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Meera Chand - One of the best experts on this subject based on the ideXlab platform.

  • global outbreak of severe mycobacterium Chimaera disease after cardiac surgery a molecular epidemiological study
    Lancet Infectious Diseases, 2017
    Co-Authors: Jakko Van Ingen, Barbara Hasse, Peter M Keller, Thomas Kohl, Katharina Kranzer, Anna K Szafranska, Doris Hillemann, Meera Chand
    Abstract:

    Summary Background Since 2013, over 100 cases of Mycobacterium Chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater–cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. Methods We included 24 M Chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M Chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M Chimaera genomes. Findings Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M Chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. Interpretation HCU contamination with M Chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M Chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. Funding Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

  • microbiological problems and biofilms associated with mycobacterium Chimaera in heater cooler units used for cardiopulmonary bypass
    Journal of Hospital Infection, 2017
    Co-Authors: Jimmy Walker, Mark I Garvey, Ginny Moore, Samuel Collins, Simon Parks, Theresa Lamagni, Grace Smith, Lincoln Dawkin, Simon D Goldenberg, Meera Chand
    Abstract:

    Summary The role of heater–cooler units (HCUs) in the transmission of Mycobacterium Chimaera during open heart surgery has been recognized since 2013. Subsequent investigations uncovered a remarkable global outbreak reflecting the wide distribution of implicated devices. HCUs are an essential component of cardiopulmonary bypass operations and their withdrawal would severely affect capacity for life-saving cardiac surgery. However, studies have demonstrated that many HCUs are contaminated with a wide range of micro-organisms, including M. Chimaera and complex biofilms. Whole genome sequencing of M. Chimaera isolates recovered from one manufacturer's HCUs, worldwide, has demonstrated a high level of genetic similarity, for which the most plausible hypothesis is a point source contamination of the devices. Dissemination of bioaerosols through breaches in the HCU water tanks is the most likely route of transmission and airborne bacteria have been shown to have reached the surgical field even with the use of ultraclean theatre ventilation. Controlling the microbiological quality of the water circulating in HCUs and reducing biofilm formation has been a major challenge for many hospitals. However, enhanced decontamination strategies have been recommended by manufacturers, and, although they are not always effective in eradicating M. Chimaera from HCUs, UK hospitals have not reported any new cases of M. Chimaera infection since implementing these mitigation strategies. Water safety groups in hospitals should be aware that water in medical devices such as HCUs may act as a vector in the transmission of potentially fatal water-borne infections.

  • insidious risk of severe mycobacterium Chimaera infection in cardiac surgery patients
    Clinical Infectious Diseases, 2017
    Co-Authors: Katharina Kranzer, Meera Chand, Ginny Moore, Samuel Collins, Simon Parks, Theresa Lamagni, Jessica Hedge, Carlos Del Ojo Elias
    Abstract:

    BACKGROUND An urgent UK investigation was launched to assess risk of invasive Mycobacterium Chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and The Netherlands. METHODS Parallel investigations were pursued: (1) identification of cardiopulmonary bypass-associated M. Chimaera infection through national laboratory and hospital admissions data linkage; (2) cohort study to assess patient risk; (3) microbiological and aerobiological investigations of heater-coolers in situ and under controlled laboratory conditions; and (4) whole-genome sequencing of clinical and environmental isolates. RESULTS Eighteen probable cases of cardiopulmonary bypass-associated M. Chimaera infection were identified; all except one occurred in adults. Patients had undergone valve replacement in 11 hospitals between 2007 and 2015, a median of 19 months prior to onset (range, 3 months to 5 years). Risk to patients increased after 2010 from <0.2 to 1.65 per 10000 person-years in 2013, a 9-fold rise for infections within 2 years of surgery (rate ratio, 9.08 [95% CI, 1.81-87.76]). Endocarditis was the most common presentation (n = 11). To date, 9 patients have died. Investigations identified aerosol release through breaches in heater-cooler tanks. Mycobacterium Chimaera and other pathogens were recovered from water and air samples. Phylogenetic analysis found close clustering of strains from probable cases. CONCLUSIONS We identified low but escalating risk of severe M. Chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

Philip D Greenberg - One of the best experts on this subject based on the ideXlab platform.

  • cytoplasmic domains of the interleukin 2 receptor β and γ chains mediate the signal for t cell proliferation
    Nature, 1994
    Co-Authors: Brad H Nelson, James D Lord, Philip D Greenberg
    Abstract:

    THE interleukin-2 receptor (IL-2R) consists of three distinct chains (α, β, γ) which bind IL-2 and generate a proliferative signal in T cells1. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2Rβ or IL-2Rγ and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF) 2. We report here that binding of SCF to the β-chain Chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the β- and γ-chain Chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor β and γ chains constructed with the heterodimeric extracellular regions of the granulocyte–macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2Rβ and -γ appears necessary and sufficient for signalling in T cells.

  • cytoplasmic domains of the interleukin 2 receptor β and γ chains mediate the signal for t cell proliferation
    Nature, 1994
    Co-Authors: Brad H Nelson, James D Lord, Philip D Greenberg
    Abstract:

    The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha, beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2R beta or IL-2R gamma and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF). We report here that binding of SCF to the beta-chain Chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the beta- and gamma-chain Chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells.

Hugo Sax - One of the best experts on this subject based on the ideXlab platform.

  • detection limit of mycobacterium Chimaera in water samples for monitoring medical device safety insights from a pilot experimental series
    Journal of Hospital Infection, 2018
    Co-Authors: Peter W Schreiber, Nora Kohler, Rosita Cervera, Barbara Hasse, Hugo Sax, Peter M Keller
    Abstract:

    Summary Background A growing number of Mycobacterium Chimaera infections after cardiosurgery have been reported by several countries. These potentially fatal infections were traced back to contaminated heater–cooler devices (HCDs), which use water as a heat transfer medium. Aerosolization of water contaminated with M. Chimaera from HCDs enables airborne transmission to patients undergoing open chest surgery. Infection control teams test HCD water samples for mycobacterial growth to guide preventive measures. The detection limit of M. Chimaera in water samples, however, has not previously been investigated. Aim To determine the detection limit of M. Chimaera in water samples using laboratory-based serial dilution tests. Methods An M. Chimaera strain representative of the international cardiosurgery-associated M. Chimaera outbreak was used to generate a logarithmic dilution series. Two different water volumes, 50 and 1000 mL, were inoculated, and, after identical processing (centrifugation, decantation, and decontamination), seeded on mycobacteria growth indicator tube (MGIT) and Middlebrook 7H11 solid media. Findings MGIT consistently showed a lower detection limit than 7H11 solid media, corresponding to a detection limit of ≥1.44 × 104 cfu/mL for 50 mL and ≥2.4 cfu/mL for 1000 mL water samples. Solid media failed to detect M. Chimaera in 50 mL water samples. Conclusion Depending on water volume and culture method, major differences exist in the detection limit of M. Chimaera. In terms of sensitivity, 1000 mL water samples in MGIT media performed best. Our results have important implications for infection prevention and control strategies in mitigation of the M. Chimaera outbreak and healthcare water safety in general.

  • global health estimate of invasive mycobacterium Chimaera infections associated with heater cooler devices in cardiac surgery
    Emerging Infectious Diseases, 2018
    Co-Authors: Rami Sommerstein, Barbara Hasse, Hugo Sax, Jonas Marschall, Michele Genoni, Matthias Schlegel, Andreas F Widmer
    Abstract:

    Investigations of a worldwide epidemic of invasive Mycobacterium Chimaera associated with heater-cooler devices in cardiac surgery have been hampered by low clinical awareness and challenging diagnoses. Using data from Switzerland, we estimated the burden of invasive M. Chimaera to be 156-282 cases/year in 10 major cardiac valve replacement market countries.

  • Global Health Estimate of Invasive Mycobacterium Chimaera Infections Associated with Heater–Cooler Devices in Cardiac Surgery
    'Centers for Disease Control and Prevention (CDC)', 2018
    Co-Authors: Rami Sommerstein, Barbara Hasse, Hugo Sax, Jonas Marschall, Michele Genoni, Matthias Schlegel, Andreas F Widmer
    Abstract:

    Investigations of a worldwide epidemic of invasive Mycobacterium Chimaera associated with heater–cooler devices in cardiac surgery have been hampered by low clinical awareness and challenging diagnoses. Using data from Switzerland, we estimated the burden of invasive M. Chimaera to be 156–282 cases/year in 10 major cardiac valve replacement market countries

  • transmission of mycobacterium Chimaera from heater cooler units during cardiac surgery despite an ultraclean air ventilation system
    Emerging Infectious Diseases, 2016
    Co-Authors: Rami Sommerstein, Guido V Bloemberg, Philipp Kohler, Stefan P Kuster, Christian Ruegg, Hugo Sax
    Abstract:

    Heater-cooler units (HCUs) were recently identified as a source of Mycobacterium Chimaera causing surgical site infections. We investigated transmission of this bacterium from HCUs to the surgical field by using a thermic anemometer and particle counter, videotape of an operating room equipped with an ultraclean laminar airflow ventilation system, and bacterial culture sedimentation plates in a nonventilated room. Smoke from the HCU reached the surgical field in 23 s by merging with ultraclean air. The HCU produced on average 5.2, 139, and 14.8 particles/min in the surgical field at positions Off, On/oriented toward, and On/oriented away, respectively. Culture plates were positive for M. Chimaera <5 m from the HCU in the test room. These experiments confirm airborne transmission of M. Chimaera aerosols from a contaminated HCU to an open surgical field despite ultraclean air ventilation. Efforts to mitigate infectious risks during surgery should consider contamination from water sources and airflow-generating devices.

  • prolonged outbreak of mycobacterium Chimaera infection after open chest heart surgery
    Clinical Infectious Diseases, 2015
    Co-Authors: Hugo Sax, Barbara Hasse, Guido V Bloemberg, Rami Sommerstein, Philipp Kohler, Yvonne Achermann, Matthias Rossle, Volkmar Falk, Stefan P Kuster, Erik C Bottger
    Abstract:

    BACKGROUND:  Invasive Mycobacterium Chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. METHODS:  We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium Chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. Chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. RESULTS:  We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. Chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium Chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. Chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. Chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. CONCLUSIONS:  The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. Chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.

Mark I Garvey - One of the best experts on this subject based on the ideXlab platform.

  • decontamination of an extracorporeal membrane oxygenator contaminated with mycobacterium Chimaera
    Infection Control and Hospital Epidemiology, 2017
    Co-Authors: Mark I Garvey, Natalie Phillips, C W Bradley, Elisabeth Holden
    Abstract:

    Water samples taken from extracorporeal membrane oxygenator (ECMO) devices used at University Hospitals Birmingham yielded high total viable counts (TVCs) containing a variety of microorganisms, including M. Chimaera . Disinfection resulted in the reduction of TVCs and eradication of Mycobacterium Chimaera . Weekly disinfection and water sampling are required to manage the water quality in these devices. Infect Control Hosp Epidemiol 2017;38:1244–1246

  • decontamination of an extracorporeal membrane oxygenator contaminated with mycobacterium Chimaera
    Infection Control and Hospital Epidemiology, 2017
    Co-Authors: Mark I Garvey, Natalie Phillips, C W Bradley, Elisabeth Holden
    Abstract:

    Water samples taken from extracorporeal membrane oxygenator (ECMO) devices used at University Hospitals Birmingham yielded high total viable counts (TVCs) containing a variety of microorganisms, including M. Chimaera . Disinfection resulted in the reduction of TVCs and eradication of Mycobacterium Chimaera . Weekly disinfection and water sampling are required to manage the water quality in these devices. Infect Control Hosp Epidemiol 2017;38:1244–1246

  • microbiological problems and biofilms associated with mycobacterium Chimaera in heater cooler units used for cardiopulmonary bypass
    Journal of Hospital Infection, 2017
    Co-Authors: Jimmy Walker, Mark I Garvey, Ginny Moore, Samuel Collins, Simon Parks, Theresa Lamagni, Grace Smith, Lincoln Dawkin, Simon D Goldenberg, Meera Chand
    Abstract:

    Summary The role of heater–cooler units (HCUs) in the transmission of Mycobacterium Chimaera during open heart surgery has been recognized since 2013. Subsequent investigations uncovered a remarkable global outbreak reflecting the wide distribution of implicated devices. HCUs are an essential component of cardiopulmonary bypass operations and their withdrawal would severely affect capacity for life-saving cardiac surgery. However, studies have demonstrated that many HCUs are contaminated with a wide range of micro-organisms, including M. Chimaera and complex biofilms. Whole genome sequencing of M. Chimaera isolates recovered from one manufacturer's HCUs, worldwide, has demonstrated a high level of genetic similarity, for which the most plausible hypothesis is a point source contamination of the devices. Dissemination of bioaerosols through breaches in the HCU water tanks is the most likely route of transmission and airborne bacteria have been shown to have reached the surgical field even with the use of ultraclean theatre ventilation. Controlling the microbiological quality of the water circulating in HCUs and reducing biofilm formation has been a major challenge for many hospitals. However, enhanced decontamination strategies have been recommended by manufacturers, and, although they are not always effective in eradicating M. Chimaera from HCUs, UK hospitals have not reported any new cases of M. Chimaera infection since implementing these mitigation strategies. Water safety groups in hospitals should be aware that water in medical devices such as HCUs may act as a vector in the transmission of potentially fatal water-borne infections.

Elisabeth Holden - One of the best experts on this subject based on the ideXlab platform.