ORIGINAL ARTICLE

Epidemiological changes in rotavirus gastroenteritisin children under 5 years of age after the introductionof rotavirus vaccines in Korea

Ui Yoon Choi & Soo Young Lee & Sang Hyuk Ma &

Young Taek Jang & Jae Young Kim & Hwang Min Kim &

Jong Hyun Kim & Dong Soo Kim & Yong Soo Kim &

Jin Han Kang

Received: 16 August 2012 /Revised: 4 February 2013 /Accepted: 11 February 2013 /Published online: 27 February 2013# Springer-Verlag Berlin Heidelberg 2013

Abstract Rotavirus gastroenteritis is the leading cause ofsevere acute gastroenteritis in children worldwide and isassociated with high hospitalization and mortality rates inchildren younger than 5 years of age. Vaccination is neces-sary to prevent rotavirus infection. Two live attenuated and

orally administered rotavirus vaccines became commercial-ly available in Korea. The aim of this study is to describeepidemiological changes in rotavirus gastroenteritis after theintroduction of rotavirus vaccines in Korea. The medical recordsof 11,199 children younger than 5 years of age and hospitalizedfor acute gastroenteritis from August 2007 to July 2010 in eightKorean hospitals were reviewed. Rotavirus was detected in stoolsamples obtained from 2,959 children (26.42 %). The authorsevaluated the percentage of rotavirus gastroenteritis among allacute gastroenteritis hospitalizations in eight hospitals located indifferent geographical areas and analyzed epidemiologicalchanges in rotavirus gastroenteritis according to age, geograph-ical area, and season. According to the findings, the percentageof rotavirus gastroenteritis showed a decrease in children eligiblefor vaccination during the study period. After introduction of thevaccine, reduced rates of rotavirus detection were observed in allof the geographical areas, and the greatest reduction was ob-served in Seoul. In Seoul, there was a marked delay of therotavirus season. Conclusion: Epidemiologic changes in Koreaafter the introduction of rotavirus vaccine are consistent withchanges observed in other countries.

Keywords Epidemiology . Rotavirus . Rotavirusgastroenteritis . Rotavirus vaccine

Introduction

Rotavirus is a double-stranded RNA virus that is highlyinfectious at small doses (<100 particles). The virus can

U. Y. Choi : S. Y. Lee : J. H. Kim : J. H. Kang (*)Department of Pediatrics, College of Medicine, The CatholicUniversity of Korea, Seoul St. Mary’s Hospital, 222 Banpodaero,Seochogu, Seoul 137-701, Republic of Koreae-mail: kjhan@catholic.ac.kr

S. H. MaDepartment of Pediatrics, Changwon Fatima Hospital,Changwon, Korea

Y. T. JangDepartment of Pediatrics, Jeonju Presbyterian Hospital,Jeonju, Korea

J. Y. KimDepartment of Pediatrics, Chungnam National University Schoolof Medicine, Daejeon, Korea

H. M. KimDepartment of Pediatrics, Wonju College of Medicine, YonseiUniversity, Wonju, Korea

D. S. KimDepartment of Pediatrics, Yonsei University College of Medicine,Seoul, Korea

Y. S. KimMerck, Sharp, and Dohme (MSD), Seoul, Korea

Eur J Pediatr (2013) 172:947–952DOI 10.1007/s00431-013-1974-y

survive under conditions of low temperature, low pH, a dryenvironment, and ultraviolet light exposure, which facilitateits survival for a few days. Furthermore, it may spread viarespiratory routes [9, 17]. Due to these microbiologicalcharacteristics, rotavirus is the most common cause of acutegastroenteritis in advanced countries and developing coun-tries. In developing countries, rotavirus gastroenteritiscauses the deaths of as many as 360,000–600,000 childrenyounger than 5 years of age each year [15, 19]. In advancedcountries, one out of 67 children younger than 5 years of ageis hospitalized at least once for rotavirus-related disease [8].Rotavirus gastroenteritis usually occurs in children aged 6–24 months [5, 12, 20]. The detection rates of rotavirus aresimilar throughout the year in the tropics but are higher fromNovember to April, with a peak detection rate betweenJanuary and March, in temperate climates [11, 20].

Rotavirus is spread through airborne droplets or bythe fecal–oral route, and frequent exposure to the virus-es, such as in daycare centers, increases the risk ofinfection [3, 9]. Rotavirus disease begins with feverand vomiting, followed by frequent watery diarrhea[2]. Research on vaccines for rotavirus gastroenteritisstarted in 1970, and various products have been devel-oped. However, the first rotavirus vaccine was not in-troduced in Korea until 2007. The Korean vaccinationrate has increased annually from 7 % in 2007, 35 % in2008, to 50 % in 2009 based on registered vaccinesales. In the USA, rotavirus season was delayed by 2–4 months after the introduction of rotavirus vaccine [4],and at a sample of ten regional hospitals, an 85 %decrease in rotavirus detection rates was observed [6].Furthermore, in Germany, rotavirus-related morbiditieswere found to be lower in regions with high vaccinationcoverage [22].

No epidemiological study on rotavirus gastroenteritis hasbeen conducted since rotavirus vaccine was introduced in

Korea. In the present study, we evaluated the percentage ofrotavirus gastroenteritis in children younger than 5 yearshospitalized for symptoms of acute gastroenteritis at eightKorean hospitals between August 2007 and July 2010, thatis, after the introduction of the rotavirus vaccine, and weinvestigated epidemiological changes in rotavirus gastroen-teritis according to age, geographical area, and season.

Methods

From August 2007 to July 2010, 11,199 children youngerthan 5 years were hospitalized for acute gastroenteritis ateight Korean hospitals (Seoul St. Mary’s Hospital, IncheonSt. Mary’s Hospital, St. Vincent’s Hospital, Sinchon Sever-ance Hospital, Wonju Christian Hospital, Jeonju Presbyteri-an Hospital, Changwon Fatima Hospital, and ChungnamNational University Hospital) and underwent stool exami-nations for detection of rotavirus antigen. Each of the hos-pitals used different methods (Table 1); however, sensitivityabove 90 % and specificity above 99 % were reported foreach screening method. Of this sample, 2,959 children werediagnosed with rotavirus gastroenteritis (26.42 %) and in-vestigated for demographic data, clinical symptoms, andtiming of hospitalization using medical records. The studyprotocol was approved by institutional review board at eachof the above-mentioned hospitals.

Percentage of children hospitalized with rotavirusgastroenteritis among children hospitalized for acutegastroenteritis was estimated with 95 % confidence in-tervals with respect to age, geographical area, andtiming of hospitalization. The chi-squared test was usedto compare categorical data. SAS software version 9.2(SAS Institute Inc., Cary, NC, USA) was used for dataanalysis, and P values of less than 0.05 were consid-ered statistically significant throughout.

Table 1 Method of rotavirus antigen detection for each hospital

Region Hospital Method Antigen test kit

Seoul Seoul St. Mary’s Hospital Immunochromatography Biocard Rotastick; Ani Biotech Oy, Finland

Seoul Sinchon Severance Hospital Latex agglutination Rotatex; Orion Diagnostica, Finland

Incheon Incheon St. Mary’s Hospital Immunochromatography Dipstick Eiken Rota; SA Scientific, Japan

Suwon St. Vincent’s Hospital Latex agglutination Rotavirus Latex Test; Remel Europe,England

Wonju Wonju Christian Hospital Enzyme-linked fluorescentimmunoassay

VIDAS system; bioMerieux, France

Jeonju Jeonju Presbyterian Hospital Latex agglutination Rotavirus Latex Test; Remel Europe,England

Changwon Changwon Fatima Hospital Immunochromatography Biocard Rotastick; Ani Biotech Oy, Finland

Daejeon Chungnam National UniversityHospital

Latex agglutination Slidex Rota-kit 2; bioMerieux, France

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Results

Percentages of children hospitalized for rotavirusgastroenteritis by age

The mean age of children hospitalized due to rotavirusgastroenteritis was 16.55±13.40 months. Among childrenhospitalized for acute gastroenteritis in 2008, 2009, and2010, the percentages of children hospitalized with rotavirusgastroenteritis were significantly lower than 2007 baselinepercentage for children aged 2–5, 6–11, 12–23, and 24–59 months (P<0.001) (Table 2).

Percentages of children hospitalized for rotavirusgastroenteritis by geographical area

Among children hospitalized for acute gastroenteritis in2008, 2009, and 2010, the percentages of children hospital-ized with rotavirus gastroenteritis were significantly lowerthan 2007 baseline percentage for all regions (P<0.001)(Table 3).

Percentages of children hospitalized for rotavirusgastroenteritis by season

During the study period, among children hospitalizedfor acute gastroenteritis, the monthly distributions ofpercentages of children hospitalized with rotavirus gas-troenteritis varied according to geographical area

(Fig. 1). However, in Seoul, there was a marked delayof the rotavirus season (P<0.001) (Fig. 2). The highestpercentages were observed from January to March, andpercentages showed a marked reduction after April in2008. However, the highest percentages were observedfrom January to April in 2009 and from January to Junein 2010. The epidemic season was delayed by 2–3 months.

Discussion

Rotavirus is themajor cause of acute gastroenteritis in infants andoccurs worldwide across socioeconomic levels and geographicalenvironments. Major symptoms depend on the level of infectionand vary from no symptoms to fever, vomiting, diarrhea, anddehydration, and the latter can lead to death if not properlytreated [10, 23], and thus, the maintenance of immunity byvaccination is essential. A pentavalent rotavirus vaccine,containing live attenuated and rearranged rotaviruses derivedfrom bovines and humans (RotaTeq, Merck and Co.,Whitehouse Station, NJ, USA), was introduced in June 2007 inKorea, whereas a univalent vaccine containing live attenuatedrotaviruses derived from humans (Rotarix, GlaxoSmithKlineBiologicals, Rixensart, Belgium) was introduced inMarch 2008.

In a previous study, conducted in Ohio, Tennessee,and New York, the percentages of children with rotavi-rus gastroenteritis among children hospitalized for acutegastroenteritis were 51 % in 2006, 52 % in 2007, 8 %

Table 2 Rotavirus gastroenteritis-related hospitalizations by age group, 2007–2010

Percentages of children hospitalized with rotavirus gastroenteritis among children hospitalized for acute gastroenteritis (%)

Age 2007 2008 2009 2010

<2 months 54.29 50.87 53.46 50.54

2–5 months 52.63 25.77 8.09 4.76

6–11 months 48.87 26.54 2.80 1.90

12–23 months 54.46 38.27 11.87 6.35

24–59 months 46.18 34.98 13.57 8.68

Table 3 Rotavirus gastroenteritis-related hospitalizations by geographical area, 2007–2010

Percentages of children hospitalized with rotavirus gastroenteritis among children hospitalized for acute gastroenteritis (%)

Geographical area 2007 2008 2009 2010

Seoul 34.68 20.01 16.46 16.14

Incheon 31.83 26.63 18.27 17.99

Suwon 44.10 41.60 32.40 27.37

Wonju 30.55 26.05 21.98 19.66

Jeonju 33.80 28.88 28.53 27.89

Changwon 37.80 33.42 31.27 26.99

Daejeon 55.28 46.99 39.87 31.17

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in 2008, and 26 % in 2009. Thus, as compared with2006, when rotavirus vaccination was initiated, hospital-ization percentages for rotavirus infection among acutegastroenteritis cases decreased in 2008 and 2009 [18].In Brazil, percentages of hospitalization for rotavirusgastroenteritis reduced by 26 % in 2006 and 48 % in2007, and reductions were much higher in geographicalareas with high vaccination rates [13].

Rotavirus is prevalent in children aged 6 months to2 years [5, 12, 20]. In the present study, the percentage ofchildren hospitalized with rotavirus gastroenteritis showed asignificant decrease in 2008, 2009, and 2010, comparedwith 2007 baseline percentage for children aged 2–5, 6–11, 12–23, and 24–59 months (P<0.001) (Table 2). Over thestudy period, percentages of children hospitalized with ro-tavirus gastroenteritis were similar in children younger than

Fig. 1 Monthly distributions of rotavirus gastroenteritis-related hospitalizations in all geographical areas

Fig. 2 Monthly distributions ofrotavirus gastroenteritis-relatedhospitalizations in Seoul

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2 months. This finding may reflect age at rotavirusvaccination. Currently, rotavirus vaccine is orally admin-istered two or three times in children from 2 to 6 monthsold. In the present study, older children who may havereceived rotavirus vaccination showed a reduction inrotavirus gastroenteritis-related hospitalizations, and chil-dren 6 to 11 months old who recently completed athree-vaccination schedule showed the greatest reduction(P<0.001) (Table 2).

Rotavirus vaccines are expensive in Korea becausethey are not incorporated into a national immunizationprogram, and thus, the likelihood of vaccination isprobably dictated by parental income and socioeconom-ic status. In the present study, vaccination coveragerates were not investigated by geographical area, whichis undoubtedly a study limitation. For all regions,among children hospitalized for acute gastroenteritis in2008, 2009, and 2010, the percentages of childrenhospitalized with rotavirus gastroenteritis were signifi-cantly lower than 2007 baseline percentage. Thegreatest reduction was observed in Seoul and Incheon.Children in Seoul, the capital city of Korea, and In-cheon, one of the metropolitan areas, are much morelikely to be immunized (P<0.001) (Table 3).

Rotavirus gastroenteritis is most prevalent in winterand early spring according to Korean studies [11, 20],and studies conducted in other countries with a temper-ate climate, including USA [7], Japan [21], and China[15]. Furthermore, it has been reported that a lowtemperature and a dry climate favors the survival ofrotaviruses [1, 14]. In 2008, the US Center for DiseaseControl and Prevention reported that the rotavirus sea-son was delayed by 2–4 months after introduction ofrotavirus vaccine [4]. Although peak of rotavirus fre-quency varied according to geographical region (Fig. 1),in Seoul, the capital city of Korea, which probablyhad the highest rate of vaccination coverage, this patternof seasonal epidemiologic change was significant(Fig. 2). In 2008, the year after rotavirus vaccine intro-duction, the percentage of hospitalized children withrotavirus gastroenteritis was highest from January toMarch, whereas in 2009, it was from January to Apriland in 2010 from January and June (Fig. 2). We sup-pose that rates of infection decreased during the winterand early spring due to increased immunity throughvaccination, changes in virus serotype after vaccineintroduction, and climate changes caused by globalwarming.

In conclusion, among children hospitalized for acutegastroenteritis, the percentage of children hospitalizedwith rotavirus gastroenteritis showed a significant de-crease in children eligible for vaccination during thestudy period. Rotavirus detection rates showed a

reduction in all of the geographical areas, and thegreatest reduction was observed in Seoul. In Seoul, theepidemic season was delayed by 2–3 months. Epidemiologicchanges in Korea after the introduction of rotavirus vaccine areconsistent with changes observed in other countries.

Conflict of interest The authors declare the following financialinterest: All authors received research grants for this study fromMSD Korea Ltd.; however, this had no influence on conduct of thestudy, interpretation of results, and writing of this article. All authorsstate that they have no conflict of interest.

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