Since the beginning of the current Ebola epidemic, several patients with Ebola virus disease have been cared for in the United States and Europe. In this report, the clinical course and care of these ...27 patients are described.
The Ebola virus disease (EVD) epidemic in West Africa had resulted in more than 28,600 reported cases and more than 11,300 deaths through December 2015; mortality reported for patients with EVD cared for in Ebola treatment units in West Africa has ranged from 37 to 74%.
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The provision of clinical care to patients with EVD in Ebola treatment units in West Africa has involved the need to balance many challenges, such as overwhelming numbers of severely ill patients, limited medical and nonmedical supplies, insufficient numbers of caregivers and resources, and hot and humid working conditions that limit the time . . .
Antimicrobial choices for community-acquired pneumonia in hospitalized patients who do not require ICU-level care continue to be debated. In this trial, empirical beta-lactam–based therapy with or ...without a macrolide was compared with fluoroquinolones as initial treatment.
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and death worldwide.
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Most guidelines recommend that antibiotic treatment be based on the severity of disease at presentation, assessed either on the basis of the level of care needed or on the basis of a prognostic risk score.
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For patients with clinically suspected CAP who are admitted to a non–intensive-care-unit (ICU) ward, guidelines recommend either combination therapy with a beta-lactam plus a macrolide or plus ciprofloxacin or monotherapy with moxifloxacin or levofloxacin for empirical treatment. These guidelines have increased the use of macrolides and fluoroquinolones, although these antibiotic classes . . .
In key subgroups of the HIV-infected patients in the MOTIVATE 1 and MOTIVATE 2 studies, a consistent treatment benefit of maraviroc over placebo was seen at 48 weeks. These subgroups include patients ...with a low baseline CD4 cell count and a high HIV viral load at screening and those receiving no active background antiretroviral agents. In patients in whom maraviroc failed, the CXCR4-using virus was often present at failure.
In key subgroups of HIV-infected patients, a consistent treatment benefit of maraviroc over placebo was seen at 48 weeks. These subgroups include patients with a low baseline CD4 cell count and a high HIV viral load at screening and those receiving no active background antiretroviral agents.
The CC chemokine receptor 5 (CCR5) antagonist maraviroc has shown potent antiviral activity in vitro and in vivo against the R5 human immunodeficiency virus type 1 (HIV-1).
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As reported by Gulick et al.
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elsewhere in this issue, treatment with maraviroc plus optimized background therapy was associated with significantly greater virologic and immunologic efficacy and had a similar safety profile, as compared with placebo plus optimized background therapy, in the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2 studies at 48 weeks.
Subgroup analyses of data from recent trials evaluating new drugs in patients . . .
Background CD27 is a lymphocyte costimulatory molecule that regulates T-cell, natural killer (NK) cell, B-cell, and plasma cell function, survival, and differentiation. On the basis of its function ...and expression pattern, we considered CD27 a candidate gene in patients with hypogammaglobulinemia. Objective We sought to describe the clinical and immunologic phenotypes of patients with genetic CD27 deficiency. Methods A molecular and extended immunologic analysis was performed on 2 patients lacking CD27 expression. Results We identified 2 brothers with a homozygous mutation in CD27 leading to absence of CD27 expression. Both patients had persistent symptomatic EBV viremia. The index patient was hypogammaglobulinemic, and immunoglobulin replacement therapy was initiated. His brother had aplastic anemia in the course of his EBV infection and died from fulminant gram-positive bacterial sepsis. Immunologically, lack of CD27 expression was associated with impaired T cell–dependent B-cell responses and T-cell dysfunction. Conclusion Our findings identify a role for CD27 in human subjects and suggest that this deficiency can explain particular cases of persistent symptomatic EBV viremia with hypogammaglobulinemia and impaired T cell–dependent antibody generation.
We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular ...diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval CI, 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.
Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence ...and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.
Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm(3) (interquartile range IQR; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100 pyar 95% CI 2.82-3.49); incidence rates at 0-3, 3-6, 6-12 and 12-24 months were 11.25 (9.58-13.21), 6.27 (4.99-7.87), 2.47 (1.87-3.36) and 1.02 (0.80-1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm(3) (hazard ratio HR 1.84 1.25-2.70, P = 0.002) and male gender (HR 1.68 1.34-2.11, P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm(3) IQR; 107, 258, n = 118 vs 209 cells/mm(3) 124, 309, n = 2166, P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm(3): 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm(3): 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunological failure definitions.
Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm(3). Incident TB during ART is associated with long-term impairment in immune recovery.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically ...review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.
Abstract
This study assessed the experiences of elite aquatic athletes with coronavirus disease 2019 (COVID-19) during the first World Championship conducted without social distancing and an ...isolation “bubble”. An online questionnaire was completed by 812 athletes (22.7 ± 5.9 years, 467 females) to provide data on demographics, sports activity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates, symptoms, reinfection, vaccination status, and psychological aspects. The answers revealed that 49.4% of athletes had experienced SARS-CoV-2 infection. The infection rates varied significantly across different aquatic sports, with open water swimmers having the lowest (28%) and water polo players (67%) and artistic swimmers (61%) having the highest infection rates (p < 0.0001). The majority reported mild (51%) or moderate (27%) symptoms, while 16% remained asymptomatic. Reinfection occurred in 13%, and 10% of initial infections led to long COVID, with fatigue (65%) and shortness of breath (48%) being the most common long-term symptoms. Significantly, 92% of athletes received at least two vaccine doses and reported a positive vaccination experience (median score of 8 out of 10 for each shot). Mood changes and subjective performance drops significantly correlated with the overall experience scores (rho: 0.617, p < 0.0001, and rho: 0.466, p < 0.0001, respectively). In conclusion, most athletes experienced a benign disease course despite a relatively high infection rate. This study provides valuable insights into the COVID-19 experiences of elite aquatic athletes. The findings emphasize the importance of vaccination initiatives, monitoring psychological well-being and the need to fortify athletes’ resilience in the face of future health challenges.
Macrolides are known to possess immunomodulatory properties, next to their antimicrobial effects. These immunomodulatory activities have been proven beneficial in chronic pulmonary inflammatory ...diseases. Whether macrolides also exert favourable immunomodulatory effects during acute inflammation, and therefore can act as adjuvant therapy in community-acquired pneumonia (CAP), is less clear. We aimed to give an overview of the existing evidence from in vitro and in vivo studies on the immunomodulatory effects of macrolides during CAP. A comprehensive search in the PubMed/MEDLINE and Embase databases was performed. Two investigators independently examined the eligible literature. Studies that dealt with the effects of macrolides on the immune response, in terms of cytokine secretion and the number or function of inflammatory and structural cells during acute inflammation, were included. A total of 27 studies were included, of which 15 were in vitro studies, 9 in vivo, 2 both in vivo and in vitro, and 1 was in human subjects. Although the methods and experimental model systems used in these studies are very heterogeneous, macrolides in general tempered inflammation caused by viable and non-viable bacteria or their products. Cytokine secretion decreased, as did inflammatory and structural cell activation and histological inflammatory signs. Not all data, however, are consistent and sometimes pro-inflammatory effects were found. To conclude, the available literature suggests that macrolides can temper the inflammatory response during CAP, independent of their antimicrobial activity. However, because the studies differ in their methodology, no definite conclusions can be drawn.
To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients ...and controls.
14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis).
Frequencies of activated CD4(+) and CD8(+) T-cells were higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono-infected individuals. Coinfected patients also showed high expression of the exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences T-cell activation and exhaustion. Interestingly, increased percentages of effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis compared to those with no to minimal fibrosis (F0-F2).
HIV/HCV coinfected patients display a high level of T-cell activation and exhaustion in the peripheral blood. Our data suggest that T-cell activation and exhaustion are influenced by the level of HCV viremia. Furthermore, high percentages of cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV monoinfected and HIV/HCV coinfected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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