The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory ...cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.
•Temporal analysis of the daily viral load and cytokine levels in hospitalized dengue patients identified the pattern of cytokine dynamics.•Elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 ...and decreased IL-12, MIP-1β on the third day after symptom onset is predictive of severe dengue.•The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.
The immunopathogenesis of dengue severity is convoluted. The primary objective of the research was to examine the dynamics of cytokine storm and its correlation with disease development in individuals affected by DENV infection. Additionally, the study aimed to discover potential biomarkers that could indicate severe dengue infection and determine the most suitable timeframe for predicting the severity of these biomarkers during the acute stage of dengue infections. We conducted a temporal analysis of the daily viral load and cytokine levels in 60 hospitalized dengue patients until discharge. Our findings reveal a distinct cytokine profile (elevated IL-8, IL-10, IL-6, GM-CSF, MCP-1, IL-13, and IL-4 and decreased IL-12, MIP-1β) on the third day after symptom onset is predictive of severe dengue in secondary dengue infection. The imbalanced cytokine signature may inform clinical decision-making in treating severe dengue infections.
Introduction: Dengue virus (DENV) infection is a significant global public health problem, caused by four antigenically distinct serotypes of DENV, namely, DENV-1, DENV-2, DENV-3, and DENV-4. The ...disease manifestations range from asymptomatic or mild undifferentiated fever to severe diseases such as dengue hemorrhagic fever and dengue shock syndrome. Extensive research has been done on pathogenesis of DENV infection and the factors responsible for its severe manifestations. However, there is no ideal prognostic biomarker available yet. In various studies, it has been observed that DENV nonstructural-1 (NS1) protein plays a crucial role in pathogenesis. DENV NS1 protein acts by various mechanisms such as direct effect on vascular endothelium and activation of alternate complement pathway, which causes the release of inflammatory cytokines, leading to plasma leakage. It has also been observed that DENV NS1 levels correlate with disease severity. Until the present date, no commercial quantitative DENV NS1 ELISA is available for quantifying DENV NS1 levels in patients of DENV infection. Aim: Standardization of quantitative DENV NS1 ELISA. Methods: This study utilizes an already available NS1 ELISA kit and known concentrations of recombinant DENV NS1 protein to standardize quantitative DENV NS1 ELISA to estimate the NS1 concentration in human sera. Conclusion: Commercially available DENV NS1 detection kits can be standardized for quantification of DENV NS1 in human sera and use this data to find the association between NS1 concentration and disease severity.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) is of utmost clinical importance because they challenge the armamentarium of the treating clinicians, hampering current treatment strategies. ...Aim: The aim of the study is to detect carbapenemase-producing Enterobacteriaceae by phenotypic and molecular methods. Materials and Methods: Nonrepetitive isolates of Enterobacteriaceae were identified by conventional phenotypic methods from various clinical samples. All these isolates were screened for carbapenem resistance by meropenem (10μg) or ertapenem (10μg) disc. All the isolates which were found to be carbapenem-resistant by screening test were subjected to phenotypic confirmatory test in the form of modified Hodge test (MHT). These isolates were then subjected to polymerase chain reaction for the detection of various carbapenemase-producing genes, namely New Delhi metallo-β-lactamase 1 (NDM), verona integron-encoded metallo-β-lactamase (VIM), imipenem-resistant Pseudomonas (IMP), KPC, and OXA-48. Results: Out of 1254 isolates of Enterobacteriaceae, 230 isolates (18.3%) were found to be positive for carbapenemase production by screening test. A total of 150 out of 230 isolates (65.2%) tested positive for carbapenemase production by MHT. Out of these 150 phenotypically confirmed carbapenemase-producing isolates, blaNDM gene was found in 85, blaVIM in 32, and blaIMP in 22 isolates. blaOXA-48 and blaKPC genes were not found in any isolate. Moreover, there were 19 isolates, in which no gene was detected. Conclusion: The prevalence of phenotypically confirmed carbapenemase resistance among Enterobacteriaceae is 11.96% (150/1254). Genes responsible for carbapenemase production are widely prevalent in Enterobacteriaceae Routine detection will help in the management of these broadly-resistant pathogens and implementation of appropriate infection control measures, thus limiting their spread.
Abstract The emergence of resistance to multiple antimicrobial agents in Gram-negative bacteria is a significant threat to public health, as it restricts the armamentarium of the clinician against ...these infections. The aim of this study was to determine the burden of extensively drug-resistant (XDR) and pandrug-resistant (PDR) Gram-negative bacteria at a tertiary-care centre. Antimicrobial susceptibility testing of 1240 clinical isolates of Gram-negative bacteria obtained from various clinical samples during the study period was carried out by the Kirby-Bauer disc diffusion method. Minimum inhibitory concentration of all antibiotics including tigecycline and colistin was determined by Vitek-2 automated susceptibility testing system. Out of 1240 isolates of Gram-negative bacteria, 112 isolates (9%) were resistant to all the antibiotics tested by Kirby-Bauer disc diffusion method. This finding was corroborated by Vitek-2. In addition, Vitek-2 found that 67 isolates were resistant to all antibiotics except tigecycline and colistin. A total of 30 isolates were susceptible to only colistin, and four isolates were susceptible to only tigecycline. It was also found that six isolates (excluding five isolates of Proteus spp.) were resistant to both colistin and tigecycline. Thus, 101 (8.1%) out of 1240 isolates were XDR and 11 isolates (0.9%) were PDR. The findings of this study reveal increased burden of XDR and PDR Gram-negative bacteria in our centre. It also highlights the widespread dissemination of these bacteria in the community. This situation warrants the regular surveillance of antimicrobial resistance of Gram-negative bacteria and implementation of an efficient infection control program.
Dengue virus (DENV) was discovered by P. M. Ashburn and Charles F. Craig in 1907. Evidence of dengue-like illness was observed before 1907 and DENV epidemics have been reported from different parts ...of the world since then, with increased morbidity rates every year. DENV typically causes a febrile illness that ranges from mild asymptomatic infection to fatal dengue haemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). Host mechanisms through which mild infection progresses to the fatal forms are still unknown. Few factors have been associated to aid severe disease acquisition, DENV non-structural 1 (NS1) protein being one of them. NS1 is a highly conserved glycoprotein among the Flavivirus and is often used as a biomarker for dengue diagnosis. This review focuses on assessing the role of NS1 in severe dengue. In this review, hospital-based studies on the association of dengue NS1 with severe dengue from all over the world have been assessed and analysed and the majority of the studies positively correlate high NS1 levels with DHF/DSS acquisition. The review also discusses a few experimental studies on NS1 that have shown it contributes to dengue pathogenesis. This review assesses the role of NS1 and disease severity from hospital-based studies and aims to provide better insights on the kinetics and dynamics of DENV infection with respect to NS1 for a better understanding of the role of NS1 in dengue.
Enterococci have assumed great clinical importance because of their increasing resistance to various antimicrobial agents. Thus, knowledge about the antibiogram of these multidrug resistant isolates ...is of utmost importance in formulating an effective antibiotic policy to treat these infections and reducing the morbidity and mortality. Aim of this study was to assess the antimicrobial resistance pattern of enterococci and determine the prevalence of multidrug resistance among them.
This cross sectional study was carried out from August 2011 to February 2014, in which 200 non-repetitive clinical isolates of enterococci were included. Antimicrobial susceptibility testing was done by disc diffusion method. Minimum inhibitory concentration (MIC) of gentamicin, streptomycin, vancomycin, teicoplanin and linezolid was determined by E-test method.
The prevalence of multidrug resistance among enterococcal isolates was found to be 63%. Varying levels of resistance was seen to various antibiotics. Most of the isolates were resistant to penicillin (95%), ampicillin (95%) and cotrimoxazole (90%). High level aminoglycoside resistance (HLAR) and glycopeptide resistance was seen in 39% and 14% isolates respectively. Only 4 isolates (2%) were found to be resistant to linezolid.
The prevalence of multidrug resistance among enterococci was found to be 63%, the resistance being more common in Enterococcus faecium as compared to Enterococcus faecalis. The study highlights the emergence and increased prevalence of multidrug resistant enterococci which pose a serious therapeutic challenge.
Abstract Background Dengue virus (DENV) infection is an important public health problem and causes significant morbidity and mortality. DENV typically causes a febrile illness that ranges from mild ...asymptomatic infection to fatal dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). Early prediction of severe dengue disease is of utmost importance for providing prompt monitoring and treatment. The search for an ideal biomarker (host or viral factors) for early prediction of severe dengue remains elusive. Aim To standardize a real time qRT-PCR for quantifying dengue viremia in serum samples and evaluate the kinetics of dengue viremia and its significance in disease severity. Results In this ambispective study of 126 laboratory confirmed dengue patients, 72 were primary infections and 54 were secondary infections. The most common serotype was serotype 1 (n = 37) followed by serotype 2 (n = 34). According to WHO 1997 dengue case classification, 111 patients were cases of dengue fever (DF), 13 from DHF and 02 from DSS. Day 3 viremia levels were significantly elevated in severe dengue patients (DHF/DSS) as compared to that of DF ( p < 0.05). However, no such association was found between viremia levels and serotype or immune status. Conclusion Dengue viremia has a significant association with disease severity and day 3 viremia levels may be used as a predictor for dengue disease severity.
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