Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 7 Articles
Background: Timely and accurate identification of people with latent tuberculosis infection (LTBI) is important for\ncontrolling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as\ninterferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information.\nThis systematic review compared two types of IGRAs QuantiFERON�®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB\nwith TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children,\nimmunocompromised people, and those recently arrived from countries with high TB burden.\nMethods: Cohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and\nother databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed\nrisk of bias with cross checking by a second reviewer. Strength of association between test results and incidence\nof TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio\nof CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using\nChi-squared and I2 statistics.\nResults: Seventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised\npeople, and two in those recently arrived) were included. In children, while in two studies, there was no significant\ndifference between QFT-GIT and TST (â�¥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed\nQFT-GIT to outperform TST (â�¥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was\nnot significant different from TST (â�¥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest\nplot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent\nfindings (high heterogeneity; I2 = 92%).\nConclusions: Prospective studies comparing IGRA testing against TST on the progression from LTBI to TB were\nsparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained\nheterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately\ncompare the performance of IGRA with TST in people at high risk of TB....
Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain.\nWe describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods.\nRetrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics,\ncomorbidities, case-mix, illness severity, and 30-daymortalitywere captured.MultivariableCox regression analyseswere performed\nto identify predictors of mortality. Results. Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male.Median (IQR)\nCD4 count and plasma viral load (PVL)were 125 cells/mm3 (30ââ?¬â??300) and 28,000 copies/mL (110ââ?¬â??270,000). Fifty-five (20%) patients\ndied within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12;\n95% CI 1.08ââ?¬â??1.16; ...
Background: The role of pathogen specific cellular immune responses against the eliciting pathogen in development\nof post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of\nthis study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection\ncompared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a\nGiardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for\nCFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by\nproliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10\nhealthy unexposed individuals were recruited as controls.\nResults: Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes\n(n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between\nthese Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia\nexposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days\ncultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after\nGiardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling.\nConclusion: Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia\nand increased sCD40L in fatigued patients....
One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an\naberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome\n(IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of\n53 cells/mm3 (3,3%) and HIV RNA = 890000 copies/mL (6 log). Four weeks later he was admitted to the intensive care unit with\nsevere sepsis. The diagnostic pathway identified progressive multifocal leukoencephalopathy, digestive Kaposi sarcoma, and P.\naeruginosa bacteraemia. Five weeks after starting ART, TCD4+ cell count was 259 cells/mm3 (15%) and HIV RNA = 3500 copies/mL\n(4 log). He developed respiratory failure and progressed to septic shock and death. Those complications might justify the outcome\nbut its autopsy opened Pandora�s box: cerebral and cardiac toxoplasmosis was identified, as well as hemophagocytic syndrome,\nsystemic candidiasis, and Mycobacterium avium complex infection. IRIS remains a concern and eventually a barrier to ART. Male\ngender, young age, low TCD4 cell count, and high viral load are risk factors. The high prevalence of subclinical opportunistic\ndiseases highlights the need for new strategies to reduce IRIS incidence....
Trypanosoma cruzi causes a cardiac infection characterized by an inflammatory imbalance that could become the inciting factor\nof the illness. To this end, we evaluated the role of carvedilol, a beta-blocker with potential immunomodulatory properties, on the\nimmune response in C57BL/6 mice infected with VL-10 strain of T. cruzi in the acute phase. Animals (...
Abstract\nBackground: Levels of non-neutralising antibodies (AB) to the C5 domain of HIV Env gp120 are inversely related\nto progression of HIV infection. In this phase I/II clinical study we investigated safety of Vacc-C5, a peptide-based\ntherapeutic vaccine candidate corresponding to C5/gp41732ââ?¬â??744 as well as the effects on pre-existing AB levels to\nC5/gp41732ââ?¬â??744, immune activation and T cell responses including exploratory assessments of Vacc-C5-induced T\ncell regulation. Our hypothesis was that exposure of the C5 peptide motif may have detrimental effects due to\nseveral of its HLA-like features and that enhancement of non-neutralising anti-C5 AB by vaccination could reduce\nC5 exposure and thereby chronic immune activation.\nMethods: Thirty-six HIV patients on effective antiretroviral therapy were randomised to one of three dose levels of\nVacc-C5 administered intramuscularly with Alhydrogel or intradermally with GM-CSF as adjuvant through initial\nimmunisation and two booster periods over 26 weeks. Vacc-C5-specific AB were measured by ELISA and T cell\nresponses by both IFN-Ã?³ ELISPOT and proliferative assays analysed by flow cytometry. Immune regulation was\nassessed by functional blockade of the two inhibitory cytokines IL-10 and TGF-Ã?² in parallel cultures. Non-parametric\nstatistical tests were applied.\nResults: Vacc-C5 was found safe and well tolerated in all patients. Only marginal changes in humoral and cellular\nresponses were induced, without any effect on immune activation. Overall, anti-Vacc-C5 AB levels seemed to decrease\ncompared to pre-existing levels. Whereas Vacc-C5-specific CD8+ T cell proliferative responses increased after the first\nbooster period (p = 0.020; CD4+, p = 0.057), they were reduced after the second. In contrast, Vacc-C5-induced T cell\nregulation increased after completed vaccination (p ââ?°Â¤ 0.027) and was lower at baseline in the few AB responders\nidentified (p = 0.027).\nConclusions: The therapeutic HIV vaccine candidate Vacc-C5 safely induced only marginal immune responses,\nwhereas Vacc-C5-induced T cell regulation markedly increased. Our data support further attention on immune\nregulation during therapeutic HIV vaccination studies....
Background: While tumor necrosis factor alpha (TNF-�±) inhibitors (TNFi) and other biologics are very effective\nagainst autoimmune diseases, they can also cause infectious diseases. Therefore, it is important to clarify whether\nthe TNFi sometimes used to treat patients with rheumatoid arthritis (RA) complicated with human T-lymphotropic\nvirus type-I (HTLV-I) infection have the unintended side effect of promoting HTLV-I proliferation.\nMethods: We used the HTLV-I-infected cell line HCT-5, derived from spinal fluid cells of a patient with HTLV-I\nassociated myelopathy, to evaluate the production of cytokines and chemokines, TNF-�± receptor (TNFR), the\nexpression of HTLV-I associated genes, the HTLV-I proviral load (PVL), the expression of HTLV-I structural protein,\nand apoptosis. We used Jurkat cells as a control.\nResults: Supernatants of HCT-5 showed time-dependent elevations of IL-6, RANTES and ICAM-1. HCT-5\nsupernatants treated with infliximab, adalimumab, etanercept (ETN), golimumab and certolizumab pegol showed\nno significant differences in the levels of these molecules compared to the control. Neither TNFR1 nor TNFR2\nexpression was altered by any TNFi treatment, relative to phosphate-buffered saline (PBS) treatment, with the\nexception that TNFR2 was significantly decreased and internalized in HCT-5 cells by ETN treatment. The HTLV-I\nassociated genes Tax and HBZ and the PVL levels were not significantly changed. Immunofluorescence staining\nof HCT-5 for an HTLV-I-associated protein, GAG, was also not significantly different between any of the TNFi\ntreatments and the PBS treatment. DNA ladders as an index of apoptosis were not detected. Apoptotic cells were\nnot increased by the addition of any TNFi.\nConclusions: In vitro, TNFi did not affect the cytokine profiles, expression of associated genes and proteins, proviral\nload or apoptosis of HCT-5 cells. The results suggested that TNFi treatment of RA patients complicated with HTLV-I\nmight have no effect on HTLV-I infection....
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