Advertisement

Burden of norovirus in healthcare facilities and strategies for outbreak control

Published:February 04, 2015DOI:https://doi.org/10.1016/j.jhin.2015.01.011

      Summary

      Norovirus is the most frequently occurring cause of community-acquired acute gastroenteritis in people of all ages. It is also one of the most frequent causes of outbreaks in healthcare settings, affecting both long-term care facilities and acute care hospitals. Whereas norovirus gastroenteritis is typically mild and resolves without medical attention, healthcare-associated infections often affect vulnerable populations, resulting in severe infections and disruption of healthcare services. Globally, most norovirus outbreaks in hospitals and residential care institutions are associated with genogroup II type 4 (GII.4) strains. Recent data demonstrate that excess mortality occurs during outbreak periods in healthcare facilities. Nosocomial outbreaks can result in large economic and societal costs. Current control measures for norovirus are largely based on general infection control principles, and treatment is mainly supportive and non-specific. While neither vaccines nor antiviral agents are currently available, both are being developed with encouraging results.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hospital Infection
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ahmed S.M.
        • Hall A.J.
        • Robinson A.E.
        • et al.
        Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis.
        Lancet Infect Dis. 2014; 14: 725-730
        • Hall A.J.
        • Lopman B.A.
        • Payne D.C.
        • et al.
        Norovirus disease in the United States.
        Emerg Infect Dis. 2013; 19: 1198-1205
        • Lopman B.A.
        • Reacher M.H.
        • Vipond I.B.
        • et al.
        Epidemiology and cost of nosocomial gastroenteritis, Avon, England, 2002‒2003.
        Emerg Infect Dis. 2004; 10: 1827-1834
        • Lopman B.A.
        • Adak G.K.
        • Reacher M.H.
        • Brown D.W.
        Two epidemiologic patterns of norovirus outbreaks: surveillance in England and Wales, 1992–2000.
        Emerg Infect Dis. 2003; 9: 71
        • Kroneman A.
        • Verhoef L.
        • Harris J.
        • et al.
        Analysis of integrated virological and epidemiological reports of norovirus outbreaks collected within the Foodborne Viruses in Europe network from 1 July 2001 to 30 June 2006.
        J Clin Microbiol. 2008; 46: 2959-2965
        • Lopman B.
        • Vennema H.
        • Kohli E.
        • et al.
        Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant.
        Lancet. 2004; 363: 682-688
        • Godoy P.
        • Ferrus G.
        • Torner N.
        • et al.
        High incidence of norovirus GII.4 outbreaks in hospitals and nursing homes in Catalonia (Spain), 2010–2011.
        Epidemiol Infect. 2014; https://doi.org/10.1017/S0950268814001204
        • Hall A.J.
        • Wikswo M.E.
        • Manikonda K.
        • Roberts V.A.
        • Yoder J.S.
        • Gould L.H.
        Acute gastroenteritis surveillance through the National Outbreak Reporting System, United States.
        Emerg Infect Dis. 2013; 19
        • Rhinehart E.
        • Walker S.
        • Murphy D.
        • O'Reilly K.
        • Leeman P.
        Frequency of outbreak investigations in US hospitals: results of a national survey of infection preventionists.
        Am J Infect Control. 2012; 40: 2-8
        • Tam C.C.
        • Rodrigues L.C.
        • Viviani L.
        • et al.
        Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice.
        Gut. 2012; 61: 69-77
        • Beersma M.F.
        • Sukhrie F.H.
        • Bogerman J.
        • et al.
        Unrecognized norovirus infections in health care institutions and their clinical impact.
        J Clin Microbiol. 2012; 50: 3040-3045
        • Patel M.M.
        • Hall A.J.
        • Vinjé J.
        • Parashar U.D.
        Noroviruses: a comprehensive review.
        J Clin Virol. 2009; 44: 1-8
        • Kroneman A.
        • Vega E.
        • Vennema H.
        • et al.
        Proposal for a unified norovirus nomenclature and genotyping.
        Arch Virol. 2013; 158: 2059-2068
        • Teunis P.F.
        • Moe C.L.
        • Liu P.
        • et al.
        Norwalk virus: how infectious is it?.
        J Med Virol. 2008; 80: 1468-1476
        • Atmar J.
        • Mullen E.
        Norovirus in immunocompromised patients.
        Oncol Nurs Forum. 2013; 40: 434-436
        • Repp K.K.
        • Keene W.E.
        A point-source norovirus outbreak caused by exposure to fomites.
        J Infect Dis. 2012; 205: 1639-1641
        • Hall A.J.
        • Wikswo M.E.
        • Pringle K.
        • et al.
        Vital signs: foodborne norovirus outbreaks ‒ United States, 2009‒2012.
        Morb Mortal Wkly Rep. 2014; 63: 491-495
        • Arvelo W.
        • Sosa S.M.
        • Juliao P.
        • et al.
        Norovirus outbreak of probable waterborne transmission with high attack rate in a Guatemalan resort.
        J Clin Virol. 2012; 55: 8-11
        • Cheesbrough J.S.
        • Green J.
        • Gallimore C.I.
        • Wright P.A.
        • Brown D.W.
        Widespread environmental contamination with Norwalk-like viruses (NLV) detected in a prolonged hotel outbreak of gastroenteritis.
        Epidemiol Infect. 2000; 125: 93-98
        • Glass R.I.
        • Parashar U.D.
        • Estes M.K.
        Norovirus gastroenteritis.
        N Engl J Med. 2009; 361: 1776-1785
        • Morter S.
        • Bennet G.
        • Fish J.
        • et al.
        Norovirus in the hospital setting: virus introduction and spread within the hospital environment.
        J Hosp Infect. 2011; 77: 106-112
        • Thornley C.N.
        • Emslie N.A.
        • Sprott T.W.
        • Greening G.E.
        • Rapana J.P.
        Recurring norovirus transmission on an airplane.
        Clin Infect Dis. 2011; 53: 521-526
        • Nenonen N.P.
        • Hannoun C.
        • Svensson L.
        • et al.
        Norovirus GII.4 detection in environmental samples from patient rooms during nosocomial outbreaks.
        J Clin Microbiol. 2014; 52: 2352-2358
        • Phillips G.
        • Tam C.C.
        • Rodrigues L.C.
        • Lopman B.
        Prevalence and characteristics of asymptomatic norovirus infection in the community in England.
        Epidemiol Infect. 2010; 138: 1454-1458
        • Atmar R.L.
        • Opekun A.R.
        • Gilger M.A.
        • et al.
        Norwalk virus shedding after experimental human infection.
        Emerg Infect Dis. 2008; 14: 1553
        • García C.
        • DuPont H.L.
        • Long K.Z.
        • Santos J.I.
        • Ko G.
        Asymptomatic norovirus infection in Mexican children.
        J Clin Microbiol. 2006; 44: 2997-3000
        • Lopman B.A.
        • Reacher M.H.
        • Vipond I.B.
        • Sarangi J.
        • Brown D.W.
        Clinical manifestation of norovirus gastroenteritis in health care settings.
        Clin Infect Dis. 2004; 39: 318-324
        • Frange P.
        • Touzot F.
        • Debré M.
        • et al.
        Prevalence and clinical impact of norovirus fecal shedding in children with inherited immune deficiencies.
        J Infect Dis. 2012; 206: 1269-1274
        • Kaufman S.S.
        • Green K.Y.
        • Korba B.E.
        Treatment of norovirus infections: moving antivirals from the bench to the bedside.
        Antiviral Res. 2014; 105: 80-91
        • Munir N.
        • Liu P.
        • Gastañaduy P.
        • Montes J.
        • Shane A.
        • Moe C.
        Norovirus infection in immunocompromised children and children with hospital-acquired acute gastroenteritis.
        J Med Virol. 2014; 86: 1203-1209
        • Wingfield T.
        • Gallimore C.I.
        • Xerry J.
        • et al.
        Chronic norovirus infection in an HIV-positive patient with persistent diarrhoea: a novel cause.
        J Clin Virol. 2010; 49: 219-222
        • Hall A.J.
        • Jan Vinjé D.V.M.
        • Lopman B.
        • et al.
        Updated norovirus outbreak management and disease prevention guidelines.
        MMWR Recomm Rep. 2011; 60: 1-18
        • Sukhrie F.H.
        • Siebenga J.J.
        • Beersma M.F.
        • Koopmans M.
        Chronic shedders as reservoir for nosocomial transmission of norovirus.
        J Clin Microbiol. 2010; 48: 4303-4305
        • Siebenga J.J.
        • Beersma M.F.
        • Vennema H.
        • van Biezen P.
        • Hartwig N.J.
        • Koopmans M.
        High prevalence of prolonged norovirus shedding and illness among hospitalized patients: a model for in vivo molecular evolution.
        J Infect Dis. 2008; 198: 994-1001
        • Ludwig A.
        • Adams O.
        • Laws H.J.
        • Schroten H.
        • Tenenbaum T.
        Quantitative detection of norovirus excretion in pediatric patients with cancer and prolonged gastroenteritis and shedding of norovirus.
        J Med Virol. 2008; 80: 1461-1467
        • Harris J.P.
        • Edmunds W.J.
        • Pebody R.
        • Brown D.W.
        • Lopman B.A.
        Deaths from norovirus among the elderly, England and Wales.
        Emerg Infect Dis. 2008; 14: 1546-1552
        • Hall A.J.
        • Curns A.T.
        • McDonald L.C.
        • Parashar U.D.
        • Lopman B.A.
        The roles of Clostridium difficile and norovirus among gastroenteritis-associated deaths in the United States, 1999‒2007.
        Clin Infect Dis. 2012; 55: 216-223
        • Gustavsson L.
        • Andersson L.M.
        • Lindh M.
        • Westin J.
        Excess mortality following community-onset norovirus enteritis in the elderly.
        J Hosp Infect. 2011; 79: 27-31
        • Koo H.L.
        • DuPont H.L.
        Noroviruses as a potential cause of protracted and lethal disease in immunocompromised patients.
        Clin Infect Dis. 2009; 49: 1069-1071
        • Desai R.
        • Hembree C.D.
        • Handel A.
        • et al.
        Severe outcomes are associated with genogroup 2 genotype 4 norovirus outbreaks: a systematic literature review.
        Clin Infect Dis. 2012; 55: 189-193
        • van Asten L.
        • Siebenga J.
        • van den Wijngaard C.
        • et al.
        Unspecified gastroenteritis illness and deaths in the elderly associated with norovirus epidemics.
        Epidemiology. 2011; 22: 336-343
        • van Asten L.
        • van den Wijngaard C.
        • van Pelt W.
        • et al.
        Mortality attributable to 9 common infections: significant effect of influenza A, respiratory syncytial virus, influenza B, norovirus, and parainfluenza in elderly persons.
        J Infect Dis. 2012; 206: 628-639
        • Lindesmith L.C.
        • Donaldson E.F.
        • Lobue A.D.
        • et al.
        Mechanisms of GII.4 norovirus persistence in human populations.
        PLoS Med. 2008; 5: e31
        • Siebenga J.J.
        • Vennema H.
        • Zheng D.P.
        • et al.
        Norovirus illness is a global problem: emergence and spread of norovirus GII.4 variants, 2001–2007.
        J Infect Dis. 2009; 200: 802-812
        • Debbink K.
        • Lindesmith L.C.
        • Donaldson E.F.
        • et al.
        Emergence of new pandemic GII.4 Sydney norovirus strain correlates with escape from herd immunity.
        J Infect Dis. 2013; 208: 1877-1887
        • Sakon N.
        • Yamazaki K.
        • Nakata K.
        • et al.
        Impact of genotype-specific herd immunity on the circulatory dynamism of norovirus: a 10-year longitudinal study of viral acute gastroenteritis.
        J Infect Dis. 2014; https://doi.org/10.1093/infdis/jiu496
        • Siebenga J.J.
        • Vennema H.
        • Renckens B.
        • et al.
        Epochal evolution of GGII.4 norovirus capsid proteins from 1995 to 2006.
        J Virol. 2007; 81: 9932-9941
        • Bull R.A.
        • Tu E.T.
        • McIver C.J.
        • Rawlinson W.D.
        • White P.A.
        Emergence of a new norovirus genotype II.4 variant associated with global outbreaks of gastroenteritis.
        J Clin Microbiol. 2006; 44: 327-333
        • White P.A.
        Evolution of norovirus.
        Clin Microbiol Infect. 2014; 20: 741-745
        • Trivedi T.K.
        • DeSalvo T.
        • Lee L.
        • et al.
        Hospitalizations and mortality associated with norovirus outbreaks in nursing homes, 2009‒2010.
        JAMA. 2012; 308: 1668-1675
        • Rondy M.
        • Koopmans M.
        • Rotsaert C.
        • et al.
        Norovirus disease associated with excess mortality and use of statins: a retrospective cohort study of an outbreak following a pilgrimage to Lourdes.
        Epidemiol Infect. 2011; 139: 453-463
        • Harris J.P.
        • Lopman B.A.
        • Cooper B.S.
        • O'Brien S.J.
        Does spatial proximity drive norovirus transmission during outbreaks in hospitals?.
        BMJ Open. 2013; 3
        • Johnston C.P.
        • Qiu H.
        • Ticehurst J.R.
        • et al.
        Outbreak management and implications of a nosocomial norovirus outbreak.
        Clin Infect Dis. 2007; 45: 534-540
        • Sukhrie F.H.
        • Teunis P.
        • Vennema H.
        • et al.
        Nosocomial transmission of norovirus is mainly caused by symptomatic cases.
        Clin Infect Dis. 2012; 54: 931-937
        • Harris J.
        • Lopman B.
        • O'Brien S.
        Infection control measures for norovirus: a systematic review of outbreaks in semi-enclosed settings.
        J Hosp Infect. 2010; 74: 1-9
        • Barclay L.
        • Park G.W.
        • Vega E.
        • et al.
        Infection control for norovirus.
        Clin Microbiol Infect. 2014; 20: 731-740
        • MacCannell T.
        • Umscheid C.A.
        • Agarwal R.K.
        • Lee I.
        • Kuntz G.
        • Stevenson K.B.
        • Healthcare Infection Control Practices Advisory Committee ‒ HICPAC
        Guideline for the prevention and control of norovirus gastroenteritis outbreaks in healthcare settings.
        Infect Control Hosp Epidemiol. 2011; 32: 939-969
        • Friesema I.H.
        • Vennema H.
        • Heijne J.C.
        • et al.
        Norovirus outbreaks in nursing homes: the evaluation of infection control measures.
        Epidemiol Infect. 2009; 137: 1722-1733
        • Zingg W.
        • Colombo C.
        • Jucker T.
        • Bossart W.
        • Ruef C.
        Impact of an outbreak of norovirus infection on hospital resources.
        Infect Control Hosp Epidemiol. 2005; 26: 263-267
        • Arias A.
        • Emmott E.
        • Vashist S.
        • Goodfellow I.
        Progress towards the prevention and treatment of norovirus infections.
        Future Microbiol. 2013; 8: 1475-1487
        • Bartsch S.M.
        • Lopman B.A.
        • Hall A.J.
        • Parashar U.D.
        • Lee B.Y.
        The potential economic value of a human norovirus vaccine for the United States.
        Vaccine. 2012; 30: 7097-7104
        • Vesikari T.
        • Blazevic V.
        Norovirus vaccine: one step closer.
        J Infect Dis. 2014; https://doi.org/10.1093/infdis/jiu498
        • Jones M.K.
        • Watanabe M.
        • Zhu S.
        • et al.
        Enteric bacteria promote human and murine norovirus infection of B cells.
        Science. 2014; 346: 755-759
        • Richardson C.
        • Bargatze R.F.
        • Goodwin R.
        • Mendelman P.M.
        Norovirus virus-like particle vaccines for the prevention of acute gastroenteritis.
        Expert Rev Vaccines. 2013; 12: 155-167
        • Atmar R.L.
        • Estes M.K.
        Norovirus vaccine development: next steps.
        Expert Rev Vaccines. 2012; 11: 1023-1025
        • Debbink K.
        • Lindesmith L.C.
        • Baric R.S.
        The state of norovirus vaccines.
        Clin Infect Dis. 2014; 58: 1746-1752
        • Roldão A.
        • Mellado M.C.
        • Castilho L.R.
        • Carrondo M.J.
        • Alves P.M.
        Virus-like particles in vaccine development.
        Exp Rev Vaccines. 2010; 9: 1149-1176
        • Atmar R.L.
        • Bernstein D.I.
        • Harro C.D.
        • et al.
        Norovirus vaccine against experimental human Norwalk virus illness.
        N Engl J Med. 2011; 365: 2178-2187
        • Bernstein D.I.
        • Atmar R.L.
        • Lyon G.M.
        • et al.
        Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.
        J Infect Dis. 2014; https://doi.org/10.1093/infdis/jiu497
        • Treanor J.J.
        • Atmar R.L.
        • Frey S.E.
        • et al.
        A novel intramuscular bivalent norovirus virus-like particle vaccine candidate ‒ reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults.
        J Infect Dis. 2014; 210: 1763-1771
        • Velasquez L.S.
        • Shira S.
        • Berta A.N.
        • et al.
        Intranasal delivery of Norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine.
        Vaccine. 2011; 29: 5221-5231
        • Tamminen K.
        • Lappalainen S.
        • Huhti L.
        • Vesikari T.
        • Blazevic V.
        Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
        PLoS One. 2013; 8: e70409
        • Tan M.
        • Jiang X.
        Norovirus P particle: a subviral nanoparticle for vaccine development against norovirus, rotavirus and influenza virus.
        Nanomedicine (Lond). 2012; 7: 889-897
        • Fang H.
        • Tan M.
        • Xia M.
        • Wang L.
        • Jiang X.
        Norovirus P particle efficiently elicits innate, humoral and cellular immunity.
        PloS One. 2013; 8: e63269
        • Kocher J.
        • Bui T.
        • Giri-Rachman E.
        • et al.
        Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs.
        J Virol. 2014; 88: 9728-9743
        • Ramani S.
        • Atmar R.L.
        • Estes M.K.
        Epidemiology of human noroviruses and updates on vaccine development.
        Curr Opin Gastroenterol. 2014; 30: 25-33
        • Parrino T.A.
        • Schreiber D.S.
        • Trier J.S.
        • Kapikian A.Z.
        • Blacklow N.R.
        Clinical immunity in acute gastroenteritis caused by Norwalk agent.
        N Engl J Med. 1977; 297: 86-89
        • Johnson P.C.
        • Mathewson J.J.
        • DuPont H.L.
        • Greenberg H.B.
        Multiple-challenge study of host susceptibility to Norwalk gastroenteritis in US adults.
        J Infect Dis. 1990; 161: 18-21
        • Wyatt R.G.
        • Dolin R.
        • Blacklow N.R.
        • et al.
        Comparison of three agents of acute infectious nonbacterial gastroenteritis by cross-challenge in volunteers.
        J Infect Dis. 1974; 129: 709-714