Hydrogen bonds van der Waals contacts and electrostatic interactions formed

In two clusters, possible interdepartment spread was observed. The heterogeneous cluster 1 contained sequences from four different departments over a time span of nearly half a year. One of the later samples in this cluster was taken from a patient without earlier hospital contact within 48 hours after admission, thus indicating a new introduction of the virus from the community into the hospital. However, inter-department spread could have occurred in temporarily related samples from this cluster. An example of this could be the simultaneously occurring norovirus infections in the cardiology department and the internal medicine department 1 in week 5�C7/2008. In other temporary and/or locally related cases with sequences differing by no more than one nucleotide the transmission route was unclear. Identical sequences belonging to cluster 1 were for example found in three patients on three different wards in week 13�C15/2008. Both nosocomial transmission and repeated introduction from the community could ACET explain these infections. The same is true for the first two samples from cluster 2 which were from patients from two different departments. In the nephrology department and both internal medicine departments, consecutive 22-Oxacalcitriol outbreaks with distinct clusters of the GII.4 variant Den Haag 2006b were detected, indicating repeated introductions of different strains from the community. As opposed to this, a prolonged outbreak over 12 weeks with the same cluster occurred in the hematology department. Sequencing of the capsid gene has previously been shown to be helpful for investigating outbreaks. Comparable to our study, which found a presumed larger hospital outbreak to consist of several distinct smaller outbreaks, Xerry et al. could differentiate two distinct simultaneous outbreaks in different departments of the same hospital and Sukhrie et al. found that one of four epidemiological outbreaks involved several unrelated strains. However, in the study of Xerry et al., P2 sequences also detected links between presumably unrelated outbreaks in different departments and even two different hospitals. Similarly, in another study by Sukhrie and coworkers only three out of 14 molecular clusters found by sequencing of the P2 region had been identified through epidemiological investigations, even though the conservative approach of defining a molecular cluster by 100% sequence identity was chosen. The frequency of nucleotide changes found in our study is in concordance with previous studies investigating nosocomial NoV GII.4 outbreaks: Dingle et al. showed a diversity of six nucleotide changes in the entire NoV genome in a 1-week outbreak with presumed person-to-person transmission, whereas the strains of an outbreak with a presumed point source only differed by one substitution. Sukhrie found a similar sequence variation of two to 22 nucleotide changes in the P2 domain within prospectively monitored nosocomial outbreaks, where patients and health care workers were sampled once weekly for one to two months.

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