Paul A. Gastañaduy

Norovirus Disease in the United States

Although recognized as the leading cause of epidemic acute gastroenteritis 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. Persons >65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age 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 ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease.

Environmental transmission of norovirus gastroenteritis

The advent of molecular techniques and their increasingly widespread use in public health laboratories and research studies has transformed the understanding of the burden of norovirus. Norovirus is the most common cause of community-acquired diarrheal disease across all ages, the most common cause of outbreaks of gastroenteritis, and the most common cause of foodborne disease in the United States. They are a diverse group of single-stranded RNA viruses that are highly infectious and stable in the environment; both symptomatic and asymptomatic infections are common. Through shedding in feces and vomit, norovirus can be transmitted directly through an array of routes: person-to-person, food or the environment. The relative importance of environmental transmission of virus is yet to be fully quantified but is likely to be substantial and is an important feature that complicates control.

Burden of Norovirus Gastroenteritis in the Ambulatory Setting—United States, 2001–2009

BACKGROUND Gastroenteritis remains an important cause of morbidity in the United States. The burden of norovirus gastroenteritis in ambulatory US patients is not well understood. METHODS Cause-specified and cause-unspecified gastroenteritis emergency department (ED) and outpatient visits during July 2001-June 2009 were extracted from MarketScan insurance claim databases. By using cause-specified encounters, time-series regression models were fitted to predict the number of unspecified gastroenteritis visits due to specific pathogens other than norovirus. Model residuals were used to estimate norovirus visits. MarketScan rates were extrapolated to the US population to estimate national ambulatory visits. RESULTS During 2001-2009, the estimated annual mean rates of norovirus-associated ED and outpatient visits were 14 and 57 cases per 10 000 persons, respectively, across all ages. Rates for ages 0-4, 5-17, 18-64, and ≥65 years were 38, 10, 12, and 15 ED visits per 10 000 persons, respectively, and 233, 85, 35, and 54 outpatient visits per 10 000 persons, respectively. Norovirus was estimated to cause 13% of all gastroenteritis-associated ambulatory visits, with ~50% of such visits occurring during November-February. Nationally, norovirus contributed to approximately 400 000 ED visits and 1.7 million office visits annually, resulting in

Gastroenteritis Hospitalizations in Older Children and Adults in the United States Before and After Implementation of Infant Rotavirus Vaccination

284 million in healthcare charges. CONCLUSIONS Norovirus is a substantial cause of gastroenteritis in the ambulatory setting.

Effect of Rotavirus Vaccine on Diarrhea Mortality in Different Socioeconomic Regions of Mexico

Gastroenteritis Hospitalizations in Older Children and Adults in the United States Before and After Implementation of Infant Rotavirus Vaccination Implementation of infant rotavirus vaccination in 2006 has substantially reduced the burden of severe gastroenteritis among US children younger than 5 years. The role of rotavirus in adult gastroenteritis has been less well appreciated. Recent studies report rotavirus detection rates of 18% in emergency departments1 and 5% from February through May in hospitalized patients,2 and estimates of 81 000 emergency department visits3 and 18 000 hospitalizations4 in the United States annually. Whether indirect protection (due to reduced transmission of rotavirus) extends to adults remains unclear. Previous studies suggesting such indirect protection were limited to 1 postintroduction season5 or 1 hospital setting,6 so prudent interpretation was warranted. We assessed patterns of gastroenteritis hospitalizations among children aged 5 years or older and among adults before and after implementation of infant rotavirus immunization. Methods | Rotavirus-coded and cause-unspecified gastroenteritis discharges from January 2000 through December 2010 were retrieved from a nationally representative database of hospital inpatient stays, the Nationwide Inpatient Sample, as previously described.5 Cause-unspecified discharges were examined because testing for rotavirus is infrequently performed in adults. We fitted time series regression models assuming a Poisson distribution of 2 separate outcomes: monthly counts of rotavirus-coded or cause-unspecified discharges. We estimated annual and monthly incidence rate ratios (RR) of the postvaccine years (2008, 2009, and 2010) separately and combined vs the prevaccine years (2000-2006), controlling for month, secular trends, and population size; 2007 was a transition year with limited coverage and was excluded. Separate models were fit for each of the 6 age groups. The study was exempt from institutional review board approval because deidentified aggregated data were used. Significance was assessed as a 2-sided P value of .05 using Stata version 12.0 (StataCorp).

Impact of Rotavirus Vaccination on Hospitalizations and Deaths From Childhood Gastroenteritis in Botswana.

OBJECTIVE: In Mexico, declines in childhood diarrhea deaths have been documented during 2008–2010 after rotavirus vaccine introduction in 2007. Because of concerns about variation in rotavirus vaccine efficacy by socioeconomic status, we compared reductions in diarrhea mortality in the lesser developed southern region versus the more developed northern and central regions of Mexico. METHODS: We obtained data from national vital statistics on diarrhea deaths among children aged <5 years from 2002 through 2011. We compared region-specific diarrhea mortality before (2003–2006) and after (2009–2011) vaccine introduction. Regional vaccine coverage was estimated from administrative data, and socioeconomic status was assessed by using the Human Development Index. RESULTS: In northern, central, and southern Mexico, the 2007 Human Development Index was 0.84, 0.82, and 0.77, respectively, and by 2010 an estimated 99%, 84%, and 89% of children aged <12 months had completed rotavirus vaccination. Diarrhea mortality among children <5 years old declined from 8.3, 17.9, and 28.5 deaths per 100 000 children during 2003–2006 to 4.5, 8.1, and 16.2 in 2009–2011 in northern, central, and southern Mexico, respectively, corresponding to rate reductions of 45%, 55%, and 43%. No significant differences were observed in rate reductions between regions (P > .8). CONCLUSIONS: After introduction of rotavirus vaccination, marked and sustained declines in diarrhea deaths were seen among children in all regions of Mexico, including in the least developed southern region with the highest baseline diarrhea mortality. This finding indicates equitable vaccine delivery to children with varying risk of mortality and reaffirms the beneficial effects of rotavirus vaccination against fatal diarrheal disease.

Hospital-based Surveillance for Rotavirus Gastroenteritis Among Young Children in Bangladesh: Defining the Potential Impact of a Rotavirus Vaccine Program

BACKGROUND A monovalent human rotavirus vaccine (RV1) was introduced in Botswana in July 2012. We assessed the impact of RV1 vaccination on childhood gastroenteritis-related hospitalizations and deaths in 2013 and 2014. METHODS We obtained data from registers of 4 hospitals in Botswana on hospitalizations and deaths from gastroenteritis, regardless of cause, among children <5 years of age. Gastroenteritis hospitalizations and deaths during the prevaccine period (January 2009-December 2012) were compared to the postvaccine period (January 2013-December 2014). Vaccine coverage was estimated from data collected through a concurrent vaccine effectiveness study at the same hospitals. RESULTS By December 2014, coverage with ≥1 dose of RV1 was an estimated 90% among infants <1 year of age and 76% among children 12-23 months of age. In the prevaccine period, the annual median number of gastroenteritis-related hospitalizations in children <5 years of age was 1212, and of gastroenteritis-related deaths in children <2 years of age was 77. In the postvaccine period, gastroenteritis-related hospitalizations decreased by 23% (95% confidence interval [CI], 16%-29%) to 937, and gastroenteritis-related deaths decreased by 22% (95% CI, -9% to 44%) to 60. Declines were most prominent during the rotavirus season (May-October) and among infants <1 year of age, with reductions of 43% (95% CI, 34%-51%) in gastroenteritis hospitalizations and 48% (95% CI, 11%-69%) in gastroenteritis deaths. CONCLUSIONS Following introduction of RV1 into the national immunization program, significant declines in hospitalizations and deaths from gastroenteritis were observed among children in Botswana, suggestive of the beneficial public health impact of rotavirus vaccination.

A Comparison of Postelimination Measles Epidemiology in the United States, 2009-2014 Versus 2001-2008.

Background: In anticipation of introduction of a rotavirus vaccine into the national immunization program of Bangladesh, active hospital-based surveillance was initiated to provide prevaccine baseline data on rotavirus disease. Methods: Children 5 years of age and younger admitted with acute gastroenteritis (AGE) (≥3 watery or looser-than-normal stools or ≥1 episode of forceful vomiting) at 7 hospitals throughout Bangladesh were identified. Clinical information and stool specimens were collected from every 4th patient. Specimens were tested for rotavirus antigen by enzyme immunoassays; 25% of detected rotaviruses were genotyped. Results: From July 2012 to June 2015, rotavirus was detected in 2432 (64%) of 3783 children hospitalized for AGE. Eight enrolled children died, including 4 (50%) who were rotavirus positive. Rotavirus was detected year-round in Bangladesh with peak detection rates of >80% during November–February. Most (86%) rotavirus AGE cases were 6–23 months of age. Sixty-nine percent of children with rotavirus had severe disease (Vesikari score, ≥11). Among 543 strains genotyped, G1P[8] (31%) and G12P[8] (29%) were the most common. Conclusions: Rotavirus is a major cause of morbidity in Bangladeshi children, accounting for nearly two-thirds of AGE hospitalizations. These data highlight the potential value of rotavirus vaccination in Bangladesh, and will be the key for future measurement of vaccine impact.

TRANSMISSION OF NOROVIRUS WITHIN HOUSEHOLDS IN QUININDE, ECUADOR

Background Measles, a vaccine-preventable disease that can cause severe complications, was declared eliminated from the United States in 2000. The last published summary of US measles epidemiology was during 2001-2008. We summarized US measles epidemiology during 2009-2014. Methods We compared demographic, vaccination, and virologic data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2009-December 31, 2014 and January 1, 2001-December 31, 2008. Results During 2009-2014, 1264 confirmed measles cases were reported in the United States, including 275 importations from 58 countries and 66 outbreaks. The annual median number of cases and outbreaks during this period was 130 (range, 55-667 cases) and 10 (range, 4-23 outbreaks), respectively, compared with an annual median of 56 cases (P = .08) and 4 outbreaks during 2001-2008 (P = .04). Among US-resident case-patients during 2009-2014, children aged 12-15 months had the highest measles incidence (65 cases; 8.3 cases/million person-years), and infants aged 6-11 months had the second highest incidence (86 cases; 7.3 cases/million person-years). During 2009-2014, 865 (74%) of 1173 US-resident case-patients were unvaccinated and 188 (16%) had unknown vaccination status; of 917 vaccine-eligible US-resident case-patients, 600 (65%) were reported as having philosophical or religious objections to vaccination. Conclusions Although the United States has maintained measles elimination since 2000, measles outbreaks continue to occur globally, resulting in imported cases and potential spread. The annual median number of cases and outbreaks more than doubled during 2009-2014 compared with the earlier postelimination years. To maintain elimination, it will be necessary to maintain high 2-dose vaccination coverage, continue case-based surveillance, and monitor the patterns and rates of vaccine exemption.

Incidence of Measles in the United States, 2001-2015

We studied the transmission of norovirus infection in households in Quininde, Ecuador. Among household contacts of norovirus positive children with diarrhea, norovirus negative children with diarrhea and asymptomatic controls, infection attack rates were 33%, 8% and 18%, respectively (N = 45, 36, 83). Infection attack rates were higher when index children had a higher viral load.