Christianne Biggs

Effects and Clinical Significance of GII.4 Sydney Norovirus, United States, 2012–2013

During 2012, global detection of a new norovirus (NoV) strain, GII.4 Sydney, raised concerns about its potential effect in the United States. We analyzed data from NoV outbreaks in 5 states and emergency department visits for gastrointestinal illness in 1 state during the 2012–13 season and compared the data with those of previous seasons. During August 2012–April 2013, a total of 637 NoV outbreaks were reported compared with 536 and 432 in 2011–2012 and 2010–2011 during the same period. The proportion of outbreaks attributed to GII.4 Sydney increased from 8% in September 2012 to 82% in March 2013. The increase in emergency department visits for gastrointestinal illness during the 2012–13 season was similar to that of previous seasons. GII.4 Sydney has become the predominant US NoV outbreak strain during the 2012–13 season, but its emergence did not cause outbreak activity to substantially increase from that of previous seasons.

Diagnostic Accuracy and Analytical Sensitivity of IDEIA Norovirus Assay for Routine Screening of Human Norovirus

ABSTRACT Noroviruses (NoVs) are recognized as the leading cause of epidemic and sporadic acute gastroenteritis. Early detection of NoV is crucial to control the spread of the disease. In this study, we evaluated the diagnostic accuracy, analytical sensitivity, and analytical reactivity of the IDEIA Norovirus assay (an enzyme immunoassay [EIA]) in a prospective and retrospective study design. A total of 557 prospectively collected fecal samples and a panel of 97 archived fecal samples, including 21 different GI and GII genotypes, were tested by conventional reverse transcription-PCR (RT-PCR)/bidirectional sequencing, real-time RT-PCR, and electron microscopy. The sensitivity and specificity of the EIA were 57.6% and 91.9%, respectively. The sensitivity for detecting NoV in fecal samples from outbreaks improved from 44.1% when three samples were tested to 76.9% when five samples per outbreak were tested. The EIA was able to detect strains from 7 GI and 11 GII genotypes. The analytical sensitivity of the EIA was 3.1 × 106 and 1.6 × 107 virus particles g−1 of fecal sample for NoV GI and GII strains, respectively. Most GII samples positive by EIA had a threshold cycle (CT ) of <26.5, and 50% of the GII samples negative by EIA had a CT of >25.6, suggesting that, although strains from genotypes GI.8, GII.10, and GII.16 were not detected, the low sensitivity of the EIA is primarily caused by low virus concentration. In conclusion, the current EIA may be of use as a rapid screening test during a norovirus outbreak investigation when multiple fecal samples are available; however, sporadic samples should be tested by molecular methods.

Epidemiologic, Virologic, and Host Genetic Factors of Norovirus Outbreaks in Long-term Care Facilities

BACKGROUND In the Unites States, long-term care facilities (LTCFs) are the most common setting for norovirus outbreaks. These outbreaks provide a unique opportunity to better characterize the viral and host characteristics of norovirus disease. METHODS We enrolled 43 LTCFs prospectively to study the epidemiology, virology, and genetic host factors of naturally occurring norovirus outbreaks. Acute and convalescent stool, serum, and saliva samples from cases, exposed and nonexposed controls were collected. Norovirus infection was confirmed using quantitative polymerase chain reaction testing of stool samples or 4-fold increase in serum antibody titers. The presence of histo-blood group antigens (secretor, ABO, and Lewis type) was determined in saliva. RESULTS Sixty-two cases, 34 exposed controls, and 18 nonexposed controls from 10 norovirus outbreaks were enrolled. Forty-six percent of acute, 27% of convalescent case, and 11% of control stool samples tested norovirus positive. Outbreak genotypes were GII.4 (Den Haag, n = 3; New Orleans, n = 4; and Sydney, n = 2) and GI.1 (n = 1). Viral load in GII.4 Sydney outbreaks was significantly higher than in outbreaks caused by other genotypes; cases and controls shed similar amounts of virus. Forty-seven percent of cases shed virus for ≥ 21 days. Symptomatic infections with GII.4 Den Haag and GII.4 New Orleans were detected among nonsecretor individuals. CONCLUSIONS Almost half of all symptomatic individuals shed virus for at least 21 days. Viral load was highest in GII.4 viruses that most recently emerged; these viruses also infect the nonsecretor population. These findings will help to guide development of targeted prevention and control measures in the elderly.

Incidence of Norovirus and Other Viral Pathogens That Cause Acute Gastroenteritis (AGE) among Kaiser Permanente Member Populations in the United States, 2012-2013.

Noroviruses and other viral pathogens are increasingly recognized as frequent causes of acute gastroenteritis (AGE). However, few laboratory-based data are available on the incidence of AGE caused by viral pathogens in the U.S. This study examined stool specimens submitted for routine clinical diagnostics from patients enrolled in Kaiser Permanente (KP) health plans in metro Portland, OR, and the Maryland, District of Columbia, and northern Virginia geographic areas to estimate the incidence of viral enteropathogens in these populations. Over a one-year study period, participating laboratories randomly selected stools submitted for routine clinical diagnostics for inclusion in the study along with accompanying demographic and clinical data. Selected stools were tested for norovirus, rotavirus, sapovirus, and astrovirus using standardized real-time RT-PCR protocols. Each KP site provided administrative data which were used in conjunction with previously published data on healthcare utilization to extrapolate pathogen detection rates into population-based incidence rates. A total of 1,099 specimens collected during August 2012 to September 2013 were included. Mean age of patients providing stool specimens was 46 years (range: 0–98 years). Noroviruses were the most common viral pathogen identified among patients with AGE (n = 63 specimens, 6% of specimens tested). In addition, 22 (2%) of specimens were positive for rotavirus; 19 (2%) were positive for sapovirus; and 7 (1%) were positive for astrovirus. Incidence of norovirus-associated outpatient visits was 5.6 per 1,000 person-years; incidence of norovirus disease in the community was estimated to be 69.5 per 1,000 person-years. Norovirus incidence was highest among children <5 years of age (outpatient incidence = 25.6 per 1,000 person-years; community incidence = 152.2 per 1,000 person-years), followed by older adults aged >65 years (outpatient incidence = 7.8 per 1,000 person-years; community incidence = 75.8 per 1,000 person-years). Outpatient incidence rates of rotavirus, sapovirus, and astrovirus were 2.0, 1.6, 0.6 per 1,000 person-years, respectively; community incidence rates for these viruses were 23.4, 22.5, and 8.5 per 1,000 person-years, respectively. This study provides the first age-group specific laboratory-based community and outpatient incidence rates for norovirus AGE in the U.S. Norovirus was the most frequently detected viral enteropathogen across the age spectrum with the highest rates of norovirus disease observed among young children and, to a lesser extent, the elderly. These data provide a better understanding of the norovirus disease burden in the United States, including variations within different age groups, which can help inform the development, targeting, and future impacts of interventions, including vaccines.

Specimen Collection and Confirmation of Norovirus Outbreaks

We evaluated data from gastroenteritis outbreaks in Oregon to assess sensitivity of stool testing for norovirus and determine number of specimens needed to confirm norovirus as the cause. Norovirus can be readily confirmed if 3–6 specimens are collected any time <7 days after onset of diarrhea and for almost that long after symptoms resolve.