Humoral and Mucosal Immune Responses to Human Norovirus in the Elderly.

BACKGROUND: Most information on mucosal and systemic immune response to norovirus infection is derived from human challenge studies, birth cohort studies, or vaccine trials in healthy adults. However, few data are available on immune responses to norovirus in the elderly. METHODS: To study the mucosal and systemic immune response against norovirus, 43 long-term care facilities were enrolled prospectively in 2010-2014. Baseline saliva samples from 17 facilities, cases and controls up to day 84 from 10 outbreaks, as well as acute and convalescent sera were collected. RESULTS: Norovirus-specific immunoglobulin A (IgA) levels in baseline saliva samples were low and increased in both symptomatic patients and asymptomatic shedders at day 5 after onset during outbreaks. Receiver operating characteristics analysis correctly assigned prior norovirus infection in 23 (92%) of 25 participants. Cases and asymptomatic shedders showed seroconversion for IgG (80%), IgA (78%), and blockade antibodies (87%). Salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies. CONCLUSIONS: Salivary IgA levels strongly correlated with serum IgA titers and blockade antibodies and remained elevated 3 months after a norovirus outbreak. A single salivary sample collected on day 14 could be used to identify recent infection in a suspected outbreak or to monitor population salivary IgA.

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.

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.

Sapovirus outbreaks in long-term care facilities, Oregon and Minnesota, USA, 2002-2009.

We tested fecal samples from 93 norovirus-negative gastroenteritis outbreaks; 21 outbreaks were caused by sapovirus. Of these, 71% were caused by sapovirus genogroup IV and 66% occurred in long-term care facilities. Future investigation of gastroenteritis outbreaks should include multi-organism testing.

Vaccine-era varicella epidemiology and vaccine effectiveness in a public elementary school population, 2002-2007.

OBJECTIVE: We conducted ongoing varicella surveillance of public elementary school students to track changes in incidence from 2002 to 2007. In school year 2002-2003, we also conducted a retrospective cohort study to measure varicella vaccine effectiveness, assess relationships between risk factors for varicella in vaccine recipients (breakthrough varicella) identified in earlier studies, and assess the ability of school nurse surveillance to detect varicella cases. PATIENTS AND METHODS: Varicella was defined as acute illness with maculo-papulo-vesicular rash without another apparent cause persisting >24 hours, regardless of previous episodes of the same or a similar illness. Using case data reported by school nurses, we described breakthrough varicella rates (percentage of vaccinated students with varicella), annual varicella-incidence rates (varicella cases per 100 public elementary school students), vaccine effectiveness, risk factors for breakthrough varicella, clinical characteristics of vaccinated and susceptible varicella patients, and sensitivity and positive predictive value of school nurse surveillance. RESULTS: During school years 2002-2007, 502 elementary school students met the varicella case definition. Breakthrough varicella rates among exposed students ranged from 6% to 8% per school year; annual incidence rates ranged from 0.2% to 0.3% of public elementary school students; and varicella was more severe and lasted longer in susceptible than in vaccinated students. The positive predictive value of school nurse surveillance was 94%, and sensitivity was 90%. Vaccine effectiveness was 81%. CONCLUSIONS: School nurse surveillance has both high positive predictive value and sensitivity and is a useful means of tracking varicella occurrence. Annual incidence rates of varicella are low. Vaccine effectiveness and breakthrough varicella rates are comparable to findings of other studies.

Transmission of group A Streptococcus limited to healthcare workers with exposure in the operating room.

BACKGROUND: Nosocomial transmission of group A Streptococcus (GAS) has been well described. A recent report of an outbreak investigation suggested that transmission can be extensive and that standard infection control measures may not be adequate to prevent transmission from patients with severe, invasive disease to healthcare workers (HCWs). OBJECTIVE: A case of pharyngitis in an HCW caring for a patient with GAS pharyngitis and necrotizing fasciitis prompted an investigation of the extent and risk factors for nosocomial transmission of GAS. SETTING: A 509-bed, tertiary care center in Portland, Oregon with 631,100 patient visits (hospital and clinic) and 11,500 employees in the year 2003. METHODS: HCWs with exposure to the index patient ("contacts") were identified for streptococcal screening and culture and completion of a questionnaire regarding the location and duration of exposure, use of personal protective equipment, and symptoms of GAS infection. RESULTS: We identified 103 contacts of the index patient; 89 (86%) submitted oropharyngeal swabs for screening and culture. Only 3 (3.4%) of contacts had a culture that yielded GAS; emm typing results and pulsed-field gel electrophoresis patterns of GAS isolates from 2 HCWs were identical to those for the isolate from the index patient. Both HCWs were symptomatic, with febrile pharyngitis and reported prolonged contact with the open wound of the patient in the operating room. CONCLUSIONS: In this investigation, nosocomial transmission was not extensive, and standard precautions provided adequate protection for the majority of HCWs. Transmission was restricted to individuals with prolonged intraoperative exposure to open wounds. As a result, infection control policy for individuals was modified only for HCWs with exposure to GAS in the operating room.

Chickenpox outbreak in a highly vaccinated school population.

OBJECTIVE: We investigated a chickenpox outbreak that started in an Oregon elementary school in October 2001, after public schools began phasing in a varicella vaccination requirement for enrollment. We sought to determine the rate of varicella vaccination and effectiveness and risk factors for breakthrough disease. METHODS: A chickenpox case was defined as an acute maculopapulovesicular rash without other explanation occurring from October 30, 2001 through January 27, 2002 in a student without a prior history of chickenpox. We reviewed varicella vaccination records and history of prior chickenpox, and we calculated vaccine effectiveness. We evaluated the effects of age, gender, age at vaccination, and time since vaccination on risk of breakthrough disease (ie, chickenpox occurring >42 days after vaccination). RESULTS: Of 422 students, 218 (52%) had no prior chickenpox. Of these, 211 (97%) had been vaccinated before the outbreak. Twenty-one cases occurred in 9 of 16 classrooms. In these 9 classrooms, 18 of 152 (12%) vaccinated students developed chickenpox, compared with 3 of 7 (43%) unvaccinated students. Vaccine effectiveness was 72% (95% confidence interval: 3%-87%). Students vaccinated >5 years before the outbreak were 6.7 times (95% confidence interval: 2.2-22.9) as likely to develop breakthrough disease as those vaccinated 5 years before the outbreak were at risk for breakthrough disease. Booster vaccination may deserve additional consideration.