

Abnormal Blood Bacteriome, Gut Dysbiosis, and Progression to Severe Dengue Disease.

Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-ß-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.