The contribution of community and hospital sources to the transmission of extended-spectrum β-lactamase producing Enterobacterales (ESBL-PE) remains elusive.
To investigate the extent of community ...dissemination and the contribution of hospitals to the spread of ESBL-PE by exploring their spatiotemporal distribution in municipal wastewater of the central European city of Basel.
Wastewater samples were collected monthly for two consecutive years throughout Basel, Switzerland, including 21 sites across 10 postcode areas of the city collecting either community wastewater (urban sites,
= 17) or community and hospital wastewater (mixed sites,
= 4). Presumptive ESBL-PE were recovered by selective culture methods. Standard methodologies were applied for species identification, ESBL-confirmation, and quantification.
Ninety-five percent (477/504) of samples were positive for ESBL-PE. Among these isolates,
(85%, 1,140/1,334) and
(11%, 153/1,334) were most common. They were recovered throughout the sampling period from all postcodes, with
consistently predominating. The proportion of
isolates was higher in wastewater samples from mixed sites as compared to samples from urban sites, while the proportion of
was higher in samples from urban sites (
= 0.003). Higher numbers of colony forming units (CFUs) were recovered from mixed as compared to urban sites (median 3.2 × 10
vs. 1.6 × 10
CFU/mL).
-counts showed moderate correlation with population size (rho = 0.44), while this correlation was weak for other ESBL-PE (rho = 0.21).
ESBL-PE are widely spread in municipal wastewater supporting that community sources are important reservoirs entertaining the spread of ESBL-PE. Hospital-influenced abundance of ESBL-PE appears to be species dependent.
The involvement of non-human-to-human transmission of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) remains elusive. Foodstuffs may serve as reservoirs for ESBL-PE and contribute ...to their spread.
We aimed to systematically investigate the presence and spatiotemporal distribution of ESBL-PE in diverse unprocessed foodstuffs of different origin purchased in a central European city.
Chicken and green (herbs, salad, sprouts, vegetables) samples were collected monthly for two consecutive years, from June 2017 to June 2019, from large supermarket chains and small local food retailers, representing all ten postcode areas of the City of Basel (Switzerland), and the kitchen of the University Hospital Basel (Basel, Switzerland). After enrichment, presumptive ESBL-PE were isolated by selective culture methods and identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ESBL production was confirmed by phenotypic testing.
Among 947 food samples, 14.8% were positive for ESBL-PE isolate/s belonging to eight different ESBL-producing bacterial species.
and
were predominant across samples (9 and 2%, respectively). Higher ESBL-PE prevalence was observed in chicken (25.9%) than in green (3.8%) samples (
< 0.001). Among greens, ESBL-PE were most frequently isolated from sprouts (15.2%). High ESBL-PE species diversity was observed among chicken samples, with
as predominant (17.6%). ESBL-producing
was detected among different greens. Yet, ESBL-producing
was predominant in sprouts (12.1%). In total, 20.5% of samples from organic farming and 14.2% of samples from conventionally raised animals harbored an ESBL-producing isolate. Detection of ESBL-PE across samples differed between organic and non-organic when stratified by food source (
< 0.001), particularly among greens (12.5% organic, 2.4% conventional). High proportion of organic chicken samples was positive for ESBL-
(33.3%), while the detection of several species characterized the conventional chicken samples. No significant differences in ESBL-PE frequences were detected between national (13.4%) and international samples (8.0%) (
= 0.122). Instead, differences were observed between regions of food production and countries (
< 0.001). No significant differences were found when comparing the proportion of ESBL-PE positive samples across districts, shop sizes and the hospital kitchen. The percentage of ESBL-PE positive samples did not differ monthly across the two-year sampling period (
= 0.107).
Our findings indicate moderate dissemination of ESBL-PE in foodstuffs, especially between chicken products and sprouts. Chicken meat represents a source for several ESBL-producing Enterobacterales, especially
, while greens are more prone to carry ESBL-
and
. We disclose the importance of food type, food production system and production origin when assessing the risk of contamination with different ESBL-PE species.
The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of ...concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs.
Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV ...infection.
IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study.
64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range IQR 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older).
T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Legionella species cause severe forms of pneumonia with high mortality and complication rates. Accurate clinical predictors to assess the likelihood of Legionella community-acquired pneumonia (CAP) ...in patients presenting to the emergency department are lacking.
We retrospectively compared clinical and laboratory data of 82 consecutive patients with Legionella CAP with 368 consecutive patients with non-Legionella CAP included in two studies at the same institution.
In multivariate logistic regression analysis we identified six parameters, namely high body temperature (OR 1.67, p < 0.0001), absence of sputum production (OR 3.67, p < 0.0001), low serum sodium concentrations (OR 0.89, p = 0.011), high levels of lactate dehydrogenase (OR 1.003, p = 0.007) and C-reactive protein (OR 1.006, p < 0.0001) and low platelet counts (OR 0.991, p < 0.0001), as independent predictors of Legionella CAP. Using optimal cut off values of these six parameters, we calculated a diagnostic score for Legionella CAP. The median score was significantly higher in Legionella CAP as compared to patients without Legionella (4 (IQR 3-4) vs 2 (IQR 1-2), p < 0.0001) with a respective odds ratio of 3.34 (95%CI 2.57-4.33, p < 0.0001). Receiver operating characteristics showed a high diagnostic accuracy of this diagnostic score (AUC 0.86 (95%CI 0.81-0.90), which was better as compared to each parameter alone. Of the 191 patients (42%) with a score of 0 or 1 point, only 3% had Legionella pneumonia. Conversely, of the 73 patients (16%) with > or =4 points, 66% of patients had Legionella CAP.
Six clinical and laboratory parameters embedded in a simple diagnostic score accurately identified patients with Legionella CAP. If validated in future studies, this score might aid in the management of suspected Legionella CAP.
The outcome of Kaposi sarcoma varies. While many patients do well on highly active antiretroviral therapy, others have progressive disease and need chemotherapy. In order to predict which patients ...are at risk of unfavorable evolution, we established a prognostic score.
The survival analysis (Kaplan-Meier method; Cox proportional hazards models) of 144 patients with Kaposi sarcoma prospectively included in the Swiss HIV Cohort Study, from January 1996 to December 2004, was conducted. OUTCOME ANALYZED: use of chemotherapy or death. VARIABLES ANALYZED: demographics, tumor staging T0 or T1 (16), CD4 cell counts and HIV-1 RNA concentration, human herpesvirus 8 (HHV8) DNA in plasma and serological titers to latent and lytic antigens.
Of 144 patients, 54 needed chemotherapy or died. In the univariate analysis, tumor stage T1, CD4 cell count below 200 cells/microl, positive HHV8 DNA and absence of antibodies against the HHV8 lytic antigen at the time of diagnosis were significantly associated with a bad outcome. Using multivariate analysis, the following variables were associated with an increased risk of unfavorable outcome: T1 hazard ratio (HR) 5.22; 95% confidence interval (CI) 2.97-9.18, CD4 cell count below 200 cells/microl (HR 2.33; 95% CI 1.22-4.45) and positive HHV8 DNA (HR 2.14; 95% CI 1.79-2.85). We created a score with these variables ranging from 0 to 4: T1 stage counted for two points, CD4 cell count below 200 cells/microl for one point, and positive HHV8 viral load for one point. Each point increase was associated with a HR of 2.26 (95% CI 1.79-2.85).
In the multivariate analysis, staging (T1), CD4 cell count (<200 cells/microl), positive HHV8 DNA in plasma, at the time of diagnosis, predict evolution towards death or the need of chemotherapy.
In chronic HIV infection, antiretroviral therapy-induced normalization of CD4(+) T cell counts (immune reconstitution IR) is associated with a decreased incidence of opportunistic diseases. However, ...some individuals remain at risk for opportunistic diseases despite prolonged normalization of CD4(+) T cell counts. Deficient Epstein-Barr virus (EBV)-specific CD4(+) T cell function may explain the occurrence of EBV-associated opportunistic malignancy-such as primary central nervous system (PCNS) lymphoma-despite recovery of absolute CD4(+) T cell counts.
Absolute CD4(+) T cell counts and EBV-specific CD4(+) T cell-dependent interferon-gamma production were assessed in six HIV-positive individuals prior to development of PCNS lymphoma ("cases"), and these values were compared with those in 16 HIV-infected matched participants with no sign of EBV-associated pathology ("matched controls") and 11 nonmatched HIV-negative blood donors. Half of the PCNS lymphoma patients fulfilled IR criteria (defined here as CD4(+) T cell counts >or=500/microl blood). EBV-specific CD4(+) T cells were assessed 0.5-4.7 y prior to diagnosis of lymphoma. In 0/6 cases versus 13/16 matched controls an EBV-specific CD4(+) T cell response was detected (p = 0.007; confidence interval for odds ratio 0-0.40). PCNS lymphoma patients also differed with regards to this response significantly from HIV-negative blood donors (p < 0.001, confidence interval for odds ratio 0-0.14), but there was no evidence for a difference between HIV-negative participants and the HIV-positive matched controls (p = 0.47).
Irrespective of absolute CD4(+) T cell counts, HIV-positive patients who subsequently developed PCNS lymphoma lacked EBV-specific CD4(+) T cell function. Larger, ideally prospective studies are needed to confirm these preliminary data, and clarify the impact of pathogen-specific versus surrogate marker-based assessment of IR on clinical outcome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive ...specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay.
The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (< or = 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%-46%).
Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line ...immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it.
Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms.
HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients.
The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
We report a cluster of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sequence type 101, derived from 1 poultry and 2 clinical samples collected within the setting ...of a prospective study designed to determine the diversity and migration of ESBL-producing Enterobacterales between humans, foodstuffs, and wastewater.
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