Over the past 5 years, substantial improvements have been made in our understanding of the burden of norovirus disease in the United States, which now represents the leading contributor to acute gastroenteritis across all age groups. By summarizing findings from studies using different methods and published over the past 5 years, we conclude that norovirus causes on average 570–800 deaths, 56,000–71,000 hospitalizations, 400,000 ED visits, 1.7–1.9 million outpatient visits, and 19–21 million total illnesses each year in the United States (). On the basis of these rates of disease and a life expectancy of 79 years, a US resident would experience 5 episodes of norovirus gastroenteritis in his or her lifetime and an average lifetime risk for norovirus-associated outpatient visit, ED visit, hospitalization, and death of 1 in 2, 1 in 9, 1 in 50–70, and 1 in 5,000–7,000, respectively. Through age-group specific analyses, we identified that older Americans >65 years of age have the greatest risk for norovirus-associated deaths, and children <5 years of age have the highest rates of norovirus-associated medical care visits. In addition, we consistently observed across the reviewed studies increases in norovirus disease during the winter months and during years in which pandemic strains emerged.
Figure 3 Estimates of annual burden (annual number of illnesses and associated outcomes) and individual lifetime risks for norovirus disease across all age groups, United States. Data were derived from estimates of deaths (6,9), hospitalizations (6,10), emergency (more ...)
Although the estimates summarized herein were developed by using distinct methods, each with their own strengths and limitations, the broad agreement among them is reassuring and provides a clearer picture of the norovirus disease burden in the United States. Population-based surveillance for laboratory-confirmed norovirus disease provides the most direct assessment of disease incidence, but depending on the study population, might have limited generalizability. Indirect attribution from regression modeling makes use of the most nationally representative data available but relies on temporality of acute gastroenteritis to ascribe etiology, as opposed to diagnostic testing. Attributable proportion extrapolation is somewhat of a hybrid between these 2 methods, being limited primarily by the comparability of the 2 populations involved in the extrapolation. Aside from differences in methods, the variation between estimates from the different studies might be partly caused by different time periods from which they were derived, given major year-to-year fluctuations in norovirus disease driven by the emergence of new strains.
Comparison of US norovirus incidence estimates with the few similar such estimates available from other industrialized countries showed general consistency in magnitude, especially when one considers that the uncertainty surrounding these estimates often exceeds 50% (). For example, a recent study in the Netherlands (13
) reported a slightly higher norovirus-associated mortality rate (0.40 deaths/10,000 population) than the 2 recent US estimates (0.027 and 0.019 deaths/10,000 population) but a lower hospitalization rate (1.2 vs. 2.4 and 1.9 hospitalizations/10,000 population, respectively) (6,9,10
). Rates of outpatient norovirus incidence from 2 studies in the United Kingdom (21 and 54 outpatient visits/10,000 population) (14,15
) and 1 study in Germany (63 outpatient visits/10,000 population) (16
) were consistent with 2 recent US estimates of 57 and 64 outpatient visits/10,000 population (7,11
). Estimates of community norovirus incidence determined on the basis of 2 large-scale prospective cohort studies in the United Kingdom (470 and 450 illnesses/10,000 population) (14,15
) and 1 study in the Netherlands (380 illnesses/10,000 population) (13
) were all lower than the 2 recent US estimates (650 and 700 illnesses/10,000 population) (6,7
). In contrast, a recent estimate in Canada (17
) (1,040 illnesses/10,000 population) (17
) was higher than estimates in the United States. However, the uncertainty bounds for the US estimates overlaps with those surrounding estimates for the United Kingdom, the Netherlands, and Canada (). Although differences in health care delivery systems and payment structures confound direct comparisons of health care visits and associated costs between countries, the substantial burden of norovirus disease is clearly not unique to the United States.
Great strides have been made in characterizing the incidence of norovirus disease in the United States; however, additional work is needed to fill some key gaps. Age-specific rates of norovirus disease, ideally from direct laboratory testing among population-based community cohorts, would help identify groups most often infected and thus those likely serving as primary human reservoirs for transmission. The causal role of norovirus and common concurrent conditions in norovirus-associated deaths also requires further clarification to help protect the most vulnerable populations. In addition, stable surveillance platforms that enable systematic and ongoing assessment of endemic norovirus disease are needed to characterize long-term trends, annual fluctuations, and effects of emergent norovirus strains.
As progress continues in the arena of norovirus vaccine development (5
), such endemic norovirus disease data will be critical to guide formulation and quantify potential effects of vaccine. The burden of norovirus disease in the United States justifies continued efforts toward developing potential norovirus vaccines and identification of specific groups for such interventions. Our review suggests that for a vaccine to have maximal impact, it would need to demonstrate safety and effectiveness in young children and the elderly, groups at the highest risk for severe norovirus disease. Other groups at risk for epidemic disease might also include health care workers, travelers, and military personnel. Data from our review can inform cost-effectiveness and modeling studies to define an investment case and public health strategy for controlling norovirus disease in anticipation of completion of vaccine development and licensure.