Over the 6-year period of our study, the total number of deaths in persons >65 years of age that may be attributable to norovirus was 453 (228 from infectious ID and 225 from noninfectious ID). On average, this equates to ≈80 deaths each year attributable to norovirus infection. Norovirus was the only gastrointestinal pathogen that was consistently significant in the 2 regression models.
Of the recorded deaths from infectious ID, 13% had viral gastroenteritis listed as the underlying cause. For deaths from noninfectious ID, 48% had an underlying cause of unspecified noninfectious gastroenteritis and colitis. Because these are unspecified causes, and given their similar seasonality with infectious ID, many of these are likely to be infectious causes that were misclassified.
In years with higher norovirus activity, more deaths were associated with norovirus infection. However, we found no evidence of increased pathogenicity in years with higher recorded norovirus activity. The season when a new variant of the genotype II.4 virus emerged (2002–03) did not coincide with an increase in death/laboratory-report ratio. Indeed, the opposite was observed; fewer deaths as a proportion of positive laboratory reports were observed, the interaction term showed a negative coefficient for that season, and the relative risk for death during that season was lower than during other seasons.
One of the assumptions in our regression model was that laboratory reporting was consistent over the time of the study. Laboratory reporting processes did not change during the years of the study and are unlikely to have caused bias in this study. Testing and reporting behavior, however, may have changed over time. The number of specimens identified by PCR and ELISA increased from ≈70% to ≈90% in the study period. Thus, the decreased ratio of deaths/laboratory reports may have resulted from increased testing during the 2002–03 season rather than from the virus being less pathogenic during that year.
The modeling approach may underestimate the contribution of norovirus and other pathogens because the method estimates how much of the seasonal variation in death is associated with the seasonal variation in laboratory reports. Less-seasonal pathogens are less likely to show an association, and nonseasonal components (i.e., background levels) will not be attributed to a pathogen. Indeed, a substantial constant term in our models represented these unattributed deaths. The model for deaths from noninfectious ID did not appear to be as good a fit as the model for deaths from infectious ID. There was, in our opinion, enough evidence of a correlation between infectious and noninfectious ID to make a case for including this model.
This method has been used in the past for other pathogens (rotavirus, respiratory syncytial virus, pneumococcus, influenza virus) and unexplained deaths; when we used it in this study, we found an association between norovirus and death. Until our study, most reports of norovirus-associated deaths have been anecdotal (13
). Although deaths associated with norovirus infection have been documented (14
), these are usually singular reports of patients having died subsequent to infection with norovirus, rather than in-depth analysis of time trends of death.
In this study we attempted to go further and estimate the extent of death from norovirus. Norovirus is usually considered a mild, self-limiting disease, and most of those infected with the disease make a full recovery with no long-lasting effects. However, this study shows that part of the population, those >
65 years of age, have a small risk of dying as a result of contracting norovirus. Rates of infection are higher within healthcare settings than in the community (4
). Previous studies have shown that hospital patients who are involved in outbreaks of norovirus are ill longer than those who become infected in other settings (15
). In England the proportion of the population >
65 years of age is increasing. In years to come, this will be a substantial proportion of persons at risk, and deaths associated with this disease may well increase.
Noroviruses are known to evolve quickly. Emergence of new variants of the most commonly circulating strain can cause epidemic years in which more outbreaks occur and many more persons are infected. New variants are also associated with out-of-season activity, i.e., more outbreaks and infections than usual occurring in summer. When this happens, most of the population may be susceptible to infection. Our study suggests that when such epidemics occur, the number of norovirus-associated deaths increases as a result of the large number of persons infected rather than from increased virulence. Nevertheless, a measurable amount of death is associated with norovirus infection every year.