Lessons from a one-year hospital-based surveillance of acute respiratory infections in Berlin- comparing case definitions to monitor influenza

<p>Abstract</p> <p>Background</p> <p>Surveillance of severe acute respiratory infections (SARI) in sentinel hospitals is recommended to estimate the burden of severe influenza-cases. Therefore, we monitored patients admitted with respiratory infections (RI) in 9 Berlin hospitals from 7.12.2009 to 12.12.2010 according to different case definitions (CD) and determined the proportion of cases with influenza A(H1N1)pdm09 (pH1N1). We compared the sensitivity and specificity of CD for capturing pandemic pH1N1 cases.</p> <p>Methods</p> <p>We established an RI-surveillance restricted to adults aged ≤ 65 years within the framework of a pH1N1 vaccine effectiveness study, which required active identification of RI-cases. The hospital information-system was screened daily for newly admitted RI-patients. Nasopharyngeal swabs from consenting patients were tested by PCR for influenza-virus subtypes. Four clinical CD were compared in terms of capturing pH1N1-positives among hospitalized RI-patients by applying sensitivity and specificity analyses. The broadest case definition (CD1) was used for inclusion of RI-cases; the narrowest case definition (CD4) was identical to the SARI case definition recommended by ECDC/WHO.</p> <p>Results</p> <p>Over the study period, we identified 1,025 RI-cases, of which 283 (28%) met the ECDC/WHO SARI case definition. The percentage of SARI-cases among internal medicine admissions decreased from 3.2% (calendar-week 50-2009) to 0.2% (week 25-2010). Of 354 patients tested by PCR, 20 (6%) were pH1N1-positive. Two case definitions narrower than CD1 but -in contrast to SARI- not requiring shortness of breath yielded the largest areas under the Receiver-Operator-Curve. Heterogeneity of proportions of patients admitted with RI between hospitals was significant.</p> <p>Conclusions</p> <p>Comprehensive surveillance of RI cases was feasible in a network of community hospitals. In most settings, several hospitals should be included to ensure representativeness. Although misclassification resulting from failure to obtain symptoms in the hospital information-system cannot be ruled out, a high proportion of hospitalized PCR-positive pH1N1-patients (45%) did not fulfil the SARI case-definition that included shortness of breath or difficulty breathing. Thus, to assess influenza-related disease burden in hospitals, broader, alternative case definitions should be considered.</p

Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency

MRSA Transmission on a Neonatal Intensive Care Unit: Epidemiological and Genome-Based Phylogenetic Analyses

<div><h3>Background</h3><p>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) may cause prolonged outbreaks of infections in neonatal intensive care units (NICUs). While the specific factors favouring MRSA spread on neonatal wards are not well understood, colonized infants, their relatives, or health-care workers may all be sources for MRSA transmission. Whole-genome sequencing may provide a new tool for elucidating transmission pathways of MRSA at a local scale.</p> <h3>Methods and Findings</h3><p>We applied whole-genome sequencing to trace MRSA spread in a NICU and performed a case-control study to identify risk factors for MRSA transmission. MRSA genomes had accumulated sequence variation sufficiently fast to reflect epidemiological linkage among individual patients, between infants and their mothers, and between infants and staff members, such that the relevance of individual nurses’ nasal MRSA colonization for prolonged transmission could be evaluated. In addition to confirming previously reported risk factors, we identified an increased risk of transmission from infants with as yet unknown MRSA colonisation, in contrast to known MRSA-positive infants.</p> <h3>Conclusions</h3><p>The integration of epidemiological (temporal, spatial) and genomic data enabled the phylogenetic testing of several hypotheses on specific MRSA transmission routes within a neonatal intensive-care unit. The pronounced risk of transmission emanating from undetected MRSA carriers suggested that increasing the frequency or speed of microbiological diagnostics could help to reduce transmission of MRSA.</p> </div

Definition of MRSA-related patient status.

<p>Initially, birth or a negative swab result in the status “MRSA-negative”. A few days later another swab is taken, which turns out MRSA-positive. MRSA is presumed to have been acquired latest one day before the positive swab was taken, because it takes time for the bacteria to multiply and spread from the location of transmission to the location being swabbed. Therefore, the infant’s status is “unknown MRSA-positive” from one day before the positive swab until the positive result is received on the ward. Thereafter, the infant’s status is “known MRSA-positive”.</p

Characteristics of the cases and controls matched for weight at birth and age during exposure time.

*<p>from birth or last negative swab to first positive.</p>#<p>Kruskal Wallis, Chi2.</p>†<p>as opposed to colonisation.</p>‡<p>In pairs with two controls, the average value of the controls was used for the calculation.</p

Maximum clade credibility tree based on BEAST analysis of MRSA genome sequences.

<p>Tips of the tree are constrained by bacterial isolation dates, the time scale is shown at the bottom. Node support is indicated for posterior probabilities ≥0.9. The case-control study period (February 8 to August 31, 2010) is indicated by grey shading. MRSA from patients (patient numbers are indicated), healthcare workers (HCW A, HCW B) and two mothers of patients are included. Colours indicate patient positions on wards A, B, and C, respectively. Blue bars indicate 95% Bayesian credibility intervals of bacterial divergence dates (node heights).</p

Risk factor analysis in univariable logistic regression.

<p>Significant findings (5% level of confidence) and some selected variables previously reported as risk factors for MRSA transmission are shown. Ordered by statistical significance.</p

Prospective hospital-based case–control study to assess the effectiveness of pandemic influenza A(H1N1)pdm09 vaccination and risk factors for hospitalization in 2009–2010 using matched hospital and test-negative controls

<p>Abstract</p> <p>Background</p> <p>We performed a case–control study to estimate vaccine effectiveness (VE) for prevention of hospitalization due to pandemic influenza A(H1N1)pdm09 (pH1N1) and to identify risk factors for pH1N1 and acute respiratory infection (ARI) in 10 hospitals in Berlin from December 2009 to April 2010.</p> <p>Methods</p> <p>Cases were patients aged 18–65 years with onset of ARI ≤10 days before admission testing positive for pH1N1 by PCR performed on nasal and throat swabs or by serological testing. Cases were compared to (1) matched hospital controls with acute surgical, traumatological or other diagnoses matched on age, sex and vaccination probability, and (2) ARI patients testing negative for pH1N1. Additionally, ARI cases were compared to matched hospital controls. A standardized interview and chart review elicited demographic and clinical data as well as potential risk factors for pH1N1/ARI. VE was estimated by 1-(Odds ratio) for pH1N1-vaccination ≥10 days before symptom onset using exact logistic regression analysis.</p> <p>Results</p> <p>Of 177 ARI cases recruited, 27 tested pH1N1 positive. A monovalent AS03-adjuvanted pH1N1 vaccine was the only pandemic vaccine type identified among cases and controls (vaccination coverage in control group 1 and 2: 15% and 5.9%). The only breakthrough infections were observed in 2 of 3 vaccinated HIV positive pH1N1 patients. After exclusion of HIV positive participants, VE was 96% (95%CI: 26-100%) in the matched multivariate analysis and 46% (95%CI: -376-100%) in the test-negative analysis. Exposure to children in the household was independently associated with hospitalization for pH1N1 and ARI.</p> <p>Conclusions</p> <p>Though limited by low vaccination coverage and number of pH1N1 cases, our results suggest a protective effect of the AS03-adjuvanted pH1N1 vaccine for the prevention of pH1N1 hospitalization. The use of hospital but not test-negative controls showed a statistically protective effect of pH1N1-vaccination and permitted the integrated assessment of risk factors for pH1N1-infection. To increase statistical power and to permit stratified analyses (e.g. VE for specific risk groups), the authors suggest pooling of future studies assessing effectiveness of influenza vaccines for prevention of severe disease from different centres.</p