Acute Psychosis Presenting With Dengue Fever Complicated by Dengue Encephalitis.

Dengue is an infection with a wider spectrum of disease manifestations, ranging from simple dengue fever to expanded dengue syndrome. Expanded dengue syndrome encompasses multiorgan involvement, including neurological manifestations such as dengue encephalitis, seizures, encephalopathy, coma, hemiparesis, etc. Herein, we present a case of a 50-year-old female with a background history of well-controlled type 2 diabetes mellitus and hypertension for five years on oral medication. The patient presented with a one-day history of altered levels of consciousness, agitation, and aggressive behavior. Before admission, she had a history of high-grade fever with chills and rigors for three days. Serial investigations were performed, and the diagnosis of dengue encephalitis was made amidst the absence of positive findings for encephalitis in most of the imaging modalities except in electroencephalogram (EEG), making this case unique. Initially, it was presumed to be meningoencephalitis. Hence, the patient was initiated on intravenous acyclovir and cefotaxime. After the definitive diagnosis of dengue encephalitis, the given medication was stopped after seven days of administration, and with supportive management, the patient made a successful recovery within 10 days.

Dengue Hemorrhagic Fever Causing Postpartum Hemorrhage and Hemophagocytic Lymphohistiocytosis in a Young Woman: A Case Report.

Dengue viral infection can present as a spectrum of disorders ranging from uncomplicated fever to dengue shock syndrome. Dengue fever during pregnancy or delivery is associated with serious complications during pregnancy, especially severe postpartum hemorrhage (PPH) following delivery. Dengue is an uncommon and highly fatal cause of secondary hemophagocytic lymphohistiocytosis (HLH). Both PPH and HLH in a pregnant woman lead to unfavorable outcomes even with appropriate treatment. Here, we report the case of a 28-year-old woman who presented with PPH and HLH following dengue hemorrhagic fever and completely recovered with appropriate treatment.

Leptospirosis and Dengue Coinfection-Associated Multi-Organ Dysfunction Syndrome: A Case Report.

Dengue and leptospirosis are frequently discussed separately, with dengue causing rash and leptospirosis causing jaundice. Currently, there are more and more reports of coinfections. The comparable clinical symptoms of both infections make it challenging to distinguish between leptospirosis and dengue. Differentiating between leptospirosis and dengue is crucial since leptospirosis has a more favorable prognosis with early antibiotic therapy, whereas dengue does not have a specific treatment, although early detection is essential for close monitoring and cautious fluid management. Here, we highlight a case of dengue virus and leptospirosis coinfection in a female who presented with acute febrile illness, dyspnea, and altered sensorium, which progressed to multiorgan dysfunction syndrome, involving the neurological, respiratory, hepatic, and hematological systems.

Oro-Pharyngeal Candidiasis in Two Dengue Patients.

Dengue, a prevalent arboviral disease, has witnessed a resurgence in India, with outbreaks frequently reported. However, dengue-associated oral (oro-pharyngeal) candidiasis (DAOC) was never reported. We present two severe dengue cases with oral/oro-pharyngeal pseudomembranous candidiasis. Case 1 of a young man without any comorbidities or abuse or immunosuppression presented with fever, headache, altered sensorium, throat pain on recovery, and laboratory reports confirmed dengue with leukopenia, thrombocytopenia, and severe hepatic involvement with oro-pharyngeal candidiasis. Similarly, case 2 of a middle-aged man with a history of smoking and diabetes presented with fever, gum bleeding, and throat pain, later confirmed to be dengue NS1 positive with thrombocytopenia, and mild-moderate hepatic involvement along with oral-oro-pharyngeal candidiasis. Both cases showed improvement with conservative management and oral nystatin suspension. These cases prompt consideration of superadded candida infections in dengue patients, emphasizing the need for further study and clinical vigilance.

Association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness.

Objective: To determine the association of different blood groups in patients with Dengue fever and their relationship with the severity of the illness. Methods: A hospital-based descriptive study was conducted in the Dengue Isolation Ward of Lady Reading Hospital Peshawar from March 2020 to September 2020. Patients with Dengue fever were included in the study. The severity of the illness was categorized as "Dengue fever (DF)", "Dengue hemorrhagic fever (DHF)", and "Dengue shock syndrome (DSS)". The patients' blood groups were determined as A, B, AB, and O groups. All the data were recorded and analyzed using SPSS® version 23. Chi-square (χ2) and student t-test were applied, and a p-value of ≤0.05 was considered significant. Results: Out of 160 patients, 119(74.4%) were males; the patient's mean age was 38.09±15.68 SD, IQR=25 years. Greater proportion (28%) of the young men (up to 40 years) was affected compared to 9% young women. Fever (99%) and body aches (96%) were the most common presentation of DF, complicated by bleeding in 30.6% and shock in 9.4% of the patients. The majority (63.1%) of the patients had DF; 27.5% had DHF, and 9.4% had DSS. Sixty three (39.4%) patients had blood Group-B and 5.6% had Group-AB (p=0.97). The proportion of patients with different blood groups and the type/severity of the DF were almost identical except the fact that none of the patient with group AB had DSS. There was significant gender difference of hemoglobin (p=0.008, 95%CI=0.439, 2.844), hematocrit (p=0.012, 95%CI=0.00974, 0.07946); and Alanine Aminotransferase levels (p=0.002, 95%CI=-332.032, -72.233). Conclusion: Patients with blood Group-B were more frequent and AB was least commonly affected by the Dengue-virus infections. However, no association was found between a particular blood group and disease severity. Greater proportions of the younger men had Dengue infections.

Dengue, Chikungunya, and Zika: The Causes and Threats of Emerging and Re-emerging Arboviral Diseases.

The recent emergence and re-emergence of viral infections transmitted by vectors, Zika, chikungunya, dengue, and others, is a cause for international concern. Here, we provide a summary of the current understanding of the transmission, clinical features, diagnosis, global burden, and the likelihood of future epidemics by these viruses. Arboviruses transmitted by mosquitoes are challenging to diagnose and can have surprising clinical complications. Dengue, chikungunya, and Zika are the most important diseases caused by arboviruses worldwide, especially in tropical and subtropical regions. These are transmitted to humans by day-biting Aedes aegypti and Aedes albopictus mosquitoes. In India, the increase in the incidence of dengue and chikungunya cases is primarily linked to the dissemination of Aedes aegypti. A rapid and accurate diagnosis is paramount for effectively controlling dengue outbreaks. As there is no vaccination or specific treatment available for these viruses, vector control is the only comprehensive solution available.

Dengue overview: An updated systemic review.

Dengue is caused by the dengue virus (DENVs) infection and clinical manifestations include dengue fever (DF), dengue hemorrhagic fever (DHF), or dengue shock syndrome (DSS). Due to a lack of antiviral drugs and effective vaccines, several therapeutic and control strategies have been proposed. A systemic literature review was conducted according to PRISMA guidelines to select proper references to give an overview of DENV infection. Results indicate that understanding the virus characteristics and epidemiology are essential to gain the basic and clinical knowledge as well as dengue disseminated pattern and status. Different factors and mechanisms are thought to be involved in the presentation of DHF and DSS, including antibody-dependent enhancement, immune dysregulation, viral virulence, host genetic susceptibility, and preexisting dengue antibodies. This study suggests that dissecting pathogenesis and risk factors as well as developing different types of therapeutic and control strategies against DENV infection are urgently needed.

Uncovering the Hidden Threat: A Case Report of Suspected Dengue Fever in Armenia.

Dengue is a viral infection transmitted by mosquitoes that causes fever, headache, joint pain, nausea, vomiting, and pain behind the eyes. In severe cases, it can progress to dengue hemorrhagic fever and dengue shock syndrome, which can be life-threatening. Armenia has not reported a single case of dengue to date and is non-endemic for this disease. However, it has been found that the vector of the disease, Aedes albopictus, is present in Armenia since 2016. The aim of this report is to present the imported case of suspected dengue hemorrhagic fever. A 23-year-old female who was admitted to the University Hospital experienced symptoms of general weakness, fever, joint pain, and chills after her return from Bali and had a three-day febrile period. A thorough examination revealed mosquito bites on her skin. On the fourth day of hospitalization, the patient's condition deteriorated. She started experiencing vaginal bleeding. On the same day, the patient noted a small petechiae rash sized 1-2 mm in diameter in the upper and lower extremities. The patient deteriorated, with progressive leukopenia and thrombocytopenia, and hypertransaminasemia. Screening tests for HIV and hepatitis A, B, C, and E were performed, and the results showed that the anti-hepatitis C antibody was positive, while the hepatitis C virus polymerase chain reaction was negative. The case was reported to the National Center for Disease Control and Prevention as an imported case of hemorrhagic fever. Unfortunately, no lab test was available there for confirmation of the diagnosis. The patient received IV infusion and symptomatic treatment. Her condition improved, and upon discharge, she was in a state of recovery. This case report highlights the importance of early diagnosis and appropriate treatment for hemorrhagic fevers, particularly dengue fever. The unavailability of diagnostic kits for dengue in Armenia highlights the need to invest in improving their availability. It also emphasizes the importance of maintaining dengue surveillance in non-endemic nations and carefully evaluating and monitoring febrile patients who have returned from dengue-endemic countries.

Dengue hepatitis: Incidence, spectrum and outcome.

BACKGROUND AND AIMS: While dengue infection is common in India, there is scarce information on dengue hepatitis. The aim of this study was to analyze the incidence, spectrum and outcome of dengue hepatitis. METHODS: We retrospectively analyzed consecutive patients, who had hepatitis among those with dengue infection admitted to two tertiary care hospitals in western India from January 2016 to March 2021. Diagnosis of dengue infection was made by serology. Dengue hepatitis was diagnosed and the severity of dengue was categorized by standard criteria. RESULTS: Of 1664 patients admitted with dengue fever during the study period, 199 patients had hepatitis (i.e. incidence of dengue hepatitis was 11.9%). Of the 199 dengue hepatitis patients (age: 29 [13 - 80] years, median [range], 67% males), 100 patients (50%) had severe dengue, 73 (36%) had severe dengue hepatitis, 32 (16%) had dengue shock syndrome and eight (4%) had acute liver failure. Forty-five patients (23%) had acute lung injury and 32 (16%) had acute kidney injury. The dengue hepatitis patients were treated with standard medical care, including vital organ support, as needed-166 (83%) patients survived, while 33 patients (17%) died (cause of death: multi-organ failure: 24 patients, septic shock: nine patients). The presence of shock independently predicted mortality (odds ratio 6.4, 95% confidence interval: 1.2 - 34). Among patients with dengue hepatitis, mortality rate was higher in those with severe dengue (23%), dengue shock syndrome (47%), severe dengue hepatitis (24%) and acute liver failure (38%). CONCLUSION: In this large series of hospitalized patients with dengue infection, the incidence of dengue hepatitis was 11.9%. Among 199 dengue hepatitis, 17% died; multi-organ failure was the commonest cause for death and death rate was higher in patients with more severe disease. The presence of shock at presentation independently predicted mortality.

A short communication of 2022 dengue outbreak in Bangladesh: a continuous public health threat.

Dengue virus infection, a highly prominent health concern, has caused many health complications, positive cases, and deaths in Bangladesh in previous years. However, the prevalence of this infection and fatality rates in 2022 has shattered all prior records. The dengue virus vector, mosquitoes, found a high prevalence of infection due to the weather's favorable conditions for breeding in the months of June and July. While there is presently no particular vaccination for dengue infection, awareness of its epidemiology, pathogenesis, signs, and symptoms may aid in the development of improved diagnostic and treatment strategies. The government should also improve the infrastructure of cities to make prevent mosquito breeding and the spread of dengue infection.

Dengue hemorrhagic fever with bleeding and fluid overload in a patient with active lupus nephritis: a case report of diagnostic and therapeutic challenges.

BACKGROUND: Diagnosis and management of dengue hemorrhagic fever (DHF) can be challenging in the presence of confounding comorbidities. Important confounders are conditions that alter hematological parameters and intra/extra vascular fluid distribution. We report the case of a patient with active lupus nephritis, who developed DHF with subsequent bleeding and fluid overload. This is the first case report to highlight a unique set of diagnostic and therapeutic challenges in DHF in this context. CASE PRESENTATION: A seventeen-year-old girl with lupus nephritis class IV developed a renal flare of lupus and subsequently developed DHF with bleeding per vaginum. Due to acute kidney injury, she was managed with a restrictive fluid approach during the ascending limb with blood transfusion when required, and close monitoring for hemodynamic instability. During the descending limb, hourly input was transiently increased due to a rise in hematocrit. This precipitated nephrogenic pulmonary edema, which was managed with mechanical ventilation and continuous renal replacement therapy. CONCLUSIONS: This patient posed two diagnostic challenges: diagnosis of dengue in a patient with lupus-related bicytopenia, and diagnosis of dengue leakage in a patient with nephrotic syndrome-related ascites. There were three therapeutic difficulties: deciding the fluid quota for DHF in the presence of renal impairment, and balancing the risks and benefits of steroids and anticoagulation in lupus nephritis with dengue. As decisions in such instances are patient-specific, sharing of individual experiences will help guide management decisions.

Aminotransferases in Relation to the Severity of Dengue: A Systematic Review.

A systematic review was conducted to investigate the relationship between aminotransferases and the severity of dengue infection, which is a prevalent and significant infection in tropical and subtropical regions. Aminotransferases are enzymes that are often elevated in dengue due to the liver's physiological and immunological response to the infection. This review focused on analyzing various studies that examined the correlation between aminotransferase levels and the severity of dengue. Extensive literature searches were performed using ("dengue*" OR "dengue fever*" OR "dengue haemorrhagic fever*" OR "dengue shock syndrome*") AND ("alanine aminotransferase*" OR "aspartate aminotransferase*") on PubMed. The selected articles were thoroughly reviewed, encompassing epidemiology, pathogenesis, and clinical manifestations of dengue. The consistent findings across the studies indicated that aminotransferases can serve as predictive markers for dengue severity. Therefore, early assessment of liver enzyme levels is crucial in dengue cases, and elevated levels should be closely monitored to prevent adverse outcomes.

Spontaneous splenic hematoma secondary to dengue infection: a rare case report.

Dengue infection may have various surgical complications. Splenic hematoma is a rare complication of dengue hemorrhagic fever and may be life-threatening. Case Presentation: A 54-year-old male, diagnosed with dengue infection detected at another hospital, presented on the 10th day of fever with left upper abdominal pain for 7 days without history of trauma. Urgent ultrasonography of the abdomen revealed findings suggestive of a splenic subcapsular hematoma, which was confirmed by computed tomography scan. The grade II splenic hematoma was being managed conservatively. Unfortunately, the patient developed hospital acquired pneumonia and died from septic shock. Clinical Discussion: Hemorrhagic manifestations are seen in the febrile and critical phase of dengue, but the spleen is infrequently involved. Splenic hematoma can lead to splenic rupture, which can be rapidly fatal. Specific treatment guidelines of such hematomas are needed in the context of dengue infection, as the treatment modality is controversial. Conclusion: Patients must be carefully evaluated for the complications and surgical manifestations of dengue as abdominal pain and hypotension from splenic hematoma may be misinterpreted as components of dengue hemorrhagic fever and dengue shock syndrome.

Integrated systems immunology approach identifies impaired effector T cell memory responses as a feature of progression to severe dengue fever.

BACKGROUND: Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with increased vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. METHODS: To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell (PBMC) transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia. RESULTS: After a secondary infection, progression to uncomplicated dengue featured transcriptional profiles associated with increased cell proliferation and metabolism, and an expansion of ICOS+CD4+ and CD8+ effector memory T cells. These responses were virtually absent in cases progressing to severe DHF, that instead mounted an innate-like response, characterised by inflammatory transcriptional profiles, high circulating levels of inflammatory chemokines and with high frequencies of CD4low non-classical monocytes predicting increased odds of severe disease. CONCLUSIONS: Our results suggests that effector memory T cell activation might play an important role ameliorating severe disease symptoms during a secondary dengue infection, and in the absence of that response, a strong innate inflammatory response is required to control viral replication. Our research also identified discrete cell populations predicting increased odds of severe disease, with potential diagnostic value.

A Case Report on CNS Hemophagocytic Lymphohistiocytosis in an Infant With Dengue Hemorrhagic Fever.

India is an endemic country for dengue. The incidence of hemophagocytic lymphohistiocytosis (HLH) with dengue in children has been well-reported. However, central nervous system (CNS) HLH associated with dengue has not been described in the literature yet. We hereby report a novel case of CNS HLH triggered by dengue infection. An eight-month-old, well-grown male infant with uneventful antenatal, perinatal, and neonatal history was admitted with a history of febrile illness associated with cough, cold, vomiting, and loose motions and one episode of hematochezia and hepatosplenomegaly on examination. Investigations revealed bi-cytopenia, hyper-ferritinemia, deranged coagulation profile, liver function test, and hypo-fibrinogenemia. Dengue non-structural protein 1 ( NS1) antigen was positive. The child was given dexamethasone and continued supportive care with a diagnosis of dengue shock syndrome. The child showed an overall transient improvement, however, he had rebound fever followed by right focal convulsion on Day 9 of steroids. MRI brain revealed areas of diffusion-restricted embolic infarcts with diffuse leptomeningeal enhancement and mild cerebral edema, and CSF showed a total leukocyte count of 80 cells with 75% lymphocytic picture, histiocytes with hemophagocytosis, confirmatory of CNS HLH. Intrathecal methotrexate, hydrocortisone, and intravenous (IV) etoposide were started. However, the child succumbed to his illness. CNS involvement in dengue-triggered HLH needs to be suspected despite subtle neurological signs and aggressively managed following a multi-departmental approach to ensure the best clinical and neuro-developmental outcomes.

Vitamin D Deficiency (VDD) and Susceptibility towards Severe Dengue Fever-A Prospective Cross-Sectional Study of Hospitalized Dengue Fever Patients from Lahore, Pakistan.

Dengue is a mosquito-borne flaviviral serious febrile illness, most common in the tropical and subtropical regions including Pakistan. Vitamin D is a strong immunomodulator affecting both the innate and adaptive immune responses and plays a pivotal role in pathogen-defense mechanisms. There has been considerable interest in the possible role of vitamin D in dengue viral (DENV) infection. In the present prospective cross-sectional study, we assessed a possible association between serum vitamin D deficiency (VDD) and susceptibility towards severe dengue fever (DF) illness. Serum vitamin D levels were measured at the time of hospitalization in 97 patients diagnosed with dengue fever (DF), dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) at Mayo Hospital, King Edward Medical University, Lahore, PK, from 16 November 2021 to 15 January 2022. In terms of disease severity, 37 (38.1%) patients were DF, 52 (53.6%) were DHF grade 1 and 2, and 8 (8.2%) were DSS. The results revealed that most patients (75 (77.3%)) were vitamin-D-deficient (i.e., serum level < 20 ng/mL), including 27 (73.0%) in DF, 41 (78.8%) in DHF grade 1 and 2, and 7 (87.5%) in DSS. The degree of VDD was somewhat higher in DSS patients as compared to DF and DHF grade 1 and 2 patients. Overall, serum vitamin D levels ranged from 4.2 to 109.7 ng/mL, and the median (IQR) was in the VDD range, i.e., 12.2 (9.1, 17.8) ng/mL. Our results suggest that there may be a possible association between VDD and susceptibility towards severe dengue illness. Hence, maintaining sufficient vitamin D levels in the body either through diet or supplementation may help provide adequate immune protection against severe dengue fever illness. Further research is warranted.

Dengue and Chikungunya Co-Infection-Associated Multi-Organ Dysfunction Syndrome: A Case Report.

Dengue and chikungunya infections are increasing globally, especially in India. While the majority of patients settle with symptomatic management, some develop life-threatening complications. Here we discuss a case of co-infection between dengue virus (DENV-2) and chikungunya virus (CHIKV) in a young Indian male who presented with an acute febrile illness that progressed to multi-organ dysfunction involving the hepatic, nervous, respiratory, and hematological systems. We discuss the management of this complicated case and attempt to generate awareness regarding the severity of co-infection by these viruses.

Analysis of gene expression profile and construction of ceRNA regulatory network after DENV-2 infection with HUVECs / 西安交通大学学报(医学版)

【Objective】 To establish a co-expression lncRNA-mRNA ceRNA network and explore the potential molecular mechanism of lncRNA in dengue fever. 【Methods】 DENV-2-infected and normal pHUVEC were sequenced and screened for differentially expressed lncRNA and mRNA by gene microarray technology. Differentially expressed mRNA was analyzed by protein-protein interaction (PPI), and significantly related co-expressed lncRNA-mRNA was screened by Pearson’s correlation coefficient. The microRNA (miRNA) that bound to co-expressed lncRNA-mRNA was predicted by the database. The ceRNA network of co-expressed lncRNA-mRNA was constructed by Cytoscape software. Finally differentially expressed mRNAs and co-expressed lncRNA-mRNA were analyzed by GO and KEGG enrichment, and co-expressed lncRNA-mRNA was verified by RT-qPCR. 【Results】 At 48 h and 72 h after infection, 105 and 51 differentially expressed mRNAs were obtained, respectively, while 59 and 29 differentially expressed lncRNAs were obtained, respectively. Furthermore, at the two time intervals, there were 10 differential mRNAs and 5 differential lncRNAs, respectively. PPI analysis of differential mRNAs showed that isocratic values of interleukin 6 (IL6), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), and 2’-5’-oligoadenylate synthetase 2 (OAS2) were relatively high. The pairing results of lncRNA-mRNA co-expression analysis with the highest correlation coefficients at 48 h and 72 h after infection were XLOC_001966-SMTNL1 and XLOC_001966-ESR2, respectively. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the functions of differentially expressed mRNA and co-expressed lncRNA-mRNA were mainly involved in virus epidemic prevention response, immune response, and signal transduction, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, type I interferon, and cytokine receptor interaction. RT-qPCR revealed that lncRNA XLOC-I2-8991 was upregulated in the co-expressed lncRNA-mRNA, whereas all the other lncRNA and mRNA were downregulated. 【Conclusion】 This study initially revealed the potential lncRNA-mRNA co-expression network during dengue virus infection, and found that co-expressed lncRNA-mRNA was mainly enriched in the immune regulation and signal transduction pathways during virus infection. The findings will help further exploration into the infection mechanism of DENV-2.

Major Histocompatibility Complex Class I and Dengue Hemorrhagic Fever: A Meta-Analysis of Human Leukocyte Antigens A*24 and B*44.

INTRODUCTION: Dengue fever (DF) is a disease caused by dengue virus (DENV) from the family Flaviviridae. The role of human leukocyte antigens (HLAs) in dengue fever (DF) and its more severe manifestation, dengue hemorrhagic fever (DHF), has been a topic of great research interest. In addition to HLA profile, race, age, DENV serotype, infection while having certain chronic diseases, and secondary infection are risk factors for DHF susceptibility. Antibody-dependent enhancement (ADE) of dengue virus infection is a mechanism for DHF infection. Individual studies have examined the effects of HLA-A*24 and HLA-B*44 presence on DHF, but none have analyzed these in a meta-analysis. The objective of this study was to determine the effects of HLA-A*24 and HLA-B*44 presence on DHF and DF susceptibility. MATERIALS AND METHODS: A meta-analysis on DHF and DF susceptibility in patients with HLA-A*24 and HLA-B*44 was conducted. Google Scholar was used to find studies that contained patients with HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF. Studies containing patients diagnosed using the 1997 WHO guidelines and possessing HLA-A*24 or HLA-B*44 that were diagnosed with DHF or DF, including primary or secondary infection, and studies measuring odds ratios (ORs) were included. Patients diagnosed using the 2009 WHO guidelines and studies in a foreign language, using animals, or lacking odds ratios were excluded. The National Institutes of Health (NIH) quality assessment of the case-control study tool was used, and a Doi plot was generated using MetaXL to assess for risk of bias. Review Manager version 5.4 was used to generate odds ratios and forest plots with subgroup analysis from allele and phenotype frequency data. Ten studies from 2001 to 2015 met the inclusion criteria. The studies included 2837 DHF/DF patients and 4880 healthy control (HC) patients. RESULTS:  HLA-A*24 was associated with a 1.39 times susceptibility to DHF while those possessing HLA-B*44 were 0.62 times susceptible to DHF (OR=1.39 and 95% CI=1.17-1.66; OR=0.62 and 95% CI=0.39-0.99). Neither HLA-A*24 nor HLA-B*44 presence was associated with DF susceptibility (OR=1.04 and 95% CI=0.82-1.33; OR=0.88 and 95% CI=0.68-1.14). CONCLUSION: These results indicate that two different major histocompatibility complex (MHC) class I alleles, HLA-A*24 and HLA-B*44, have opposing effects on DHF susceptibility but none on DF susceptibility. The study's specificity is limited in that it examines HLA allele groups and not specific HLA proteins. The results of this study can be used clinically to identify patients that may be at a higher risk of developing DHF based on their HLA profile.

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.