The launch of CaliciNet in March 2009 was a milestone in the surveillance of norovirus gastroenteritis in the United States. CaliciNet enables standardized genotyping of norovirus strains, comparison of sequences from outbreaks that have a common source, and identification of new strains in real-time. The usefulness of CaliciNet was demonstrated during the winter of 2009–2010 when the emergence of a new GII.4 variant (GII.4 New Orleans) was identified. This new variant caused 60% of the outbreaks and replaced GII.4 Minerva as the predominant GII.4 strain. In addition, a new GII.12 strain caused 17% of the outbreaks during the winter of 2009–2010 (35
GII.4 New Orleans was first detected in October 2009, and the proportion of all norovirus outbreaks it caused increased gradually to >50% during the winter months. Compared with known GII.4 viruses, GII.4 New Orleans had several changes in key amino acids in the P2 region of VP1 and around the sites that have been shown to be important in HBGA binding (20
). Because most GII.4 variants that have been identified since 2004 are conserved at these sites, it has been speculated that mutations that change the HBGA binding pattern would decrease the fitness of the virus (36
). During the last transitional period when GII.4 Minerva (GII.4 2006b) was identified, another GII.4 variant was co-circulating (21
CaliciNet uses the same software as the US bacterial enteric pathogen surveillance network (PulseNet) (38
), but it is customized with plug-ins to add CaliciNet-specific functionality. CaliciNet uses sequence data, whereas PulseNet is based on pulsed-field gel electrophoresis restriction digestion patterns of bacterial enteric pathogens. Current typing regions of CaliciNet target small regions of the norovirus genome, which makes it difficult to discern closely related norovirus strains, although the implications to human health may be significant. Our data and data from other studies (39
) demonstrated that P2 region analysis enables more sensitive identification of new GII.4 variant strains compared with currently used CaliciNet regions. Use of these analyses would increase the sensitivity of outbreak surveillance to track strains that are part of a single outbreak and likely to have a common source. Hence, P2 is under consideration to be included in CaliciNet.
Like CaliciNet, the Foodborne Viruses in Europe network (FBVE) uses a central database to which users can submit norovirus sequences (40
). Compared with the FBVE network, CaliciNet focuses primarily on noroviruses, is not web-based, and is based on a secured network connection to CaliciNet servers at CDC where the states log on as clients, enabling them to upload, view, and query outbreak data submitted by other states. CaliciNet also organizes training workshops and sends standardized protocols and annual proficiency panels to its members. The benefit of the FBVE network is that it can be more easily expanded to include laboratories outside its network, whereas to date CaliciNet allows only participants from state and local health laboratories in the US to participate.
The success of CaliciNet in linking multistate outbreaks to a common source (e.g., contaminated food) will depend on joint efforts of state and local epidemiologists to rapidly identify the likely common source and on CaliciNet laboratories for the timely upload of outbreak sequences to the national CaliciNet database. Although CaliciNet has selected region D as its preferred sequence region, a region C and soon a P2 region sequence database will be maintained to enable exchange of information with other norovirus surveillance networks. Because the region D assay targets a genetically highly heterogeneous region of VP1, the performance of this assay will be closely monitored over time, and necessary changes will be implemented to improve assay sensitivity and specificity. Future CaliciNet expansion will include other gastroenteritis viruses, such as sapovirus and astrovirus, as well as add capability for CaliciNet members to submit fecal samples from patients involved in norovirus-negative outbreaks to CDC for further testing, including novel pathogen discovery sequencing technologies (18
CaliciNet was launched in March 2009 and helped in the rapid identification of a new GII.4 variant. P2 analysis confirmed that this variant was divergent from previous GII.4 viruses. The widespread presence of GII.4 New Orleans across the US coupled with the decreasing prevalence of the GII.4 Minerva variant, which has been the major cause of outbreaks during 2006–2009, suggests gradual strain displacement. Data from the 2009–2010 winter season showed the importance of CaliciNet and its future potential for norovirus surveillance in the US. To enhance norovirus surveillance globally, CaliciNet will collaborate with other norovirus surveillance networks, such as ViroNet in Canada and the global norovirus network, NoroNet (15
), to better predict or determine norovirus epidemiologic or outbreak trends. International surveillance of viral foodborne outbreaks is essential because of the increasing globalization of the food industry.
Additional members of the Calicivirus network who contributed data (state represented): Chao-Yang Pan, Tasha Padilla (CA); Justin Nucci, Mary-Kate Cichon (CO); Gregory Hovan (DE); Precilia Calimlim, Cheryl-Lynn Daquip (HI); Edward Simpson (IN); Amanda Bruesch, Kari Getz (ID); Jonathan Johnston, Julie Haendiges (MD); Heather Grieser, John Martha (ME); Laura Mosher (MI); Elizabeth Cebelinski (MN); Alisha M. Nadeau, Fengxiang Gao (NH); Ondrea Shone (NJ); Frederick Gentry (NM); Gino Battaglioli (NY), Eric Brandt, Rebekah Carmen, Steven York (OH); Andrea Maloney (SC); Amy M. Woron, Christina Moore (TN); Chun Wang (TX); Valarie Devlin (VT); Tim Davis, Tonya Danz, and Jose Navidad (WI).