Comparison of a whole-blood interferon-gamma assay and tuberculin skin testing in patients with active tuberculosis and individuals at high or low risk of Mycobacterium tuberculosis infection

BACKGROUND: QuantiFeron-TB (QIFN) is a whole-blood interferon-;gamma assay for the recognition of cell-mediated immune response to Mycobacterium tuberculosis infection. OBJECTIVES: To compare the QIFN assay with the tuberculin skin test (TST) in patients with newly diagnosed culture-proven tuberculosis (TB) and healthy volunteers with high or low risk of latent M tuberculosis infection and to identify factors associated with discordance between tests. METHOD: Two-hundred fifty-eight subjects underwent both assays. All participants completed a detailed questionnaire, and data from TB patients' medical records were collected. RESULTS: In the entire study population, agreement between tests was moderate and the correlation between the magnitude of QIFN response and the TST induration diameter was significant. In volunteers with no known risk of exposure to M tuberculosis, the specificity of the assays was comparable. However, in subjects with active TB or those vaccinated with bacille Calmette-Guérin, the QIFN assay detected more reactors than did the TST. In these individuals, agreement between assays was poor and no correlation or only a weak correlation was found between the diameter of TST induration and the magnitude of the interferon-gamma responses. CONCLUSIONS: The sensitivity of the QIFN assay is greater than that of the TST in patients with active TB before the initiation of anti-TB chemotherapy, but its specificity is influenced more by bacille Calmette-Guérin vaccination. The QIFN assay may provide an improvement over the current practice of the use of the TST to support diagnosis of active M tuberculosis infection in the clinic; however, QIFN cannot be considered an adequate replacement for the TST in the screening for latent infection.     

Novel therapeutic targets in depression: Minocycline as a candidate treatment

Mood disorders are marked by high rates of non-recovery, recurrence, and chronicity, which are insufficiently addressed by current therapies. Several patho-etiological models have been proposed that are not mutually exclusive and include but are not limited to the monoamine, inflammatory, neurotrophic, gliotrophic, excitatory, and oxidative stress systems. A derivative of these observations is that treatment(s) which target one or more of these mechanistic steps may be capable of mitigating, or preventing, disparate psychopathological features. Minocycline is an agent with pleiotropic properties that targets multiple proteins and cellular processes implicated in the patho-etiology of mood disorders. Moreover, preclinical and preliminary clinical evidence suggests that minocycline possesses antidepressant properties. Herein, we provide the rationale for conducting a randomized, controlled trial to test the antidepressant properties of minocycline.     

Findings of the International Nosocomial Infection Control Consortium (INICC), Part II: Impact of a multidimensional strategy to reduce ventilator-associated pneumonia in neonatal intensive care units in 10 developing countries

Design.?Before-after prospective surveillance study to assess the efficacy of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control program to reduce the rate of occurrence of ventilator-associated pneumonia (VAP). Setting.?Neonatal intensive care units (NICUs) of INICC member hospitals from 15 cities in the following 10 developing countries: Argentina, Colombia, El Salvador, India, Mexico, Morocco, Peru, Philippines, Tunisia, and Turkey. Patients.?NICU inpatients. Methods.?VAP rates were determined during a first period of active surveillance without the implementation of the multidimensional approach (phase 1) to be then compared with VAP rates after implementation of the INICC multidimensional infection control program (phase 2), which included the following practices: a bundle of infection control interventions, education, outcome surveillance, process surveillance, feedback on VAP rates, and performance feedback on infection control practices. This study was conducted by infection control professionals who applied National Health Safety Network (NHSN) definitions for healthcare-associated infections and INICC surveillance methodology. Results.?During phase 1, we recorded 3,153 mechanical ventilation (MV)-days, and during phase 2, after the implementation of the bundle of interventions, we recorded 15,981 MV-days. The VAP rate was 17.8 cases per 1,000 MV-days during phase 1 and 12.0 cases per 1,000 MV-days during phase 2 (relative risk, 0.67 [95% confidence interval, 0.50-0.91]; [Formula: see text]), indicating a 33% reduction in VAP rate. Conclusions.?Our results demonstrate that an implementation of the INICC multidimensional infection control program was associated with a significant reduction in VAP rate in NICUs in developing countries.     

Evaluation of a model to improve collection of blood cultures in patients with sepsis in the emergency room

Sepsis begins outside of the hospital for nearly 80% of patients and the emergency room (ER) represents the first contact with the health care system. This study evaluates a project to improve collection of blood cultures (BCs) in patients with sepsis in the ER consisting of staff education and completion of the appropriate BC pre-analytical phase. A retrospective observational study performed to analyse the data on BC collection in the ER before and after a three-phase project. The first phase (1 January to 30 June 2015) before the intervention consisted of evaluation of data on BCs routinely collected in the ER. The second phase (1 July to 31 December 2015) was the intervention phase in which educational courses on sepsis recognition and on pre-analytical phase procedures (including direct incubation) were provided to ER staff. The third phase (1 January to 30 June 2016; after the intervention) again consisted of evaluation. Before the intervention, out of 24,738 admissions to the ER, 103 patients (0.4%) were identified as septic and had BCs drawn (359 BC bottles); 19 out of 103 patients (18.4%) had positive BCs. After the intervention, out of 24,702 admissions, 313 patients (1.3%) had BCs drawn (1,242 bottles); of these, 96 (30.7%) had positive BCs. Comparing the first and third periods, an increase in the percentage of patients with BCs collected (from 0.4% to 1.3% respectively, p < 0.0001) and an increase in the percentages of patients with true-positive BCs (from 0.08% to 0.39% of all patients evaluated respectively, p < 0.0001) were observed. The isolation of bacteria by BCs increased 3.25-fold after project implementation. These results can be principally ascribed to an improved awareness of sepsis in the staff associated with improved pre-analytical phase procedures in BC collection.     

Seroepidemiology,morbidity and vaccination strategies against rubella infection. Eight years experience in oltrepo pavese

Selective rubella vaccination of schoolgirls in Italy started 14 years ago following the United Kingdom strategy that was adopted in 1970. The aims of this program were to eliminate the risk of rubella among women of childbearing age, encourage the acquisition of immunity by natural infection during early childhood and allow the vaccine-induced antibody production by the circulating virus.On the basis of this program, between 1982 to 1990, a prospective serosurvey for rubella antibody in the province of Pavia was performed.The results showed a decline in the overall seropositivity rate for rubella antibodies from 57.7% in 1982 to 41.9% in 1984 followed by a remarkable increase in 1985 (53.3%) and in 1987 (56.5%). This trend was confirmed by the number of cases reported to the local Public Health Service. The results of this study provide further evidence of the need to change the current selective immunization policy in order to obtain a significant reduction of risk of the infection in the population.     

Effects of 3′-hydroxyfarrerol (IdB 1031), a novel flavonoid agent,on phagocyte products

The novel flavonoid compound 3-hydroxyfarrerol (IdB 1031) was tested in a number of in vitro experiments in order to ascertain its effects on some functions and products of human phagocytes. We found that IdB 1031 did not depress neutrophil phagocytosis and chemotaxis, whereas at a concentration of 10^–4 M it significantly (p}<0.05) reduced the fMLP-triggered neutrophil production of superoxide anion. At the same concentration, the compound decreased the release of neutrophil elastase and myeloperoxidase from neutrophils (p}<0.05). We also found evidence that IdB 1031 is a non competitive, reversible inhibitor of human neutrophil elastase (K _i 200m). Finally, IdB 1031 at the concentration of 10^–5 M significantly reduced the release of tumor necrosis factor- and interleukin-8 from monocytes (p < 0.05). We conclude that, in spite of the moderate activity displayed by IdB 1031, these findings add to our current knowledge on the spectrum of the antiinflammatory activities of flavonoids.     

Extent of allergic inflammation depends on intermittent versus continuous sensitization to house dust mite

Objective: House dust mite (HDM) exposure is used to model experimental asthma in mice. However, a direct comparison of inflammatory responses following continuous versus intermittent HDM exposure has not been reported. Therefore, we investigated whether the HDM dose at sensitization or challenge affects extent of inflammation in mice that were either continuously or intermittently sensitized with HDM.

Materials and methods: C57BL/6 mice received either 10 continuous exposures with 10?μg HDM per exposure or two intermittent HDM exposures over a period of two weeks and were subsequently challenged by three instillations with HDM during the third week. For the intermittent model, mice were sensitized with 1 or 10?μg HDM and challenged on three consecutive days with 1 or 10?μg HDM. Inflammatory cells in the bronchoalveolar lavage fluid and epithelial cell hyperplasia and mucous cell metaplasia were quantified.

Results: Significantly higher levels of inflammation and mucous cell metaplasia were observed when mice were sensitized intermittently compared with continuously. Intermittent sensitization and challenge with 10?μg HDM caused maximum inflammation, mucous cell metaplasia, and epithelial cell hyperplasia. However, sensitization with 1?μg HDM only also showed increased inflammation when challenged with 10?μg HDM.

Discussion: These findings suggest major differences in adaptive immunity, depending on the sensitization protocol.

Conclusions: Because of significant differences, the HDM sensitization protocol should be carefully considered when designing studies to investigate the underlying mechanisms of immunity in mouse models of asthma.     

Incidence of, and risk factors for, nosocomial infections among hematopoietic stem cell transplantation recipients, with impact on procedure-related mortality.

OBJECTIVES: To determine the incidence of, and risk factors for, nosocomial infections (NIs) occurring among hematopoietic stem cell transplantation (HSCT) recipients during hospitalization and to evaluate the impact of these NIs on patient outcome. DESIGN: A two-year prospective observational study in two HSCT units. PATIENTS: All patients admitted to the HSCT units between February 1997 and March 1999. SETTING: A teaching hospital. METHODS: After admission to the HSCT units, the patients were followed prospectively on a daily basis to collect all pertinent variables for the development of NIs. RESULTS: 49 NIs were identified in 34 of the 143 patients screened. The incidence of NIs and infected patients was 34.2% and 23.7%, respectively. The incidence density of NI was 8.96 per 1,000 patient-days. The most frequent NIs were bloodstream infections ([BSIs], 42.8%) and respiratory tract infections (28.6%). Other sites involved were as follows: eye (8.2%), urinary tract (6.1%), gastrointestinal tract (6.1%), skin (4.1%), ear (2%), and central venous catheter ([CVC], 2%). Because of the predominance and clinical relevance of BSIs, we examined both intrinsic and extrinsic risk factors associated with these infections. Independent risk factors for BSIs were allograft from matched unrelated or partially matched family donor, graft-versus-host disease (GVHD) prophylaxis without methotrexate (MTX), type of CVC, and duration of total parenteral nutrition. Four variables were independently associated with mortality occurring during hospitalization: culture-proven BSIs, advanced disease phase at transplant, type of transplant, and absence of MTX for GVHD prophylaxis. CONCLUSIONS: The study identified several factors associated with increased risk of BSIs among HSCT patients. Because BSIs are life-threatening complications for HSCT recipients, preventive measures aimed at reducing the incidence of these infections among patients given HSCT should be adopted.     

Comparison of the metabolic effects of mixed meal and standard oral glucose tolerance test on glucose,insulin and C-peptide response in healthy,impaired glucose tolerance,mild and severe non-insulin-dependent diabetic subjects

Dietary constituents other than glucose can influence insulin secretion in non-insulin-dependent diabetes mellitus and administration of a standard mixed meal has been proposed as a more physiological test in regard to human diet for evaluating the patient both at the time of diagnosis and during follow-up. This study was carried out to compare the effects of a standard meal and the oral glucose tolerance test on glucose, insulin and C-peptide plasma levels in four groups of subjects: healthy controls, subjects with impaired glucose tolerance, patients with mild non-insulin-dependent diabetes, and non-insulin-dependent diabetic patients with secondary failure to oral agents. Plasma glucose values were significantly higher after the oral glucose tolerance test than after the mixed meal in all four groups of subjects. Plasma insulin and C-peptide values were similar during the two tests in all groups of subjects except in non-insulin-dependent diabetics with secondary failure (flattened curves). Insulin and C-peptide responses per unit rise in blood glucose were significantly higher after the oral glucose tolerance test than after the mixed meal both in mild non-insulin-dependent diabetics (P<0.05 andP<0.05) and in non-insulin-dependent diabetics in secondary failure (P<0.01 andP<0.05). There was significant correlation between oral glucose tolerance test and mixed meal glucose incremental areas (r=0.511,P<0.001). The diagnostic relevance of the test was evaluated by comparing the 120 min plasma glucose levels following mixed meal and oral glucose tolerance test: there was a significant correlation between the values in the two tests (r=0.956,P<0.001); the differences among the four groups were statistically significant and there was a partial overlap between healthy controls and impaired glucose tolerance patients: 93±3 versus 111±7 mg/dl for controls; 107±3 versus 161±5 mg/dl for impaired glucose tolerance patients; 204±11 versus 284±12 mg/dl for mild non-insulin-dependent diabetics; 309±9 versus 440±17 mg/dl for NID diabetics in secondary failure. The sensitivity of the test was 73% and specificity 100%. The mixed meal is proposed for clinical practice as a more physiological test than the standard oral glucose tolerance test for further characterization and longitudinal evaluation of patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus.