Challenges to Estimating Norovirus Disease Burden

In the United States, acute gastroenteritis (AGE) is a significant cause of morbidity, accounting for approximately 179 million illnesses annually [1]. Noroviruses are recognized as the leading cause of AGE across all ages and are responsible for approximately 21 million annual illnesses. However, before 2006, rotaviruses accounted for the majority of severe AGE cases among children under 5 years of age [2]. The introduction of rotavirus vaccines into the recommended infant immunization schedule in 2006 has resulted in a substantial overall decline in pediatric rotavirus disease (and thus AGE) in the United States, with evidence of indirect benefits among some older age groups [3, 4]. Given these declines in the postrotavirus vaccine era, it is thought that noroviruses are now likely the leading cause of AGE among children, although substantiating this assumption with robust data on the burden of norovirus disease is not a straightforward endeavor. There are several challenges to estimating norovirus disease burden, many of which relate to the lack of a rapid and sensitive clinical assay for diagnosis of norovirus infections. Because norovirus disease is a relatively nonspecific syndrome that can manifest similar symptoms as other agents of AGE, laboratory confirmation is necessary to identify sporadic cases. However, current diagnostics rely on molecular methods that are largely restricted to public health and research laboratories, and no commercial assay has been approved for use in the United States to diagnose individual norovirus cases. As a result, there is no case or clinical laboratory-based reporting system for sporadic norovirus disease. Likewise, norovirus-specific codes in administrative data, such as insurance claims, are typically used only when there is laboratory confirmation and thus are highly insensitive. Moreover, only approximately 15% of patients with AGE in the community seek medical attention, and of those who seek medical attention, diagnostic testing is requested from only 13% [5]. These healthcare use indicators can vary significantly based on patient factors (eg, age, socioeconomic status, insurance coverage) and healthcare provider practices, which further complicate attempts to extrapolate findings from inpatients and outpatients to the community. Given these challenges, national surveillance for norovirus disease in the United States is limited to outbreaks, which are reported passively and therefore are subject to tremendous variability, and vastly underestimate the overall burden of disease. In this month’s edition of the Journal of the Pediatric Infectious Diseases, Koo et al present an impressive longitudinal epidemiologic study to assess trends in viral etiologies of AGE at a large pediatric hospital [6]. The authors tested over 3000 stool specimens for enteric viruses over an 8.5-year period, during which time they report significant reduction in rotavirus prevalence after introduction of rotavirus vaccine and subsequent emergence of norovirus as the leading viral enteropathogen. Although there likely was a real shift in the etiologic distribution of pediatric AGE over the study period, interpretation of the reported disease trends is complicated by the surveillance limitations mentioned above. For example, the authors tested stool specimens that were submitted for viral testing, presumably for rotavirus antigen detection primarily. This selection and screening process may have yielded a biased sample of all patients with AGE (eg, inclusion criterion of physician request may result in overrepresentation of the pathogen being ordered for testing and thereby underrepresent other etiologies), thus making it more difficult to generalize the study findings. In addition, the absence of an approved commercial diagnostic assay for norovirus necessitated reliance on nonstandard diagnostic techniques, which changed over the course of the study from conventional Editorial Commentary