Science Collected Works - Research Publications
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ItemEmergence of new norovirus variants on spring cruise ships and prediction of winter epidemics(CENTERS DISEASE CONTROL & PREVENTION, 2008-02)In June 2006, reported outbreaks of norovirus on cruise ships suddenly increased; 43 outbreaks occurred on 13 vessels. All outbreaks investigated manifested person-to-person transmission. Detection of a point source was impossible because of limited investigation of initial outbreaks and data sharing. The most probable explanation for these outbreaks is increased norovirus activity in the community, which coincided with the emergence of 2 new GGII.4 variant strains in Europe and the Pacific. As in 2002, a new GGII.4 variant detected in the spring and summer corresponded with high norovirus activity in the subsequent winter. Because outbreaks on cruise ships are likely to occur when new variants circulate, an active reporting system could function as an early warning system. Internationally accepted guidelines are needed for reporting, investigating, and controlling norovirus illness on cruise ships in Europe.
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ItemGastroenteritis caused by norovirus GGII.4, the Netherlands, 1994-2005(CENTER DISEASE CONTROL, 2007-01)From 1994 through 2005, gastroenteritis outbreaks caused by norovirus generally increased in the Netherlands, with 3 epidemic seasons associated with new GGII.4 strains. Increased percentages of GGII.4 strains during these epidemics, followed by a sharp decrease in their absolute and relative numbers, suggest development of immunity.
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ItemAn Integrated Approach to Identifying International Foodborne Norovirus Outbreaks(CENTERS DISEASE CONTROL & PREVENTION, 2011-03)International foodborne norovirus outbreaks can be difficult to recognize when using standard outbreak investigation methods. In a novel approach, we provide step-wise selection criteria to identify clusters of outbreaks that may involve an internationally distributed common foodborne source. After computerized linking of epidemiologic data to aligned sequences, we retrospectively identified 100 individually reported outbreaks that potentially represented 14 international common source events in Europe during 1999-2008. Analysis of capsid sequences of outbreak strains (n = 1,456), showed that ≈7% of outbreaks reported to the Foodborne Viruses in Europe database were part of an international event (range 2%-9%), compared with 0.4% identified through standard epidemiologic investigations. Our findings point to a critical gap in surveillance and suggest that international collaboration could have increased the number of recognized international foodborne outbreaks. Real-time exchange of combined epidemiologic and molecular data is needed to validate our findings through timely trace-backs of clustered outbreaks.
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ItemPhylodynamic Reconstruction Reveals Norovirus GII. 4 Epidemic Expansions and their Molecular Determinants(PUBLIC LIBRARY SCIENCE, 2010-05)Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3-9.0x10(-3) mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern.