Jpn. J. Infect. Dis., 57, 166-171, 2004 Original Article Estimation of Annual Incidence, Age-Specific Incidence Rate, and Cumulative Risk of Rotavirus Gastroenteritis among Children in Japan Michiyo Yokoo, Kokichi Arisawa and Osamu Nakagomi* Division of Molecular Epidemiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan (Received October 21, 2003. Accepted April 20, 2004) SUMMARY: Rotavirus gastroenteritis is a common childhood infection, but the exact morbidity of the disease is not well described in Japan. We aimed at estimating morbidity measures to determine the magnitude of rotavirus gastroenteritis. An estimate for acute infectious gastroenteritis of all causes, to which rotavirus gastroenteritis belongs, has been available since the enactment in 1999 of the Law concerning the Prevention of Infectious Diseases and Medical Care of Patients with Infectious Diseases. Using this estimate and another estimate for the detection proportion of rotavirus among outpatients with acute infectious gastroenteritis, we calculated the annual incidence, the age-specific annual incidence rate, and the cumulative risk by the age of 6 years for rotavirus gastroenteritis. The latter estimate was obtained by a meta-analysis of four independent studies previously performed in Japan. According to our estimates, approximately 800,000 children in Japan under the age of 6 years visit pediatric practices or the outpatient department of hospitals because of rotavirus gastroenteritis at a rate of 11 cases/100 persons/year, and one in two children will visit pediatricians before they go to primary school. Such pediatrician visits most frequently occur at the age of 1 year (27 cases/100 persons/year). Thus, the magnitude of the burden of rotavirus disease among Japanese children is substantial. classifies infectious diseases into five categories according INTRODUCTION to the level of the potential seriousness of the infectious Group A rotavirus, hereafter referred to as rotavirus, is the diseases in question. Acute infectious gastroenteritis, a larger most common cause of severe gastroenteritis in infants and disease category to which rotavirus gastroenteritis belongs, young children across the world (1). Almost all children are is one of 42 infectious diseases of Category V. As regards infected by the age of 3-5 years, but rotavirus infection acute infectious gastroenteritis, doctors in approximately continues to occur throughout life (2). However, the con- 3,000 sentinel clinics (pediatric practices) and outpatient sequences of rotavirus infection in developing and indus- departments of hospitals distributed throughout the nation are trialized countries are in sharp contrast. Whereas the estimated requested to provide weekly reports of the number and certain annual number death rates attributable to rotavirus infection attributes of the patients with this disease to a local health is 670,000 to 800,000 in developing countries, the correspond- center, and then this information is collectively transferred to ing figures in developed countries are considered to be the Infectious Disease Surveillance Center (IDSC) at the minimal (3). Nevertheless, the overall incidence of children National Institute of Infectious Diseases (NIISD), through seeking medical care at pediatric practices or the outpatient each local IDSC. On the basis that these sentinel points department of hospitals is thought to be extremely high. In represent approximately 10% of the pediatric practices and the USA, it has been estimated by the Centers for Disease hospitals in Japan, Nagai et al. recently reported for the first Control and Prevention (CDC) that one in 8 children will time that the annual incidence of acute infectious gastro- annually visit a doctor’s office due to rotavirus gastroenteritis enteritis in Japan was estimated to be 8.65 million cases for during the first few years of life and that the direct medical the year 2000 (5). The IDSC also publishes the Infectious costs alone will total approximately 500 million US dollars Agents Surveillance Report in which, among other pathogens, (4). the number of rotavirus cases detected by local public health However, in Japan such estimates of the rotavirus disease institutes is listed; however, the size of and the age distribu- burden are lacking, and rotavirus infection has only captured tion of cases in the denominator from which rotavirus was marginal public attention. Major reforms in Japan’s public detected are neither available nor directly linked to the health system against infectious diseases were implemented gastroenteritis cases reported by the aforementioned sentinel at the turn of the century; among these reforms was the surveillance points. It is therefore impossible to estimate the enactment in 1999 of the Law concerning the Prevention of number of rotavirus gastroenteritis cases (i.e., the annual Infectious Diseases and Medical Care of Patients with incidence) by simply multiplying the estimated number of cases Infectious Diseases (or the “Infectious Disease Control Law”). of infectious gastroenteritis (8.65 million) by the proportion This new law, which was further reformed in November 2003, (%) of rotavirus cases detected among patients with infec- tious gastroenteritis, a number which is not available for the *Corresponding author: Mailing address: Division of Molecular reasons stated above. Epidemiology, Nagasaki University Graduate School of Bio- The aim of this study was therefore to obtain an estimate medical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. of the annual incidence, the age-specific annual incidence Tel: +81-95-849-7063, Fax: +81-95-849-7064, E-mail: rate, and the cumulative risk by the age of 6 years of rotavirus [email protected] gastroenteritis by multiplying the estimate for the annual 166 incidence of acute infectious gastroenteritis (obtained from under 1 year old was divided into 0-5 months and 6-11 the IDSC’s published record) by our estimate of the propor- months, because the number of cases varied between these tion of rotavirus detected among outpatients with acute two age categories. For both of these two categories, the infectious gastroenteritis. The latter estimate was obtained detection proportion of rotavirus among those under 1 year by a meta-analysis of four papers selected from the literature old was used. that contained a sufficient amount of information to perform Estimation of the annual incidence rate of rotavirus such an analysis. gastroenteritis in each age category and the cumulative risk of rotavirus disease by the age of 6 years: The annual incidence rate of rotavirus gastroenteritis was estimated by MATERIALS AND METHODS dividing the number at all sentinels of rotavirus gastroenteritis Meta-analysis estimation of the rotavirus proportion cases in each age category by the virtual catchment population detected among outpatients with acute infectious gastro- of the corresponding age category. The virtual catchment enteritis in Japan: A meta-analysis was performed to population for each age category was defined as the popula- estimate the percentage of rotavirus detected in the stool spec- tion for each age category derived from the census of 2000 imens of outpatients with acute infectious gastroenteritis (i.e., multiplied by the ratio of the number of sentinels over the the rotavirus detection proportion) in Japan. The literature was total number of pediatric practices and hospitals (i.e., 31,000). extensively searched according to the following criteria. (i) However, one-half of the infant population was assigned to The study was conducted in Japan, (ii) Study subjects were the 0-5 month-old group, and one-half was assigned to the or included pediatric outpatients with acute diarrhea or gastro- 6-11 month-old group. Calculation of 95% confidence enteritis, (iii) The study was carried out throughout the year intervals was performed using the STATA software package. and at least for 1 year, and (iv) The study reported the The cumulative incidence or risk of rotavirus gastroenteritis number of subjects and the rotavirus detection proportion for from 0 to 5 years of age was calculated using the following each age-category. The fourth criterion was the most difficult equation: cumulative risk (%) =1 – {Π(1 – IRi×Δti)}, where to fulfill because different age categories were employed, IR denotes the incidence rate and Δt stands for the length of depending on the paper. In this study, pediatric patients were the subinterval (13). grouped into four age-categories, i.e., <1 year old, 1 year old, 2-3 years old, and 4-5 years old. Four papers were finally RESULTS selected that met these criteria (6-11). However, one (7) was used only for the age-category <1 year, since the method of Four studies selected for the meta-analysis to estimate the categorization of the age category ≥1 year was different from detection proportion of rotavirus infections were performed that of the other studies. A pooled estimate of the rotavirus in four geographically diverse locations in Japan and during detection proportion for each age category was calculated as temporarily distinct periods spanning from 1980 to 1997; the a weighted average; this was done by weighting each study first study was performed in the early 1980s, and the second estimate by the inverse of its variance. The 95% confidence and the third ones were in the early 1990s; the last one was in interval of the rotavirus detection proportion was calculated as the mid