FACTORS PREDICTING SEVERITY OF ILLNESS IN DENGUE FEVER: AN OBSERVATIONAL STUDY

Introduction: Dengue is a systemic viral infection caused by the virus from genus Flaviviridae. Dengue infection has got a wide clinical spectrum that includes both severe and non-severe clinical manifestations. The group progressing from non-severe to severe disease is difcult to dene. Early detection and access to proper medical care signicantly lower fatality rates and would help to reduce the burden of hospital stay and economy loss. Objectives: To study the inammatory markers predicting the severity of dengue infection. Methods: 250 diagnosed patients were evaluated with detailed history, physical examination and blood investigations. Inammatory markers associated with severity of dengue were studied. Observations and conclusions- 97 patients (39%) had dengue without warning signs, 62(25%) had dengue with warning signs, 63(25%) had severe dengue and 28(11%) had expanded dengue. Low CRP, ESR, HDL and LDL cholesterol were observed in dengue fever, without any statistical signicance. Ferritin levels more than 1000 and triglyceride more than 200 was signicantly associated with severity of dengue.

Immunophenotyping and transcriptional profiling of human plasmablasts in dengue.

Previous studies have shown that plasmablasts expand massively in dengue patients as compared to many other situations such as influenza infection or vaccination. However, a detailed understanding of the phenotypes and transcriptional features of these cells is lacking. Moreover, despite India having nearly a third of global dengue disease burden, there is virtually no information on plasmablasts responses in dengue patients from India. Here, we provide a detailed characterization of plasmablast responses from dengue confirmed febrile children in India. Immunophenotyping and RNA seq analysis showed that in addition to secreting dengue specific antibodies, these massively expanding cells expressed several adhesion molecules, chemokines and chemokine receptors that are involved in endothelial interactions, homing to skin or mucosal tissues including intestine. Surprisingly, we found that these cells also upregulated expression of several cytokine genes that are involved in angiogenesis, leukocyte extravasation and vascular permeability. These transcriptional features were qualitatively similar to plasmablasts from influenza vaccinees. Interestingly, the expansion of the plasmablasts in dengue patients was significantly lower in patients with primary dengue infection compared to those with secondary dengue. Moreover, within the primary dengue patients, their expansion was significantly lower in patients with mild dengue infection (DI) compared to patients with dengue with warning signs (DW) or severe dengue (SD). These results significantly improve our understanding of human plasmablast responses in dengue.

CARDIAC MANIFESTATIONS OF DENGUE FEVER IN CHILDREN

Introduction: Dengue fever represents a signicant public health problem in tropical and subtropical regions. 70% of total cases are from Asia, especially India. Caused by 4 dengue virus serotypes( DENV-1, DENV-2 DENV-3 and DENV-4), DENV-2 being the most prevalent in India. Incidence and range of cardiac manifestations in dengue fever vary widely. Aims & objectives: To study the incidence and range of cardiac manifestations of dengue fever in children. Material & methods:This is an observational study, conducted in department of pediatrics at National Institute of Medical Sciences & Research, Jaipur in study period of 18 months. A total of 94 patients were included in the study fullling the inclusion criteria. Results: The overall incidence of cardiac manifestations was found to be 31.9%. The incidence of cardiac manifestations in dengue without warning signs was 4.4%, in dengue with warning signs was 52.5% and in severe dengue was 77.7%. Conclusion: Incidence of cardiac manifestations increases with increase in disease severity

Cytokine Signature of Dengue Patients at Different Severity of the Disease

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

“CLINICAL PROFILE AND PREDICTORS OF ILLNESS SEVERITY IN CHILDREN WITH DENGUE FEVER”

BACKGROUND & OBJECTIVES: Dengue illness has become exceedingly common over the last few years globally. Due to their unique characteristics, incidence as well as mortality is higher in pediatric population as compared to adults. This study was undertaken to study clinical pattern of dengue fever in children and to identify factors predicting a more severe disease. METHODS: We conducted this hospital based prospective study at A.N.M.M.C.H, Gaya, Bihar over 2 years from January 2016- December 2017. Children >1 month and <15 years age with fever ≥ 3 days and symptoms suggestive of Dengue infection were included and evaluated for dengue infection by testing for NS1 antigen, IgM and IgG against Dengue infection. Children were classied into 3 clinical groups: Dengue without warning signs (DWWS), Dengue with warning signs (DWS) and severe Dengue (SD) as per WHO classication. Clinical and laboratory parameters were compared in the 3 groups. RESULTS: 114 children with Dengue were studied. 62 (54.4%) were males as compared to 52 (45.6%) females. 41 (36%) had DWWS, 53 (46.5%) had DWS and 20 (17.5%) had SD. Mean age was 74.1 months (SD 18.2 months) and mean weight was 21.4 kg (S.D 5.1 kg). Common symptoms were fever (100%), myalgia (76.6%), chills (62.3%), nausea/ vomiting (63.2%) and rash (53.5%). Common signs were ushed appearance (36.8%), positive Hess test (27.2%), bleeding manifestation (13.2%) and hypotension (36.8%). Laboratory investigations revealed anaemia (18.4%), thrombocytopenia (81.6%), Leucopenia (69.3%), elevated transaminase (41.2%), abnormal RFT (5.3%). 27.1% had prolonged aPTT while 21% had prolonged PT. Nausea/vomiting, bleeding, oliguria, capillary leak and liver enlargement (>2 cm) were signicantly more common in severe dengue (p<0.05) whereas rash was commoner in non severe dengue. Lab parameters signicantly more common in SD included rising hematocrit, falling platelets, high urea/creatinine/ALT and hypoalbuminemia & hypocholesterolemia. CONCLUSIONS: DF affects children irrespective of age. Symptoms more common in SD were nausea/vomiting, bleeding and decreased urine. Signs commoner in SD were features of capillary leak and hepatomegaly (>2 cm). Rising hematocrit, falling platelets, high urea, creatinine and ALT but hypoalbuminemia and low cholesterol were found to be statistically signicant laboratory parameters associated with SD.

Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity

The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (− 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.

Comparing the 2009 and 1997 World Health Organization dengue case classifications in a large cohort of South Asian patients

Introduction: Due to the shortcomings in the 1997-World Health Organisation (WHO) dengue case classification (DCC), a revised classification was proposed in 2009. This study was aimed to assess the clinical usefulness of the two classifications during a large dengue epidemic. Methodology: Clinical data of dengue patients admitted to selected units at National Hospital of Sri Lanka, Panadura Base Hospital and Nawaloka Hospital Colombo between June and August 2017 were collected prospectively. Cases were classified using the 1997 and 2009 WHO DCCs. Results: 1,878 patients [adult = 1,573 (83.8%)] were studied. Based on 1997-WHO-DCC-DF (Dengue Fever): 1,316 (70.1%), DHF (Dengue Haemorrhagic Fever) -1: 468 (24.9%), DHF-2: 86 (4.6%) and DHF-3: 8 (0.4%). Based on 2009-WHO-DCC–Dengue with warning signs (WS): 1647 (87.7%), Dengue without WS: 231 (12.3%) and severe dengue (SD): 41 (2.18%). A total of 1,088 (82.7%) DF and 559 (99.5%) DHF patients developed WS. Of those without WS, 228 (17.3%) were DF patients and 3 (0.5%) were DHF patients. Three (0.23%) DF and 38 (6.76%) DHF patients had SD. All SD patients had WS. The level of agreement between the two systems of classification was poor (Kappa = - 0.035, p < 0.001). Conclusions: The 2009-WHO-DCC was more useful than 1997-WHO-DCC in predicting dengue disease severity as few DF patients also had SD. Furthermore, the presence of WS identified patients with SD. However, the 2009-WHO-DCC may not suit the resource limited countries as WS are non-specific, and lack of diagnostic tests can result in case overload.

Clinical profile, laboratory investigations and outcome in dengue positive children in south India

Dengue fever is one of the most commonly occurring mosquito borne-viral illnesses that has a wide range of presentation in children and is common during the monsoon season. The severity of illness ranges from mild undifferentiated fever, dengue with warning signs, severe dengue fever and dengue fever with organ dysfunction. The symptoms of dengue may be easily mistaken for those of flu or other viral infections. Contrary to other fevers, complications in dengue occur during the phase of defervescence and can be life threatening in children due to shock or profuse hemorrhage. 55 dengue positive children who were diagnosed by dengue antigen detection or dengue antibody positive were included in the study. Most of children were above 10 years and the commonest presenting symptoms were fever, headache, body pain, nausea, anorexia, abdominal pain and vomiting. Most of the children presented with two or more warning signs like persistent vomiting, thrombocytopenia, increasing hematocrit and hepatomegaly. Few children developed features of early shock, which was diagnosed early and treated effectively. All the children responded well to treatment measures and recovered well during hospital stay. Having a high of suspicion and careful monitoring of children is crucial for reducing occurrence of complications and death due to this severe infection.

Dengue with Scrub Typhus Coinfection in Northern India

Background: Amongst the many vector and water-borne diseases prevalent in tropics, dengue occupies a prominent place. Dengue epidemics are frequent and at times, during such epidemic, coinfections may occur causing diagnostic dilemmas. Case Report: A 36 years old lady, from a rural background, presented during the 2019 dengue epidemic with fever, vomiting, and non-colicky abdominal pain. The evaluation showed hepatosplenomegaly, leukocytosis, and thrombocytopenia. The investigations confirmed the diagnosis and she was treated conservatively as a case of dengue with warning signs. A longer than anticipated duration of fever and clinical deterioration prompted reassessment, which revealed the presence of an eschar over the right upper thigh. The Weil-Felix test using Proteus OX-K stain was positive at a titer of 1:320. Following treatment with oral doxycycline, she showed rapid defervescence and clinical improvement. Conclusions: Coinfection with scrub typhus is rare with dengue. If left untreated, it adversely affects the outcome. The key to diagnosing such coinfections includes a high index of suspicion, repeated clinical examination, and the knowledge of local endemicity.

Clinical correlation of cardiac functions and troponin I and CPK-MB in dengue fever in children

Background: Dengue is the most rapidly spreading mosquito-borne viral disease in the World. The spectrum of manifestations includes mild fever to severe and life-threatening disease, though uncommon complications such as myocarditis have also been reported in many cases. We conducted this study to analyze association between Clinical Profile, Cardiac Functions and Troponin I and CPK-MB (cardiac biochemical markers) in children with Dengue Fever. Aims and objectives of the study was the association between Clinical Profile, Cardiac Functions and Troponin I and CPK-MB (cardiac biochemical markers) in children with Dengue Fever.Methods: This was a prospective observational study in which 80 paediatric patients who were hospitalized anddiagnosed to be having Dengue fever were included. All patients were stratified into either of the 3 groups- Dengue without warning signs, Dengue with warning signs and severe Dengue. A detailed history and thorough clinical examination were done for all patients. A complete blood count, electrolytes, hepatic and renal function tests were done in all children. Cardiac function was assessed by 2D Echo, CPK-MB and Troponin-I, p value less than 0.05 was taken as statistically significant.Results: Of the 80 studied cases there were 53 (66.25%) males and 27 (33.75%) females with a M:F ratio of 1.9:1. Dengue with and without warning signs was seen in 27.5% and 60% cases respectively whereas severe dengue was seen in 12.5% cases. The ejection fraction was comparable across the 3 groups. On 2D echo ejection fraction was 62.95%, 63.21% and 65.1% in cases with warning signs, without warning signs and severe dengue respectively. Additionally, ECG abnormalities were seen in 8.75% patients. All 80 patients had a normal CPK-MB and Troponin-I levels.Conclusions: Cardiac markers (CPK-MB and Troponin-I) remain unaffected during Dengue illness and do not have significant correlation between Dengue without warning signs, Dengue with warning signs and severe Dengue.