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.
ABSTRACT
Clinical diagnosis of scrub typhus is often difficult because the symptoms are very similar to those of other febrile illness such as dengue, leptospirosis, malaria and other viral ...hemorrhagic fevers. Though better diagnostic tests are available for rickettsial diseases and scrub typhus elsewhere, the Weil–Felix test is still commonly used in India, mainly because microimmunofluorescence assays (M‐IFA) were not available in India till recently and relevant staff had insufficient training. The present study was performed to investigate the performance of M‐IFA, IgM ELISA, and Weil–Felix test on 546 non‐repeated serum samples from subjects suspected of having scrub typhus. One hundred and forty‐three of these 546 samples were positive by M‐IFA; these cases were also confirmed clinically to have scrub typhus based on their dramatic responses to doxycycline therapy. IgM ELISA was positive in 122 of the 143 M‐IFA positive cases and the Weil–Felix test in 96. Though the Weil–Felix test is a heterophile agglutination test, it was found in this study to have good specificity but far too little sensitivity to use as a routine diagnostic test. IgM ELISA can be a good substitute for M‐IFA. Incorporation of multiple prototype antigens on M‐IFA slides is likely one of the reasons for its superior performance. As newer and better diagnostic assays become available for scrub typhus diagnosis in developed countries, it will be imperative to also use such tests in other endemic countries to prevent over‐ or under‐diagnosis of scrub typhus.
We present a case of a 43-year-old immunocompromised female patient diagnosed with disseminated histoplasmosis on bone marrow examination, at clinical laboratory of Kasturba Hospital, Manipal, ...Karnataka, India. The patient, presenting with symptoms like weight loss, appetite loss, and pancytopenia, underwent bone marrow aspiration and biopsy. The bone marrow studies revealed HIV-associated changes and the yeast form of
, confirming disseminated histoplasmosis. Bone marrow examination is highlighted as a diagnostic tool with significant sensitivity in such cases. The report stresses on the importance of awareness and early diagnosis of histoplasmosis in immunocompromised patients, given its potential lethality and the need for timely therapeutic intervention for better prognosis.
•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.
This study had two objectives: 1) to determine the clinical and microbiological profiles of patients developing intravascular catheter-related local (localized catheter colonization and exit site) ...and systemic infections and their predisposing factors; 2) to study the antibiotic sensitivity patterns of the organisms isolated.
This case-control study was conducted over 19 months involving 232 patients at a tertiary care hospital. Non-tunneled central venous catheters and midline catheters were the two types studied. Catheter tips were processed using Maki's roll plate and endoluminal flush techniques. Blood cultures were drawn under strict aseptic precautions and processed by the BacT ALERT system. A "case" was any patient with proven localized catheter colonization, exit site infection or blood-stream infection and a "control" was any patient from whom the intravascular catheter yielded no organism in semi-quantitative cultures.
The incidence of catheter-related blood-stream infections (CRBSI) in our institute was 8.75 per 1,000 catheter days. The commonest organisms causing local infections were coagulase-negative Staphylococci, and those causing CRBSI were Staphylococcus aureus. Multidrug-resistant organisms accounted for 30.2% of the infections. Risk factors for development of catheter-related infections included an immune compromised state, duration of the catheter in situ, femoral venous cannulation, and triple lumen catheters. Choice of venous cannulation to minimize the risk of catheter-related infection in ascending order for risk of infection is the subclavian vein, jugular vein, basilic vein and then the femoral vein. There was no role for empirical antibiotic therapy to prevent intravascular catheter-related local or systemic infections.
Background and objective Differentiating tropical infections are difficult due to its homogenous nature of clinical and laboratorial presentations among them. Sophisticated differential tests and ...prediction tools are better ways to tackle this issue. Here, we aimed to develop a clinician assisted decision making tool to differentiate the common tropical infections. Methodology A cross sectional study through 9 item self-administered questionnaire were performed to understand the need of developing a decision making tool and its parameters. The most significant differential parameters among the identified infections were measured through a retrospective study and decision tree was developed. Based on the parameters identified, a multinomial logistic regression model and a machine learning model were developed which could better differentiate the infection. Results A total of 40 physicians involved in the management of tropical infections were included for need analysis. Dengue, malaria, leptospirosis and scrub typhus were the common tropical infections in our settings. Sodium, total bilirubin, albumin, lymphocytes and platelets were the laboratory parameters; and abdominal pain, arthralgia, myalgia and urine output were the clinical presentation identified as better predictors. In multinomial logistic regression analysis with dengue as a reference revealed a predictability of 60.7%, 62.5% and 66% for dengue, malaria and leptospirosis, respectively, whereas, scrub typhus showed only 38% of predictability. The multi classification machine learning model observed to have an overall predictability of 55-60%, whereas a binary classification machine learning algorithms showed an average of 79-84% for one vs other and 69-88% for one vs one disease category. Conclusion This is a first of its kind study where both statistical and machine learning approaches were explored simultaneously for differentiating tropical infections. Machine learning techniques in healthcare sectors will aid in early detection and better patient care.
Despite the high number of coronavirus disease-19 (COVID-19) cases from India, there are few reports from India describing the clinical epidemiology of COVID-19. This study aimed to describe the ...clinical/epidemiological characteristics and outcomes of asymptomatic vs. symptomatic COVID-19 patients. This was a retrospective chart review of all admitted patients with COVID-19 above 18 years with a history of travel within one month of the admission. The patients were categorized into asymptomatic and symptomatic. The symptomatic patients were further classified into mild, moderate and severe. The demographic profile, risk factors, clinical features, laboratory parameters, treatment details and outcome of all patients were recorded. The clinical and laboratory parameters were compared between symptomatic patients and asymptomatic patients. Of the 127 recruited patients, 75 were asymptomatic. Of the 52 symptomatic patients, 41 patients were classified as a mild illness. The mean age of the patients was 44.5 ± 15 years. A total of 73 patients had one or more risk factors. The male patients were more commonly found to be symptomatic compared to female patients. Neutrophil-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were significantly elevated in symptomatic patients. A total of five individuals required supplemental oxygen therapy, and one of them required mechanical ventilation. All the patients had favourable outcomes. Asymptomatic and mild illness form a significant proportion of positive patients and have excellent outcomes without therapeutic interventions.
Hyponatremia is commonly noted with cardiovascular disorders, but its role in infective endocarditis (IE) is limited to being a marker of increased morbidity in IE patients with intravenous drug use. ...This was a 5-year retrospective review from an Indian Intensive Care Unit (ICU). Patients >18 years with IE and available serum sodium levels were included in the study. Pediatric and pregnant patients were excluded from the study. Hyponatremia was defined as admission sodium <135 mmol/L. Detailed data were abstracted from the medical records. Primary outcomes were need for invasive mechanical ventilation, ICU length of stay, and in-hospital mortality. Secondary outcomes included development of acute kidney injury, acute decompensated heart failure (ADHF), acute respiratory distress syndrome, stroke, and severe sepsis in the ICU. Two-tailed P < 0.05 was considered statistically significant. Between January 2010 and December 2014, 96 patients with IE were admitted to the ICU with 85 (88.5%) (median age 46 34.5-55 years, 51 60.0% males) meeting our inclusion criteria. The comorbidities, echocardiographic, and microbiological characteristics were comparable between patients with hyponatremia (56; 65.9%) and eunatremia (29; 34.1%). Median sodium in the hyponatremic cohort was 131 mmol/L (127.25-133) compared to the eunatremic cohort 137 mmol/L (135-139) (P < 0.001). The primary outcomes were not different between the two groups. Hyponatremia was associated more commonly with ADHF (12 21.4% vs. 0; P = 0.007) during the ICU stay. Hyponatremia is commonly seen in IE patients and is not associated with worse hospital outcomes. ADHF was seen more commonly in the hyponatremic patients in comparison to those with eunatremia.
Vitamin D deficiency (VDD) has become a growing global public health issue, which is placing increasing burdens on healthcare systems worldwide due to its multifactorial clinical manifestations. ...However, epidemiological findings pertaining to VDD's link with various disease pathologies, especially type 2 diabetes mellitus (T2DM), remain contradictory. Through a retrospective cross-sectional analysis, this study aimed to contribute towards the construction of a novel framework for understanding the relationship between VDD and T2DM to subsequently inform relevant public health policy.
A retrospective cross-sectional analysis of the prevalence of diabetes in both VDD and non-VDD groups was conducted. Data pertaining to various biochemical parameters was obtained from the Kasturba hospital database for 500 patients tested for both serum 25(OH)D and blood glucose levels i.e. random, fasting, post-prandial, and/or hemoglobin A1c (HbA1C) between 1st January and 30th April 2018.
Within the study sample, 117 (41.1%) of patients with VDD had T2DM, whereas 72 (33.5%) of patients without VDD had T2DM. This indicates no association between VDD and T2DM (χ2 = 2.98; p = 0.084). Still, an OR value of 1.4, despite statistical insignificance (95%CI:0.96–2.0, p = 0.084) indicates that there is an approximately 40% greater odds of developing T2DM in VDD patients relative to non-VDD patients. Moreover, the likelihood ratio (LR) is 2.99, which indicates an approximately 3-fold chance of having T2DM as a VDD patient, relative to a non-VDD patient.
Despite the lack of statistical significance, the findings of this study make important contributions to the existing literature and must be considered in light of their inherent limitations. Taking these into account, it becomes clear that these results should not be extrapolated nor assumed to entirely invalidate the hypothesized link between VDD and T2DM. Rather, such gaps warrant need for further research and more robust study designs to draw sufficiently significant conclusions to justify reforms in clinical practice.
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