PEDIATRICS Vol. 122 No. 5 November 2008, pp. 971-977 (doi:10.1542/peds.2007-1609)
ARTICLE |
Burden of Rotavirus Disease Among Children Visiting Pediatric Emergency Departments in Cincinnati, Ohio, and Oakland, California, in 1999–2000
a Epidemic Intelligence Service Program, Office of Workforce and Career Development
b Epidemiology Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
c Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
d Department of Pediatrics, Children's Hospital and Research Center Oakland, Oakland, California
e Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
f Department of Pediatrics, Center for Pediatric Research, Norfolk, Virginia
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
OBJECTIVE. We assessed the incidence of rotavirus disease requiring an emergency department visit among children <5 years of age.
METHODS. We conducted active surveillance for acute gastroenteritis in pediatric emergency departments in Cincinnati, Ohio, and Oakland, California, from March 1999 to May 2000, among children 2 weeks to 59 months of age with acute diarrhea and/or vomiting. We obtained clinical and demographic information from participants and tested their stool specimens for rotavirus.
RESULTS. Approximately 9% of all emergency department visits at the study sites were attributable to acute gastroenteritis. A total of 1433 children were eligible at the 2 sites; 85% were enrolled and 68% provided a stool specimen. Overall, rotavirus was detected in specimens from 27% of children (30% in Cincinnati and 24% in Oakland). Rotavirus detection was higher in bulk stools, compared with rectal swabs, at both Cincinnati (37% vs 23%) and Oakland (46% vs 18%). Patients with rotavirus had more-severe disease than did those with nonrotavirus gastroenteritis. We estimated that the mean annual incidence of emergency department visits attributable to rotavirus was 12 cases per 1000 children in Cincinnati and 15 cases per 1000 children in Oakland. Through extrapolation, we estimated that rotavirus infection causes 
260 910 emergency department visits per year among US children.
CONCLUSION. Active surveillance demonstrated that the burden of laboratory-confirmed rotavirus disease treated in emergency department settings among US children is substantial and greater than estimated previously.
Key Words: rotavirus • epidemiology • incidence • emergency department • gastroenteritis
Abbreviations: ED—emergency department
Rotavirus has been estimated to cause 2.1 to 3.2 million episodes of diarrhea, 410 000 to 600 000 outpatient visits, 160 000 emergency department (ED) visits, 50 000 to 70 000 hospitalizations, and 20 to 70 deaths each year among US children <5 years of age, with health care and societal costs estimated at almost $1 billion.1–8 To reduce this large disease burden, the US Food and Drug Administration licensed a new rotavirus vaccine (Rotateq; Merck and Co, Inc, Whitehouse Station, NJ) on February 3, 2006, and the vaccine was approved for routine immunization of young children by the Advisory Committee on Immunization Practices.9
Previous estimates of the burden of severe rotavirus disease among US children were derived through analysis of data from computerized administrative databases (eg, the National Hospital Discharge Survey database), which contain limited clinical information and often do not reflect any laboratory confirmation of rotavirus infection.10–13 Because no direct data on disease treated in EDs exist, estimates of ED burden have been based on the assumption that the rotavirus detection rates among children with acute gastroenteritis are similar in outpatient and ED settings. This may underestimate the role of rotavirus, because children who present at an ED are more likely to be rotavirus-positive than are children with milder disease who are treated as outpatients. To determine a population-based incidence of laboratory-confirmed rotavirus disease among children with acute gastroenteritis seen in EDs, we conducted active surveillance at 2 sentinel pediatric EDs in the United States.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Study Sites and Populations
This study was conducted at 2 hospitals, in Cincinnati, Ohio, and Oakland, California. Cincinnati Children's Hospital Medical Center is a 331-bed hospital located in Hamilton County, Ohio. The population of Hamilton Country in 2000 was 845 303 individuals, of whom an estimated 56 635 were children <5 years of age; of those children, 67% were white and 31% black.14–16
Children's Hospital and Research Center Oakland is a 181-bed hospital located in Alameda County, California. Alameda County has a racially diverse population of 1.5 million individuals, of whom 98 174 were children <5 years of age; of those children, 58% were white, 23% Asian, and 17% black.14–16
Description of Active Surveillance
Active surveillance for acute gastroenteritis was conducted from March 1, 1999, through May 31, 2000, at the 2 study hospitals. Children 2 weeks to 59 months of age were screened for vomiting and/or diarrhea every fourth day in two 12-hour shifts during the study period, to ensure a fairly equal sampling of children visiting the ED on weekdays, weekends, and holidays. The study protocol was reviewed and approved by the institutional review board at each study site, and parents and/or legal guardians of all enrolled participants provided written informed consent.
Case Definition and Scoring of Episodes of Acute Gastroenteritis
We defined acute gastroenteritis as an illness of <7-day duration during which the patient had 
3 loose stools in a 24-hour period, 3 episodes of vomiting in a 24-hour period, or 1 episode vomiting and 1 loose stool in a 24-hour period. We graded the severity of episodes of acute gastroenteritis by using a modified form of an accepted diarrhea scoring system.17 Because an accurate assessment of hydration status at presentation was not recorded in the medical charts for most patients, we modified this scoring system by not including hydration status; therefore, the maximal score was 17, rather than 20. Illnesses with a score of 12 were classified as severe disease.
Inclusion and Exclusion Criteria
To calculate a population-based incidence of ED visits attributable to acute gastroenteritis caused by rotavirus, we included only children who were residents of either Hamilton County or Alameda County. We excluded children with noninfectious causes for their symptoms and those who had made additional ED visits because of acute gastroenteritis within a 14-day period.
Enrollment Procedures
Parents were interviewed to obtain the child's demographic and clinical information, including date of illness onset, duration of illness, and symptoms of fever, diarrhea, vomiting, and abdominal pain/cramping. Additional data on the child's clinical presentation and case management were extracted from the child's medical record. A bulk stool or rectal swab specimen was collected at the time of the ED visit. Bulk stool specimens were preferred; however, a rectal swab was accepted when a bulk stool specimen could not be obtained.
Laboratory Procedures
Bulk stool specimens were collected into individual stool storage containers and promptly transferred to the hospital laboratory. Rectal swabs were placed in viral culture medium and placed on ice until they were transported to the hospital laboratory. Only rectal swabs with visible fecal material on the swab were accepted. Specimens from both sites were tested for rotavirus with an enzyme immunoassay (RotaClone; Meridian Bioscience, Cincinnati, OH) in the research laboratory of Cincinnati Children's Hospital Medical Center.
Characteristics of Rotavirus-Positive Children
All eligible children from both counties were included in this analysis, regardless of the type of specimen collected from them (bulk stool or rectal swab). Demographic and clinical characteristics of children with and without rotavirus disease were compared according to site. For patients for whom full clinical data were available, we coded the severity score by using the modified scoring system described above.
Population-Based Incidence and Risk Calculation for Sites
Because the frequency of rotavirus detection was significantly higher in bulk stool specimens than in rectal swab specimens, we based our disease incidence estimates solely on the results from bulk stool specimens. We considered this appropriate because we found no significant difference in epidemiological factors that might affect rotavirus detection rates (eg, disease severity) between children who provided bulk specimens and those who provided rectal swab specimens and because the detection of rotavirus in rectal swabs may be compromised by the limited amount of fecal material obtained.
We calculated the annual population-based incidence of ED visits attributable to rotavirus illness for each site by using the following method. First, we estimated the total number of eligible children (from Hamilton County or Alameda County) who presented to the ED with gastroenteritis per year by multiplying the number of eligible children identified during a 12-month period by 4, because the surveillance was conducted only on every 4th day. Because the study was conducted over 15 months, including likely 2 rotavirus seasons in Cincinnati and 1 in Oakland, we preselected 4 consecutive 12-month periods (March 1999 to February 2000, April 1999 to March 2000, May 1999 to April 2000, and June 1999 to May 2000) to arrive at a range of 4 annual incidence figures. Next, we estimated the total number of ED rotavirus cases per year by multiplying the proportion of children who provided bulk stool specimens that tested positive for rotavirus by the total number of eligible children for each 12-month period. Then we calculated the annual incidence of ED cases per 1000 children by dividing the total number of ED rotavirus cases per year by the number of county children <5 years of age in the catchment area of each site. The total population in each county was determined from the 2000 US Census,15 and the proportion of this population that fell in the catchment area of each ED was determined through written personal communication with each hospital management office (J. Keebaugh, written personal communication, 2005; K. Creighton, personal communication, 2006). For the Cincinnati site, rates for Hamilton County children <3 years of age were also presented, to allow comparisons with current surveillance, which includes only that age group. Approximately 88.9% of all children <5 years of age from Hamilton County seek emergency care at Cincinnati Children's Hospital Medical Center, and 56% of children <5 years of age from Alameda County seek emergency care at Children's Hospital and Research Center Oakland. The cumulative risk for an ED visit attributable to rotavirus illness per child from birth to age 5 was calculated as the inverse of ED cases of rotavirus per 1000 children, multiplied by 5.
Data Analysis
We used univariate analyses (SAS 9.0; SAS Institute, Cary, NC) to describe the demographic and clinical characteristics of the study participants with and without rotavirus, and we used the Mantel-Haenszel 
2 test to test for significant differences. We used Fisher's exact test when appropriate, and we used the Wilcoxon rank-sum test to identify significant differences (P < .05) in median age and severity scores.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
Study Sites and Specimens Collected
Between March 1, 1999, and May 31, 2000, Cincinnati Children's Hospital Medical Center had 35 789 ED visits for all causes among children 2 weeks to 59 months of age who were residents of Hamilton County; of those children, 9% (N = 3229) had an International Classification of Diseases, Ninth Revision, Clinical Modification code for acute gastroenteritis as the presenting complaint. Children's Hospital and Research Center Oakland had 14 604 ED visits from Alameda County children of the same age, of whom 10% (N = 1415) had acute gastroenteritis as the presenting complaint.
We identified 1433 eligible children for our study, 910 from Cincinnati and 523 from Oakland. We enrolled 817 eligible children (90%) from Cincinnati and obtained fecal specimens from 449 (55%) of those enrolled. Of the fecal specimens obtained, 44% were bulk stools and 53% were rectal swabs; 3% of eligible children were excluded because details on the type of specimen collected were missing or unclear. In Oakland, we enrolled 401 eligible children (77%) and obtained fecal specimens from 375 (93%) of those enrolled. Of the fecal specimens obtained, 22% were bulk stools, 77% were rectal swabs, and 1% were excluded (Fig 1). At both sites, there was a clear increase in rotavirus disease in the winter and spring, and few rotavirus cases were detected in the summer and autumn months (Fig 2).
|
|
Comparison of Children With and Without Rotavirus Disease
Overall, during the 15-month study period, we found rotavirus in 27% of all samples (both bulk stools and rectal swabs), 30% in Cincinnati and 24% in Oakland. At both sites, most children with rotavirus were 6 to 23 months of age (61% of those at Cincinnati and 64% of those at Oakland). At Cincinnati, the median age of study subjects with rotavirus disease was slightly older than that of subjects without disease (12 vs 10 months; P = .003). Among Oakland subjects, children with rotavirus infection were older (14 vs 13 months) but this difference was not statistically significant (P = .79) (Table 1). At Cincinnati, rotavirus was detected more often among female patients than among male patients (59% vs 41%; P = .02); at Oakland, the reverse was true (34% vs 66%; P = .06). The racial distribution of patients at the 2 sites differed and reflected the racial distribution of the county in which the hospital was located. At both sites, however, the racial distribution of patients with rotavirus infection was similar to that of patients without infection.
|
Most study participants were discharged from the hospital after their visit regardless of whether they had rotavirus or not. Overall, in Cincinnati, 7.7% of children with rotavirus were hospitalized, compared with 8.5% of children without rotavirus. In Oakland, however, 23.6% of children with rotavirus were hospitalized, compared with 12.4% of children without rotavirus.
Disease Severity
Patients who presented with rotavirus more often reported symptoms of diarrhea, vomiting, and fever, compared with patients with nonrotavirus gastroenteritis. Nearly one third of Cincinnati children and 49% of Oakland children with rotavirus required intravenous fluids, compared with only 14% and 23% of children without rotavirus, respectively (P < .0001 for both sites). By using the modified disease severity scoring system described above, we found that children with rotavirus had a significantly higher mean severity score, compared with those with nonrotavirus gastroenteritis (scores of 12 and 8, respectively; P < .0005). In addition, more than one half of all rotavirus-confirmed cases were classified as severe gastroenteritis, compared with only 22% of rotavirus-negative cases (Table 2).
|
Bulk Stool Specimens Versus Rectal Swab Specimens
Bulk specimens were more likely than rectal swabs to be positive for rotavirus (37% vs 23% in Cincinnati and 46% vs 18% in Oakland) (Table 3). In Cincinnati, the median age of children who provided bulk stools was not significantly different from the median age of those who provided rectal swab specimens (10 vs 11 months; P = .076). In Oakland, the median age of children who provided rectal swab specimens was significantly different (10 vs 14.5 months; P = .0017), but the rotavirus-positive proportions were very similar in this age range, and this was unlikely to introduce bias. We found no significant difference in disease severity between children who provided bulk specimens and those who provided rectal swab specimens (median severity scores were 11 for those with bulk specimens and 9 for those with rectal swab specimens; P = .927).
|
Incidence of Rotavirus Illness
We estimated that the mean annual incidence of ED visits attributable to rotavirus illness in Cincinnati was 12 cases per 1000 children <5 years of age (range: 8–19 cases per 1000) and that, by age 5, 1 in 17 children in Hamilton County would have visited the ED because of rotavirus gastroenteritis (Table 4). The annual incidence of ED visits attributable to rotavirus disease for children <3 years of age in Cincinnati was 15 cases per 1000 children <3 years of age (range: 10–25 cases per 1000) and, by age 3, 1 in 22 children would have visited the ED because of rotavirus gastroenteritis. For Oakland, we estimated that the mean annual incidence of ED visits attributable to rotavirus illness was 15 cases per 1000 children <5 years of age (range: 14–15 cases per 1000) and that, by age 5, 1 in 13 children in Alameda County would have visited the ED because of rotavirus gastroenteritis (Table 4).
|
To obtain a point estimate of the national burden in EDs, we used a rate of 13 cases per 1000 children per year (range: 8–19 cases per 1000 per year), consistent with findings for both sites. Through extrapolation of this rate to the 2004 birth cohort of children in the United States, we estimated a total of 260 910 ED visits attributable to rotavirus per year in the United States (range: 160 400–380 950 visits per year).
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
We found a substantial burden of rotavirus disease in 2 EDs in the United States, with rotavirus accounting for a mean of 22% of ED visits attributable to gastroenteritis in Cincinnati and 46% of visits in Oakland. We estimated that the mean annual incidence of ED visits attributable to rotavirus illness in Cincinnati was 12 cases per 1000 children and that in Oakland was 15 cases per 1000 children <5 years of age. In other words, by 5 years of age, 1 in 15 children <5 years of age (range: 1 in 10–24 children) would have visited the ED with rotavirus illness, which extrapolates to 260 910 ED visits per year (range: 160 400–380 950 visits per year) in the United States. Moreover, rotavirus illness was clinically more severe, as measured with an objective clinical scale, and required more-aggressive treatment than did other causes of diarrhea.
The burden of rotavirus disease requiring an ED visit among US children observed in this study is greater than estimated previously. A previous study based on analysis of discharge data for a cohort of children from several health maintenance organizations reported that 1 in 21 children visited the ED because of an illness with an International Classification of Diseases, Ninth Revision, Clinical Modification code for gastroenteritis by the age of 5 years.18 Although many of those episodes would be attributable to rotavirus, this rate is considerable lower than our estimates. In addition, 2 separate cost-effectiveness analyses of a US rotavirus immunization program assumed empirically that 20% to 28% of ED visits attributable to diarrhea nationally were attributable to rotavirus, and they estimated 160 000 to 213 946 ED visits with rotavirus gastroenteritis per year.1,3 Finally, a 3-year study involving active surveillance in a Seattle ED reported a rotavirus detection rate of 22% among 417 patients evaluated, although the population in that study ranged from birth to 28 years of age, making direct comparison with our data difficult.19
The rotavirus detection rates in our study were considerably higher than rates in those reports and were more comparable to those in a study conducted in multiple ambulatory settings in Toronto, Canada, from November 1997 to June 1998, in which 45% of 64 stool specimens obtained from children who presented at the ED with acute gastroenteritis tested positive for rotavirus.20 Like our study, the Toronto study was conducted by using rigorous active surveillance, with timely collection of fecal specimens and testing using a reliable diagnostic assay, factors that could explain in part the higher rotavirus detection rate seen in these studies. In addition, we found that the rotavirus detection rate was significantly higher among patients who provided bulk stool samples than among those whose samples were collected with rectal swabs. Many early studies of rotavirus prevalence relied on testing of rectal swabs along with fecal specimens, which might have led to underestimation of rotavirus disease prevalence.
Our study has several limitations. First, our findings were based on only 2 EDs, which may not be nationally representative. However, although the rate of rotavirus positivity in Oakland was almost double that in Cincinnati, the overall incidences of ED visits attributable to rotavirus disease were comparable (12 vs 15 visits per 1000 children <5 years of age per year), which gave us confidence in extrapolating results to calculate national estimates. Second, our study was conducted for only 15 months, which included the middle of 2 rotavirus seasons in Cincinnati and 1 full season in Oakland. As observed in this study, rotavirus incidence may vary considerably from one year to the next, and our results may not be generalizable to other years. Finally, it is possible that children from whom a fecal specimen (either bulk stool or rectal swab) was obtained might have had more-severe disease than those from whom a specimen could not be obtained, which might have led us to overestimate rotavirus prevalence on the basis of data for children who provided bulk stool specimens. This limitation would particularly affect data for Cincinnati, where a specimen was not obtained for 41% of patients who were enrolled. Although enrolled children who did not provide specimens did not seem to be significantly different from those who did provide specimens, with respect to the epidemiological and clinical characteristics we compared, it is possible that we could not account for all of the differences between the 2 groups.
|
CONCLUSIONS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
This active surveillance study demonstrates that the burden of laboratory-confirmed rotavirus disease treated in ED settings among US children is substantial and higher than estimated previously. The introduction of the new rotavirus vaccine into the national immunization program will likely reduce this burden substantially, and future efforts should focus on documenting this decrease. Some evidence suggests that rotavirus vaccines might prevent more gastrointestinal illness than predicted on the basis of etiologic studies alone; therefore, efforts to determine vaccine impact should concentrate on measurement of decreases in both rotavirus and all-cause diarrhea in these settings, in addition to vaccine effectiveness studies.21
|
ACKNOWLEDGMENTS |
|---|
This research study was supported by grants from Merck.
We acknowledge Marina Bischoff, Mary Sandquist, Jareen K. Meinzen-Derr, Carla Hanekamp, and Jacquelyn Keebaugh from Cincinnati Children's Hospital Medical Center and Catherine Morimoto, Midge Maritzen, and Kevin Creighton from Children's Hospital and Research Center Oakland for their technical assistance and Jon Gentsch and Tara Kerin for their laboratory assistance.
|
FOOTNOTES |
|---|
Accepted Jan 24, 2008.
Address correspondence to Eileen L. Yee, MD, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS-E02, Atlanta, GA 30333. E-mail: eyee{at}cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
Financial Disclosure: Dr Staat received research funding from Wyeth Laboratories and Merck and served on the rotavirus advisory board for Merck and GlaxoSmithKline. Dr Azimi received research funding from Wyeth Laboratories, MedImmune, and Merck and was a member of the MedImmune and Merck advisory committee and speaker program. Dr Bernstein received research funding from GlaxoSmithKline, Merck, and Wyeth Laboratories and holds the patent for the GlaxoSmithKline rotavirus vaccine. Dr Ward received research funding from GlaxoSmithKline, Merck, and Wyeth Laboratories and holds the patent for the GlaxoSmithKline rotavirus vaccine. Dr Matson received research funding from Wyeth Laboratories and Merck and served on the rotavirus advisory board for Merck and GlaxoSmithKline.
| What's Known on This Subject The disease burden of rotavirus illness has been studied most intensely among hospitalized children. However, data on the disease burden of rotavirus illness among children visiting emergency departments have been very limited.
|
| What This Study Adds Active surveillance demonstrated that the burden of laboratory-confirmed rotavirus disease treated in emergency department settings among US children is substantial and greater than estimated previously, and use of a rotavirus vaccine will likely reduce this burden.
|
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
|---|
1. Widdowson MA, Meltzer MI, Zhang X, Bresee JS, Parashar UD, Glass RI. Cost-effectiveness and potential impact of rotavirus vaccination in the United States. Pediatrics. 2007;119 (4):684 –697
2. Lee BP, Azimi PH, Staat MA, et al. Nonmedical costs associated with rotavirus disease requiring hospitalization. Pediatr Infect Dis J. 2005;24 (11):984 –988[CrossRef][Web of Science][Medline]
3. Tucker AW, Haddix AC, Bresee JS, Holman RC, Parashar UD, Glass RI. Cost-effectiveness analysis of a rotavirus immunization program for the United States.
JAMA. 1998;279
(17):1371
–1376
4. Zimmerman CM, Bresee JS, Parashar UD, Riggs TL, Holman RC, Glass RI. Cost of diarrhea-associated hospitalizations and outpatient visits in an insured population of young children in the United States. Pediatr Infect Dis J. 2001;20 (1):14 –19[Web of Science][Medline]
5. Matson DO, Estes MK. Impact of rotavirus infection at a large pediatric hospital. J Infect Dis. 1990;162 (3):598 –604[Web of Science][Medline]
6. Charles MD, Holman RC, Curns AT, Parashar UD, Glass RI, Bresee JS. Hospitalizations associated with rotavirus diarrhea in the United States, 1993–2002. Pediatr Infect Dis J. 2006;25 (6):489 –493[CrossRef][Web of Science][Medline]
7. Fischer TK, Viboud C, Parashar U, Malek M, Steiner C, Glass R, Simonsen L. J Infect Dis. 2007;195 (3):1117 –1125[CrossRef][Web of Science][Medline]
8. Malek MA, Curns AT, Holman RC, Fischer TK, Bresee JS, Glass RI, Steiner CA, Parashar UD. Diarrhea- and rotavirus-associated hospitalizations among children less than 5 years of age: United States, 1997 and 2000.
Pediatrics. 2006;117
(6):1887
–1892
9. Parashar UD, Alexander JP, Glass RI. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55 (RR-12):1 –13[Medline]
10. Parashar UD, Holman RC, Clarke MJ, Bresee JS, Glass RI. Hospitalizations Associated with Rotavirus Diarrhea in the United States, 1993 through 1995: Surveillance Based on the New ICD-9-CM Rotavirus-Specific Diagnostic Code. J Infect Dis. 1998;177 :13 –17[Web of Science][Medline]
11. Jin S, Kilgore PE, Holman RC, Clarke MJ, Gangarosa EJ, Glass RI. Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J. 1996;15 :397 –404[CrossRef][Web of Science][Medline]
12. Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimates of disease burden. J Infect Dis. 1996;174 (suppl 1):S5 –S11[Web of Science][Medline]
13. Ho MS, Glass RI, Pinsky PF, Anderson LJ. Rotavirus as a cause of diarrheal morbidity and mortality in the United States. J Infect Dis. 1988;158 :1112 –1116[Web of Science][Medline]
14. United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Bridged-Race Population Estimates, United States, 1990–2003, July 1st resident population by state, county, age, sex, race, and Hispanic origin, on CDC WONDER On-line Database, June 2005. Available at: http://wonder.cdc.gov/population.html. Accessed on January 31, 2007
15. United States Census Bureau: State and County QuickFacts. Data derived from Population Estimates, 2000 Census of Population and Housing, 1990 Census of Population and Housing, Small Area Income and Poverty Estimates, County Business Patterns, 1997 Economic Census, Minority-and-Women-Owned Business, Building Permits, Consolidated Federal Funds Report, 1997 Census of Governments. Available at: http://quickfacts.census.gov. Accessed on January 14, 2005
16. United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Bridged-Race Population Estimates, United States, 1990–2004, By Age-Groups. Compiled from the April 1, 2000 resident population developed by the Bureau of the Census in collaboration with National Center for Health Statistics on CDC WONDER On-line Database. Available at: http://wonder.cdc.gov/population.html. Accessed on January 31, 2007
17. Ruuska T, Vesikari T. Rotavirus disease in Finnish children: use of numerical scores for clinical severity of diarrhoeal episodes. Scand J Infect Dis. 1990;22 (3):259 –267[Web of Science][Medline]
18. Parashar UD, Holman RC, Bresee JS, et al. Epidemiology of diarrheal disease among children enrolled in four West Coast health maintenance organizations. Pediatr Infect Dis J. 1998;17 (7):605 –611[CrossRef][Web of Science][Medline]
19. Klein EJ, Boster DR, Stapp JR, et al. Diarrhea etiology in a children's hospital emergency department: a prospective cohort study. Clin Infect Dis. 2006;43 (7):807 –813[CrossRef][Web of Science][Medline]
20. Ford-Jones EL, Wang E, Petrie M, et al. Rotavirus-associated diarrhea in outpatient settings and child care centers. The Greater Toronto Area/Peel Region PRESI Study Group. Pediatric Rotavirus Epidemiology Study for Immunization.
Arch Pediatr Adolesc Med. 2000;154
(6):586
–593
21. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.
N Engl J Med. 2006;354
(1):23
–33
PEDIATRICS (ISSN 1098-4275). ©2008 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. R. Flores, P. G. Szilagyi, P. Auinger, and S. G. Fisher Estimated Burden of Rotavirus-Associated Diarrhea in Ambulatory Settings in the United States Pediatrics, February 1, 2010; 125(2): e191 - e198. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
