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Impact of Acute Rotavirus Gastroenteritis on Pediatric Outpatient Practices in the United States

Coffin, Susan E. MD, MPH*; Elser, Joseph MD; Marchant, Colin MD; Sawyer, Mark MD§; Pollara, Bernard MD; Fayorsey, Ruby MD; Nelson, Linda MSN; Lawley, Diane RN*; Goveia, Michelle MD; Stek, Jon MS; Hille, Darcy MS, EMBA; DiNubile, Mark J. MD

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The Pediatric Infectious Disease Journal: July 2006 - Volume 25 - Issue 7 - p 584-589
doi: 10.1097/01.inf.0000220251.27595.74
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Abstract

Rotavirus is the leading cause of acute gastroenteritis in infants and young children; virtually all children are infected within the first 5 years of life.1,2 Although rotavirus accounts for an estimated 440,000 deaths each year in the developing world,3 the public health burden of rotavirus gastroenteritis in the United States is largely measured in infant morbidity, healthcare costs, missed day care and loss of time from work for parents/guardians.2,4–14 In industrialized nations, rotavirus gastroenteritis results in an estimated 1.8 million clinic visits and 223,000 hospitalizations annually.2

Despite the prevalence of rotavirus gastroenteritis, our understanding of the burden of this disease among children who do not require hospitalization is limited.9,14–17 Most children with gastroenteritis do not require hospitalization; the majority of rotavirus-infected children are managed by general pediatricians during office visits or by phone consultation. Because healthcare practitioners do not routinely perform diagnostic testing on children with acute gastroenteritis, we have limited data addressing the impact of rotavirus gastroenteritis on office practices and on families. Although rotavirus is not a reportable disease at either the state or national level in the United States, it is generally accepted that vomiting, diarrhea and fever tend to be more severe in rotavirus than nonrotavirus gastroenteritis.13,18–20

The typical rotavirus epidemic season in the United States begins in the late autumn in the Southwest and spreads across the country, ending in the midspring of the next calendar year in the Northeast.21,22 The purpose of the present study was to describe the clinical presentation of rotavirus gastroenteritis and its impact on pediatric outpatient practices in the United States during the annual epidemic season. Specific objectives were to compare the relative frequency, clinical characteristics and burden of illness among young children with rotavirus and nonrotavirus gastroenteritis.

METHODS

Study Sites.

Prospective cohort studies were independently conducted at 5 academic centers: Children's Hospital of Philadelphia (CHOP) with 6 sites (2 urban and 2 suburban primary care practices, one urban emergency department and one after-hours phone care system); Boston Medical Center (BMC) with 2 sites (suburban primary care practices); University of Arkansas for Medical Sciences (UAMS) with one site (urban primary care practice); University of California School of Medicine at San Diego (UCSD) with 5 sites (3 urban and 2 suburban primary care practices); and University of South Florida (USF) with one site (urban primary care practice). The 5 study centers developed protocols with consistent guidance to ensure similar designs, case definitions and eligibility criteria so that results could be combined into a single comprehensive database. Protocols were approved by the ethical review committee at each center. Informed consent was obtained from a parent/guardian of all participants.

Case Definition and Eligibility Criteria.

Gastroenteritis was defined as ≥3 watery or looser-than-normal stools and/or a single episode of forceful vomiting within a 24-hour period. Children <36 months of age who presented for initial evaluation within 72 hours of symptom onset were considered eligible. Potential subjects were excluded if they had chronic gastrointestinal tract disease (other than gastroesophageal reflux), had diarrhea for >72 hours at the time of first evaluation, were immunodeficient or were participants in a rotavirus vaccine study. Patients with acute gastroenteritis were screened between December 2002 and May 2003 at CHOP, and between December 2003 and May 2004 at BMC, UAMS, UCDS and USF.

Stool Collection and Testing.

Stool specimens were to be obtained at the initial visit to the study site. If a stool sample was not available, the parent/guardian was asked to bring a specimen back to the office within 48 hours. Rectal swabs were not used. Specimens were tested for rotavirus antigen by PremierRotaclone (Meridian Diagnostics, Cincinnati, OH) at CHOP and UAMS, ImmunoCardSTAT! Rotavirus (Meridian Diagnostics) at BMC and UCSD, and Rotazyme (Abbott Laboratories, Abbott Park, IL) at USF.23 Results of stool rotavirus antigen assays were used to classify subjects into 3 categories: rotavirus gastroenteritis (stool sample positive for rotavirus antigen), nonrotavirus gastroenteritis (stool sample negative for rotavirus antigen) or indeterminate (no stool sample collected).

Subject Follow Up.

Data on healthcare contacts were collected from review of electronic medical records at one participating center (CHOP). At the other 4 participating centers, follow-up telephone calls were conducted approximately 7 to 10 days after the initial contact. Details regarding the child's illness and any healthcare resources used during the illness were solicited, including information about diarrhea and vomiting, loss of time from day care, loss of time from work for parents/guardians and healthcare contacts (including family-initiated phone calls, office visits, emergency department visits and hospitalizations).

Data Analysis.

Participants were considered evaluable if they satisfied the case definition for acute gastroenteritis, had a stool sample tested for rotavirus antigen and could be assessed for the outcome of interest (eg, diarrhea, hospitalization, lost days of day care and so on). A subject could be evaluable for none, some or all outcomes. Symptom frequencies were compared for subjects with rotavirus versus nonrotavirus gastroenteritis by Fisher exact test. The distribution of gastrointestinal symptoms (diarrhea and vomiting, diarrhea without vomiting and vomiting without diarrhea) between subjects with and without rotavirus gastroenteritis was also compared by Fisher's exact test. Age and family burden days (number of healthcare contacts, lost days of work and lost days of day care) were compared by the median 2-sample test. Statistical significance was set a priori at an α level of 0.05.

RESULTS

A total of 303 subjects were enrolled from the 5 study centers (Fig. 1), of whom 284 (94%) had a stool sample assayed for rotavirus antigen. Overall, 115 of 284 cases of acute gastroenteritis (40%; 95% confidence interval, 35–46%; range, 31–50% across the 5 sites) were caused by rotavirus. The mean age and gender were similar for children with and without laboratory-confirmed rotavirus (Table 1). Compared with nonrotavirus gastroenteritis, cases of rotavirus gastroenteritis were associated with higher rates of vomiting (P = 0.003) and fever (P = 0.010) at presentation. Although not significantly different between the 2 groups (P = 0.083), the overall frequency of diarrhea was numerically higher in subjects with rotavirus gastroenteritis. Combined diarrhea and vomiting was more frequently associated with rotavirus gastroenteritis; in contrast, diarrhea without vomiting and vomiting without diarrhea were more frequently observed in subjects with nonrotavirus gastroenteritis (P < 0.001).

F1-4
FIGURE 1.:
Percentage of gastroenteritis cases caused by rotavirus at each study center. The number above the bar represents the percentage of gastroenteritis cases at each study center with laboratory-confirmed rotavirus infection. The bars give the 95% confidence interval around the point estimate.
T1-4
TABLE 1:
Baseline Characteristics and Outcomes of Subjects With Rotavirus and Nonrotavirus Gastroenteritis

Approximately half of both the rotavirus (51%) and nonrotavirus (49%) cases occurred in subjects ≤12 months of age. However, rotavirus gastroenteritis occurred most frequently among subjects between the ages of 7 to 12 months, whereas frequency of nonrotavirus gastroenteritis peaked between 4 and 6 months of age (Fig. 2). Fifteen (13%) of the 115 rotavirus cases versus 45 (27%) of 169 nonrotavirus gastroenteritis cases occurred in subjects ≤6 months old (P=0.007).

F2-4
FIGURE 2.:
Age distribution for subjects with rotavirus and nonrotavirus gastroenteritis. The number inside the bar represents the percentage of gastroenteritis cases in each 3-month age interval with laboratory-confirmed rotavirus infection.

Within the 7- to 10-day follow-up period, the proportion of children seeking additional medical care was similar among participants with rotavirus and nonrotavirus gastroenteritis (Table 1). Overall, 73% of the parents/guardians of subjects with rotavirus gastroenteritis versus 57% of the parents/guardians of subjects with nonrotavirus gastroenteritis made at least one follow-up telephone call after the initial healthcare contact (P = 0.017) (Fig. 3A). In addition, 28% of children with rotavirus gastroenteritis as compared with 14% of children with nonrotavirus gastroenteritis required 4 or more healthcare contacts (data not shown).

F3-4
FIGURE 3.:
Family burden imposed by rotavirus and nonrotavirus gastroenteritis. Modified box and whiskers plots are shown adjacent to the histograms. The left and right sides of the box represent the first (Q1) and third (Q3) quartiles, respectively. The line inside the box represents the median. The whiskers extend outward to 1.5 times the interquartile range (IQR = Q3 − Q1) from the median or to the most extreme value if <1.5 × IQR from the median. Asterisks represent individual outliers, defined as values >1.5 × IQR from the median. (A) Number of telephone calls to healthcare providers by parents/guardians of subjects with rotavirus versus nonrotavirus gastroenteritis after the initial healthcare contact. Two or more telephone calls were made by 59% of the parents/guardians of subjects with rotavirus gastroenteritis and 41% of the parents/guardians of subjects with nonrotavirus gastroenteritis. (B) Number of lost days of day care for subjects with rotavirus versus nonrotavirus gastroenteritis. Two or more days of day care were missed by 70% subjects with rotavirus gastroenteritis and 45% of subjects with nonrotavirus gastroenteritis. (C) Number of lost days of work for parents/guardians of subjects with rotavirus versus nonrotavirus gastroenteritis. Two or more days of work were lost by 57% of the parents/guardians of subjects with rotavirus gastroenteritis and 26% of the parents/guardians of subjects with nonrotavirus gastroenteritis.

Subjects with rotavirus gastroenteritis missed significantly more day care than subjects with nonrotavirus gastroenteritis (P = 0.002) (Fig. 3B). As a result of their illness, 70% of subjects with rotavirus gastroenteritis missed at least one day of day care compared with 55% of children with nonrotavirus gastroenteritis. Additionally, the parents/guardians of children with rotavirus gastroenteritis lost significantly more days of work (P = 0.007) (Fig. 3C), with 62% of such parents/guardians missing at least 1 day of work compared with 40% of parents/guardians of children with nonrotavirus gastroenteritis.

DISCUSSION

In this multicenter study, rotavirus consistently caused a substantial proportion of acute gastroenteritis cases among infants and children in the United States. Approximately 40% of infants and young children with acute gastroenteritis seen in pediatric primary care practices during the winter and spring months were attributable to rotavirus, similar to the proportion of rotavirus infections reported among hospitalized children with gastroenteritis.2,5,7,10,11,18,20 During the 2 seasons encompassed by our study, the frequency of rotavirus infection among children with acute gastroenteritis was similar regardless of the geographic location of the study sites.

Acute gastroenteritis is a common reason for parents/guardians of young children to seek medical attention. In our study, 57% of all subjects required a follow-up office visit, 8% visited an emergency department and 5% were hospitalized. Rotavirus gastroenteritis was associated with higher rates of fever, any vomiting, and combined diarrhea and vomiting at presentation than nonrotavirus gastroenteritis. However, no constellation of presenting symptoms was sufficiently distinct to help clinicians discriminate rotavirus from nonrotavirus gastroenteritis, consistent with previously published observations.18–20 In addition, the total number of healthcare contacts, including family-initiated telephone calls, was greater for children with rotavirus than nonrotavirus gastroenteritis. Finally, the indirect burden of disease was greater for families of children with rotavirus compared with nonrotavirus gastroenteritis, presumably related to the increased severity and/or duration of disease. We found that families of children with rotavirus experienced more lost time from day care and work as has been noted by other investigators.4–6,9,14,17 In particular, the median lost time from work was 2 days for the parents/guardians of children with rotavirus gastroenteritis compared with no lost time for the parents/guardians of children with nonrotavirus gastroenteritis.

There were several noteworthy limitations to our study. The mechanism of case finding differed slightly at the 5 participating centers and the associated 15 sites. However, differences were minimized by the use of the identical case definition and similar inclusion and exclusion criteria at all participating sites. For the most part, only variables comparably collected across all sites were included in the composite analysis. Omission of fever from the case definition of acute gastroenteritis possibly reduced the observed proportion of cases resulting from rotavirus, because fever has been reported to occur more commonly with rotavirus gastroenteritis than with other viral and noninfectious etiologies of acute gastroenteritis in young children.19,20 Selection and referral bias could restrict the generalizability of our findings to different populations and settings, particularly because every participating site was affiliated with a large academic center, which is not representative of pediatric outpatient practices in the United States. Nonetheless, patients were enrolled from both urban and suburban locations.

For certain outcome variables, data collection was incomplete. The uncollected data may not have been missing at random and therefore could have been informative. The accuracy and precision of the collected data might be limited by recall bias. Only one center (BMC) captured follow-up data prospectively through the use of a diary card. However, recall bias was minimized in data collected at other sites by active telephone surveillance of all participants within 7 to 10 days of presentation. The sample size may have been too small to demonstrate differences in healthcare utilization rates between children with and without rotavirus gastroenteritis. Finally, not all parents/guardians of children with acute gastroenteritis seek healthcare, so our results were likely skewed toward the more severe end of the disease spectrum.

This observational study contributes to a better understanding of the presenting signs and symptoms of rotavirus gastroenteritis and its impact on families and healthcare resource utilization. At each study location, approximately 40% of children with acute gastroenteritis presenting to a primary care practice had rotavirus infections. The large majority of rotavirus gastroenteritis cases (87%) was seen in subjects older than 6 months of age, as expected from previous reports.6,18,19 A safe and effective rotavirus vaccine program targeted to complete dosing by 6 months of age could reduce childhood morbidity and the negative impact on families and pediatric practices in urban and suburban settings throughout the United States during rotavirus epidemic seasons.12,24–27

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Keywords:

rotavirus; gastroenteritis; healthcare; diarrhea; vomiting

© 2006 Lippincott Williams & Wilkins, Inc.