Background: blood cytokines and chemokines have been proposed as biomarkers for tuberculosis (TB). Recently, some immune mediators found in the urine of patients with renal dysfunctions have also been suggested as potential biomarkers. Finding biomarkers for TB in urine would present several advantages over blood in terms of collection and safety. The objective of this study was to investigate the presence of cytokines and chemokines in the urine of patients with pulmonary TB at the time of diagnosis. In a subgroup, the evaluation was also performed during TB treatment and at therapy completion. Patients with lung diseases other than TB, and healthy subjects were also enrolled.Methods: urine samples from 138 individuals, after exclusion of renal dysfunctions, were collected during an 18 month-period. Among them, 58 received a diagnosis of pulmonary TB, 28 resulted having lung diseases other than TB, and 34 were healthy subjects. Moreover, 18 TB patients, 9 of whom were tested 2 months after AFB smear sputum reversion and 9 of whom were cured of TB were also included. Cytokines and chemokines in urine were evaluated using a Cytometric-Bead-Array-Flex-Set. IP-10 detection in 49 subjects was also carried out in parallel by using an Enzyme Linked ImmunoSorbent Assay (ELISA).Results: IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES were poorly detected in all urine samples. Conversely, IP-10 was consistently detected in urine and its level was significantly increased in patients with lung disease compared to healthy subjects (p < 0.001). Increased IP-10 levels were found in both pulmonary TB and lung diseases other than TB. Moreover lower IP-10 levels were found in cured-TB patients compared to the levels at the time of diagnosis, and this difference was close to significance (p = 0.06). Interestingly, we demonstrated a significant correlation between the data obtained by flow cytometry and ELISA (r²0.82, p < 0.0001).Conclusions: IP-10, in contrast to IFN-γ, TNF-α, IL-2, IL-8, MIP-1α, MIP-1β and RANTES, is detectable in the urine of patients with pulmonary diseases in the absence of renal dysfunctions. Moreover, the IP-10 level in cured-TB patients is comparable to that found in healthy subjects. More studies are needed to further investigate the clinical utility of these findings.

Background: Computer Tomography (CT) is considered the gold standard for assessing the morphological changes of lung parenchyma. Although novel CT techniques have substantially decreased the radiation dose, radiation exposure is still high. Magnetic Resonance Imaging (MRI) has been established as a radiation- free alternative to CT for several lung diseases, but its role in infectious diseases still needs to be explored further. Therefore, the purpose of our study was to compare MRI with high resolution CT (HRCT) for assessing pulmonary tuberculosis. Methods: 50 patients with culture-proven pulmonary tuberculosis underwent chest HRCT as the standard of reference and were evaluated by MRI within 24 h after HRCT. Altogether we performed 60 CT and MRI examinations, because 10 patients were also examined by CT and MRI at follow- up. Pulmonary abnormalities, their characteristics, location and distribution were analyzed by two readers who were blinded to the HRCT results. Results: Artifacts did not interfere with the diagnostic value of MRI. Both HRCT and MRI correctly diagnosed pulmonary tuberculosis and identified pulmonary abnormalities in all patients. There were no significant differences between the two techniques in terms of identifying the location and distribution of the lung lesions, though the higher resolution of MRI did allow for better identification of parenchymal dishomogeneity, caseosis, and pleural or nodal involvement. Conclusion: Technical developments and the refinement of pulse sequences have improved the quality and speed of MRI. Our data indicate that in terms of identifying lung lesions in non-AIDS patients with non- miliary pulmonary tuberculosis, MRI achieves diagnostic performances comparable to those obtained by HRCT but with better and more rapid identification of pulmonary tissue abnormalities due to the excellent contrast resolution.

To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases "L. Spallanzani" as indirect indicator of usage of both tests under actual programmatic conditions. Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute "L. Spallanzani" showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results.

Background: The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm. Methods: An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information. Results: Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding. Conclusions: Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.

In the current Ebola epidemic in Western Africa, many healthcare workers have become infected. Some of these have been medically evacuated to hospitals in Europe and the USA. These clinical experiences provide unique insights into the course of Ebola virus disease under optimized condition within high level isolation units. A 50-year-old Caucasian male physician contracted Ebola virus diseases in Sierra Leone and was medically evacuated to Italy. Few days after the admission the course of the illness was characterized by severe gastro-intestinal symptoms followed by respiratory failure, accompanied by pulmonary infiltration and high Ebola viral load in the bronchial aspirate and Plasmodium vivax co-infection. The patient received experimental antiviral therapy with favipiravir, convalescent plasma and ZMAb. Ebola viral load started to steadily decrease in the blood after ZMAb administration and became undetectable by day 19 after admission, while it persisted longer in urine samples. No temporal association was observed between viral load decay in plasma and administration of favipiravir. The patient completely recovered and was discharged 39 days after admission. This is the first case of Ebola-related interstitial pneumonia documented by molecular testing of lung fluid specimens. This reports underlines the pivotal role of fluid replacement and advanced life support with mechanical ventilation in the management of patients with Ebola virus diseases respiratory failure. Beside our finding indicates a close temporal association between administration of cZMAb and Ebola virus clearance from blood.

The influenza virus infection may be severe in non-immune people. Common complications of influenza virus include upper and lower respiratory tract infections, otitis media, myocarditis, acute respiratory distress syndrome and multi-organ failure. There have been cases of vasculitis following influenza vaccination, and rash and acute purpura may occur in certain viral infections. To the best of our knowledge, there are no reports concerning cases of systemic vasculitis associated with pandemic 2009 (H1N1) infection.