SIADH (Syndrome of Inappropriate ADH Secretion): Perplexing Look of Dengue Fever

Dengue is a mosquito-borne disease (female mosquitoes of the Aedes genus, principally Aedes aegypti) caused by any one of four closely related dengue viruses. It is endemic in tropical and subtropical continent. World health organization (WHO) currently estimates there may be 50 -100 million dengue infections worldwide every year with over 2.5 billion people at risk of dengue. Symptomatic dengue virus infection may manifests as undifferentiated fever, classical dengue fever (with or without unusual hemorrhages), and dengue hemorrhagic fever (with or without shock). Isolated organopathy or expanded dengue syndrome (EDS) was coined by WHO in the year 2012 to describe cases, which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. The atypical manifestations noted in expanded dengue are multisystemic and multifaceted with organ involvement, such as liver, brain, heart, kidney, central/peripheral nervous system, gastrointestinal tract, lympho reticular system. Dengue virus has long been considered as a non-neurotropic virus, as animal studies have shown that virus does not cross blood brain barrier. Hyponatremia may be found in association with dengue fever and is thought to be caused by peripheral fluid extravasation and resulting intravascular hypovolaemia. But hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in Dengue fever is rare. We report a 40 years old male who was diagnosed as Dengue fever (Dengue Ns1Ag positive) with thrombocytopenia and hyponatremia. He was admitted and further investigations revealed SIADH. He responded well to cautious sodium replacement and addition of tolvaptan. He recovered completely and was discharged after one week. Thus, all clinicians should keep in mind the possibility of SIADH as a part of expanded dengue syndrome.

Correlation Analysis between Ratio of C-Reactive Protein/Albumin and Severity of Dengue Hemorrhagic Fever in Children

Dengue Hemorrhagic Fever (DHF) is a dengue infection which can cause shock and leads to mortality. Hypoalbuminemia is a marker of plasma leakage in DHF and correlated with severity of in fl ammatory response triggered by infection, including DHF. C-Reactive Protein (CRP) is a proin fl ammatory marker that also increases in DHF. This study aims to determine a correlation of CRP/albumin ratio with severity of DHF. Cross sectional study on pediatric patients diagnosed as DHF at Saiful Anwar Malang Hospital was done in July-December 2016. CRP levels were examined using immunoturbidimetry method, while albumin was examined by using Bromocresol Green (BCG) method. Correlation of CRP/albumin ratio with DHF severity was analyzed by using Pearson correlation test.The result showed that there were signi fi cant diff erences in CRP levels and CRP/albumin ratios in the Dengue Shock Syndrome (DSS) and non-DSS group (p = 0.002, p = 0.001, α<0.05). There was no signi fi cant diff erence in albumin level in the same group (p = 0.207, α <0.05). Positive correlation found in CRP and CRP/albumin ratio (r = 0.46, r = 0.49, α <0.01). On the contrary the negative correlation was found in albumin (r = -0.21, α <0.01). This is presumably because albumin is an acute phase protein which will decrease along with the severity of infection. In contrast, CRP will increase during the critical phase of infection. It can be concluded that the CRP/albumin ratio was positively correlated with DHF severity, as well as CRP levels, but not positively correlatedwith albumin.

Comparison of NS1 Antigen Detection by Rapid Immunochromatography Test and ELISA for Early Diagnosis of Dengue at a Government General Hospital, Ananthapuramu

Background: The incidence of Dengue hemorrhagic fever, Dengue shock syndrome associated with Dengue can be reduced by diagnosing Dengue early and by initiating early treatment to Dengue patients. This study was conducted to compare results of NS1 antigen rapid test and ELISA in clinically suspected dengue patients. Materials and Methods: Present study was a comparative study conducted on 100 Patients presented with clinical history of Dengue. At Microbiology Laboratory, serum of all samples was assessed for NS1 detection using antigen Rapid test and ELISA. Sensitivity & specificity values were calculated for NS1 antigen rapid test, compared with ELISA. Results: Out of 100 serum samples collected from suspected cases of Dengue in and around Anantapuramu, 30 (30%) were positive for ELISA and 28 (28%) were positive for Rapid diagnostic test. Sensitivity & specificity when only NS1 was considered on rapid test kits when compared with ELISA were 93.33%, 98.57%, Conclusion: It is concluded that ELISA test was superior in the diagnosis of Dengue and recommended on improvement in sensitivity of RDTs.

A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

Dengue Virus (DENV) infection can cause severe illness such as highly fatality dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Innate immune activation by Nod-like receptors (NLRs) is a critical part of host defense against viral infection. Here, we revealed a key mechanism of NLRP12-mediated regulation in DENV infection. Firstly, NLRP12 expression was inhibited in human macrophage following DENV or other flaviviruses (JEV, YFV, ZIKV) infection. Positive regulatory domain 1 (PRDM1) was induced by DENV or poly(I:C) and suppressed NLRP12 expression, which was dependent on TBK-1/IRF3 and NF-κB signaling pathways. Moreover, NLRP12 inhibited DENV and other flaviviruses (JEV, YFV, ZIKV) replication, which relied on the well-conserved nucleotide binding structures of its NACHT domain. Furthermore, NLRP12 could interact with heat shock protein 90 (HSP90) dependent on its Walker A and Walker B sites. In addition, NLRP12 enhanced the production of type I IFNs (IFN-α/β) and interferon-stimulated genes (ISGs), including IFITM3, TRAIL and Viperin. Inhibition of HSP90 with 17-DMAG impaired the upregulation of type I IFNs and ISGs induced by NLRP12. Taken together, we demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection, which brings up a potential target for the treatment of DENV infection.

Expanded Dengue Syndrome Presenting as Acute Pancreatitis

Dengue is a painful, debilitating mosquito-borne disease(female mosquitoes of the Aedes genus, principally Aedes aegypti)caused by any one of four closely related dengue viruses.It is endemic in tropical and subtropical continent. World health organization (WHO) currently estimates there may be 50 -100 million dengue infections worldwide every year with over 2.5 billion people at risk of dengue. Symptomatic dengue virus infection may manifests as undifferentiated fever, classical dengue fever (with or without unusual hemorrhages), and dengue hemorrhagic fever(with or without shock). Expanded dengue syndrome (EDS) was coined by WHO in the year 2012 to describe cases, which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. The atypical manifestations noted in expanded dengue are multisystemic and multifaceted with organ involvement, such as liver, brain, heart, kidney, central/peripheral nervous system, gastrointestinal tract, lympho reticular system. Here we present a case of 35 years old female without any comorbidities who was serologically diagnosed with dengue developed severe upper abdominal pain on 2ndafebrile day and eventually diagnosed as acute pancreatitis both by raised serum lipase and ultrasonographic evidence of swollen pancreas. She was treated conservatively and improved. Thus, all clinicians should keep in mind the possibility of acute pancreatitis as a part of expanded dengue syndrome.

Pathogenesis of Dengue virus in Host immune system and its genomic variation

Dengue viruses are the most prevalent arthropod-borne viral diseases in humans, infecting 50-100 million people each year. Its serotypes are the most common causes of arboviral illness, putting half of the world's population at risk of infection. Because there is no vaccine or antiviral medicines, the only way to manage the disease is to reduce the Aedes mosquito vectors. DENV infection can be asymptomatic or cause a self-limiting, acute febrile illness with varying degrees of severity. High fever, headache, stomach discomfort, rash, myalgia, and arthralgia are the typical symptoms of dengue fever (DF). Thrombocytopenia, vascular leakage, and hypotension are symptoms of severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Systemic shock characterizes DSS, which can be deadly. Dengue virus infection pathogenesis is linked to a complex interaction between virus, host genes, and host immune response. Major drivers of disease vulnerability include host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity, and genetic variables. The NS1 protein and anti-DENV NS1 antibodies were thought to be involved in the development of severe dengue. The progressive infection may change the cytokine response of cross reactive CD4+ T cells. The need for dengue vaccines that can generate strong protective immunity against all four serotypes is required. To create such vaccines, a thorough understanding of DENV adaptive immunity is required. Structural and functional research have shown that the degree of prM protein cleavage as well as the ensemble of conformational states sampled by virions influence DENV sensitivity to antibody-mediated neutralization, which has crucial implications for vaccine formulation.

Dengue Shock Syndrome: Its Similarity with Anaphylaxis and with the Homeopathic Medicine Apis mellifica (European Honeybee)

Dengue, with four viral serotypes, causes epidemics in tropical and sub-tropical regions. Allopathic antiviral therapies and a vaccine of general use are lacking. The homeopathic medicine Apis mellifica, advised in anaphylaxis from honeybee sting, is proposed to address the life-threatening dengue shock syndrome, which develops from dengue hemorrhagic fever and has features of anaphylaxis. In both dengue and anaphylaxis, immunoglobulin E activates, and released vasoactive mediators (importantly histamine, tryptase and platelet-activating factor) cause, a vascular permeability enabling shock. In dengue, another mechanism, namely antibody-dependent enhancement, due to secondary infection with a heterologous dengue serotype, is associated with release of vasoactive mediators. The homeopathic medicine Apis mellifica indicates plasma leak, shock, and the serous effusion that is noted in dengue patients, and is a suggested prophylactic and therapeutic medicine for dengue shock syndrome.

Serum IL-18 Is a Potential Biomarker for Predicting Severe Dengue Disease Progression

Background. Dengue virus (DENV) infection is the most common arboviral disease that affects tropical and subtropical regions. Based on the clinical hallmarks, the different severities of patients range from mild dengue fever (MDF) to severe dengue diseases (SDDs) and include dengue hemorrhagic fever or dengue shock syndrome. These are commonly associated with cytokine release syndrome (CRS). The types and levels of cytokines/chemokines, which are suppressed or enhanced, are varied, indicating CRS’s pathogenic and host defensive effects. Principal Finding. In this study, we created an integrated and precise multiplex panel of cytokine/chemokine assays based on our literature analysis to monitor dengue CRS. A 24-plex panel of cytokines/chemokines was evaluated to measure the plasma levels of targeting factors in dengue patients with an MDF and SDD diagnosis without or with comorbidities. As identified in sixteen kinds of cytokines/chemokines, ten were significantly ( P < 0.05 ) (10/16) increased, one was significantly ( P < 0.01 ) (1/16) decreased, and five were potentially (5/16) altered in all dengue patients ( n = 30 ) in the acute phase of disease onset. Compared to MDF, the levels of IL-8 (CXCL-8) and IL-18 in SDD were markedly ( P < 0.05 ) increased, accompanied by positively increased IL-6 and TNF-α and decreased IFN-γ and RANTES. With comorbidities, SDD significantly ( P < 0.01 ) portrayed elevated IL-18 accompanied by increased IL-6 and decreased IFN-α2 and IL-12. In addition, decreased platelets were significantly ( P < 0.05 ) associated with increased IL-18. Significance. These results demonstrate an efficient panel of dengue cytokine/chemokine assays used to explore the possible level of CRS during the acute phase of disease onset; also, we are the first to report the increase of IL-18 in severe dengue with comorbidity compared to severe dengue without comorbidity and mild dengue.

Prognosis factors for dengue shock syndrome in children

Background: Varied clinical manifestations, complex pathogenesis, and different viral serotypes make it difficult to predict the course of dengue disease. Many studies have been conducted on the prognostic factors for the occurrence of dengue shock syndrome (SSD), but all use the 2017 World Health Organization (WHO) guidelines. Aim: This study aims to determine the prognostic factors for the occurrence of SSD based on WHO guidelines in 2011. Method: Retrospective study using medical record data of pediatric patients aged 0 to <18 years with a diagnosis of dengue fever dengue (DHF), SSD, and expanded dengue syndrome (EDS) that meet WHO criteria in 2011 at the reputable database from 2017 to December 2020. Independent variables, namely gender, age, nutritional status, secondary dengue infection, leukopenia, abdominal pain, gastrointestinal bleeding, hepatomegaly, and plasma leakage. Shock is the dependent variable. Multivariate analysis using logistic regression analysis. Results: Subjects who met the study criteria were 145 patients, 52 (35.8%) of whom had SSD. Five of 52 SSD patients went into shock during hospitalization. The bivariate analysis yielded significant factors including, malnutrition, overnutrition and obesity, gastrointestinal bleeding, hemoconcentration, ascites, leukocytes 5,000 mm 3, encephalopathy, enzyme elevation heart, and overload. The results of multivariate analysis showed that hemoconcentration variables and elevated liver enzymes were factors of SSD Prognosis. Conclusion: Hemoconcentration and elevated liver enzymes are prognostic factors for SSD.