Changing distribution of age, clinical severity, and genotypes of rotavirus gastroenteritis in hospitalized children after the introduction of vaccination: a single center study in Seoul between 2011 and 2014

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Abstract

Background

This study aimed to explore changes in clinical epidemiology and genotype distribution and their association among hospitalized children with rotavirus gastroenteritis after the introduction of vaccines.

Methods

Between November 2010 and October 2014, hospitalized children with acute gastroenteritis were enrolled. Rotavirus genotypes were confirmed through reverse transcription-polymerase chain reaction (RT-PCR), semi-nested PCR, and sequencing. Clinical information including vaccination status and the modified Vesikari scores were collected.

Results

Among 179 children with rotavirus infection, nineteen (10.6 %) were completely vaccinated. During the study period, the number of children between three and 23 months of age decreased significantly compared to the number of children older than 24 months of age ( P = 0.010), who showed lower diarrhea severity (duration, P = 0.042; frequency, P = 0.021) but higher vomiting severity ( P = 0.007, 0.036) compared to the former. Vaccination status was also significantly associated with lower vomiting severity after adjustment for age (frequency only, P = 0.018). The predominant genotypes were G2P[4] (18.4 %), G1P[8] (14.5 %), and G1P[4]P[8] (12.8 %), and the prevalence of genotypes with uncommon and mixed combinations was more than 50 %. Children infected with G2P[4] strains tended to be older ( P = 0.005) and had more severe vomiting ( P = 0.018, 0.006) than those with G1P[8].

Conclusions

Increase in age of infected, hospitalized children was accompanied by change in clinical severity during 2011–2014 after the introduction of vaccines in Seoul. Clinical severity was also associated with vaccination status and genotype. Long-term large scale studies are needed to document the significance of the increase in genotypes of uncommon and mixed combinations.

Electronic supplementary material

The online version of this article (doi:10.1186/s12879-016-1623-y) contains supplementary material, which is available to authorized users.

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Most cited references 49

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Effect of human rotavirus vaccine on severe diarrhea in African infants.

Shabir Madhi, Nigel Cunliffe, Duncan Steele … (2010)

Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children. We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale. A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group. Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.) 2010 Massachusetts Medical Society

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Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens.

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The rotavirus gene segment coding for the major outer capsid glycoprotein vp7 was amplified directly from stool specimens by the polymerase chain reaction (PCR). Double-stranded RNA extracted from stool samples was used as the template for reverse transcription, which was followed immediately and in the same reaction mix with amplification, using the Taq polymerase. Various conditions were examined to optimize the yield of the amplified gene. The concentrations of MgCl2, dimethyl sulfoxide, and template RNA were critical. The choice of primer pairs allowed amplification of the entire segment or specific portions. By using type-specific primers derived from distinct regions on the gene, we devised a PCR typing method in which each human serotype virus produced a characteristic segment size, readily identifiable in agarose gels. The PCR typing method was applied to 10 rotavirus reference strains, including all 6 known human serotypes (serotypes 1, 2, 3, 4, 8, and 9), and to 34 stool specimens previously serotyped by an enzyme immunoassay with monoclonal antibodies. An absolute correlation was found between the molecular and serologic methods. In addition, 14 stool specimens nonserotypable by an enzyme immunoassay with monoclonal antibodies could be typed by the PCR method. Besides the application for rotavirus detection and typing directly from stools, the PCR method provides a rapid and efficient means of obtaining large quantities of cDNA suitable for sequencing, cloning, and other genetic studies, precluding the need for cell culture and virus purification.

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Identification of group A rotavirus gene 4 types by polymerase chain reaction.

J R Gentsch, R Glass, P. Woods … (1992)

Five genetically distinct human rotavirus (HRV) gene 4 groups have been described on the basis of comparative nucleotide sequencing and the predicted amino acid sequences, and at least four of them represent distinct VP4 antigenic types. To identify each gene 4 type and investigate its distribution in HRV isolates from patients with diarrhea, we developed a polymerase chain reaction (PCR) typing method using sequence information available for four genetically distinct gene 4 types. Rotavirus double-stranded RNAs (dsRNAs) isolated from stool samples were first reverse transcribed and amplified by PCR by using two oligonucleotide primers that correspond to regions that are highly conserved among all known HRV gene 4 types. The 876-bp dsDNA products were then reamplified by PCR in the presence of a cocktail containing one conserved plus-sense primer and four type-specific minus-sense primers (selected from the hypervariable region of gene 4), resulting in products of 345, 483, 267, and 391 bp corresponding to gene 4 types 1, 2, 3, and 4, respectively. This method reliably identified the gene 4 types of 16 well-characterized HRV isolates. Our results were independently confirmed for all 16 strains by reverse transcription and PCR amplification of HRV dsRNA in the presence of alternate type-specific primer pairs. For direct gene 4 typing of HRV in stool samples, we developed a method to extract rotavirus dsRNA from stool specimens by using glass powder. Our results suggest that gene 4 typing will be useful in providing more a complete characterization of HRV strains of epidemiologic or vaccine-related interest.

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Author and article information

Contributors

Jung Ok Shim: shimjo@korea.ac.kr

Ju Young Chang: +82-2-870-2362 , +82-2-870-3866 , jychangmd@hanmail.net

Sue Shin: jeannie@snu.ac.kr

Jin Soo Moon: mjschj@snu.ac.kr

Jae Sung Ko: kojs@snu.ac.kr

Journal

Journal ID (nlm-ta): BMC Infect Dis

Journal ID (iso-abbrev): BMC Infect. Dis

Title: BMC Infectious Diseases

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2334

Publication date (Electronic): 14 June 2016

Publication date PMC-release: 14 June 2016

Publication date Collection: 2016

Volume: 16

Electronic Location Identifier: 287

Affiliations

[ ]Department of Pediatrics, Korea University College of Medicine, 148, Gurodong-ro, Guro-gu, Seoul 152-703 South Korea

[ ]Department of Pediatrics, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul 110-744 South Korea

[ ]Seoul Metropolitan Government Seoul National University Boramae Medical Center Seoul, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul 156-707 South Korea

[ ]Department of Laboratory Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul 110-744 South Korea

Article

Publisher ID: 1623

DOI: 10.1186/s12879-016-1623-y

PMC ID: 4906974

PubMed ID: 27296987

SO-VID: 904fa080-0143-48c5-8707-5743bfa4ec0e

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 January 2016

Date accepted : 4 June 2016

Funding

Funded by: FundRef , Basic Science Research Program through the National Research Foundation of Korea;

Award ID: NRF-2012R1A1A3010058

Award Recipient : Ju Young Chang

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ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: rotavirus,genotype,age,clinical severity,vaccine

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ScienceOpen disciplines: Infectious disease & Microbiology

Keywords: rotavirus, genotype, age, clinical severity, vaccine

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Changing distribution of age, clinical severity, and genotypes of rotavirus gastroenteritis in hospitalized children after the introduction of vaccination: a single center study in Seoul between 2011 and 2014

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Abstract

Background

Methods

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Conclusions

Electronic supplementary material

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Vaccines

Most cited references 49

Effect of human rotavirus vaccine on severe diarrhea in African infants.

Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens.

Identification of group A rotavirus gene 4 types by polymerase chain reaction.

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