Identifying Sources and Transmission Routes of Norovirus Outbreaks : Molecular epidemiological methods as the basis for targeted prevention strategies

__Abstract__ Norwalk virus, the prototype norovirus was first recognized as a cause of gastroenteritis in 1972 by means of electron microscopy (EM) on stool samples. Norwalk virus was identified by visualization of small round virus particles in stool samples from infected students and contacts during an outbreak in Norwalk, Ohio, in 1968. Originally norovirus was characterized based on the shape and structure by electron microscopic analysis. Later, immunological methods were applie

Shedding of norovirus in symptomatic and asymptomatic infections

Norovirus is the most frequent cause of acute infectious gastroenteritis and it is difficult to control in crowded environments like hospitals and nursing homes. Transmission depends on oral intake of virus deposited in the environment by infectious subjects. Data from volunteer studies indicate that virus concentrations in stool are highly variable, but systematic studies of the time-course of shedding and its individual variation are lacking. This paper quantifies norovirus shedding in a large population of 102 subjects, including asymptomatic shedders, and uses a longitudinal model to generalize shedding patterns. Enhanced surveillance for studies of transmission of norovirus in hospital outbreaks has yielded a considerable number of faecal samples from symptomatic and asymptomatic shedders, both from patients and staff. Norovirus concentrations were determined by real-time PCR. A quantitative dynamic model was fitted to the shedding data, in a multilevel Bayesian framework, to study the time-course of shedding and its variation. The results indicate that shedding in asymptomatic subjects is similar to that in symptomatic infections, both showing considerable variation in peak levels (average 10(5)-10(9) /g faeces) as well as duration of virus shedding (average 8-60 days). Patients appear to shed higher numbers of virus than staff, for slightly longer durations, but the differences are too small to be significant. Given equal shedding, the greater contribution of symptomatic cases to transmission must be caused by their higher efficiency in spreading these viruses. The results of this study will be helpful for risk studies that need to quantify the deposition of virus in the environment

Nosocomial Transmission of Norovirus Is Mainly Caused by Symptomatic Cases

Background. Nosocomial norovirus (NoV) infection is common and may increase the burden of disease in healthcare settings, particularly in vulnerable hospitalized patients. Implementing effective infection control during and after admission may limit further spread, but evidence-based measures are lacking. Methods. In this study, we performed a systematic evaluation of sources and modes of transmission during NoV outbreaks within 2 types of healthcare facilities. An outbreak protocol was developed to sample all patients and healthcare workers (HCWs) with and without symptoms on wards involved in outbreaks. Data on clinical history and possible high-risk exposures were collected. Five outbreaks were investigated, involving 28 patients with recognized symptomatic NoV infection. Results. Enhanced sampling, however, yielded 65 additional cases, of whom 14% (n = 9) were asymptomatic patients, 57% (n = 37) were symptomatic HCWs, and 17% (n = 11) were asymptomatic HCWs. For 12% (n = 8), clinical data were not provided (2 HCWs and 6 patients). On the basis of the shedding kinetics, the onset of infection was estimated for each case. The generation interval was then used to construct plausible transmission pathways and reproduction numbers for symptomatic and asymptomatic pat Conclusions. We found that symptomatic patients and HCWs were more often involved in transmission events than asymptomatic shedders. Asymptomatic HCWs rarely contributed to transmission, despite high levels of fecal virus shedding

Chronic Shedders as Reservoir for Nosocomial Transmission of Norovirus▿

Norovirus (NoV) infection in immunocompromised patients may lead to prolonged norovirus shedding. Here, we demonstrate the involvement of three chronic shedders in hospital outbreaks. Combined epidemiological and molecular evidence suggests that in one case, NoV transmission occurred at least 17 days after the first diagnosis

Unrecognized Norovirus Infections in Health Care Institutions and Their Clinical Impact

Noroviruses (NoVs) have emerged as the leading cause of acute viral gastroenteritis (GE) in humans. Although diagnostic facilities have greatly improved, significant underdiagnosis of NoV in hospitals may still occur, thereby increasing clinical burden and nosocomial spread. We evaluated the underdiagnosis of sporadic NoV infections in a tertiary care hospital and estimated its clinical impact. From December 2008 until July 2009, fecal samples specifically referred for bacterial but not viral examination were retrospectively tested for NoV by real-time PCR. The clinical and virological data from patients with undiagnosed NoV infection (missed patients) were evaluated and compared with those from patients with recognized NoV. During the study period, 45 patients with undiagnosed NoV were detected, whereas 50 patients were regularly diagnosed. The missed NoV cases were more frequently adults than children (80% versus 46%; P < 0.001). The viral load levels did not differ between the diagnosed and missed patients, but missed patients more frequently presented without diarrhea (20% versus 4%; P < 0.07). The newly admitted missed NoV cases with GE underwent more diagnostic imaging (24% versus 4%; P < 0.01) and tended to be hospitalized longer. When missed-NoV patients were included, the number of nosocomial clusters doubled and missed patients were index cases in 5 of the 6 clusters. These data indicate that NoV infections are frequently missed despite routine laboratory testing and demonstrate that underdiagnosis of NoV patients is associated with costly abdominal imaging and nosocomial clustering. Awareness of NoV infection in adult patients and education about the importance of viral GE should be increased