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Bothamley G.H.,University of London | Ruhwald M.,Copenhagen University | Goletti D.,National Institute For Infectious Diseases L Spallanzani Inmi
European Respiratory Monograph | Year: 2012

The diagnosis of tuberculosis (TB) depends on sputum-smear examination, mycobacterial culture and tuberculin skin testing (TST). Future diagnosis requires near-patient tests and early recognition of drug-resistant (DR) TB. Nucleic acid amplification techniques (NAAT) can detect approximately 100 bacilli?mL-1 and have moved from the laboratory into the field. Sensitivity can be improved by detecting proteins, using mass spectrometry, and their function, using reporter enzymes. Ultimately, microfluidics will permit reactions in restricted spaces with the potential to measure single molecules or sequence strains of Mycobacterium tuberculosis directly. Metabolic products released by TB and the human response to infection can be described by a characteristic metabolome and volatome of exhaled air. Interferon-γ release assays (IGRA) are blood tests that indicate the immune response to the few bacilli responsible for latent TB infection (LTBI). Their sensitivity may be improved by cytokines released by activated macrophages (inducible protein-10). The pattern of the immune response to many or all TB antigens, the immunome, may in future distinguish between active disease and latent infection. © ERS 2012.


Dimonte S.,University of Rome Tor Vergata | Dimonte S.,Biomolecular Laboratory | Dimonte S.,Polytechnic University of Mozambique | Babakir-Mina M.,University of Rome Tor Vergata | And 4 more authors.
Infection | Year: 2013

Purpose: Integrase (IN) is an enzyme produced by human immunodeficiency virus (HIV)-1 that enables its genetic material to be integrated into the DNA of the infected cell. Still now, few data are available with detailed analysis of the natural IN polymorphisms of HIV-1 subtype-C in datasets retrieved from antiretroviral-naïve patients; this study focuses on these polymorphisms. Methods: The analysis included 335 HIV-1 subtype-C IN sequences (one per patient). Multi-alignment of IN sequences was performed, and for the definition of a polymorphism, only amino acid changes with prevalence ≥3 % among treatment-naïve patients were considered. Results: Seventy IN amino acid positions were fully conserved. Differently, forty-six IN amino acid polymorphic positions were observed, 12 within the N-terminal domain and 13 within the C-terminal domain. In the DDE-catalytic motif, only one mutation per site (D64G/D116G/E152K) was found, while a low variability (<1 %) was observed for IN positions interacting with LEDGF/p75. A major drug resistance mutation for raltegravir (RAL) and elvitegravir (EVG), Q148H, was retrieved from one patient and another RAL primary resistance mutation, Y143H, was also retrieved from another patient. Conclusions: The results from the IN sequences analyzed underlined that some unexpected baseline substitutions affecting the susceptibility to RAL/EVG could be detected in drug-naïve individuals, and, therefore, it should be genotyped before the consideration of HIV-1 IN inhibitors (INIs). The impact of these mutations on the baseline drug susceptibility of HIV-1 subtype-C to INIs may need to be addressed prior to the introduction of these drugs in some Asiatic and African countries. © 2013 Springer-Verlag Berlin Heidelberg.


Urso R.,National Institute For Infectious Diseases L Spallanzani Inmi | Bevilacqua N.,National Institute For Infectious Diseases L Spallanzani Inmi | Gentile M.,National Institute For Infectious Diseases L Spallanzani Inmi | Biagioli D.,National Institute For Infectious Diseases L Spallanzani Inmi | Lauria F.N.,National Institute For Infectious Diseases L Spallanzani Inmi
Journal of Medical Case Reports | Year: 2011

Introduction. 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 (H1N 1) infection. Case presentation. A 23-year-old Caucasian woman was hospitalized at the "L. Spallanzani" National Institute for Infectious Diseases in Rome, Italy. Clinical and radiological features including laboratory findings of this case are illustrated. Notably, the patient had fever, severe abdominal pain, hematuria, arthritis, and purpuric manifestations associated with a normal platelet count. Nasopharyngeal and rectal swabs revealed pandemic 2009 (H1N1) virus by reverse-transcriptase-polymerase-chain-reaction assay. Routine laboratory analyses showed elevated inflammatory parameters. The autoimmune panel tests were normal. Steroid therapy associated with oseltamivir achieved an evident and rapid improvement. On day seven the patient chose to leave the hospital against medical advice. Conclusion: Complications related to influenza infection can be life threatening, particularly in immunocompromised patients. Henoch-Schönlein purpura triggered by the novel influenza virus infection could be an attractive pathogenetic hypothesis. We have discussed both the diagnosis and the challenge of therapy protocols. Steroid therapy is part of the management of severe vasculitis. Our case suggests that steroid therapy associated with antivirals can prevent the risk of further complications such as hemorrhage and multi-organ failure during severe vasculitis, without enhancing the virulence of the influenza virus. The possible role of pandemic 2009 (H 1N1) in the pathogenesis of hemorrhagic manifestations should be further investigated. © 2011 Urso et al; licensee BioMed Central Ltd.

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