Hospitalizations and Mortality Associated With Norovirus Outbreaks in Nursing Homes, 2009-2010

Trivedi, Tarak; DeSalvo, Traci; Lee, Lore; Palumbo, Aimee J.; Moll, María Adalid; Curns, Aaron T.; Hall, Aron J.; Patel, Manish; Parashar, Umesh D.; Lopman, Benjamin A.

doi:10.1001/jama.2012.14023

Cited by 93 publications

(72 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12,13 This outcome is especially true for immunocompromised patients and others at high risk for infection, such as neonates. [14][15][16][17] Despite increased national emphasis and progress on developing strategies for prevention of health care-associated infections, 18 little attention has been directed toward understanding and preventing pathogen transmission from ill HCWs to patients. Numerous reports have documented that HCWs often provide patient care while symptomatic rather than staying home.…”

mentioning

confidence: 99%

Reasons Why Physicians and Advanced Practice Clinicians Work While Sick

et al. 2015

View full text Add to dashboard Cite

IMPORTANCE When clinicians work with symptoms of infection, they can put patients and colleagues at risk. Little is known about the reasons why attending physicians and advanced practice clinicians (APCs) work while sick.OBJECTIVE To identify a comprehensive understanding of the reasons why attending physicians and APCs work while sick. DESIGN, SETTING, AND PARTICIPANTS We performed a mixed-methods analysis of a cross-sectional, anonymous survey administered from January 15 through March 20, 2014, in a large children's hospital in Philadelphia, Pennsylvania. Data were analyzed from April 1 through June 1, 2014. The survey was administered to 459 attending physicians and 470 APCs, including certified registered nurse practitioners, physician assistants, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives. MAIN OUTCOMES AND MEASURES Self-reported frequency of working while experiencing symptoms of infection, perceived importance of various factors that encourage working while sick, and free-text comments written in response to open-ended questions. RESULTS Of those surveyed, we received responses from 280 attending physicians (61.0%) and 256 APCs (54.5%). Most of the respondents (504 [95.3%]) believed that working while sick put patients at risk. Despite this belief, 446 respondents (83.1%) reported working sick at least 1 time in the past year, and 50 (9.3%) reported working while sick at least 5 times. Respondents would work with significant symptoms, including diarrhea (161 [30.0%]), fever (86 [16.0%]), and acute onset of significant respiratory symptoms (299 [55.6%]). Physicians were more likely to report working with each of these symptoms than APCs (109 [38.9%] vs 51 [19.9%], 61 [21.8%] vs 25 [9.8%], and 168 [60.0%] vs 130 [50.8%], respectively [P < .05]). Reasons deemed important in deciding to work while sick included not wanting to let colleagues down (521 [98.7%]), staffing concerns (505 [94.9%]), not wanting to let patients down (494 [92.5%]), fear of ostracism by colleagues (342 [64.0%]), and concern about continuity of care (337 [63.8%]). Systematic qualitative analysis of free-text comments from 316 respondents revealed additional reasons why attending physicians and APCs work while sick, including extreme difficulty finding coverage (205 [64.9%]), a strong cultural norm to come to work unless remarkably ill (193 [61.1%]), and ambiguity about what constitutes "too sick to work" (180 [57.0%]). CONCLUSIONS AND RELEVANCE Attending physicians and APCs frequently work while sick despite recognizing that this choice puts patients at risk. The decision to work sick is shaped by systems-level and sociocultural factors. Multimodal interventions are needed to reduce the frequency of this behavior.

show abstract

mentioning

confidence: 99%

Reasons Why Physicians and Advanced Practice Clinicians Work While Sick

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Globally, NoV-associated deaths are estimated at 200,000 per year (3). Usually, disease severity is modest, but our awareness of morbidity and mortality rates, particularly among the young, elderly, and immunocompromised, is increasing (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). An effective vaccine would benefit not only these highly susceptible populations, but also military, child care, health care, and food industry personnel.…”

mentioning

confidence: 99%

Particle Conformation Regulates Antibody Access to a Conserved GII.4 Norovirus Blockade Epitope

Lindesmith

Donaldson

Beltramello³

et al. 2014

J Virol

105

View full text Add to dashboard Cite

GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade epitopes, we have identified monoclonal antibodies (MAbs) that recognize a blockade epitope conserved across time-ordered GII.4 strains. Uniquely, the blockade potencies of MAbs that recognize the conserved GII.4 blockade epitope were temperature sensitive, suggesting that particle conformation may regulate functional access to conserved blockade non-surface-exposed epitopes. To map conformation-regulating motifs, we used bioinformatics tools to predict conserved motifs within the protruding domain of the capsid and designed mutant VLPs to test the impacts of substitutions in these motifs on antibody cross-GII.4 blockade. Charge substitutions at residues 310, 316, 484, and 493 impacted the blockade potential of cross-GII.4 blockade MAbs with minimal impact on the blockade of MAbs targeting other, separately evolving blockade epitopes. Specifically, residue 310 modulated antibody blockade temperature sensitivity in the tested strains. These data suggest access to the conserved GII.4 blockade antibody epitope is regulated by particle conformation, temperature, and amino acid residues positioned outside the antibody binding site. The regulating motif is under limited selective pressure by the host immune response and may provide a robust target for broadly reactive NoV therapeutics and protective vaccines. IMPORTANCEIn this study, we explored the factors that govern norovirus (NoV) cross-strain antibody blockade. We found that access to the conserved GII.4 blockade epitope is regulated by temperature and distal residues outside the antibody binding site. These data are most consistent with a model of NoV particle conformation plasticity that regulates antibody binding to a distally conserved blockade epitope. Further, antibody "locking" of the particle into an epitope-accessible conformation prevents ligand binding, providing a potential target for broadly effective drugs. These observations open lines of inquiry into the mechanisms of human NoV entry and uncoating, fundamental biological questions that are currently unanswerable for these noncultivatable pathogens.

show abstract

“…In the United States, NoVs cause 19 to 21 million cases each year (4,5). NoV outbreaks have been identified in children (6), the elderly (7), military personnel (8,9), immunocompromised individuals (10), restaurant patrons (11,12), travelers to developing countries (13,14), passengers of cruise ships (15), residents of health care facilities such as nursing homes (16,17) and hospitals (18), and other populations housed in close quarters (19). The increasing incidence of NoV infections emphasizes the need to quickly detect and identify the causative agent, because early diagnosis of NoV infection can be crucial in the effective control of outbreaks and can decrease the secondary attack rate (20).…”

mentioning

confidence: 99%