In-vitro problems of screening (Anti-HCV) and confirmatory tests (RIBA) for the diagnosis of HCV infections : The relation of neopterin and sCD14 with low Anti-HCV reactivity and different RIBA patterns (original) (raw)
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Role of Cytokines as Molecular Marker of Dengue Severity
Mediterranean journal of hematology and infectious diseases, 2018
Dengue infection is a rapidly spreading vector-borne disease and is endemic in the Indian subcontinent. It has varied manifestations ranging from subclinical infection to severe fatal shock syndrome. This study aimed to estimate cytokine level in dengue patients and correlate them with dengue severity. Cases of dengue fever diagnosed in the department of medicine of our institute from July 2015 to November 2016 were included in the study. The clinical features, biochemical, hematological and radiological parameters along with cytokine levels (Interferon-gamma, Interleukin-6, and Tumour Necrosis Factor-alpha) were recorded in all patients. Out of 80 confirmed cases of dengue included in the study, 50 had nonsevere dengue (Group 1), and 30 patients had severe dengue (Group 2). The median level of serum TNF-α in group 2 (62.5 pg/mL) was significantly higher than the median level in group 1 (20 pg/mL), (=0.043). Similarly, the median level of serum IFN-γ in group 2 (10.25 pg/mL) was sig...
PLOS Neglected Tropical Diseases, 2016
Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14 + CD16 + intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.
Cellular and Cytokine Correlates of Severe Dengue Infection
PLoS ONE, 2012
Background: The occurrence of dengue haemorrhagic fever (DHF) is thought to result from a complex interplay between the virus, host genetics and host immune factors. Existing published data are not consistent, in part related to relatively small sample sizes. We set out to determine possible associations between dengue virus (DEN-V) NS3 specific T cells and cytokine and chemokine levels and the pathogenesis of severe disease in a large cohort of individuals with DHF.
Cytokine Signature of Dengue Patients at Different Severity of the Disease
International Journal of Molecular Sciences, 2021
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...
Cytokine Expression Profile of Dengue Patients at Different Phases of Illness
Plos One, 2012
Background: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease. Methods and Findings: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1 beta was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1b beta and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study. Conclusions: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.
PLoS ONE, 2010
Secondary dengue infections are frequently associated with increased risk for dengue hemorrhagic fever and dengue shock syndrome. Surprisingly, we observed no dengue hemorrhagic fever cases among 353 hospitalized dengue-infected patients including 212 with primary, and 141 with secondary dengue 1 infection in China. To explore virological and immunological mechanisms which may account for this unexpected clinical observation, we assessed dengue viremia, type I interferon and inflammatory cytokine levels in these patients. While the levels of viremia and inflammatory cytokines are indistinguishable between primary and secondary infections, IFNa levels are significantly higher in primary than that in secondary infection. However, IFNa levels are positively correlated with dengue viremia levels (p,0.0001), but negatively correlated with the platelet counts (p,0.0001) and serum ALT levels (p = 0.0003). These results provide direct in vivo evidence that clinical dengue disease severity is affected by both viral and human immune factors.
The Association of Cytokines with Severe Dengue in Children
Tropical Medicine and Health, 2014
Background: Dengue virus infection is a major public health problem. A hypothesis put 32 forward for severe dengue is the cytokine storm, a sudden increase in cytokines that 33 induces vascular permeability. Previous studies and our recent meta-analysis showed that 34 IL-6, IL-8, IFNγ, TNFα, VEGF-A and VCAM-1 are associated with dengue shock 35 syndrome. Therefore, in this study we aim to validate the association of these cytokines 36 with severe dengue. 37 Methods & Findings: In a hospital based case control study in Vietnam, children with 38 dengue fever, other febrile illness and healthy controls were recruited. Dengue virus 39 infection was confirmed by several diagnostic tests. Multiplex Immunoassay using 40 Luminex technology was used to measure cytokines simultaneously. A positive 41 association with dengue shock syndrome was found for VCAM-1, whereas a negative 42 association was found for IFNγ. Furthermore, the multivariate logistic analysis also 43 showed that VCAM-1 and IFNγ were independently correlated with dengue shock 44 syndrome. 45 Conclusion: IFNγ and VCAM-1 were associated with dengue shock syndrome, although 46 their role in the severe dengue pathogenesis remains unclear. Additional studies are 47 required to further investigate the function of these cytokines in severe dengue.
Cytokine Signature Associated with Disease Severity in Dengue
Viruses
Dengue is the most rapidly spreading viral disease transmitted by the bite of infected Aedes mosquitos. The pathogenesis of dengue is still unclear; although host immune responses and virus serotypes have been proposed to contribute to disease severity. In this study, we examined the circulating dengue virus (DENV) and measured plasma levels of inflammatory mediators. Ninety-eight patients during a dengue outbreak in eastern India in 2016 were included in the study. The presence of DENV was demonstrated by detecting NS1 antigen; IgM capture ELISA and serotypes were discriminated by type-specific RT-PCR and/or sequencing. Plasma samples were assayed for 41-plex cytokine/chemokines using multiplex Luminex assay. Eighty-five (87%) samples were positive by NS1/IgM capture ELISA/RT-PCR. All four serotypes of DENV were detected in this outbreak, with DENV-2 as the predominant type, seen in 55% of cases. Mixed infections were seen in 39% of subjects. Among the host inflammatory biomarkers,...
American Journal of Tropical Medicine and Hygiene, 2012
Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.
Primary dengue virus infections induce differential cytokine production in Mexican patients
Memórias do Instituto Oswaldo Cruz, 2016
Severe dengue pathogenesis is not fully understood, but high levels of proinflammatory cytokines have been associated with dengue disease severity. In this study, the cytokine levels in 171 sera from Mexican patients with primary dengue fever (DF) and dengue haemorrhagic fever (DHF) from dengue virus (DENV) 1 (n = 116) or 2 (n = 55) were compared. DF and DHF were defined according to the patient's clinical condition, the primary infections as indicated by IgG enzymatic immunoassay negative results, and the infecting serotype as assessed by real-time reverse transcriptionpolymerase chain reaction. Samples were analysed for circulating levels of interleukin (IL)-12p70, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, IL-6, and IL-8 using a commercial cytometric bead array. Significantly higher IFN-γ levels were found in patients with DHF than those with DF. However, significantly higher IL-12p70, TNF-α, and IL-6 levels were associated with DHF only in patients who were infected with DENV2 but not with DENV1. Moreover, patients with DF who were infected with DENV1 showed higher levels of IL-12p70, TNF-α, and IL-6 than patients with DHF early after-fever onset. The IL-8 levels were similar in all cases regardless of the clinical condition or infection serotype. These results suggest that the association between high proinflammatory cytokine levels and dengue disease severity does not always stand, and it once again highlights the complex nature of DHF pathogenesis.