BACKGROUND: Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear. METHODS AND FINDINGS: We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017. Nursing piglets (less than one month of age) had higher detection rate for rotavirus than older age groups. Five VP7 (G) genotypes and 5 VP4 (P) genotypes were found in a total of 14 different G/P genotype combinations. In addition, porcine RVA strains had 2 NSP4 (E) genotypes and 3 VP6 (I) genotypes. A P[3]-like genotype was also discovered among strains collected in 2016 and 2017. CONCLUSIONS: Most of the genes from Taiwanese porcine strains clustered with each other and the lineages formed by these strains were distinct from the sequences of numerous regional variants or globally circulating porcine strains, suggesting an independent evolutionary history for Taiwanese rotavirus genotypes. The close relationship among porcine RVA strains and some unique porcine-like genotypes detected sporadically among human children in swine farms illustrates that pigs might serve as a reservoir for potential zoonotic transmission and novel genotype evolution in Taiwan's insular environment.

In 2006, two rotavirus vaccines were licensed in Taiwan but were not added to the national immunization schedule. National Health Insurance data from 2003 through 2017 were used to compare rotavirus-associated pediatric hospitalizations before and after vaccine introduction. Rotavirus hospitalization rates among children < 5 years of age significantly declined by 24% (95% confidence interval [CI] 23 - 25%) in post-vaccine compared to pre-vaccine rotavirus seasons. Rotavirus hospitalization rates declined by 42% (95% CI 39 - 44%) among infants < 12 months of age, and by 38% (95% CI 36 - 40%) among children 12 - 23 months of age. These findings suggest that, despite not being included in the national immunization schedule, rotavirus vaccines had a measurable impact on reducing rotavirus hospitalization burden among Taiwanese children.

Background: Despite the increasingly recognized role of norovirus in global acute gastroenteritis (AGE), specific estimates of the associated disease burden remain sparse, primarily due to limited availability of sensitive norovirus diagnostics in the clinical setting. We sought to estimate the incidence of norovirus-associated hospitalizations by age group in Taiwan using a previously developed indirect regression method. Methods: AGE-related hospitalizations in Taiwan were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes abstracted from a national database; population data were provided from the Department of Household Registration Affairs. Population and hospitalizations were aggregated by month and year (July 2003-June 2013) and grouped by age: <5 years, 5-19 years, 20-64 years, and >/=65 years. Monthly counts of cause-unspecified AGE hospitalizations were modeled as a function of counts of known causes, and the residuals were then analyzed to estimate norovirus-associated hospitalizations. Results: Over the study period, an annual mean of 101400 gastroenteritis-associated hospitalizations occurred in Taiwan (44 per 10000 person-years), most of which (83%) had no specified cause. The overall estimated rate of norovirus-associated hospitalizations was 6.7 per 10000 person-years, with the highest rates in children aged <5 years (63.7/10000 person-years). Predicted norovirus peaked in 2006-2007 and 2012-2013. Conclusions: Our study is one of the first to generate a population-based estimate of severe norovirus disease incidence in Asia, and highlights the large burden of norovirus in Taiwan, particularly in children. Predicted peak norovirus seasons coincided with the emergence of new strains and resulting pandemics, supporting the validity of the estimates.

In Taiwan, acute gastroenteritis outbreaks caused by a new norovirus genotype GII.2 increased sharply toward the end of 2016. Unlike previous outbreaks, which often involved restaurants, GII.2 outbreaks mainly occurred in schools. Phylogenetic analysis indicates that these noroviruses are recombinant GII.P16-GII.2 strains.

INTRODUCTION: Rotavirus is a leading cause of acute gastroenteritis among Taiwanese children. Two globally licensed rotavirus vaccines recommended for inclusion in routine immunization programs that have been available for private market use in Taiwan since 2006 have been associated with a low risk of intussusception in post-marketing studies conducted in several countries. Our objective was to examine trends and characteristics of intussusception hospitalizations in Taiwan among children aged <12 months before and after rotavirus vaccine licensure to provide updated baseline and early post-licensure data. METHODS: We extracted data on intussusception-related hospitalizations among children aged <12 months during 2001-2013 from the National Health Insurance Research Database. We examined patient demographics, clinical outcome, and hospitalization trends, focusing on recommended ages for rotavirus vaccination (6-14 weeks, 15-24 weeks, and 25-34 weeks). We compared mean hospitalization rates for pre-vaccine licensure years 2001-2005 with those for post-vaccine licensure years 2007-2013 using Poisson regression analysis. RESULTS: During 2001-2013, 1998 intussusceptions hospitalizations were recorded. The mean age of hospitalization was 33 weeks. Almost all children recovered; 3 deaths occurred. The overall intussusception hospitalization rate was 75.1 per 100,000; seasonality was not evident. Hospitalization rates were greatest in children aged ≥25 weeks and occurred more frequently in boys. Pre-vaccine and post-vaccine licensure trends in annual hospitalization rates did not significantly differ. However, mean hospitalization rates were lower during the post-vaccine licensure period for children aged <12 months (RR: 0.84, 95% CI: 0.76-0.92) with the greatest decline among children aged 25-34 weeks (RR: 0.66, 95% CI: 0.55-0.78). CONCLUSIONS: Infant intussusception in Taiwan occurs at a rate within the range of other Asian countries, is rare among children aged <3 months, has a male predominance, and does not have a clear seasonality pattern. We did not observe a post-licensure increase in intussusception hospitalization rates in children aged 6-14 weeks.

Molecular epidemiologic studies collecting information of the spatiotemporal distribution of rotavirus VP7 (G) and VP4 (P) genotypes have shown evidence for the increasing global importance of genotype G9 rotaviruses in humans and pigs. Sequence comparison of the VP7 gene of G9 strains identified different lineages to prevail in the respective host species although some of these lineages appear to be shared among heterologous hosts providing evidence of interspecies transmission events. The majority of these events indicates the pig-to-human spillover, although a reverse route of transmission cannot be excluded either. In this study, new variants of G9 rotaviruses were identified in two children with diarrhea and numerous pigs in Taiwan. Whole genome sequence and phylogenetic analyses of selected strains showed close genetic relationship among porcine and human strains suggesting zoonotic origin of Taiwanese human G9 strains detected in 2014-2015. Although the identified human G9P[19] and G9P[13] rotaviruses represented minority strains, the repeated detection of porcine-like rotavirus strains in Taiwanese children over time justifies the continuation of synchronized strain surveillance in humans and domestic animals.

In 2012, a new norovirus GII.4 variant (GII.4 Sydney) emerged and caused the majority of the acute gastroenteritis outbreaks in Australia, Asia, Europe, and North America. We examined the epidemiologic and molecular virologic characteristics of reported acute gastroenteritis outbreaks determined to be caused by norovirus in Taiwan from January 2012 to December 2013. A total of 253 (45.7%) of 552 reported acute gastroenteritis outbreaks tested positive for norovirus, of which 165 (65.5%) were typed as GII.4 Sydney. GII.4 Sydney outbreaks were reported from all geographic areas of Taiwan and occurred most frequently in schools (35.8%) and long-term care facilities (24.2%). Person-to-person transmission was identified in 116 (70.3%) of the outbreaks. Phylogenetic analyses of full-length ORF2 of eight specimens indicated that GII.4 Sydney strains detected in Taiwan were closely related to strains detected globally. Continued outbreak surveillance and strain typing are needed to provide information on epidemiologic and virologic trends of novel norovirus strains.

In 2006, two rotavirus vaccines (Rotarix and RotaTeq) became available on the private market in Taiwan. Although vaccine coverage is currently low, molecular surveillance of rotavirus strains can provide pertinent information for evaluation of the potential impact of vaccine introduction and infection control. During January 2008-December 2011, children aged <5years hospitalized with acute gastroenteritis were enrolled from sentinel surveillance hospitals in three geographic areas of Taiwan. Fecal specimens collected from enrolled patients were tested for rotavirus by enzyme immunoassay and reverse transcriptase-polymerase chain reaction. For genotyping, gene specific primer sets were used to amplify and sequence the genes encoding the neutralization antigens, VP7 and VP4. The resulting sequences were then subjected to phylogenetic analysis. In brief, a total of 4052 fecal specimens were tested and 742 (18%) samples were positive for rotavirus. The annual range of rotavirus positive specimens varied between 16% and 20.7%. Of all specimens, genotype G1P[8] (63.3%) was the predominant strain, followed by G2P[4] (12.5%), G3P[8] (11.7%), and G9P[8] (5.1%). Uncommon strains were also detected in low percentages. We observed that the rotavirus positivity rate steadily decreased from 21% to 16% during 2008-2010, then slightly increased to 20% in 2011, when an increase in the number of G2P[4] cases was observed. Sequence and phylogenetic analysis was carried out to help understand any potential changes of G2P[4] rotaviruses over time. A number of G2P[4] strains collected between 2004 and 2011 were analyzed in detail and our analyses showed marked genetic and antigenic variability in the VP7 and VP4 genes. The Taiwanese strains could be classified into two major G2 VP7 lineages (IV and V) and two major P[4] VP4 lineages (IV and V) and several minor sublineages within lineage IV. Lineage V within both G2 and P[4] represented newly recognized genetic variants of the respective genotypes. The distribution of individual combinations of the G2 and P[4] (sub)lineages showed some temporal variations. This study provides further evidence for the great genetic diversity among G2P[4] strains and helps understand the epidemiological trends of these strains among children in Taiwan.

BACKGROUND: Two rotavirus (RV) vaccines (Rotarix and RotaTeq) are available on the private market in Taiwan, but are not recommended for routine use. We examined RV vaccine effectiveness (VE) against severe RV acute gastroenteritis (AGE) among Taiwanese infants to inform policymakers on the potential benefits of national RV vaccine introduction. METHODS: From May 2009 to April 2011, a case-control assessment of VE against severe RV AGE was conducted at 3 hospital-based surveillance sites in Taiwan. Case-patients included children aged 8-35 months, hospitalized with laboratory-confirmed RV AGE. Controls included children age-matched within 1 month of age of the case-patient, hospitalized with RV-negative AGE or seen for non-AGE illnesses at the same hospitals. Vaccination history was confirmed through vaccination card or hospital record review. VE was calculated as (1 - odds ratio of vaccination)x100%. RESULTS: We enrolled 184 case-patients with RV AGE, 904 RV-negative AGE and 909 non-AGE controls. Two-dose Rotarix series VE against RV gastroenteritis hospitalization was 90.4% [95% confidence interval (CI): 70.3%, 98.1%) and 92.5% (95% CI: 77.1%, 98.5%) with RV-negative AGE and non-AGE controls, respectively. Three-dose RotaTeq series VE was 96.8% (95% CI: 82.3%, 100%) and 97.1% (95% CI: 84%, 100%) with RV-negative AGE and non-AGE controls, respectively. CONCLUSIONS: Both vaccines provided excellent protection against severe RV AGE hospitalization. Addition of RV vaccination into Taiwan's National Immunization Program could substantially decrease AGE hospitalizations among children <3 years. Our findings should help inform policymakers in Taiwan and other similar Asian countries when deciding whether to include RV vaccination into their national immunization programs.

Systematic hospital-based surveillance of rotavirus strains has been conducted in Taiwan to track baseline strain prevalence before and during the introduction of vaccines and to document any strain changes that occur as vaccine use increases (1). Both Rotarix and RotaTeq have been available via Taiwan's private pharmaceutical market since September 2006. As a result of more rigorous surveillance and the exclusive use of gene sequencing for strain genotyping, a variety of unusual strains were detected between 2005 and 2010 (2,3). A strain with rare VP7 and VP4 genotypes, RVA/Human-wt/TWN/04-97s379/2008/G8P[14] (hereafter referred to as 04-97s379), was identified in a 23-month-old boy treated for fever, diarrhea, and vomiting at an outpatient clinic in Changhua, Taiwan. This was the only G8P[14] strain identified among the 1,273 human rotaviruses that were genotyped during this 6-year surveillance period in Taiwan. Because human G8P[14] strains have only been reported in a few countries, including only a single country in the World Health Organization Western Pacific Region, Australia (4), it was of interest to characterize the G8P[14] rotavirus strain detected in Taiwan. | The oligonucleotide primers used to amplify and sequence full-length or partial open reading frames of the VP7 (1,062 bp), VP4 (831 bp), VP6 (1,356 bp), and NSP4 (738 bp) genes (GenBank accession numbers, JX1543843, JX1542665, JX1543853, and JX1542003, respectively) have been described elsewhere (3). For phylogenetic analysis, nucleotide sequences of related strains were retrieved from GenBank and compared with the Taiwanese strain 04-97s379 using the MEGA4 software (5).

Rotavirus G3P[3] strains have been reported from a variety of species including humans, cats, dogs, monkeys, goats, and cows. Here, we report the characterization of the first human G3P[3] rotavirus from East Asia identified in a 2-year-old child who was treated in a hospital's emergency ward in Taiwan in February 2005. Sequence and phylogenetic analysis demonstrated a close genetic relationship between the VP4, VP6, VP7, and NSP4 genes of Taiwanese G3P[3] strain 04-94s51 and an Italian canine strain isolated a decade ago, suggesting a canine origin for the Taiwanese strain. In contrast, the Taiwanese strain was only moderately related to well-characterized canine-origin human G3P[3] strains Ro1845 and HCR3, suggesting a distinct origin for the rotavirus strain from Taiwan.

Genotype P[25] rotaviruses are rare and to date have been reported to occur only in a few countries of mainland Asia. Here we report the molecular characterization of a novel human rotavirus genotype combination, G3P[25], detected in a 17-month-old child hospitalized due to severe gastroenteritis during 2009 in central Taiwan. Sequencing and phylogenetic analysis of the VP4 gene demonstrated a distinct origin from other strains bearing the P[25] VP4 gene, whereas the VP7, VP6 and NSP4 gene phylogenies identified common origins with cognate genes of other, presumed human-porcine reassortment Taiwanese strains. These results suggest that interactions between human and animal strains appear to contribute to the generation of genetic and antigenic diversity of rotavirus strains, with potential public health importance in Taiwan. Clin Microbiol Infect 2011; 17: 1570-1573

We previously reported the detection of genotype P[19] rotavirus strains from children hospitalized with acute dehydrating diarrhea during a 5-year surveillance period in Taiwan. The characterization of five P[19] strains (0.4% of all typed), including three G3P[19], a novel G5P[19], and a unique G9P[19] genotype is described in this study. Phylogenetic analysis of the VP4, VP7, VP6, and NSP4 genes was performed, which demonstrated novel lineages for respective genotypes of the VP4 and the VP7 genes. The sequence similarities of the P[19] VP4 gene among Taiwanese human strains was higher (nt, 91.5-96.2%; aa, 93.7-97.6%) than to other P[19] strains (nt, 83.5-86.6%; aa, 89.4-94.1%) from different regions of the world. The VP7 gene of the three G3P[19] Taiwanese strains shared up to 93.4% nt and 97.5% aa identity to each other but had lower similarity to reference strain sequences available in GenBank (nt, <90.1%; aa, <95.6%). Similarly, the VP7 gene of the novel G5P[19] strain was only moderately related to the VP7 gene of reference G5 strains (nt, 82.2-87.3%; aa, 87.0-93.1%), while the VP7 gene of the single G9P[19] strain was genetically distinct from other known human and animal G9 rotavirus strains (nt, ≤92.0%; aa, ≤95.7%). Together, these findings suggest that the Taiwanese P[19] strains originated by independent interspecies transmission events. Synchronized surveillance of human and animal rotaviruses in Taiwan should identify possible hosts of these uncommon human rotavirus strains. J. Med. Virol. 83:1279-1287, 2011. (c) 2011 Wiley-Liss, Inc.