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  • Infectiousness of patients with smear-negative pulmonary tuberculosis, assessed by Real-time Polymerase Chain Reaction, Xpert®MTB/RIF
    J. Infect. (IF 5.099) Pub Date : 2020-01-16
    Daniel Camprubí; Aina Gomila; Maria D. Grijota-Camino; Laura Soldevila; Maria J. Luque; Fernando Alcaide; Jordi Dorca; Miguel Santin

    Currently, pulmonary tuberculosis (TB) isolation recommendations are based on serial sputum smear microscopy. To assess infectiousness of smear-negative/GeneXpert-positive (Sm-/GXpert+) pulmonary TB, we evaluated 511 contacts of pulmonary TB patients attended at a teaching hospital in Spain (2010-2018). There were no statistically significant differences in rates of Mycobacterium tuberculosis infection (46.2% contacts of smear-positive and 34.6% contacts of Sm-/GXpert+ pulmonary TB patients, p=0.112). Sm-/GXpert+ pulmonary TB poses a substantial risk of transmission of M. tuberculosis infection. Our results add evidence to support including Real-time Polymerase Chain Reaction (Xpert®MTB/RIF) in the work-up diagnosis of suspected pulmonary TB cases to make decisions on air-borne isolation.

    更新日期:2020-01-16
  • Efficacy and Safety of a Comprehensive Educational Antimicrobial Stewardship Program Focused on Antifungal Use
    J. Infect. (IF 5.099) Pub Date : 2020-01-15
    Guillermo Martín-Gutiérrez; Germán Peñalva; Maite Ruiz-Pérez de Pipaón; Manuela Aguilar; María Victoria Gil-Navarro; José Luis Pérez-Blanco; María Antonia Pérez-Moreno; Rosario Amaya-Villar; Carmen Ferrándiz-Millón; María L. Gascón; Walter A. Goycochea-Valdivia; Manuel E. Jiménez-Mejías; María Dolores Navarro; José A. Lepe; Rocío Alvarez-Marín; Olaf Neth; Ana B. Guisado-Gil; Carmen Infante-Domínguez; José M. Cisneros

    Objective Few data exist regarding the impact of antimicrobial stewardship programs on antifungal use. We evaluated the efficacy and safety of a comprehensive long-term antimicrobial stewardship program (ASP) focused on antifungal use. Methods : During a 9-year period, we quarterly assessed antifungal consumption, incidence density of hospital-acquired candidemia, Candida spp. distribution, antifungal resistance, and crude death rate per 1000 occupied bed days (OBDs) of hospital-acquired candidemia. We performed segmented regression analysis of interrupted time series. Results A significant change in trend was observed for antifungal consumption, with a sustained reduction of -0.87% per quarter (95% confidence interval [CI], -1.36 – -0.38, p<0.001), accounting for a final reduction of -38.4%. The main reduction was produced in fluconazole, with a sustained reduction of -1.37% per quarter (95%CI, -1.96 – -0.68, p<0.001). The incidence density of hospital-acquired candidemia decreased, with a change in slope of -5.06% cases per 1000 OBDs per year (95%CI, -8.23 – -1.77, p=0.009). The 14-day crude death rate per 1000 OBDs dropped from 0.044 to 0.017 (-6.36% deaths per 1000 OBDs per year; 95%CI, -13.45 - 1.31, p=0.09). Conclusions This ASP has succeeded in optimizing the use of antifungal with a long-lasting reduction without increasing the incidence, neither the mortality, of hospital-acquired candidemia.

    更新日期:2020-01-15
  • Clinical and economic burden of community-onset multidrug-resistant infections requiring hospitalization
    J. Infect. (IF 5.099) Pub Date : 2020-01-07
    López-Montesinos I; Domínguez-Guasch A; Gómez-Zorrilla S; Duran-Jordà X; Sivero-Parès A; Arenas-Miras MM; Montero MM; Sorli Redó L; Grau S; Horcajada JP

    Objectives : To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (CO-HCA) multidrug-resistant (MDR) infections requiring hospitalization. Methods : Case-control study. Adults admitted with CA or CO-HCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption. Results : 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p<0.001) and MDR hospitalization costs almost doubled those in the non-MDR group. MDR infections were associated with higher antimicrobial costs. Conclusions : Worse economic outcomes were identified with community-onset MDR infections. MDR was associated with worse clinical outcomes but mainly due to higher comorbidity of patients in MDR group, rather than multidrug resistance.

    更新日期:2020-01-07
  • Etiology, clinical presentation, outcome and the effect of initial management in immunocompromised patients with community acquired bacterial meningitis
    J. Infect. (IF 5.099) Pub Date : 2020-01-03
    Martin Glimåker; Pontus Naucler; Jan Sjölin

    Objectives . The aim was to analyze differences in clinical presentation, etiology, management, and outcome between immunocompromised and immunocompetent patients with acute bacterial meningitis (ABM). Methods . Data were extracted from 1056 adult ABM patients prospectively registered in the national Swedish quality register for ABM during 2008-2017. Primary endpoint was 30-day mortality and secondary endpoints 90-day mortality and unfavourable outcome. Results . An immunocompromised state was observed in 352 (33%) of the 1056 patients. Streptococcus pneumoniae dominated in both immunocompromised and immunocompetent patients (53% in both groups), whereas L monocytogenes occurred in 11% and 2%, respectively. The unadjusted odds ratio (OR) for 30-day mortality in immunocompromised compared to immunocompetent patients was 1.68 (95% confidence interval (CI): 1.07-2.63). Adjusted for age, sex, and mental status on admission the OR was 1.34 (CI: 0.82-2.21). Adjusted also for time to antibiotic treatment and corticosteroids the OR was 1.10 (CI: 0.59-2.05), and in patients without Listeria meningitis 0.98 (CI: 0.50-1.90). Although, the ORs were higher for 90-day mortality and unfavourable outcome the effects of adjustments were similar. Conclusion . Mortality in immunocompromised patients with ABM is only moderately increased unless caused by Listeria. This difference is further reduced in patients given early antibiotic treatment and adjunctive corticosteroids. Funding : This work was supported by Stockholm County Council.

    更新日期:2020-01-04
  • Invasive meningococcal disease: timing and cause of death in England, 2008-2015
    J. Infect. (IF 5.099) Pub Date : 2020-01-02
    Kazim Beebeejaun; Sydel R. Parikh; Helen Campbell; Steve Gray; Ray Borrow; Mary E. Ramsay; Shamez N. Ladhani

    Background Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia, with death often occurring rapidly after onset of the first symptoms. Later death can also occur later, but may be due to other causes, such as underlying comorbidities. The study aimed to assess the timing and cause of death in patients with invasive meningococcal disease (IMD) prior to the introduction of two new meningococcal immunisation programmes in England Methods Public Health England (PHE) conducts IMD surveillance in England through its national meningococcal reference unit. Laboratory-confirmed IMD cases diagnosed during 2008-2015 were linked to weekly and annual electronic death registration records as well as the online Patient Demographic Service (PDS). Results Overall, 6,734 of 6,808 (99%) laboratory-confirmed IMD cases matched to PDS, including 668 fatalities. Of these, 667 linked to an annual death registrations compared to 405 to weekly registrations. In total, 429/667 (64.3%) of all deaths and 428/502 (85.3%) of IMD-related deaths occurred within one day of diagnosis. At 30 days after IMD diagnosis, 498/667 (74.7%) had died and 98.4% (490/498) were IMD-related. Serogroup B contributed to 64% (323/502) of IMD-related deaths, followed by serogroup W (84/502, 17%) and serogroup Y (70/502, 14%). Deaths occurring after 30 days were less likely to be IMD-related, mainly among ≥65 year-olds, with malignancy, chronic respiratory and cardiac conditions predominating. Conclusions Most IMD-related deaths occurred within a day of diagnosis and nearly all IMD-related deaths occurred within 30 days of diagnosis. The rapidity of death highlights the importance of prevention through vaccination.

    更新日期:2020-01-02
  • The efficacy of topical agents used in wounds for managing chronic biofilm infections: A systematic review
    J. Infect. (IF 5.099) Pub Date : 2019-12-31
    SchwarzerS; James GA; Goeres D; Bjarnsholt T; Vickery K; Percival SL; Stoodley P; Schultz G; Jensen SO; Malone M

    Objectives Clinicians have increasingly adopted the widespread use of topical agents to manage chronic wound infections, despite limited data on their effectiveness in vivo. This study sought to evaluate the evidence for commonly employed topical agents used in wounds for the purpose of treating chronic infections caused by biofilm. Method We included in vitro, animal and human in vivo studies where topical agents were tested for their efficacy against biofilms, for use in wound care. For human studies, we only included those which utilised appropriate identification techniques for visualising and confirming the presence of biofilms. Result A total of 640 articles were identified, with 43 included after meeting eligibility. In vitro testing accounted for 90% (n = 39) of all included studies, five studies using animal models and three human in vivo studies. Sixteen different laboratory models were utilised, with the most frequent being the minimum biofilm eradication concentration (MBEC™) / well plate assay (38%, n = 15 of 39). A total of 44 commercially available topical agents were grouped into twelve categories with the most commonly tested agents being silver, iodine and polyhexamethylene biguanide (PHMB). In vitro results on efficacy demonstrated iodine as having the highest mean log10 reductions of all agents (4.81, ±3.14). Conclusion There is large disparity in the translation of laboratory studies to researchers undertaking human trials relating to the effectiveness of commercially available topical agents. There is insufficient human in vivo evidence to definitively recommend any commercially available topical agent over another for the treatment of chronic wound biofilms. The heterogeneity identified between study designs (in vitro to in vivo) further limits the generalisability of results.

    更新日期:2019-12-31
  • Measles in pregnant women: a systematic review of clinical outcomes and a meta-analysis of antibodies seroprevalence
    J. Infect. (IF 5.099) Pub Date : 2019-12-28
    Paola Congera; Alberto Enrico Maraolo; Serena Parente; Nicola Schiano Moriello; Vincenzo Bianco; Grazia Tosone

    Objectives : Pregnant women represent a category at high risk of severe measles infection, that negatively affects the fetus as well. A systematic review of clinical outcomes of measles infection in gravid subjects and a meta-analysis of antibodies prevalence among pregnant women was conducted. Methods : MEDLINE and EMBASE databases were searched up to 18 June 2018. The screening focused on: i) articles describing the outcome of measles in pregnancy, synthesized in a descriptive fashion; ii) articles addressing the measles seroprevalence in cohorts of gravid women, analysed quantitatively. Results : Twenty-nine articles met inclusion criteria. A total of 420 cases of measles in gravid subjects were described, from 1941 to 2012. Among women, 18 deaths (4.3%) occurred, and the most frequent complication was pneumonia (75/420, 17.9%). Prematurity was the most important complication concerning fetal outcomes (55 out of 410 cases with available data, 13.4%). The random-effects pooled seroprevalence of measles in 20,546 gravid women worldwide was 89.3% (95% CI: 87.3-91.1%), that decreased, although not in a statistically significant way, over time (p = 0.54). Conclusions : Measles infection in pregnancy is dangerous both for the mother and the foetus. Antibody seroprevalence among gravid women on a global scale is lower than the herd immunity threshold.

    更新日期:2019-12-29
  • Prioritising Hepatitis C treatment in people with multiple injecting partners maximises prevention: a real-world network study
    J. Infect. (IF 5.099) Pub Date : 2019-12-28
    Ryan Buchanan; Rudabeh Meskarian; Peter van der Heijden; Leonie Grellier; Julie Parkes; Salim I Khakoo

    Objective To describe an injecting network of PWID living in an isolated community on the Isle of Wight (UK) and the results of a agent-based simulation, testing the effect of Hepatitis C (HCV) treatment on transmission. Method People who inject drugs (PWID) were identified via respondent driven sampling and recruited to a network and bio-behavioural survey. The injecting network they described formed the baseline population and potential transmission pathways in an agent-based simulation of HCV transmission and the effects of treatment over 12 months. Results On average each PWID had 2.6 injecting partners (range 0-14) and 137 were connected into a single component. HCV in the network was associated with a higher proportion of positive injecting partners (p=0.003) and increasing age (p=0.011). The treatment of well-connected PWID led to significantly fewer new infections of HCV than treating at random (10 vs. 7, p<0.001). In all scenarios less than one individual was re-infected. Conclusion In our model the preferential treatment of well-connected PWID maximised treatment as prevention. In the real-world setting, targeting treatment to actively injecting PWID, with multiple injecting partners may therefore represent the most efficient elimination strategy for HCV.

    更新日期:2019-12-29
  • Long-term follow-up of post-cardiac surgery Mycobacterium chimaera infections: A 5-center case series
    J. Infect. (IF 5.099) Pub Date : 2019-12-19
    Kathleen G. Julian; Tonya Crook; Eugene Curley; A. Ben Appenheimer; Catharine I. Paules; Barbara Hasse; Daniel J. Diekema; Charles L. Daley; Jorgelina de Sanctis; Walter C. Hellinger; Adrah Levin; George McSherry; Carol Freer; Cynthia J. Whitener

    Objectives : In multiple countries, endovascular/disseminated Mycobacterium chimaera infections have occurred in post-cardiac surgery patients in association with contaminated, widely-distributed cardiac bypass heater-cooler devices. To contribute to long-term characterization of this recently recognized infection, we describe the clinical course of 28 patients with 3-7 years of follow-up for survivors. Methods : Identified at five hospitals in the United States 2010-2016, post-cardiac surgery patients in the cohort had growth of Mycobacterium avium complex (MAC)/M. chimaera from a sterile site or surgical wound, or a clinically compatible febrile illness with granulomatous inflammation on biopsy. Case follow-up was conducted in May 2019. Results : Of 28 patients, infection appeared to be localized to the sternum in four patients. Among 18 with endovascular/disseminated infection who received combination anti-mycobacterial treatment and had sufficient follow-up, 39% appeared to have controlled infection (>12 months), 56% died, and one patient is alive with relapsed bacteremia. While the number of patients is small and interpretation is limited, four (67%) of six patients who had cardiac prosthesis removal/replacement appeared to have controlled infection compared to three (25%) of 12 with retained cardiac prosthesis (p >0.14; Fisher's exact test). Conclusions : Given poor response to treatment and potential for delayed relapses, post-cardiac surgery M. chimaera infection warrants aggressive treatment and long-term monitoring.

    更新日期:2019-12-19
  • Elevated progranulin as a novel biomarker to predict poor prognosis in community-acquired pneumonia
    J. Infect. (IF 5.099) Pub Date : 2019-12-16
    Qiongzhen Luo; Xinwei He; Yali Zheng; Pu Ning; Yu Xu; Donghong Yang; Ying Shang; Zhancheng Gao

    Purpose Prognostic biomarkers help triage initial patients and inform targeted therapy selection. Here, we explored the role of progranulin (PGRN)—implicated in processes ranging from inflammation to neurodegeneration—in patients with community-acquired pneumonia (CAP). Methods A prospective observational cohort study was conducted during 2017. Patients who required invasive mechanical ventilation and/or had septic shock and were discharged from the hospital were cohort II. Those who died at the hospital were cohort III. Remaining patients discharged from the hospital were cohort I. The primary endpoint was that patients progressed to served as cohort II; the secondary endpoint was that patients progressed to served as cohort III. Serum PGRN levels were detected by ELISA. Results A total of 280 patients constituted the study cohort. 194 (69.3%) were categorized into cohort I, 61 (21.8%) were categorized into cohort II, and 25 (8.9%) were categorized into cohort III. Serum PGRN levels were increased in CAP patients, independently of etiology. Adjusting for clinical parameters, the odds ratios (95%CI) of cohort III and combined cohort II–III were 34.968 (3.743-326.692) and 3.741 (1.496-9.351), respectively, comparing lowest-to-highest quartile PGRN levels. PGRN exhibited high accuracy in predicting 30-day mortality, with AUC 0.862. PGRN combined with CURB-65 or PSI significantly improved prediction performance. Cox proportional regression analysis showed PGRN was an independent predictor for 30-day mortality risk. Cox survival curves confirmed PGRN ≥89.51 ng/mL had a significantly higher mortality rate than PGRN <89.51 ng/mL. Conclusion Higher PGRN levels at admission were associated with higher odds of poor prognosis. PGRN can improve the prognostic power of CURB-65 or PSI, so PGRN could be apparently a prognostic biomarker for assisting triage of CAP patients.

    更新日期:2019-12-17
  • Hepatitis B virus-associated B-cell non-Hodgkin lymphoma in non-endemic areas in Western Europe: Clinical characteristics and prognosis
    J. Infect. (IF 5.099) Pub Date : 2019-12-14
    Marine Lemaitre; Pauline Brice; Marco Frigeni; Olivier Hermine; Luca Arcaini; Catherine Thieblemont; Caroline Besson

    The association between B-cell non-Hodgkin lymphoma (NHL) and hepatitis B virus (HBV) is well demonstrated by epidemiological studies. Most studies concerning this association have been conducted in endemic areas. Thus, little is known concerning the clinical characteristics of HBV-related lymphomas in non-endemic areas. Here, we report the characteristics and outcomes of 39 patients with active HBV infection and B-cell NHL collected retrospectively in France and Italy. We also compared their characteristics with those of HCV-positive patients with NHL. The gender ratio (M/F) was 3.3 and the median age at NHL diagnosis, 59 years. The pathological distribution was 24 (62%) diffuse large B-cell lymphomas (DLBCLs) and 15 (38%) other lymphomas subtypes: marginal zone lymphoma (n = 6), follicular lymphoma (n = 3), mantle cell lymphoma (n = 2), Burkitt's lymphoma (n = 1), and not otherwise specified low-grade B-NHL (n = 3). Treatment included antiviral therapy for 35 patients (90%). Twenty-two (92%) DLBCL patients received an R-CHOP or R-CHOP-like regimen, leading to complete remission for 18 (75%).At one year, 21 DLBCL patients (88%) were alive, and 13 other B-cell lymphoma patients (87%) were alive. This European study underscores the predominance of DLBCL among patients with active HBV infection and their similar outcomes to non-HBV infected patients with DLBCL when treated with R-CHOP and antivirals.

    更新日期:2019-12-17
  • Donor-derived bacterial infections in lung transplant recipients in the era of multidrug resistance
    J. Infect. (IF 5.099) Pub Date : 2019-12-13
    Eleonora Bunsow; Ibai Los-Arcos; María Teresa Martin-Gómez; Irene Bello; Teresa Pont; Cristina Berastegui; Ricard Ferrer; Xavier Nuvials; María Deu; Maddalena Peghin; Juan José González-López; Mayli Lung; Antonio Román; Joan Gavaldà; Oscar Len

    Objectives Our aim was to analyze the prevalence of multidrug-resistant bacterial infections in lung transplant donors and to evaluate its influence on donor-derived bacterial infections. Methods We conducted a retrospective study of adult patients who underwent lung transplantation (2013-2016) at our hospital. Donor-derived bacterial infection was defined as the isolation of the same bacteria with identical antibiotic susceptibility patterns in the recipient and the perioperative cultures from the donor during the first month posttransplantation. We utilized a preventive antibiotic strategy adapted to the bacteria identified in donor cultures using systemic and nebulized antibiotics. Results 252 lung transplant recipients and 243 donors were included. In 138/243 (56.8%) donors, one bacterial species was isolated from at least one sample; graft colonization (118/243; 48.6%), blood cultures (5/243; 2.1%) and the contamination of preservation fluids (56/243; 23%). Multidrug-resistant bacteria were isolated from 12/243 (4.9%) donors; four Enterobacterales, four Stenotrophomonas maltophilia, three Pseudomonas aeruginosa and one methicillin-resistant Staphylococcus aureus. There was no transmission of these multidrug-resistant bacteria. Donor-derived infections, primarily tracheobronchitis due to non-MDR bacteria, were diagnosed in 7/253 (2.9%) recipients, with good clinical outcomes. Conclusions The lungs of donors colonized with multidrug-resistant bacteria may be safely used when recipients receive prompt tailored antibiotic treatment.

    更新日期:2019-12-17
  • Community-Acquired Group B Streptococcal Meningitis in Adults
    J. Infect. (IF 5.099) Pub Date : 2019-12-10
    MerelN van Kassel, KoenJ. van Haeringen, MatthijsC. Brouwer, MerijnW. Bijlsma, Diederik van de Beek

    Introduction : Streptococcus agalactiae (group B streptococci; GBS) is an uncommon cause of bacterial meningitis in adults. Methods : We reviewed literature published between 1975 and 2018. Studies were included if they reported age, sex and outcome of patients above 16 years of age with cerebrospinal fluid culture (CSF) positive for GBS. Results : Sixty-seven articles describing 141 patients were included. Median age was 56 years (IQR 41-66); 52% were male. Fifty-three patients (38%) were immunocompromised and CSF leakage was reported in 9 (10%) of 88 immunocompetent patients. Sixty-two patients (44%) had extra-meningeal foci of infection, most commonly endocarditis, which occurred in 14 patients (12%). Twenty-eight patients (23%) were described as previously healthy. Forty-four (31%) of the 141 patients died, after a median duration of 5 days after admission. Death was associated with advanced age and an immunocompromised state. Conclusion : GBS meningitis in adults mainly occurs in those with underlying conditions such as immunocompromised state, CSF leakage, and endocarditis. These conditions should be actively sought for in adults with GBS meningitis.

    更新日期:2019-12-11
  • Accumulated mutations by 6 months of infection collectively render transmitted/founder HIV-1 significantly less fit
    J. Infect. (IF 5.099) Pub Date : 2019-12-05
    Chu Wang, Donglai Liu, Tao Zuo, Bhavna Hora, Fangping Cai, Haitao Ding, John Kappes, Christina Ochsenbauer, Wei Kong, Xianghui Yu, Tanmoy Bhattacharya, Alan S Perelson, Feng Gao

    Objective Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early infection affect viral fitness has not been well studied. Methods We generated paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection from 10 infected individuals to investigate the impact of accumulated mutations on viral fitness by comparing 6-mo viruses to their cognate T/F viruses. Results We found that all ten 6-mo viruses were less fit than their cognate T/F viruses. Moreover, the fitness losses of the 6-mo viruses correlated with the decrease in viral loads from the peak of viremia. Conclusion These results show that the mutations accumulated during half a year post infection collectively reduce viral fitness and thereby contribute to lowering viral loads.

    更新日期:2019-12-05
  • Rapid syndromic molecular testing in Pneumonia: the current landscape and future potential
    J. Infect. (IF 5.099) Pub Date : 2019-12-03
    S. Poole, T.W. Clark

    Community acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) are all associated with significant mortality and cause huge expense to health care services around the world. Early, appropriate antimicrobial therapy is crucial for effective treatment. Syndromic diagnostic testing using novel, rapid multiplexed molecular platforms represents a new opportunity for rapidly targeted antimicrobial therapy to improve patient outcomes and facilitate antibiotic stewardship. In this article we review the currently available testing platforms and discuss the potential benefits and pitfalls of rapid testing in pneumonia.

    更新日期:2019-12-03
  • Systematic review and validation of diagnostic prediction models in patients suspected of meningitis
    J. Infect. (IF 5.099) Pub Date : 2019-11-30
    Ingeborg E. van Zeggeren, Merijn W. Bijlsma, Michael W. Tanck, Diederik van de Beek, Matthijs C. Brouwer

    Objectives Diagnostic prediction models have been developed to assess the likelihood of bacterial meningitis (BM) in patients presented with suspected central nervous system (CNS) infection. External validation in patients suspected of meningitis is essential to determine the diagnostic accuracy of these models. Methods We prospectively included patients who underwent a lumbar puncture for suspected CNS infection. After a systematic review of the literature, we applied identified models for BM to our cohort. We calculated sensitivity, specificity, predictive values, area under the curve (AUC) and, if possible, we evaluated the calibration of the models. Results From 2012-2015 we included 363 episodes. In 89 (24%) episodes, the patient received a final diagnosis of a CNS infection, of whom 27 had BM. Seventeen prediction models for BM were identified. Sensitivity of these models ranged from 37% to 100%. Specificity of these models ranged from 44% to 99%. The cerebrospinal fluid model of Oostenbrink reached the highest AUC of 0.95 (95% CI 0.91-0.997). Calibration showed over- or underestimation in all models. Conclusion None of the existing models performed well enough to recommend as routine use in individual patient management. Future research should focus on differences between diagnostic accuracy of the prediction models and physician's therapeutic decisions.

    更新日期:2019-11-30
  • ZIKA VIRUS SEROPREVALENCE IN BLOOD DONORS FROM THE NORTHEASTERN REGION OF SÃO PAULO STATE, BRAZIL, BETWEEN 2015 - 2017
    J. Infect. (IF 5.099) Pub Date : 2019-11-16
    Svetoslav Nanev Slavov, Rafael Rahal Guaragna Machado, Alexander Rodrigo Ferreira, Camila Pereira Soares, Danielle Bastos Araujo, Danielle Bruna Leal Oliveira, Dimas Tadeu Covas, Edison Luiz Durigon, Simone Kashima

    OBJECTIVES Although primarily transmitted by Aedes aegypti mosquitos, Zika virus (ZIKV) can also be transmitted by blood transfusion, due to the fact that some of the infected donors can establish asymptomatic viremia. ZIKV seroprevalence in Brazilian blood donors is unknown. The main reason for this gap in the knowledge originates from the difficulty in evaluating ZIKV humoral immunity due to antigenic cross-reactivity between the different Brazilian flaviviruses and, in particular, dengue virus (DENV). The objective of this study was to evaluate the anti-ZIKV IgG prevalence in blood donors from the Northeast region of the São Paulo State, Brazil, which experienced a ZIKV outbreak in 2016. METHODS We evaluated the ZIKV seroprevalence using the NS1 anti-ZIKV IgG test (Euroimmun), followed by confirmation of the positive and borderline results using the Plaque Reduction Neutralization Test (PRNT). ZIKV seroprevalence was estimated by testing plasma samples collected in 2015 (before the ZIKV outbreak), 2016 (during the outbreak) and 2017 (after the outbreak). In order to investigate possible antigenic cross - reactivity between ZIKV and DENV we also included samples that were taken well before the ZIKV outbreak, in years 2010 and 2013. RESULTS The results obtained by the Euroimmun anti-ZIKV IgG test demonstrated ZIKV seroreactivity in 2015, 2016, and 2017 with prevalences of 5.3%, 12.8% and 13.2%, respectively. The inclusion of blood donor samples from 2010 and 2013, demonstrated anti-ZIKV IgG reactivity only for 2013 (1.7%). The PRNT testing of the ZIKV positive and borderline ELISA reacting samples generated positive results only for the years of 2016 and 2017 (prevalences of 5.6% and 9.1%) which coincided with the introduction of ZIKV in our region. CONCLUSIONS Our results estimate for the first time the ZIKV seroprevalence among Brazilian blood donors from a region with apparently extensive ZIKV circulation and which, at the same time, is highly endemic for DENV. We detected relatively low ZIKV seroprevalence in blood donors from the studied region probably due to the lower intensity of the outbreak compared to other Brazilian locations. Our study adds to the global understanding of ZIKV circulation and the herd immunity of the exposed population.

    更新日期:2019-11-18
  • Agreement between Sensors and Peripheral Temperature Measurements in Febrile Patients
    J. Infect. (IF 5.099) Pub Date : 2019-11-14
    Fanyu Huang, Chloe Magnin, Philippe Brouqui

    Backgrounds Reliable non-invasive methods for measuring body temperature are essential for the diagnosis and monitoring of infectious disease. Methods This study used Intraclass Correlation Coefficients (ICC) and the Bland- Altman plot to analyse the agreement between temperature measurements using an ingestible capsule sensor, a skin sensor and two non-invasive peripheral temperature measurements (axillary and infrared non-contact), collected from a population of febrile patient admitted for infectious disease. Results Of the 77 febrile patients screened, 26 patients were enrolled. The ICC between axillary temperature measurements (Taxi) vs. non-contact measurements (Tno-c) were 0.34 [-0.18; 0.63], 0.87 [0.55; 0.94] between Taxi vs. ingestible capsule measurements (Tcap) and 0.12 [-0.09; 0.37] between Taxi vs. Tetac. The mean difference between Taxi vs Tno-c was -1.18 °C with limits of agreement (LoA) from -2.96 to 0.58 °C. The mean difference between Taxi vs Tcap was 0.48 °C, with LoA from -0.60 to 1.56 °C. The mean difference between Taxi vs Tetac was -4.23 °C with LoA from -7.22 to -1.23°C. Conclusions Ingestible capsule measurements are reliable enough to adequately estimate the core body temperature in clinical practice. Its non-invasiveness, and the real-time remote control offer new opportunities for future research into fever during infectious diseases.

    更新日期:2019-11-14
  • Higher sustained virological response rates at 12 weeks in HIV-HCV co-infection; a tertiary centre experience
    J. Infect. (IF 5.099) Pub Date : 2019-11-14
    L Carvalho, S Pillai, E Daniels, P Sellers, R Whyte, L Eveson, M Foxton, M Nelson

    Objectives The advent of direct-acting antivirals (DAAs) has revealed high rates of sustained virological response at 12 weeks (SVR 12) in Hepatitis C (HCV) treatment. Since the introduction of DAAs, in our centre, 42% of patients treated for HCV are HIV co-infected. Our study aimed to identify the SVR 12 rates between this group and HCV mono-infected patients. Methods Retrospective data analysis of HCV mono-infection and HIV-HCV co-infection patients between 1st July 2015 and 30th November 2018, who had a SVR at 12 weeks post treatment. Co-infected patients were only referred for HCV treatment if they had well controlled HIV. Patients treated with Pegylated Interferon and Ribavirin were excluded. Results During this period, 724 patients were treated for HCV and had data on SVR 12. Of those, 303 (41.8%) were co-infected with HIV. The SVR 12 was achieved in 386 (91.6%) of the HIV negative patients and 288 (95%) of the HIV positive patients (χ²= 3.10 p=0.078). Cirrhotic patients had poorer SVR 12 in both groups (90% in co-infection and 88.4% in HCV mono-infection). Conclusions Our results demonstrate a higher SVR 12 in co-infected patients compared to patients with HCV mono-infection. We hypothesise that adherence to HIV treatment could increase compliance and success of HCV treatment.

    更新日期:2019-11-14
  • Hospital clusters of invasive Group B Streptococcal disease: a systematic review
    J. Infect. (IF 5.099) Pub Date : 2019-11-13
    Simon M Collin, Peter Lamb, Elita Jauneikaite, Kirsty Le Doare, Roberta Creti, Alberto Berardi, Paul T Heath, Shiranee Sriskandan, Theresa Lamagni

    Objectives: To characterise outbreaks of invasive Group B Streptococcal (iGBS) disease in hospitals. Methods: Systematic review using electronic databases to identify studies describing iGBS outbreaks/clusters or cross-infection/acquisition in healthcare settings where ‘cluster’ was defined as ≥2 linked cases. PROSPERO CRD42018096297. Results: Twenty-five references were included describing 30 hospital clusters (26 neonatal, 4 adult) in 11 countries from 1966-2019. Cross-infection between unrelated neonates was reported in 19 clusters involving an early-onset (<7 days of life; n=3), late-onset (7-90 days; n=13) index case or colonized infant (n=3) followed by one or more late-onset cases (median serial interval 9 days (IQR 3-17, range 0-50 days, n=45)); linkage was determined by phage typing in 3 clusters, PFGE/MLST/PCR in 8, WGS in 4, non-molecular methods in 4. Postulated routes of transmission in neonatal clusters were via clinical personnel and equipment, particularly during periods of crowding and high patient-to-nurse ratio. Of 4 adult clusters, one was attributed to droplet spread between respiratory cases, one to handling of haemodialysis catheters and two unspecified. Conclusions: Long intervals between cases were identified in most of the clusters, a characteristic which potentially hinders detection of GBS hospital outbreaks without enhanced surveillance supported by genomics.

    更新日期:2019-11-13
  • Variable clinical presentation by the main capsular groups causing invasive meningococcal disease in England
    J. Infect. (IF 5.099) Pub Date : 2019-11-09
    Helen Campbell, Nick Andrews, Sydel Parikh, Sonia Ribeiro, Steve Gray, Jay Lucidarme, Mary E. Ramsay, Ray Borrow, Shamez N. Ladhani

    Background Invasive meningococcal disease (IMD) typically presents as meningitis, septicaemia or both. Atypical clinical presentations are rare but well-described. We aimed to assess the relationship between meningococcal capsular group, age, clinical presentation, diagnosis and outcome among IMD cases diagnosed in England during 2014. Methods Public Health England conducts enhanced national surveillance of IMD in England. Clinical data for laboratory-confirmed MenB, MenW and MenY cases in ≥5 year-olds were used to classify presenting symptoms, diagnosis and outcomes. Multivariable logistic regression was used to assess independent associations between meningococcal capsular group, clinical presentation, gender, age and death. Results In 2014, there were 340 laboratory-confirmed IMD cases caused by MenB (n=179), MenW (n=95) and MenY (n=66). Clinical presentation with meningitis alone was more prevalent among MenB cases (28%) and among 15-24 year-olds (20%), whilst bacteraemic pneumonia was most prevalent among MenY cases (26%) and among ≥65 year-olds (24%). Gastrointestinal symptoms were recorded preceding or during presentation in 15% (40/269) cases with available information, including 5% (7/140) MenB, 17% (8/47) MenY and 30% (25/82) MenW cases. Upper respiratory tract symptoms were reported in 16% (22/141) MenB, 23% (11/47) MenY and 31% (26/84) MenW cases. Increasing age was also independently associated with bacteraemic meningococcal pneumonia, with no cases among 5-14 year-olds compared to 24% in ≥65 year-olds. Case fatality rates increased with age but no significant associations with death were identified. Conclusions Healthcare professionals should be aware of the atypical clinical presentations associated with the less prevalent meningococcal capsular groups in different age-groups.

    更新日期:2019-11-11
  • FACTORS INFLUENCING LONG-TERM SURVIVAL AFTER HOSPITALIZATION WITH PNEUMOCOCCAL PNEUMONIA
    J. Infect. (IF 5.099) Pub Date : 2019-11-05
    Luis A Ruiz, Leyre Serrano, Pedro P España, Lorea Martinez-Indart, Ainhoa Gómez, Ane Uranga, Sonia Castro, Amaia Artaraz, Rafael Zalacain

    Objective To assess survival and identify predictors of survival more than 30-days after discharge in a cohort of consecutive patients diagnosed with pneumococcal pneumonia Methods Observational study including all consecutive immunocompetent adult patients surviving more than 30-days after hospitalization. The bacteriological diagnosis was based on the results of urinary antigen testing and/or blood culture. Life expectancy was calculated for each patient considering their sex, age and date of discharge. Results We included 1114 patients that survived more than 30 days after discharge. Of them, 431 (38.6%) died during follow-up (median follow-up of 6.7 years). Age, history of cancer, liver disease, chronic renal disease, chronic obstructive pulmonary disease, cerebrovascular disease, atrial arrhythmia and coronary disease, red cell distribution width (RDW) > 15%, positive blood culture, hematocrit < 30% and living in a nursing home were independent risk factors for reduced long-term survival after hospital discharge. Cumulative 1-, 3- and 5-year survival rates were 93.9%, 85.3% and 76% respectively. Among non-survivors, 361 (83.8%) died earlier than expected given their life expectancy. Conclusions Survival after hospital discharge is mainly associated with age and comorbidities. The findings of bacteremia and elevated RDW on admission could help identify patients at high risk of long-term mortality.

    更新日期:2019-11-06
  • Ventilator-associated pneumonia due to Stenotrophomonas maltophilia: Risk factors and outcome
    J. Infect. (IF 5.099) Pub Date : 2019-11-02
    Wafa ibn Saied, Sybille Merceron, Carole Schwebel, Alban Le Monnier, Johana Oziel, Maité Garrouste-Orgeas, Guillaume Marcotte, Stéphane Ruckly, Bertrand Souweine, Michael Darmon, Lila Bouadma, Etienne de Montmollin, Bruno Mourvillier, Jean Reignier, Laurent Papazian, Shidasp Siami, Elie Azoulay, Jean-Pierre Bédos, Jean-Francois Timsit
    更新日期:2019-11-04
  • Prevention and control of meningococcal disease: updates from the Global Meningococcal Initiative in Eastern Europe
    J. Infect. (IF 5.099) Pub Date : 2019-11-01
    Xilian Bai, Ray Borrow, Suzana Bukovski, Dominique A. Caugant, Davor Culic, Snezana Delic, Ener Cagri Dinleyici, Medeia Eloshvili, Tímea Erdősi, Jelena Galajeva, Pavla Křížová, Jay Lucidarme, Konstantin Mironov, Zuridin Nurmatov, Marina Pana, Erkin Rahimov, Larisa Savrasova, Anna Skoczyńska, Lyazzat Yeraliyeva

    The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.

    更新日期:2019-11-01
  • A different response to Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection in UK people with multiple sclerosis (PwMS) compared to controls
    J. Infect. (IF 5.099) Pub Date : 2019-10-31
    Peter A.C. Maple, Radu Tanasescu, Bruno Gran, Cris S. Constantinescu

    Objectives The nature of past cytomegalovirus (CMV) infection in multiple sclerosis (MS) populations is relatively unexplored. Relationships between CMV infection markers and Epstein-Barr virus (EBV) infection markers in a UK resident population of people with MS (PwMS) and controls have been investigated. Methods CMV and EBV nuclear antigen-1(EBNA-1)/virus capsid antigen (VCA) IgG levels were determined for 78 MS patients and anonymised controls by enzyme immunoassays. CMV IgG levels were expressed as Paul Ehrlich Institute (PEI) units/ml (U/ml) and EBNA-1/VCA IgG levels as enzyme units/ml. Results CMV IgG seroprevalence was lower (p=0.0003) in PwMS (35.9% [95%CI: 25.2–46.5]) compared to controls (62.9% [95%CI:54.4-71.4). CMV IgG geometric mean levels in PwMS (353 PEI U/ml [95%CI:272-457]) were lower (p=0.03) compared to the controls (492 PEI U/ml [95%CI:405-599]). EBNA-1 IgG levels were higher (p<0.0001) in PwMS compared to the controls and were lower (p= 0.238) in CMV seropositive PwMS (49.4 units/ml [95%CI:32.2-75.6]) compared to CMV seronegative PwMS (65.4 units/ml [95%CI:53.4-80.1]). These effects were not apparent with EBV VCA IgG. Conclusions Several aspects of CMV and EBV infection in PwMS appear to differ compared to controls. The potential immunomodulatory effect of CMV infection on MS disease and potential interactions with EBV require further investigation.

    更新日期:2019-11-01
  • Biofilm formation and induction of stress response genes is a common response of several serotypes of the pneumococcus to cigarette smoke condensate
    J. Infect. (IF 5.099) Pub Date : 2019-10-26
    Riana Cockeran, Thèrése Dix-Peek, Caroline Dickens, Helen C Steel, Ronald Anderson, Charles Feldman

    Objectives Exposure to cigarette smoke impacts on the virulence of Streptococcus pneumoniae (pneumococcus) by mechanisms including induction of biofilm formation. Most studies, however, have focused on individual strains of the pneumococcus. Accordingly, the current study has investigated the commonality of the pneumococcal stress response to cigarette smoke condensate (CSC), using five different strains of the pathogen. Methods Following exposure to CSC at final concentrations of 80 and 160 µg.mL−1 during a 16 hour incubation period, biofilm formation was measured using a crystal violet-based spectrophotometric procedure. Expression of stress genes seemingly linked to biofilm formation viz. hk11 and rr11 [histidine kinase and response regulator of the two-component regulatory system 11 (TCS11) respectively], cat eff (cation efflux system protein), abc (ATP-binding component of an ATP-binding cassette transporter) and 2005-hyp (hypothetical gene) was measured by sequential extraction of RNA, cDNA synthesis and real-time qPCR. Results Exposure of all five strains of the pneumococcus to CSC, resulted in significant biofilm formation, as well as induction of all five test stress genes. Conclusions Augmentation of induction of selective stress genes and biofilm formation are common, possibly linked, responses of various serotypes of the pneumococcus to CSC, favouring both persistence of the pathogen and decreased efficacy of antibiotics.

    更新日期:2019-10-27
  • Utility of FilmArray® ME Panel for prompt Neisseria meningitidis detection in non-cerebrospinal fluid samples. A case report.
    J. Infect. (IF 5.099) Pub Date : 2019-10-25
    Paloma García-Clemente, Juan José Menéndez-Suso, Iker Falces-Romero, Luis Escosa-García, Cristina Schüffelmann, Emilio Cendejas-Bueno

    The FilmArray® Meningitis/Encephalitis Panel detects the 14 most frequent pathogens causing meningitis and/or encephalitis. The use of FilmArray ME with non-validated samples is seldom published in the literature. We describe the case of a 3-year-old child, diagnosed with acute meningoencephalitis, in whom the FilmArray® ME technique succesfully identified Neisseria meningitidis in both skin biopsy and whole blood samples.

    更新日期:2019-10-25
  • Primary meningococcal conjunctivitis: summary of evidence for the clinical and public health management of cases and close contacts
    J. Infect. (IF 5.099) Pub Date : 2019-10-25
    Sydel R. Parikh, Helen Campbell, Sema Mandal, Mary E. Ramsay, Shamez N. Ladhani

    Background Neisseria meningitidis is a rare cause of acute bacterial conjunctivitis but can progress to invasive meningococcal disease (IMD) in the case and their close contacts. There is, however, a lack of consensus on the clinical and public health management of primary meningococcal conjunctivitis (PMC). Methods We searched Ovid MEDLINE via PubMed, EMBASE and NHS evidence (up to June 2019) for all publications relating to meningococcal conjunctivitis to provide an evidence-base for developing guidelines for the management of PMC cases and their close contacts. Results The review identified a 10-29% risk of IMD among PMC cases within two days of onset of eye infection (range: 3 hours to 4 days). In one study, the risk of IMD in PMC cases treated with systemic antibiotics was 19 times lower than topical antibiotics alone (p=0.001). IMD among close contacts of PMC cases is uncommon but potentially fatal. Whether meningococcal vaccination for PMC cases or close contacts provides any additional benefit is unclear. Conclusions Systemic antibiotic treatment significantly reduces the risk of invasive disease in PMC cases, while antibiotic chemoprophylaxis for close contacts will reduce their risk of secondary IMD. These findings need to be highlighted in relevant clinical and public health guidelines.

    更新日期:2019-10-25
  • Outbreaks of serious pneumococcal disease in closed settings in the conjugate vaccines era, 2010-2018: a systematic review to inform national guidance in the UK
    J. Infect. (IF 5.099) Pub Date : 2019-10-18
    Zahin Amin-Chowdhury, Nalini Iyanger, Mary E Ramsay, Shamez N. Ladhani

    Introduction Pneumococcal outbreaks are rare but they still occur, particularly in closed settings usually involving vulnerable groups. We undertook a systematic review to identify strategies for controlling pneumococcal outbreaks since the licensure of higher-valent pneumococcal conjugate vaccines (PCVs) Methods A systematic literature search was performed for pneumococcal outbreaks published since 2010. A cluster was defined as two or more cases of severe pneumococcal disease in a closed setting within 14 days. Results Eleven reports were identified, including seven caused by serotypes in both the 13-valent PCV (PCV13) and the 23-valent polysaccharide vaccine (PPV23); two were due to a PCV13-only serotype (6A) and one each by a PCV13-related serotype (6C) and a non-vaccine serotype (15A). Eight reported infection control measures, including reinforcing hand washing, respiratory hygiene and patient cohorting. PPV23 was used in five outbreaks, while PCV13 and both vaccines were used in one outbreak each. Different antibiotics were used for chemoprophylaxis in eight outbreaks. Conclusions Most pneumococcal outbreaks are currently caused by vaccine-preventable serotypes, and PPV23 is the preferred vaccine in more than half the outbreaks. Early implementation of infection control measures is important, and antibiotic chemoprophylaxis should be considered for high-risk individuals.

    更新日期:2019-10-19
  • The effect of antibiotics on the composition of the intestinal microbiota
    J. Infect. (IF 5.099) Pub Date : 2019-10-18
    Petra Zimmermann, Nigel Curtis

    Objective Antibiotics cause changes in the intestinal microbiota. The magnitude of the effect of antibiotics on the microbiota and whether the effects are only short-term or persist long-term remain uncertain. In this review, we summarise studies that have investigated the effect of antibiotics on the composition of the human intestinal microbiota. Methods A systematic search was done to identify original studies that have investigated the effect of systemic antibiotics on the intestinal microbiota in humans. Results We identified 129 studies investigating 2076 participants and 301 controls. Many studies reported a decrease in bacterial diversity with antibiotic treatment. Penicillin only had minor effects on the intestinal microbiota. Amoxicillin, amoxcillin/clavulanate, cephalosporins, lipopolyglycopeptides, macrolides, ketolides, clindamycin, tigecycline, quinolones and fosfomycin all increased abundance of Enterobacteriaea other than E. coli (mainly Citrobacter spp., Enterobacter spp. and Klebsiella spp.). Amoxcillin, cephalosporins, macrolides, clindamycin, quinolones and sulphonamides decreased abundance of E. coli, while amoxcillin/clavulante, in contrast to other penicillins, increased abundance of E. coli. Amoxicllin, piperacillin and ticarcillin, cephalosporins (except fifth generation cephalosporins), carbapenems and lipoglycopeptides were associated with increased abundance of Enterococcus spp., while macrolides and doxycycline decreased its abundance. Piperacillin and ticarcillin, carbapenems, macrolides, clindamycin and quinolones strongly decreased the abundance of anaerobic bacteria. In the studies that investigated persistence, the longest duration of changes was observed after treatment with ciprofloxacin (one year), clindamycin (two years) and clarithromycin plus metronidazole (four years). Many antibiotics were associated with a decrease in butyrate or butryrate-producing bacteria. Conclusion Antibiotics have profound and sometimes persisting effects on the intestinal microbiota, characterised by diminished abundance of beneficial commensals and increased abundance of potentially detrimental organisms. Understanding these effects will help tailor antibiotic treatment to minimise this ‘collateral damage’.

    更新日期:2019-10-19
  • Clinical and epidemiological characteristics of Coxsackievirus A6- and Enterovirus 71-associated clinical stage 2 and 3 severe Hand, Foot, and Mouth Disease in Guangxi, southern China, 2017
    J. Infect. (IF 5.099) Pub Date : 2019-10-17
    Yu Ju, Zhenlian Tan, Hao Huang, Minmei Chen, Yi Tan, Chao Zhang, Jin Wang, Hong Wang, Min Chen

    Clinical and epidemiological features for 2194 stage 2 and 156 stage 3 of hand, foot, and mouth disease (HFMD) cases were characterized and the dominated pathogens were coxsackievirus A6 (CV-A6) and enterovirus 71(EV-A71), respectively. Our data highlights that CV-A6 is emerging to be a pivotal pathogen for severe HFMD in southern China and clinical symptoms preference may exist among CV-A6, EV-A71, and CV-A10.

    更新日期:2019-10-17
  • Public Health England HCV Resistance Group: overview and consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection
    J. Infect. (IF 5.099) Pub Date : 2019-10-16
    Daniel Bradshaw, Jean L Mbisa, Anna Maria Geretti, Brendan J Healy, Graham S Cooke, Graham R Foster, Emma C Thomson, John McLauchlan, Kosh Agarwal, Caroline Sabin, David Mutimer, Peter Moss, William L Irving, Ellie Barnes

    The treatment of hepatitis C virus (HCV) infection has been revolutionised by the advent of oral, well-tolerated, direct acting antiviral therapies (DAA), with high cure rates. However, in some scenarios, HCV resistance to antiviral therapies may have an impact on treatment success. Public Health England's HCV Resistance Group was established to support clinicians treating people with HCV, where the issue of resistance may be a factor in clinical decision-making, and this review includes the Group's current recommendations on the use of HCV resistance testing. The authors describe the principles behind and approach to HCV resistance testing and consider evidence from in vitro studies, clinical trials and real world cohorts on the impact of HCV resistance on treatment outcomes for particular DAA regimens. Five scenarios are identified in the UK and similar settings, where, in the Group's opinion, resistance testing should be performed.

    更新日期:2019-10-17
  • Molecular Epidemiology, Diagnostics and Mechanisms of Antibiotic Resistance in Mycobacterium tuberculosis complex in Africa: A Systematic Review of Current Reports
    J. Infect. (IF 5.099) Pub Date : 2019-10-16
    John Osei Sekyere, Melese Abate Reta, Nontuthuko Excellent Maningi, Petrus Bernard Fourie

    Background Tuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting. Methods A comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology of Mycobacterium tuberculosis complex resistance in Africa from January 2007 to December 2018 was undertaken. Results and conclusion Qualitative and quantitative synthesis were respectively undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found in katG (n=3694), rpoB (n=3591), rrs (n=1272), inhA (n=1065), pncA (n=1063) and embB (n=705) in almost all included countries: S315G/I/N/R/T, V473D/F/G/I, Q471H/Q/R/Y, S303C/L etc. in katG; S531A/F/S/G, H526A/C/D/G, D516A/E/G etc. in rpoB; A1401G, A513C etc. in rrs; C15T, G17A/T, -A16G etc. in inhA; Ins456C, Ins 172G, L172P, C14R, Ins515G etc in pncA. Commonest lineages and families such as T (n=8139), LAM (n=5243), Beijing (n=5471), Cameroon (n=3315), CAS (n=2021), H (n=1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n=4964), Ghana (n=2306), and Ethiopia/Tanzania (n=799/635) respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains were limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.

    更新日期:2019-10-17
  • Safety and effectiveness of apheresis in the treatment of infectious diseases: a systematic review
    J. Infect. (IF 5.099) Pub Date : 2019-10-14
    Anand Odedra, David G. Lalloo, Glen Kennedy, Stacey Llewellyn, James S. McCarthy

    Objectives Apheresis has been used as adjunctive treatment of severe falciparum malaria, loiasis and babesiosis. This systematic review aimed to investigate the safety and efficacy of apheresis in the treatment of these conditions. Methods MEDLINE, PUBMED, EMBASE and CINAHL databases were searched to identify studies published between January 1969 and March 2018 involving patients treated using apheresis for severe falciparum malaria, loiasis or babesiosis. Data extracted included details about the apheresis intervention, populations, study methods and outcomes relating to efficacy and safety. Results A total of 67 publications met the inclusion criteria and were included in the data synthesis, 36 for malaria (70 cases), 17 for babesiosis (22 cases) and 14 for loiasis (34 cases). Publications were case reports, case series, and cohort studies; there were no randomised controlled trials identified. Potential publication bias was considered to be high. Conclusions Systematic review of the literature suggests that apheresis may be a useful adjunct in the treatment of patients hospitalised for babesiosis, and prior to chemotherapy in loiasis with microfilarial count >8000 parasites/mL. Data does not support the use of apheresis in patients with severe falciparum malaria.

    更新日期:2019-10-14
  • MRSA dynamic circulation between the community and the hospital setting: new insights from a cohort study in Argentina
    J. Infect. (IF 5.099) Pub Date : 2019-10-11
    Danilo Barcudi, Ezequiel J. Sosa, Ricardo Lamberghini, Analía Garnero, Dario Tosoroni, Laura Decca, Liliana Gonzalez, María A. Kuyuk, Teresa Lopez, Ivana Herrero, Paulo Cortes, Myrian Figueroa, Ana L. Egea, Paula Gagetti, Darío A. Fernandez Do Porto, Alejandra Corso, Adrián G. Turjanski, Claudia Sola

    Dissemination of methicillin-resistant-Staphylococcus aureus/(MRSA) is a worldwide concern both in hospitals [healthcare-associated-(HA)-MRSA] and communities [community-associated-(CA)-MRSA]. Knowledge on when and where MRSA colonization is acquired and what clones are involved is necessary, to focus efforts for prevention of hospital-acquired MRSA-infections. Methods: A prospective/longitudinal cohort study was performed in eight Argentina hospitals (Cordoba/October-December/2014). Surveillance cultures for MRSA (nose-throat-inguinal) were obtained on admission and at discharge. MRSA strains were genetically typed as CA-MRSAG and HA-MRSAG genotypes. Results: Overall, 1419 patients were screened and 534 stayed at hospital for ≥3 days. S. aureus admission prevalence was 30.9% and 4.2% for MRSA. Overall MRSA acquisition rate was 2.3/1000 patient-days-at-risk with a MRSA acquisition prevalence of 1.96% (95%CI: 1.0%-3.4%); 3.2% of patients were discharged back to community with MRSA. CA-MRSAG accounted for 84.6% of imported, 100.0% of hospital-acquired and 94% of discharged MRSA strains. Most imported and acquired MRSA strains belonged to two major epidemic CA-MRSA clones spread in Argentina: PFGEtypeI-ST5-IVa-t311-PVL+ and PFGEtypeN/ST30-IVc-t019-PVL+. Conclusions: CA-MRSA clones, particularly ST5-IV-PVL+ and ST30-IV-PVL+, with main reservoir in the community, not only enter but also are truly acquired within hospital, causing healthcare-associated-hospital-onset infections, having a transmission capacity greater or similar than HA-MRSAG. This information is essential to develop appropriate MRSA infection prevention-control programs, considering hospital and community.

    更新日期:2019-10-12
  • Bacteria and fungi in acute cholecystitis. A prospective study comparing next generation sequencing to culture
    J. Infect. (IF 5.099) Pub Date : 2019-10-02
    Ruben Dyrhovden, Kjell Kåre Øvrebø, Magnus Vie Nordahl, Randi M. Nygaard, Elling Ulvestad, Øyvind Kommedal

    Objectives Guidelines for antibiotic treatment of acute cholecystitis are based on studies using culture techniques for microbial identification. Microbial culture has well described limitations and more comprehensive data on the microbial spectrum may support adjustments of these recommendations. We used next generation sequencing to conduct a thorough microbiological characterization of bile-samples from patients with moderate and severe acute cholecystitis. Methods We prospectively included patients with moderate and severe acute cholecystitis, undergoing percutaneous or perioperative drainage of the gall bladder. Bile samples were analyzed using both culture and deep sequencing of bacterial 16S rRNA and rpoB genes and the fungal ITS2-segment. Clinical details were evaluated by medical record review. Results Thirty-six patients with moderate and severe acute cholecystitis were included. Bile from 31 (86%) of these contained bacteria (29) and/or fungi (5) as determined by sequencing. Culture identified only 40 (38%) of the 106 microbes identified by sequencing. In none of the 15 polymicrobial samples did culture detect all present microbes. Frequently identified bacteria often missed by culture included oral streptococci, anaerobic bacteria, enterococci and Enterobacteriaceae other than Klebsiella spp. and Escherichia coli. Conclusions Culture techniques display decreased sensitivity for the microbial diagnostics of acute cholecystitis leaving possible pathogens undetected.

    更新日期:2019-10-03
  • Prevalence, sequence type, and quinolone resistance of Neisseria lactamica carried in children younger than 15 years in Shanghai, China
    J. Infect. (IF 5.099) Pub Date : 2019-10-02
    Yinfang Shen, Mingliang Chen

    Objective Neisseria lactamica has an important influence on carriage and antimicrobial susceptibility of N. meningitidis, a major pathogen of septicemia and meningitis. In China, quinolone resistance is highly prevalent in N. meningitidis but unknown in N. lactamica. This study investigates the carriage rate, sequence type, and ciprofloxacin resistance of N. lactamica in children in China. Methods During 2014-2016, throat swabs were collected from 2,239 children in Shanghai. The ciprofloxacin minimum inhibitory concentrations of the isolates were determined by the agar dilution method. Results The overall carriage rate of N. lactamica was higher (8.9%) than that of N. meningitidis (0.9%) and peaked at two years (37.1%). The resistance frequency of N. lactamica to ciprofloxacin was 98.5% (197/200). There were 65 sequence types (STs). Clonal complex (cc) 640 (45.5%) dominated, while ST-14031 was predominant (37%, 74/200). All isolates possessed a GyrA mutation; 17 isolates (8.5%) harbored additionally a ParC mutation. Assigned to 39 different alleles, the gyrA sequences from these N. lactamica isolates formed an N. lactamica cluster, which also included eight alleles from N. meningitidis. Conclusion The N. lactamica isolates in China showed distinct characteristics with lower genetic diversity and a much higher prevalence of quinolone resistance than in other countries.

    更新日期:2019-10-02
  • Hyper transmission of Beijing lineage Mycobacterium tuberculosis: Systematic review and Meta-analysis
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Malancha Karmakar, James M. Trauer, David B. Ascher, Justin T. Denholm

    Objectives The globally distributed “Beijing” lineage of Mycobacterium tuberculosis has been associated with outbreaks worldwide. Laboratory based studies have suggested that Beijing lineage may have increased fitness; however, it has not been established whether these differences are of epidemiological significance with regards to transmission. Therefore, we undertook a systematic review of epidemiological studies of tuberculosis clustering to compare the transmission dynamics of Beijing lineages versus the non-Beijing lineages. Methods We systematically searched Embase and MEDLINE before 31st December 2018, for studies which provided information on the transmission dynamics of the different M. tuberculosis lineages. We included articles that conducted population-based cross-sectional or longitudinal molecular epidemiological studies reporting information about extent of transmission of different lineages. The protocol for this systematic review was prospectively registered with PROSPERO (CDR42018088579). Results Of 2855 records identified by the search, 46 were included in the review, containing 42,700 patients from 27 countries. Beijing lineage was the most prevalent and highly clustered strain in 72.4% of the studies and had a higher likelihood of transmission than non-Beijing lineages (OR 1•81 [95% 1•28-2•57], I2 = 94•0%, τ2 = 0•59, p < 0•01). Conclusions Despite considerable heterogeneity across epidemiological contexts, Beijing lineage appears to be more transmissible than other lineages.

    更新日期:2019-10-02
  • S. aureus Colonization in Healthy Australian Adults Receiving an Investigational S. aureus 3-antigen Vaccine
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Helen S. Marshall, James Baber, Peter Richmond, Michael Nissen, Sepehr Shakib, Barry N. Kreiswirth, Edward T. Zito, Joseph Severs, Joseph Eiden, William Gruber, Kathrin U. Jansen, C. Hal Jones, Annaliesa S. Anderson

    Objectives Assess Staphylococcus aureus (S. aureus) colonization in healthy Australian adults receiving an investigational S. aureus 3-antigen vaccine (SA3Ag). Methods In this phase 1, double-blind, sponsor-unblinded study, participants were randomized to receive a single dose (1 of 3 dose levels) of SA3Ag or placebo and a booster dose or placebo at 6 months. S. aureus isolates from nasal, perineal, and oropharyngeal swabs before and through 12 months post-vaccination were identified. Results Baseline S. aureus colonization prevalence was 30.6% (any site), with nasal carriage (27.0%) more common than oropharyngeal/perineal (3.2% each). Following initial vaccination (low-dose:102; mid-dose:101; high-dose:101; placebo:102) and booster (low-dose:45; mid-dose:44; high-dose:27; placebo:181), placebo and SA3Ag groups showed similar S. aureus carriage through 12 months. Most colonized participants (74.0%) were colonized by single spa types. Placebo and SA3Ag groups had similar persistence of colonization, with 19.6-30.7% due to single spa types. Acquisition was observed in mid- and high-dose recipients (∼20%) and low-dose and placebo recipients (∼12%). Vaccination resulted in substantial increases in antibodies to all 3 antigens, irrespective of carriage status. Conclusions Based on descriptive analyses of this small study, SA3Ag vaccination did not impact S. aureus acquisition or carriage. Carriage status did not impact antibody responses to SA3Ag.

    更新日期:2019-10-02
  • Asymptomatic Leishmania infantum infection in blood donors living in an endemic area, northeastern Italy
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Margherita Ortalli, Alessandra Mistral De Pascali, Serena Longo, Nadia Pascarelli, Andrea Porcellini, Deborah Ruggeri, Vanda Randi, Anna Procopio, Maria Carla Re, Stefania Varani

    Objectives : Human leishmaniasis can be severe and fatal, yet in the Mediterranean region only a small percentage of infections progress to clinical disease. We evaluated the percentage of asymptomatic Leishmania infection in the Bologna province, northeastern Italy. Methods : We examined the presence of specific antibodies by Western Blot (WB) and parasitic DNA by real time PCR in peripheral blood of 240 blood donors residing in the Bologna province. Results : Anti-Leishmania IgG were detected by WB in 27 subjects (11.2%, 95% CI 7%-15%), while Leishmania kinetoplast DNA was detected in peripheral blood specimens of 4 out of 240 donors (1.7%, 95% CI 0.2%-3.2%). Overall, the prevalence of Leishmania infection in the blood donor cohort was 12.5%, thus indicating an elevated cumulative exposure to the Leishmania parasite in the examined municipality. Conclusions : Our results suggest that a surveillance system for monitoring Leishmania infection in blood donors and/or strategies of protozoan inactivation in whole blood should be taken into consideration in areas with circulation of the Leishmania parasite.

    更新日期:2019-10-02
  • A prospective, multicenter, and non-interventional case control study about the risk factors associated to acquisition and mortality of Enterobacter species bacteremia
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Rocío Álvarez-Marín, Dolores Navarro-Amuedo, Oriol Gasch-Blasi, José Manuel Rodríguez-Martínez, Jorge Calvo-Montes, Rosario Lara-Contreras, José Antonio Lepe-Jiménez, Fe Tubau-Quintano, María Eliecer Cano-García, Fernando Rodríguez-López, Jesús Rodríguez-Baño, Miquel Pujol-Rojo, Julián Torre-Cisneros, Luis Martínez-Martínez, Álvaro Pascual-Hernández, Manuel Enrique Jiménez Mejías

    Background Enterobacter is among the main etiologies of hospital-acquired infections. This study aims to identify the risk factors of acquisition and attributable mortality of Enterobacter bacteremia. Methods Observational, case-control study for risk factors and prospective cohort for outcomes of consecutive cases with Enterobacter bacteremia. This study was conducted in five hospitals in Spain over a three-year period. Matched controls were patients with negative blood cultures and same sex, age, and hospitalization area. Results The study included 285 cases and 570 controls. E. cloacae was isolated in 198(68.8%) cases and E. aerogenes in 89(31.2%). Invasive procedures (hemodialysis, nasogastric tube, mechanical ventilation, surgical drainage tube) and previous antibiotics or corticosteroids were independently associated with Enterobacter bacteremia. Its attributable mortality was 7.8%(CI95%2.7-13.4%), being dissimilar according to a McCabe index: non-fatal=3.2%, ultimately fatal=12.9% and rapidly fatal=0.12%. Enterobacter bacteremia remained an independent risk factor for mortality among cases with severe sepsis or septic shock (OR 5.75 [CI95%2.57-12.87], p<0.001), with an attributable mortality of 40.3%(CI95%25.7-53.3). Empiric therapy or antibiotic resistances were not related to the outcome among patients with bacteremia. Conclusions Invasive procedures, previous antibiotics and corticosteroids predispose to acquire Enterobacter bacteremia. This entity increases mortality among fragile patients and those with severe infections. Antibiotic resistances did not affect the outcome.

    更新日期:2019-10-02
  • Mild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Pilar GARCIA-BRONCANO, Luz Maria MEDRANO, Juan BERENGUER, Oscar BROCHADO-KITH, Juan GONZÁLEZ-GARCÍA, Ma Ángeles JIMÉNEZ-SOUSA, Carmen QUEREDA, José SANZ, María Jesús TÉLLEZ, Laura DÍAZ, José Luis JIMÉNEZ, Salvador RESINO

    Objective There are a lack of consistency among articles in regards to the evolution of peripheral immune biomarkers after HCV therapy. We aimed to detect the most relevant changes in peripheral immune biomarkers among HIV/HCV-coinfected patients who achieved sustained virologic response (SVR) following peg-IFN-α/ribavirin therapy and to evaluate its normalization with respect to an HIV-monoinfected control group. Methods We performed a prospective cohort study in 99 HIV/HCV-coinfected patients with samples at baseline (HIV/HCV-b-group) and at week 24 after SVR (HIV/HCV-f-group). We also used a control group of 39 HIV-monoinfected patients (HIV-group) negative for HCV and HBV infections, and who had undetectable HIV viral load and CD4+ >500 cells/mm3. Peripheral T cell subsets were assessed by flow cytometry and plasma biomarkers by immunoassays. Results HIV/HCV-coinfected patients had higher values of in IL-10, IL-4, IP-10, IL-8, IL-1β, IL-18, IL-6, IFN-γ, IL-12p70, TNF-α, sVCAM-1, sICAM-1, and sTNFR-1 than HIV control subjects, both at the beginning and at the end of follow-up. Moreover, three biomarkers (CD4+CD38+, telomere length, and IL-1RA) were normalized in relation to the control group at the end of follow-up (the HIV/HCV-b group had higher values and the HIV/HCV-f group had similar values as the HIV-group). Additionally, LPS, IL-2, and IL-17A levels were higher in the HIV/HCV-f group than the HIV-group (24 weeks after SVR). During the follow-up, HIV/HCV-coinfected patients had a significant decrease by the end of follow-up in CD8+CD45RA−CD28+, CD4+CD38+, CD4+CD25+CD127−/low, CD4+CD25+CD127−/low CD45RA−, FABP2, LBP, IP-10, sVCAM1. Only CD4+CD38+ was normalized. Conclusion HIV/HCV-patients showed a slight improvement in the overall profile of immune biomarkers after achieving SVR.

    更新日期:2019-10-02
  • Association between meteorological variations and activities of influenza A and B across different climate zones: a multi-region modelling analysis across the globe
    J. Infect. (IF 5.099) Pub Date : 2019-10-01
    Ka Chun Chong, Tsz Cheung Lee, Seweryn Bialasiewicz, Jian Chen, David W Smith, Wisely S.C. Choy, Mel Krajden, Hamid Jalal, Lance Jennings, Burmaa Alexander, Hong Kai Lee, Pieter Fraaij, Avram Levy, Apple C.M. Yeung, Sarah Tozer, Steven Y.F. Lau, Katherine M. Jia, Julian W.T. Tang, Paul K.S. Chan

    OBJECTIVE To elucidate the effects of meteorological variations on the activity of influenza A and B in 11 sites across different climate regions. METHODS Daily numbers of laboratory-confirmed influenza A and B cases from 2011-2015 were collected from study sites where the corresponding daily mean temperature, relative humidity, wind speed and daily precipitation amount were used for boosted regression trees analysis on the marginal associations and the interaction effects. RESULTS Cold temperature was a major determinant that favored both influenza A and B in temperate and subtropical sites. Temperature-to-influenza A, but not influenza B, exhibited a U-shape association in subtropical and tropical sites. High relative humidity was also associated with influenza activities but were less consistent with influenza B activity. Compared with relative humidity, absolute humidity had a stronger association - it was negatively associated with influenza B activity in temperate zones, but was positively associated with both influenza A and B in subtropical and tropical zones. CONCLUSION The association between meteorological factors and with influenza activity is virus type specific and climate dependent. The heavy influence of temperature on influenza activity across climate zones implies that global warming is likely to have an impact on the influenza burden.

    更新日期:2019-10-01
  • Nanotechnology: a reality for diagnosis of HCV infectious disease
    J. Infect. (IF 5.099) Pub Date : 2019-09-30
    Sonia Arca-Lafuente, Paula Martínez-Román, Irene Mate-Cano, Ricardo Madrid, Verónica Briz

    Hepatitis C virus (HCV) is the primary etiologic agent of liver cirrhosis or hepatocellular carcinoma. HCV elevated infection rates are mostly due to the lack of an accurate and accessible screening and diagnosis, especially in low- and middle-income countries. Conventional HCV diagnostic algorithm consists of a serological test followed by a nucleic acid test. This sequence of tests is time consuming and not affordable for low-resource settings. Nanotechnology have introduced new promising tests for the diagnose of infectious diseases. Based on the employment of nanoparticles and other nanomaterials which lead to highly sensitive and specific nanoscale tests, most of them target pathogen genome. Implementation of nanoscale tests, which are affordable, portable and easy to use by non-specialized personal, would improve HCV diagnosis algorithm. In this review, we have summed up the current emerging nanotechnology tools, which will improve actual screening and treatment programs, and help to reach HCV elimination proposal.

    更新日期:2019-10-01
  • The global prevalence of multidrug-resistance among Acinetobacter baumannii causing hospital-acquired and ventilator-associated pneumonia and its associated mortality: A systematic review and meta-analysis
    J. Infect. (IF 5.099) Pub Date : 2019-09-30
    Lim S Mohd Sazlly, A Zainal Abidin, SM Liew, JA Roberts, FB Sime

    OBJECTIVE The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality. METHODS We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size. RESULTS Among 6,445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%). CONCLUSIONS We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

    更新日期:2019-09-30
  • Continuing rotavirus circulation in children and adults despite high coverage rotavirus vaccination in Finland
    J. Infect. (IF 5.099) Pub Date : 2019-09-30
    Jukka Markkula, Maria Hemming-Harlo, Carita Savolainen-Kopra, Haider al-Hello, Timo Vesikari

    Objectives To determine occurrence of residual rotavirus (RV) disease in different age groups in Finland after five to nine years of high coverage (≥90 %) mass-vaccination with RotaTeq® vaccine, and to examine the vaccine effect on circulating genotypes. Methods Since 2013 all clinical laboratories in the country were obliged to send RV positive stool samples for typing. RVs were genotyped by RT-PCR for VP7 and VP4 proteins, sequenced and compared to reference strains. Results RV continued to circulate throughout the study period at low level with a small increase in 2017-2018. There were three age-related clusters: young children representing primary or secondary vaccine failures, school-age children who may not have been vaccinated, and the elderly. Genotype distribution differed from the pre-vaccination period with a steady decline of G1P[8], emergence of G9P[8] and especially more recently G12P[8]. In the elderly, G2P[4] was predominant but was also replaced by G12P[8] in 2017-18. Conclusions RV vaccination with a high coverage keeps RV disease at low level but does not prevent RV circulation. New RV genotypes have emerged replacing largely the previously predominant G1P[8]. Increase of overall RV activity with emergence of G12P[8] in the latest follow-up season 2017-18 might be a potential alarm sign.

    更新日期:2019-09-30
  • Candida auris outbreak: Mortality, interventions and cost of sustaining control
    J. Infect. (IF 5.099) Pub Date : 2019-09-23
    Surabhi K Taori, Kirstin Khonyongwa, Iain Hayden, GID Dushyanthie AD Athukorala, Andrew Letters, Amanda Fife, Nergish Desai, Andrew M. Borman

    Objective Candida auris has recently emerged as a global cause of multidrug resistant fungal outbreaks. An outbreak occurred at a tertiary care centre in London in 2016. Transmission characteristics, interventions, patient outcomes and cost of resources are described. Methods Outbreak interventions included patient isolation, contact screening, single-use equipment, environmental screening and decontamination, staff education, and enhanced surveillance. Risk factors for infection were recorded . Survival probabilities of patients with C. auris and other Candida bloodstream infections (BSI) were calculated. Antifungal susceptibility and epidemiological typing were performed. Actual and opportunity costs of interventions were determined. Results 34 patients acquired the organism including 8 with BSI. Clinical infection was significantly associated with prolonged hospital stay, haemodialysis and antifungal therapy. Variable susceptibility to amphotericin and the triazoles was seen and isolates clustered with the South Asian strains. No significant difference was detected in the survival probabilities of C .auris BSI compared to other candidemias. Outbreak control cost in excess of £ 1 million and £58,000/month during the subsequent year. Conclusion C. auris outbreaks can be controlled by a concerted infection control strategy but can be expensive. Transmission maybe prolonged due to patient movements and unidentified transmission mechanisms.

    更新日期:2019-09-23
  • A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK
    J. Infect. (IF 5.099) Pub Date : 2019-09-21
    Kavina Manalan, Nathan Green, Amber Arnold, Graham S Cooke, Martin Dedicoat, Marc Lipman, Angela Loyse, Tom S Harrison, Onn Min Kon

    Objectives Prioritisation of oral bedaquiline over the injectable agents in the treatment of multidrug-resistant Tuberculosis (MDR-TB) in the World Health Organisations (WHO) 2019 guidelines prompted this UK analysis of cost implications. The objective was to estimate the costs of amikacin versus bedaquiline in MDR TB treatment regimens using a historical cohort where the injectable agents were the standard of care. Methods This was a retrospective study using a known cohort of UK patients treated with an injectable agent, with data available on resource use, costs for the use of amikacin were compared with those for bedaquiline, based on recommended monitoring for bedaquiline. Results The estimated cost of treatment per patient had mean (sd) of £27236 (4952) for the observed injectable group, £30264 (3392) and 36309 (3901) for the 6 and 8 month amikacin groups, and £31760 (2092) for the bedaquiline group. The cost in the bedaquiline group was £30772 (1855) with a 10 % reduction and £27079 (1234) with a 33% reduction in in-patient stay. Conclusions In most scenarios, bedaquiline is close to cost neutral compared with injectable therapy, especially if, as expected, some reduction in duration of admission is possible as a result of bedaquiline's more rapid culture conversion.

    更新日期:2019-09-22
  • Respiratory Syncytial Virus Infections in Children 0-24 Months of Age in the Community
    J. Infect. (IF 5.099) Pub Date : 2019-09-12
    Laura Toivonen, Sinikka Karppinen, Linnea Schuez-Havupalo, Tamara Teros-Jaakkola, Jussi Mertsola, Matti Waris, Ville Peltola

    Objectives Respiratory syncytial virus (RSV) is a major cause of hospitalization in young children, but there are little data on RSV infections in early childhood in the community. We conducted a prospective population-based birth-cohort study to determine the rates and characteristics of RSV infections in young children. Methods We followed 923 children for acute respiratory infections (ARIs) from birth to age 24 months with daily diaries and study clinic visits. Nasal swab samples were obtained at the onset of ARIs and analyzed for RSV by RT-PCR and antigen tests. The rates of RSV infections and associated outcomes were estimated. Results RSV was detected in 289 (6%) of 4728 ARIs with a nasal sample. The mean estimated annual rate of RSV infections was 37 (95% confidence interval [CI], 35-38) per 100 children at age 0-24 months. For RSV-associated outcomes, the estimated annual rates per 100 children were 34 (95% CI, 32-37) physician visits, 16 (95% CI, 15-17) antibiotic treatments, 12 (95% CI, 11-13) acute otitis media, and 6 (95% CI, 4-7) wheezing illnesses. The prevalence of RSV was 0.6% in asymptomatic children. Conclusions RSV infections impose a high burden of disease in healthy young children in the community.

    更新日期:2019-09-12
  • Probenecid and food effects on flucloxacillin pharmacokinetics and pharmacodynamics in healthy volunteers
    J. Infect. (IF 5.099) Pub Date : 2019-09-12
    Richard J. Everts, Ronald Begg, Sharon J. Gardiner, Mei Zhang, John Turnidge, Stephen T. Chambers, Evan J. Begg

    Objectives To measure the effect of probenecid, fasting and fed, on flucloxacillin pharmacokinetic and pharmacodynamic endpoints. Methods Flucloxacillin 1000 mg orally was given to 11 volunteers alone while fasting (‘flucloxacillin alone’), and with probenecid 500 mg orally while fasting (‘probenecid fasting’) and with food (‘probenecid fed’). Flucloxacillin pharmacokinetic and pharmacodynamic endpoints were compared. Results Probenecid, fasting and fed, increased free plasma flucloxacillin area under the concentration-time curve (zero to infinity) ∼1.65-fold (p<0.01) versus flucloxacillin alone. Probenecid fed prolonged time to peak flucloxacillin concentrations ∼2-fold versus the other two regimens (p<0.01). Probenecid fasting or fed increased free flucloxacillin concentrations exceeding 30%, 50% and 70% of the first 6, 8 and 12 hours post-dose by 1.58- to 5.48-fold compared with flucloxacillin alone. As an example of this pharmacodynamic improvement, the probability of target attainment of free concentrations above the minimum inhibitory concentration for Staphylococcus aureus (0.5 mg/L) for 50% of a 6-hour dose interval was > 80% for flucloxacillin plus probenecid (fasting or fed) and < 20% for flucloxacillin alone. Conclusions Probenecid increased flucloxacillin exposure, with predicted pharmacodynamic effects greater than pharmacokinetic effects because of the altered shape of the concentration-time curve. Probenecid may improve the applicability of oral flucloxacillin regimens.

    更新日期:2019-09-12
  • Distribution of Neisseria meningitidis serogroup B (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009-2014, prior to NmB vaccine licensure
    J. Infect. (IF 5.099) Pub Date : 2019-09-07
    How-Yi Chang, Jeni Vuong, Fang Hu, Paul Liberator, Alex Chen, Cecilia B. Kretz, Amy Blain, Li Hao, Adam C. Retchless, Melissa J. Whaley, Annaliesa S. Anderson, Xin Wang

    Objectives Two Neisseria meningitidis serogroup B (NmB) vaccines are licensed in the United States. To estimate their potential coverage, we examined the vaccine antigen diversity among meningococcal isolates prior to vaccine licensure. Methods NmB vaccine antigen genes of invasive isolates collected in the U.S. from 2009–2014 were characterized by Sanger or whole-genome sequencing. Results During 2009-2014, the predominant antigen types have remained similar to those reported in 2000-2008 for NmB and 2006-2008 for NmC, NmY, with the emergence of a few new types. FHbp of subfamily B or variant 1 (B/v1) remained prevalent among NmB whereas FHbp of subfamily A or variant 2 and 3 (A/v2-3) were more prevalent among non-NmB. FHbp peptide 1 (B24/1.1) remains the most prevalent type in NmB. Full-length NadA peptide was detected in 26% of isolates, primarily in NmB and NmW. The greatest diversity of NhbA peptides was detected among NmB, with p0005 as the most prevalent type. Conclusions The prevalence and diversity of the NmB vaccine antigens have remained stable with common antigen types persisting over time. The data collected prior to NmB vaccine licensure provide the baseline to understand the potential impact of NmB vaccines on antigen diversity and strain coverage.

    更新日期:2019-09-07
  • QuantiFERON TB Gold Plus for the diagnosis of tuberculosis: a systematic review and meta-analysis
    J. Infect. (IF 5.099) Pub Date : 2019-08-29
    Giovanni Sotgiu, Laura Saderi, Elisa Petruccioli, Stefano Aliberti, Andrea Piana, Linda Petrone, Delia Goletti

    Estimated 2017 tuberculosis (TB) incidence is 10 million and mainly depends on the reservoir of individuals with latent TB infection (LTBI). Quantiferon®-TB Gold in-Tube (QFT-GIT) is one of the tests used for LTBI detection. Since 2015 a new version, Quantiferon®-TB Gold Plus (QFT-Plus) is available. Objectives: to perform a systematic review and meta-analysis to assess the diagnostic accuracy for TB of QFT-Plus compared to QFT-GIT. Methods: PubMed and Scopus were used to detect records related to predefined strings from 2015 to 2018. Full text articles dealing with the sensitivity and/or specificity of the QFT-Plus vs. QFT-GIT for active-TB and LTBI detection were analyzed. Scientific quality and risk of bias were assessed using QADAS-2. Results: We selected 15 articles. Studies were mainly observational and cross-sectional, performed in 8 countries. Sample size differed in the TB group (27 to 164) compared to LTBI group (29 to 1,031). Pooled sensitivity of QFT-Plus for active-TB was 0.94 (0.91 and 0.95 for TB1 and TB2, respectively), whereas pooled specificity for healthy status was 0.96. Pooled sensitivity and specificity for LTBI was 0.91 and 0.95, respectively. Conclusions: we show that QFT-Plus is more sensitive compared to QFT-GIT for active-TB detection, mainly due to TB2 responses.

    更新日期:2019-08-29
  • Novel reassortant H7N2 originating from the H7N9 highly pathogenic avian influenza viruses in China, 2019
    J. Infect. (IF 5.099) Pub Date : 2019-08-29
    Yuan Qiu, Rongzhao Sun, Guangyu Hou, Xiaohui Yu, Yang Li, Jinping Li, Qiang Zhang, Fasheng Zou, Hualei Liu, Wenming Jiang

    In March 2013, the first human case of zoonotic H7N9 avian influenza virus (AIV) infection was reported in China. This virus has been circulating in domestic poultry in China while mutating to highly pathogenic AIV (HPAIV) since 2017, which caused human infections and poultry outbreaks. In 2019, a novel reassortant H7N2 HPAIV, A/chicken/China/SJZ1/2019(SJZ1), was isolated from H7–Re2-vaccinated layers. We analyzed the genetic, pathogenic, and antigenic characteristics of SJZ1. Analysis of the entire SJZ1 genomic sequence revealed that it comprised at least two different sources; the PB2, PB1, PA, HA (H7), M, and NS segments of SJZ1 were directly derived from H7N9 AIVs, whereas the NA (N2) and NP segments of SJZ1 were derived from H9N2 AIVs. Experimental infection revealed that SJZ1 was highly pathogenic in chickens but not in ducks. SJZ1 was shed from and replicated in chickens and ducks. Hemagglutination-inhibition assay and challenge test indicated that SJZ1 exhibited rapid antigenic drift and distinct antigenicity relative to the H7-Re2 vaccine strain, which provides poor protection for SJZ1. Our study reports the emergence of a new reassortant of H7N2 AIV with novel viral characteristics and warns of the challenge we still face to control the zoonotic H7N9 AIVs and their reassortants.

    更新日期:2019-08-29
  • Comparative genomic analyses of Chinese serogroup W ST-11 complex Neisseria meningitidis isolates
    J. Infect. (IF 5.099) Pub Date : 2019-08-29
    Bingqing Zhu, Jay Lucidarme, Xilian Bai, Pengbo Guo, Aiyu Zhang, Ray Borrow, Wanying Gao, Li Xu, Yuan Gao, Zhujun Shao

    Although serogroup W ST-11 complex (cc11) (W:cc11) Neisseria meningitidis has been widespread in China over the past ten years, its origin and genetic relatedness has not yet been described. In this study, we described the genetic relatedness and discuss the possible origin of Chinese W:cc11 isolates by comparing their genome sequences with those of other cc11 strains globally. Comparative genomic analysis with geo-temporally diverse cc11 isolates showed that the Chinese W:cc11 isolates exclusively formed two closely related subclusters within a distinct sublineage (proposed as the Chinese-strain sublineage) of lineage 11.1 close to the interface between the Hajj-strain sublineage and the South American-strain sublineage. Several isolates from Africa and Europe were closely related to the Chinese subclusters which were largely segregated from one another among distinct provinces of China. No alleles were identified that were unique to the Chinese isolates as a whole, though each subcluster possessed unique alleles differentiating itself from the other subcluster as well as closely related isolates within the extended sublineage. Three genes differentiated the two subclusters with allele combinations that were each present among the non-Chinese isolates within the wider sublineage. These results indicate that the Chinese W:cc11 isolates formed part of a previously undescribed W:cc11 sublineage that is closely related to, but distinct from, the Hajj-strain sublineage and South American-strain sublineage. The geographical source of the Chinese subclusters was indeterminate based on available data.

    更新日期:2019-08-29
  • Cigarette smoking and the occurrence of Influenza – Systematic Review
    J. Infect. (IF 5.099) Pub Date : 2019-08-26
    H Lawrence, A Hunter, R Murray, WS Lim, T McKeever

    Objectives The association of current smoking with influenza infection is not widely recognised. The aim of this systematic review was to summarise published evidence and quantify the risk of influenza infection in tobacco smokers compared to non-smokers. Methods We systematically searched MEDLINE, EMBASE, CINAHL, LILACS and Web of Science, from inception to 7 November 2017, to identify relevant randomised control trials, cohort and case-control studies. Study quality was assessed using the Newcastle-Ottawa Scale. We included studies defining influenza as a clinical syndrome and those using confirmatory microbiological tests. Pooled odds ratios (ORs) were estimated by using random effects model. Results The mean quality score across the nine included studies (n=40 685 participants) was 5.4 of 9 (SD 1.07). Current smokers were over 5 times more likely to develop laboratory-confirmed influenza than non-smokers (pooled OR 5.69 (95% CI 2.79 to 11.60), 3 studies). For studies reporting the occurrence of an influenza-like illness (ILI), current smokers were 34% more likely to develop ILI than non-smokers (pooled OR 1.34 (95% CI 1.13 to 1.59), 6 studies). Conclusion Current smokers have an increased risk of developing influenza compared to non-smokers. The association was strongest in studies examining cases with laboratory confirmed influenza.

    更新日期:2019-08-26
  • Incremental value of metagenomic next generation sequencing for the diagnosis of suspected focal infection in adults
    J. Infect. (IF 5.099) Pub Date : 2019-08-21
    Hao-Cheng Zhang, Jing-Wen Ai, Peng Cui, Yi-Min Zhu, Yong-Jun Li, Wen-Hong Zhang

    Objectives Microbiological diagnosis is essential during clinical management of focal infections. Metagenomic next generation sequencing (mNGS) has been reported as a promising diagnostic tool in infectious diseases. However, little is known about the clinical utility of mNGS in focal infections. Methods We conducted a single-center retrospective study to investigate impact of mNGS on focal infection diagnosis and compared it with conventional methods, including culture, pathological examination, Xpert MTB/RIF, etc. 98 suspected focal infections cases were enrolled, and medical records were reviewed to determine their rates of detection, time-to-identification, and clinical outcomes. Results mNGS showed a satisfying diagnostic positive percent agreement of 86.30% (95% CI: 75.79%-92.88%) in a variety of tissues, compared to 45.21% (95% CI: 33.68%-57.24%) for culture and 57.53% (95% CI: 45.43%-68.84%)f for conventional methods (p<0.0125), and detected an extra 34 pathogenic microorganisms. Time requirement for pathogen identification using mNGS ranges from 31 hours to 55 hours, which showed an advantage over culture. (82.36 hours; 95%CI: 65.83,98.89; P<0.05) Conclusions mNGS showed promising potential in pathogenic diagnosis during focal infections and might enable clinicians to make more timely and targeted therapeutic decisions.

    更新日期:2019-08-21
  • Diagnostic accuracy of 16S rDNA PCR in bacterial pyomyositis: a prospective study
    J. Infect. (IF 5.099) Pub Date : 2019-08-17
    Thomas Gabas, Isabelle Podglajen, Geoffrey Cheminet, Jean-Charles Gagnard, Benjamin Wyplosz

    Diagnosing bacterial pyomyositis is a challenge because most patients receive antibiotics when pus from muscle is collected, and cultures are often sterile. The diagnosis can be made more rapidly, and with substantially accuracy, if 16S rDNA PCR rather than bacterial culture is used for identification of the etiological agent bacteria.

    更新日期:2019-08-18
  • Genomic sequencing of a national emm66 group A streptococci (GAS) outbreak among people who inject drugs and the homeless community in England and Wales, January 2016-May 2017
    J. Infect. (IF 5.099) Pub Date : 2019-08-13
    Laura Bubba, Nick Bundle, Georgia Kapatai, Roger Daniel, Sooria Balasegaram, Charlotte Anderson, Vicki Chalker, Theresa Lamagni, Colin Brown, Derren Ready, Androulla Efstratiou, Juliana Coelho

    An outbreak of an uncommon emm type (emm66.0) of group A streptococcus (GAS) occurred in England and Wales between January 2016 and May 2017, involving 52 individuals who were homeless or injecting drugs users. In order to investigate the outbreak, epidemiological and network analysis were performed; moreover 55 isolates (32 outbreak, 5 non-outbreak and 13 historical -2005-2015) were tested with whole genome sequencing (WGS), antimicrobial resistance determination, Bayesian evolutionary analysis (BEAST). Forty one isolates (including 32 outbreak strains) belonged to a single emm66.0 clade (average SNP difference: 6.6; range 0-16 SNPs) separate from the other isolates and two strains previously considered part of the outbreak (SNP average: 5,876; range 93-8,417 SNPs). Antibiotic resistance was not detected in the outbreak clone. No common source of infection was identified. WGS confirmed expansion of an emm66.0 clone in a hard-to-reach population and enabled refinement of the initial case definition.

    更新日期:2019-08-14
  • Mass spectrometry-based proteomic techniques to identify cerebrospinal fluid biomarkers for diagnosing suspected central nervous system infections. A systematic review
    J. Infect. (IF 5.099) Pub Date : 2019-08-09
    Tehmina Bharucha, Bevin Gangadharan, Abhinav Kumar, Xavier de Lamballerie, Paul N. Newton, Markus Winterberg, Audrey Dubot-Pérès, Nicole Zitzmann

    Objectives : Central nervous system (CNS) infections account for a large number of disability-adjusted life years worldwide every year. An urgent research priority is scaling up diagnostic capacity, and introduction of point-of-care tests. We set out to assess current evidence for the application of mass spectrometry (MS) peptide sequencing in identification of diagnostic biomarkers for CNS infections. Methods : We performed a systematic review (PROSPERO-CRD42018104257) using PRISMA guidelines on use of MS to identify cerebrospinal fluid (CSF) biomarkers for diagnosing CNS infections. We searched PubMed, Embase, Web of Science, and Cochrane for articles published from 1 January 2000 to 1 February 2019, and contacted experts. Inclusion criteria involved primary research except case reports, on the diagnosis of infectious diseases except HIV, applying MS to human CSF samples, and English language. Results : 4,620 papers were identified, of which 11 were included, largely confined to pre-clinical biomarker discovery, and eight (73%) published in the last five years. 6 studies performed further work termed verification or validation. In 2 of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89-94% and 58-92% respectively. Conclusions : The findings demonstrate feasibility and significant potential of the methods in a variety of infectious diseases, but emphasise the need for strong interdisciplinary collaborations to ensure appropriate study design and biomarker validation.

    更新日期:2019-08-10
  • Long Term Renal Function in Asian HIV-1 Infected Adults Receiving Tenofovir Disoproxil Fumarate Without Protease Inhibitors
    J. Infect. (IF 5.099) Pub Date : 2019-08-08
    Geoffroy LIEGEON, Linda HARRISON, Anouar NECHBA, Guttiga HALUE, Sukit BANCHONGKIT, Ampaipith NILMANAT, Naruepon YUTTHAKASEMSUNT, Panita PATHIPVANICH, Suchart THONGPAEN, Rittha LERTKOONALAK, Thomas ALTHAUS, Marc LALLEMANT, Jean-Yves MARY, Gonzague JOURDAIN

    Objectives The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight. Methods Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen. Results Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84 to 1.47, P=0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48 to 3.02 for <48 kg patients and HR 1.64, 95% CI 1.20 to 2.25 for 48-59.9 kg patients, compared to those with >60kg, P<0.001) and hypertension (HR 4.03, 95% CI 2.0 to 8.0, P<0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (P=0.27). Conclusions The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.

    更新日期:2019-08-09
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