The Genetic Diversity of Norovirus from Children with Diarrhea in Gwangju Metropolitan City, Korea: 2008-2012

In order to study the characteristics of norovirus in Gwangju metropolitan city, We examined norovirus in 13,931 fecal specimens collected through five years (2008-2012) from children admitted with a chief complain of acute diarrhea. Among a total of norovirus (NoV) was most frequently detected (3,025 cases, 21.7%). Concerning the frequency of virus detected by month, NoV tended to break out frequently from October to March in the following year. NoV was detected most highly in 0~3 year infants. Through examinations on NoV genotypes, among 3,025 cases that turned out to be positive, the genotypes of 2,652 cases were determined with various results including 13 types of GI and 17 types of GII. The results of analysis on GI genotypes were as follows: GI-4 (21.9%), GI-2 (15.2%), and GI-6 (10.5%). GII genotypes were as follows: GII-4 (63.9%), GII-3 (18.9%), GII-8 (4.2%), GII-2 (3.9%), GII-6 (3.3%), and GII-1 (1.9%). Eight types of variants for GII-4 genotype (427 cases) were identified. The majority of the GII-4 variants was GII-4_Farmington (181 cases, 42.4%), which peaked in 2012, while GII-4_2008b (173 cases, 40.5%) showed a high prevalence in 2011. Concerning the circulation of variants, as many as eight types of GII-4 variants were identified in 2012, showing more varieties than in other years. Therefore, this study can be used as fundamental data for the development of vaccine candidate for the prevention of viral diarrheal diseases with high-incidence.

Detection of Rotavirus Genotypes in Korea 5 Years after the Introduction of Rotavirus Vaccines

Rotavirus (RV) is one of the most important viral etiologic agents of acute gastroenteritis (AGE) in children. Although effective RV vaccines (RVVs) are now used worldwide, novel genotypes and outbreaks resulting from rare genotype combinations have emerged. This study documented RV genotypes in a Korean population of children with AGE 5 yr after the introduction of RVV and assessed potential genotype differences based on vaccination status or vaccine type. Children less than 5-yr-old diagnosed with AGE between October 2012 and September 2013 admitted to 9 medical institutions from 8 provinces in Korea were prospectively enrolled. Stool samples were tested for RV by enzyme immunoassay and genotyped by multiplex reverse-transcription polymerase chain reaction. In 346 patients, 114 (32.9%) were RV-positive. Among them, 87 (76.3%) patients were infected with RV alone. Eighty-six of 114 RV-positive stool samples were successfully genotyped, and their combinations of genotypes were G1P[8] (36, 41.9%), G2P[4] (12, 14.0%), and G3P[8] (6, 7.0%). RV was detected in 27.8% of patients in the vaccinated group and 39.8% in the unvaccinated group (P=0.035). Vaccination history was available for 67 of 86 cases with successfully genotyped RV-positive stool samples; RotaTeq (20, 29.9%), Rotarix (7, 10.4%), unvaccinated (40, 59.7%). The incidence of RV AGE is lower in the RV-vaccinated group compared to the unvaccinated group with no evidence of substitution with unusual genotype combinations.

A Survey on the Status of Hepatitis E Virus Infection Among Slaughterhouse Workers in South Korea / 예방의학회지

OBJECTIVES: The seroprevalence of hepatitis E virus (HEV) among high-risk groups overseas is high, but studies in these groups are rare in South Korea. We conducted the present study from April to November 2012 to obtain data on the seroprevalence and associated risk factors for HEV among slaughterhouse workers in South Korea. METHODS: Slaughterhouse workers from 80 workplaces nationwide were surveyed in South Korea in 2012. The subjects comprised 1848 cases: 1434 slaughter workers and 414 residual products handlers. By visiting 80 slaughterhouses, which were mixed with 75 of which also performed residual products handling, we conducted a questionnaire survey for risk factors and obtained blood samples in order to determine the seropositivity and seroprevalence of HEV. Anti-HEV IgG and IgM were measured using HEV IgG and IgM enzyme-linked immunospecific assay kits and HEV antigen was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The seropositivity of anti-HEV IgG was 33.5% (slaughter workers 32.8% and residual products handlers 36.2%), and among the seropositive individuals the seroprevalence of anti-HEV IgM was 0.5% (slaughter workers 0.5%, residual products handlers 0.7%). The response rate of HEV-antigen as measured by RT-PCR was 0.2%. Risk factors significantly related to anti-HEV IgG seropositivity were age, sex , and working duration (slaughter workers only). CONCLUSIONS: There were significant risk factors (sex, age, and working duration) for HEV identified in our study. All three positive cases for HEV-antigen by RT-PCR were related to pig slaughter but without statistical significance. To prevent HEV, an educational program and working guidelines may be needed for high risk groups.

Comparison among Known Severity Scoring Scales in the Evaluation of Acute Gastroenteritis in Children / 소아감염

PURPOSE: This study aimed to evaluate the disease severity of children suffering from gastroenteritis using different scales. The results are compared and subsequently classified on the basis of the type of virus causing the disease in order to investigate the differences in clinical characteristics and disease severity according to pathogen. METHOD: This study was conducted prospectively with patients under 5 years of age diagnosed with acute gastroenteritis and hospitalized at 9 medical institutions in 8 regions across the Republic of Korea. Disease severity was evaluated using the Vesikari Scale, the Clark Scale, and the modified Flores Scale. Fecal samples collected from patients were used to detect rotavirus and enteric adenovirus by enzyme immunoassay, and for RT-PCR of norovirus, astrovirus, and sapovirus. RESULTS: There were a total of 214 patients with a male : female ratio of 1.58 : 1, of which 35 were under the age of 6 months (16.4%), 105 were aged 6-23 months (49.1%), and 74 were aged 24-59 months (34.5%). The rate of concordance between the Vesikari and Clark Scales was 0.521 (P<0.001) and, in severe cases, the Vesikari Scale was 60.7% and Clark Scale was 2.3%, indicating that the Clark Scale was stricter in the evaluation of severe cases. CONCLUSIONS: In children with gastroenteritis, there were differences in disease severity based on the scale used. Therefore, to achieve consistent results among researchers, either only a single scale or a measure of all scales should be used to determine disease severity.

The Molecular Epidemiology of Circulating Group A Rotavirus in Gwangju Metropolitan City, Korea: 2008~2012

Group A rotaviruses are a major cause of acute gastroenteritis in young children worldwide. For the proper management of rotavirus infections, knowledge of the distribution of G and P genotypes including detection of emerging genotype is crucial. Therefore, the aim of this study is to describe epidemiological changes in rotavirus gastroenteritis in Gwangju metropolitan city, South Korea. Stool samples were collected from 14,314 patients with diarrhea, who visited hospitals in Gwangju from 2008 to 2012. Samples were screened for rotavirus with Enzyme-Linked Immunosorbent Assay (ELISA) method and rotavirus P (VP4), G (VP7) genotypes were determined by reverse-transcription polymerase chain reaction. And we performed nucleotide sequencing analysis. Among a total of 14,314 samples investigated 1,982 samples (13.8%) were ELISA positive. Genotyping of Rotavirus was performed using 526 rotavirus samples. The most prevalent circulating G genotype was G1 (40.5%), followed by G2 (27.6%), G3 (19.4%), G9 (9.7%), G4 (2.5%) and G12 (0.4%). The predominant type of P genotypes was P[8] (69.6%), followed by P[4] (27.8%) and P[6] (2.3%). In this study, 13 G-P combinations were detected. From 2008 to 2010, G1P[8] was the most prevalent, followed by G3P[8]. Whereas, 2011 and 2012, G2P[4] was the most common, followed by G1P[8]. Rotavirus gastroenteritis is a common disease associated with significant morbidity, mortality and economic burden. Ongoing rotavirus surveillance to understand the distribution of G and P genotypes will be critical for the development of effective prevention measurements.

Epidemiology of astrovirus infection in children / 소아과

Human astrovirus (HAstV) is a major cause of acute diarrhea among children, resulting in outbreaks of diarrhea and occasionally hospitalization. Improved surveillance and application of sensitive molecular diagnostics have further defined the impact of HAstV infections in children. These studies have shown that HAstV infections are clinically milder (diarrhea, vomiting, fever) than infections with other enteric agents. Among the 8 serotypes of HAstV identified, serotype 1 is the predominant strain worldwide. In addition to serotype 1, the detection rate of HAstV types 2 to 8 has increased by using newly developed assays. HAstV is less common compared with other major gastroenteritis viruses, including norovirus and rotavirus; however, it is a potentially important viral etiological agent with a significant role in acute gastroenteritis. A better understanding of the molecular epidemiology and characteristics of HAstV strains may be valuable to develop specific prevention strategies.

Epidemiology of astrovirus infection in children / 소아과

Human astrovirus (HAstV) is a major cause of acute diarrhea among children, resulting in outbreaks of diarrhea and occasionally hospitalization. Improved surveillance and application of sensitive molecular diagnostics have further defined the impact of HAstV infections in children. These studies have shown that HAstV infections are clinically milder (diarrhea, vomiting, fever) than infections with other enteric agents. Among the 8 serotypes of HAstV identified, serotype 1 is the predominant strain worldwide. In addition to serotype 1, the detection rate of HAstV types 2 to 8 has increased by using newly developed assays. HAstV is less common compared with other major gastroenteritis viruses, including norovirus and rotavirus; however, it is a potentially important viral etiological agent with a significant role in acute gastroenteritis. A better understanding of the molecular epidemiology and characteristics of HAstV strains may be valuable to develop specific prevention strategies.

Clinical Manifestations of Norovirus Infection in Korean Pediatric Cancer Patients / 소아감염

PURPOSE: Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. METHODS: Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. RESULTS: Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. CONCLUSION: Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocom-promised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

Infection Status of Hospitalized Diarrheal Patients with Gastrointestinal Protozoa, Bacteria, and Viruses in the Republic of Korea

To understand protozoan, viral, and bacterial infections in diarrheal patients, we analyzed positivity and mixed-infection status with 3 protozoans, 4 viruses, and 10 bacteria in hospitalized diarrheal patients during 2004-2006 in the Republic of Korea. A total of 76,652 stool samples were collected from 96 hospitals across the nation. The positivity for protozoa, viruses, and bacteria was 129, 1,759, and 1,797 per 10,000 persons, respectively. Especially, Cryptosporidium parvum was highly mixed-infected with rotavirus among pediatric diarrheal patients (29.5 per 100 C. parvum positive cases), and Entamoeba histolytica was mixed-infected with Clostridium perfringens (10.3 per 100 E. histolytica positive cases) in protozoan-diarrheal patients. Those infected with rotavirus and C. perfringens constituted relatively high proportions among mixed infection cases from January to April. The positivity for rotavirus among viral infection for those aged or = 50 years. The information for association of viral and bacterial infections with enteropathogenic protozoa in diarrheal patients may contribute to improvement of care for diarrhea as well as development of control strategies for diarrheal diseases in Korea.

Distribution of Group A Rotavirus Genotypes Circulating in Gwangju, Korea

To determine the distribution of rotavirus strain genotypes in Gwangju, Korea, we performed reverse-transcription polymerase chain reaction and nucleotide sequencing analysis using the 115 rotavirus EIA positive stool specimens collected from December 2006 through April 2007. The most predominant genotype was confirmed as G1P[8] (53.9%), followed by G3P[8] (29.6%), G4P[6] (8.7%), G2P[4] (4.3%) and G9P[8] (1.7%). A special attention is drawn to the unusual findings of the genotypes G11P[25] and G12P[9] during this study period. In order to investigate the phylogenetic relationships among the same or different genotypes, the nucleotide sequences of rotavirus circulating in Korea and the foreign countries were analyzed using MegAlign and Clustal X programme. The G11P[25] strain identified in this study showed the highest nucleic acid similarity with G11 /CUK1 /2006 /Korea (99.2%) and P[25] /Dhaka /2001 /BGD (98.7%). Meanwhile, the G12P[9] strain detected in this study shared 99.4~99.5% nucleotide homology with the reference strain G12P[9] /CP1030 /2004 /Japan. This incidence of new rotavirus genotypes in our area illustrates the large diversity of rotavirus strains found worldwide. Therefore, the epidemiological surveillance of rotavirus may need to be continued in a wide geographic area.

Molecular Epidemiologic Investigation of Norovirus Infections in Incheon City, Korea, from 2005 to 2007

Noroviruses (NoVs) cause major epidemic gastroenteritis in humans. To obtain the molecular epidemiological information on gastroenteritis sporadic cases in Incheon city, Korea, we analyzed the nucleotide sequences of NoV strains detected during 2005~2007. We performed one step RT-PCR amplifying the open reading frame (ORF) 2 (capsid region) followed by semi-nested PCR from the stool samples from acute gastroenteritis patients from 2005 to 2007. Amplicons of the capsid region of norovirus strains were sequenced and analyzed using MegAlign in DNAstar software. Faecal samples were collected from 6,618 acute gastroenteritis patients during the study period. The incidence of NoV infection was about 10.7% (n=708) among patients with acute gastroenteritis and genotypes of the 320 positive samples were determined by sequence analysis. Sequence comparison of NoV strains revealed that 16 genotypes of GII NoV strains were circulated in Incheon city, from 2005 to 2007. Among norovirus strains, the most prevalent genotype GII/4 was most common 69.7% (223 strains), followed by GII/3 17.2% (55 strains), GII/12 4.4% (14 strains), GII/1 2.2% (7 strains), GII/5 1.6% (5 strains), GII/15 1.3% (4 strains) and 0.6% (2 strains) each of GII/9 and GII/16. The GII-3 strains were most frequently detected in Incheon, 2005. From the phylogenetic analysis of NoV strains, we detected 16 genotypes of GII NoV strains during 2005~2007 in Incheon. Our results suggest that various genotypes of human NoV strains in sporadic case of AGE were circulated in Incheon, Korea.