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Acute Gastroenteritis and Norovirus Outbreaks: Hospitalizations, Deaths, Vaccine


Acute gastroenteritis (AGE; defined as diarrhea or vomiting) is a major cause of illness in the United States; an estimated 179 million episodes occur annually. AGE is caused by a variety of viral, bacterial, and parasitic pathogens and by toxins, chemicals, and other noninfectious causes. Noroviruses are the leading cause of epidemic gastroenteritis, detected in approximately 50% of AGE outbreaks across Europe and the United States. However, until 2009, national surveillance for AGE outbreaks in the United States had been limited to foodborne or waterborne disease outbreaks because no national surveillance existed for AGE outbreaks spread by other transmission modes.

 

To better understand and guide appropriate interventions to prevent epidemic gastroenteritis, the CDC launched a novel national surveillance system in 2009—the National Outbreak Reporting System (NORS). This system enhanced and expanded upon two existing surveillance systems, the Foodborne Disease Outbreaks Surveillance System and the Waterborne Disease and Outbreak Surveillance System. NORS is an Internet-based system for local, state, and territorial health departments to report all outbreaks of foodborne and waterborne disease; AGE outbreaks caused by contact with infected persons, animals, or environmental sources; and AGE outbreaks caused by other or unknown modes of transmission. As such, NORS provides a national surveillance system for all pathways of AGE outbreaks in the United States.

 

Of 4,455 outbreaks reported through NORS during 2009–2010, a total of 4,376 (98%) were AGE outbreaks (1,883 in 2009, 2,493 in 2010), associated with 122,488 reported illnesses, 2,952 hospitalizations, and 168 deaths. A single suspected or confirmed etiology was implicated in 2,819 (64%) outbreaks, associated with 88,958 (73%) illnesses, 2,381 (81%) hospitalizations, and 146 (87%) deaths. Norovirus, the leading cause of single-etiology outbreaks, was responsible for 1,908 (68%) outbreaks, associated with 69,145 (78%) illnesses, 1,093 (46%) hospitalizations, and 125 (86%) deaths.

 

AGE outbreaks were reported by the District of Columbia, Puerto Rico, and all states except Delaware. A median of 42 outbreaks (range 2–331) was reported by each site, and the median rate was 7.3 outbreaks/1 million person-years (range 0.9–44.8). Overall, AGE outbreaks exhibited winter seasonality: 68% of the 4,376 outbreaks occurred between November and April. This trend was driven largely by outbreaks caused by norovirus and by unknown etiologies.

 

The primary reported mode of transmission in most AGE outbreaks was person to person (2,271 [52%]), followed by foodborne (1,513 [35%]), waterborne (65 [2%]), animal contact (44, 1%), and environmental contamination (9, 0.2%); the transmission mode was unknown in 474 (10%) outbreaks. Person-to-person transmission was implicated in most outbreaks caused by norovirus (1,261 [66%]) and Shigella spp. (86 [79%]), whereas foodborne transmission was implicated in most outbreaks caused by Salmonella spp. (254 [72%]) and STEC (64 [63%]). Among the 3,052 (70%) AGE outbreaks for which a single exposure setting was reported, health care facilities, primarily nursing homes, were the most frequent settings (1,499 [49%]), followed by restaurants or banquet facilities (657 [22%]), schools or day-care facilities (290 [10%]), and private residences (315 [7%]). Most norovirus outbreaks (64%) occurred in health care facilities, whereas shigellosis outbreaks (74%) occurred predominantly in schools or day-care facilities. Private residences and restaurants/banquet facilities were the most frequent exposure settings for outbreaks caused by Salmonella spp. (32% and 36%, respectively) and STEC (46% and 20%, respectively).

 

Although recognized as the leading cause of epidemic AGE across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570–800 deaths, 56,000–71,000 hospitalizations, 400,000 emergency department visits, 1.7–1.9 million outpatient visits, and 19–21 million total illnesses per year. People over 65 are at greatest risk for norovirus-associated death, and children under five have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by about 50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions for norovirus disease.

 

Recognition of the public health impact of noroviruses has increased in recent years, driven largely by an abundance of reported outbreaks. A systematic literature review identified over 900 published reports of laboratory-confirmed norovirus outbreaks during 1993–2011. In contrast, studies assessing endemic norovirus disease are limited primarily to etiologic studies of acute gastroenteritis among children seeking medical care. Such prevalence studies provide valuable insights into the role of norovirus among patients with acute gastroenteritis. However, robust assessment of the norovirus burden, meaning the annual number of illnesses and associated outcomes, requires population-based incidence estimates, ideally from national or nationally representative surveillance. However, there are several challenges to generating such estimates for norovirus in the United States, including lack of a widely used, rapid, and sensitive clinical assay; no public health reporting requirement for individual cases; low health care–seeking rates of patients with acute gastroenteritis; and poor sensitivity of norovirus-specific codes in national administrative databases.

 

Before 2008, only one published report estimated the burden of norovirus disease in the United States. In that report, as part of a broader effort to estimate the US burden of foodborne disease, the authors generated pathogen-specific estimates of illnesses, hospitalizations, and deaths, and they estimated the fraction of these outcomes caused by foodborne disease transmission. Annual norovirus-associated illnesses (23 million), hospitalizations (50,000), and deaths (310) were based on extrapolation of the norovirus-attributable proportion from a single community-based study in the Netherlands and applied to the US all-cause acute gastroenteritis incidence from the National Hospital Discharge Survey (NHDS) and the first Population Survey of the Foodborne Diseases Active Surveillance Network (FoodNet). Although limited by the absence of direct US data on norovirus prevalence or incidence, this landmark study demonstrated the predominant role of norovirus in causing foodborne disease and became the most widely cited estimate of the US norovirus disease burden for more than a decade.

 

CDC researchers reviewed a collection of subsequently published studies that provided population-based incidence rates of norovirus disease in the United States. By comparing the various methods and triangulating the results, we provide summary estimates of the overall US norovirus disease burden, including specific estimates by age groups and disease outcomes. This review facilitates identification of key groups that would benefit from prevention strategies aimed at controlling norovirus and provides the grist for development of appropriate interventions, including vaccines. Such data are particularly timely and relevant given that a candidate norovirus vaccine is approaching a phase 3 efficacy trial and could potentially be licensed within the next 5–7 years.

 

Over the past 5 years, substantial improvements have been made in 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, CDC researchers concluded 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. In addition, CDC researchers consistently observed across the reviewed studies increases in norovirus disease during the winter months and during years in which pandemic strains emerged.

 

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, such vaccine 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 incidence studies can help further identify specific groups for such interventions. The CDC’s 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.

 

See the CDC Report on Emerging Infectious Diseases: Norovirus

 

See the CDC Report on Emerging Infectious Diseases: Acute Gastroenteritis

 

 

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