Ralstonia spp, an environmental microorganism, has been occasionally associated with healthcare infections. The aim of this study was to investigate an outbreak caused by Ralstonia mannitolilytica in oncology patients. Case definition: Oncology outpatients attending a day ward, with positive blood and/or central venous catheter (CVC) culture for Ralstonia spp from September 2013 – June 2014. We analysed medical records, procedures and environmental samples. R. mannitolilytica was identified by 16S rRNA sequencing, and typed by Pulsed Field Gel Electrophoresis (PFGE); resistance to carbapenemes was investigated by phenotypic and molecular methods. The patients (N = 22) had different malignancies and received different therapy; all had a CVC and 16 patients presented chills and/or fever. R. mannitolilytica was isolated from both blood and CVC (n = 12) or only blood (n = 6) or CVC tips (n = 4). The isolates had indistinguishable PFGE profile, and showed resistance to carbapenems. All the isolates were negative for carbapenemase genes while phenotypic tests suggests the presence of an AmpC β-lactamase activity,responsible for carbapenem resistance. All patients had had CVC flushed with saline to keep the venous access pervious or before receiving chemotherapy at various times before the onset of symptoms. After the first four cases occurred, the multi-dose saline bottles used for CVC flushing were replaced with single-dose vials; environmental samples were negative for R. mannitolilytica. Although the source of R. mannitolilytica remains unidentified, CVC flushing with contaminated saline solution seems to be the most likely origin of R. mannitolilytica CVC colonization and subsequent infections. In order to prevent similar outbreaks we recommend removal of any CVC that is no longer necessary and the use of single-dose solutions for any parenteral treatment of oncology patients.

In Italy, TB notifications in foreign-born people (FBP) are steadily increasing. To investigate this issue we did a meta-analysis on risk factors for FBP people. A systematic search was performed in PubMed and EMBASE from Jan-1980 to Jan-2013. We analysed HIV status, previous TB-treatment, intravenous drug use and alcohol abuse, and multidrug resistant TB. Odd ratio was used as a measure of effect. One and two-stages approaches were used. In the main analysis we used a 2-stages approach to include studies with only aggregate estimates. Among 1996 references, 18 fulfilled inclusion criteria. In TB-affected FBP people positive HIV-status was about 3 times higher than among Italians, after 1996 when combined antiretroviral therapy for HIV was introduced (OR: 2.91; 95%CI: 1.37; 6.17). No association was found between FBP and intravenous drug users in adults; after 1-stage meta-analysis foreign born people from highly endemic countries had a 4 times higher risk to be multidrug resistant TB than Italian people. Finally, TB-affected FBP were less likely than Italians to be alcoholics (OR: 0.10 95%CI: 0.01; 0.84) or of having received previous TB-treatment (OR: 0.55; 95%CI: 0.43; 0.71). An association of multidrug resistant TB with immigrant status as well as an association of Tuberculosis with HIV-positive status in foreign-born people are major findings of this analysis. Drugs and alcohol abuse do not appear to be risk factors for TB in FBP, however they cannot be discharged since may depend on cultural traditions and their role may change in the future along with the migratory waves. An effective control of TB risk factors among migrants is crucial to obtain the goal of TB eradication.

Autoreactive lymphocytes are thought to contribute to tissue injury in the pathogenesis of multiple sclerosis (MS). However, reliable biomarkers reflecting myelin-specific immune responses and disease activity remain limited. In HLA-DRB1*15:01-positive individuals, the myelin basic protein (MBP) epitope MBP85–99 represents a well-characterized immunodominant target of CD4+ T cells. Using classical spectratyping, we characterized the peripheral T-cell receptor (TCR) β-chain repertoire reactive to MBP85–99 in individuals with MS, according to their HLA-DRB1 haplotypes. Selected rearrangements were further evaluated in cerebrospinal fluid (CSF), cytokine-defined T-cell subsets, and longitudinal samples collected during interferon beta-1a treatment. A restricted set of shared (“public”) MBP85–99-reactive TCR rearrangements was identified in individuals with MS and differed from the repertoire observed in healthy controls. These TCRs were more frequently detected during periods of active disease than during remission. Two disease-associated public rearrangements were enriched in active MS, whereas one rearrangement was preferentially observed in healthy controls. HLA-DRB1*15:01-restricted MBP85–99-specific public TCR signatures were associated with inflammatory disease activity in MS and may help distinguish pathogenic from non-pathogenic autoreactive responses. In a longitudinal sub-cohort (n = 15, ~10-year follow-up), the RSI of the principal disease-associated rearrangement TRBV19–TRBJ2.4 correlated positively with cumulative relapse burden (Spearman ρ = 0.782, p = 0.002), providing preliminary evidence that these TCR signatures reflect long-term inflammatory disease activity. These findings support further validation of antigen-specific TCR profiling as a biomarker strategy in MS using contemporary high-throughput immune repertoire technologies.