Recent Trends in the Circulation of Viruses Causing Acute Gastroenteritis in the Republic of Korea, 2019–2023

Abstract

Viral acute gastroenteritis is an infectious disease caused by various viruses, including norovirus, and is predominantly transmitted through contaminated water or food. This condition, one of several waterborne and foodborne infectious diseases, is characterized by symptoms such as vomiting, diarrhea, and abdominal pain. Over a 5-year period (2019–2023), we analyzed the detection rates and genotypes of 5 viruses (norovirus, group A rotavirus, enteric adenovirus, astrovirus, and sapovirus) in stool samples (54,451 cases) from patients who presented with or were hospitalized for diarrhea. Out of the samples collected, viruses were detected in 6,415 cases (11.8%), with an average detection rate of 11.7% over the 5 years. Notably, the highest detection rates were found in children under 5 years of age (68.1%), with norovirus being the most frequently detected virus (69.2%). Detection rates varied seasonally, peaking in winter and diminishing in summer. The predominant genotypes identified included norovirus GII.4, group A rotavirus G8P[8], enteric adenovirus F41, astrovirus type 1a, and sapovirus GI.

Key messages

① What is known previously?

Viral acute gastroenteritis (VAGE) is caused by the ingestion of contaminated water or food. Key pathogens include norovirus, group A rotavirus, enteric adenovirus, astrovirus, and sapovirus.

② What new information is presented?

The virus detection rate in collected stool samples (54,451 in total) was 11.8%. Among the positive samples, notably high detection rates were observed in children under 5 years of age (68.1%) and with norovirus (69.2%). The main genotypes detected were norovirus GII.4, group A rotavirus G8P[8], enteric adenovirus F41, astrovirus type 1a, and sapovirus GI.

③ What are implications?

VAGE occurs consistently each year. Additionally, given the diversity of detected genotypes for each virus, ongoing surveillance is essential to monitor and prepare for potential outbreaks.

Introduction

Gastroenteritis is classified as Class 4 infectious diseases in the Republic of Korea (ROK) and primarily manifest through symptoms such as vomiting and diarrhea, caused by pathogens including bacteria and viruses [1]. These diseases generally have a short incubation period, ranging from 24 to 72 hours, with clinical symptoms lasting between 3 and 6 days, and in some cases, up to 14 days [2]. They are common globally, affecting about one in every 10 people annually. While these conditions typically resolve on their own and are not usually severe in adults, they can be life-threatening in infants and children under 5 due to the risk of severe dehydration from diarrhea [2]. Transmission can occur through contact with an infected individual, necessitating caution.

Among the viral pathogens, noroviruses, group A rotaviruses, enteric adenoviruses, astroviruses, and sapoviruses are notable. Noroviruses, in particular, are the most frequently detected and are responsible for outbreaks in various age groups, including adults and the elderly. They are highly contagious, especially in crowded environments such as hospitals, daycare centers, and restaurants [3]. While noroviruses are divided into 10 genogroups (GI–GX), only GI, GII, and GIV have been confirmed to cause human infections. Each genogroup contains multiple genotypes, totaling 48, with GII.4 being identified as the predominant genotype responsible for human infections over the last two decades [4].

Rotaviruses are divided into seven serogroups, A through G, based on the antigenicity of their intermediate envelope (VP6). Serogroups A, B, and C are known to cause human infections [1]. Rotavirus infection is a significant cause of diarrhea in infants and young children. In the United States, group A rotavirus is detected in approximately 5–10% of infants and young children with diarrhea, with 30–50% of these cases being severe [5]. In countries where rotavirus vaccines are available, the incidence of rotavirus infection has declined, though detection rates in infants and young children remain high [5,6].

Enteric adenoviruses cause a range of illnesses, including acute respiratory disease, gastroenteritis, epidemic conjunctivitis, meningitis, and hemorrhagic cystitis, depending on the specific genotype. Genotypes 40 and 41, part of group F, are associated with gastroenteritis [7]. Astroviruses consist of genotypes 1–8, with genotype 1a showing the highest detection rate globally [1]. In some regions, astrovirus has been reported as the second most commonly detected pathogen after group A rotavirus [8]. Sapoviruses, which are part of the Caliciviridae family like noroviruses, include groups GI, GII, GIV, and GV. They are detected in humans and typically present with milder symptoms and lower detection rates compared to noroviruses [9].

The Korea Disease Control and Prevention Agency (KDCA) manages the Enteric Pathogens Active Surveillance Network (EnterNet), launched in 2003. This initiative aims to identify, characterize, and manage the causative agents (10 bacteria, 5 viruses, and 4 protozoa) of waterborne and foodborne gastroenteritis through the analysis of specimens collected from affected patients. This study focuses on analyzing the detection rates and genotypes of 5 viruses responsible for gastroenteritis.

Methods

1. Data Collection

As part of the EnterNet samples were collected through the collaboration of 76 healthcare institutions and 18 Health and Environment Research Institutes across the nation as of December 2023. Aside from minor adjustments, such as changes to some collaborating healthcare institutions (within 10) and the addition of the Sejong Special Self-Governing City Health and Environment Research Institute in August 2022, the collection system remained consistent. Specimens, either fecal or rectal swabs, were obtained from patients diagnosed with gastroenteritis. The criteria for these patients include having loose bowel movements at least 3 times per day and displaying major symptoms of waterborne and foodborne illnesses, such as vomiting, nausea, and fever (oral temperature of 37.8℃ or higher). Specimens were collected immediately after symptom onset or within 48 hours before the commencement of antimicrobial treatment. The Health and Environment Research Institutes tested these specimens using standardized methods to determine the presence of the causative pathogen. The results, along with specimen information, were reported through the web reporting system (is.kdca.go.kr).

This study analyzed specimen data and laboratory test results collected over the past 5 years (from December 30, 2018 to December 30, 2023). The data were evaluated for age and seasonal distribution trends. Specimens lacking information on patient age, gender, or collection date were excluded from the analysis to ensure the accuracy of the statistical results. The data were categorized by age as follows: 0 for 0–12 months, 1 for 12–24 months, and subsequently in age groups of 0–5, 6–9, and 10 years and older in 10-year increments. The categorization by month facilitated the identification of seasonal trends. Microsoft Excel 2021 (Microsoft) was utilized for data analysis.

2. Testing for Positive and Negative Results and Genotyping

Fecal samples from patients with gastroenteritis underwent pretreatment. The process started by mixing 1 g feces with 9 ml sterile phosphate-buffered saline, followed by vortexing for approximately 3 minutes. The vortexed samples were then centrifuged at 12,000 rpm and 4℃ for about 10 minutes, retaining only the supernatant for further analysis.

Pathogen-specific testing to determine positive and negative results was conducted using standardized methods tailored to each pathogen’s characteristics. The presence of noroviruses, astroviruses, and sapoviruses was verified by identifying their respective genes using specific gene detection techniques. Rotaviruses and enteric adenoviruses were detected through specific antigen detection methods. The testing protocols included real-time reverse transcription polymerase chain reaction (RT-PCR) for noroviruses and conventional RT-PCR for astroviruses and sapoviruses. Group A rotaviruses and enteric adenoviruses were identified using enzyme-linked immunosorbent assays for antigen detection.

Positive samples underwent amplification using pathogen-specific primers for genotyping. The amplified gene products were electrophoresed to verify amplification, followed by sequencing. The gene sequences were analyzed using the MEGA 11.0 program (Molecular Evolution Genetics Analysis 11.0 software; Pennsylvania State University, www.megasoftware.net). Sequence comparisons were conducted using the BLAST search engine provided by the National Center for Biotechnology Information (NCBI) (NCBI, https://blast.ncbi.nlm.nih.gov/Blast.cgi).

Results

1. Detection Rate Analysis

Over the 5-year period from 2019 to 2023, the EnterNet collected 56,499 fecal specimens, of which 54,451 were utilized for statistical analysis. Of these, 6,415 cases (11.8%) tested positive for one or more pathogens. The annual detection rates were 12.8% (1,294/10,136 cases) in 2019, 7.7% (720/9,377 cases) in 2020, 12.9% (1,232/9,582 cases) in 2021, 14.4% (1,659/11,542 cases) in 2022, and 10.9% (1,510/13,813 cases) in 2023, resulting in an average detection rate of 11.7% over the 5 years. Notably, both the number of specimens and the detection rate were lowest in 2020, with the highest detection rate occurring in 2022.

Over the past 5 years, the highest number of samples was in the group aged 80 or older, accounting for 13.8% (7,495 cases) of the total, but the highest detection rate was found in children aged 5 or younger, at 68.1% (4,366 cases). Within this group, the detection rate was highest among 2-year olds at 20.6% (1,320 cases) (Figure 1). This was followed by 8.8% (562 cases) in the 6 to 9 age group, 5.7% (365 cases) among those aged 10 to 19, and 5.0% or less in those aged 20 or older.

Figure 1. Detection rates of viral acute gastroenteritis by age, 2019–2023.

Regarding the positive rates by virus, norovirus had the highest detection rate among single pathogens at 69.2% (4,437 cases) (Table 1). This was followed by astrovirus at 9.5% (608 cases), group A rotavirus at 9.2% (588 cases), enteric adenovirus at 7.8% (500 cases), and sapovirus at 4.4% (282 cases). Additionally, a total of 107 co-infections were identified, where two or more pathogens were detected in a single specimen. There were 102 cases with dual infections: norovirus and rotavirus (40 cases), norovirus and astrovirus (39 cases), and rotavirus and enteric adenovirus (23 cases). Five cases involved triple infections: two instances of norovirus, rotavirus, and astrovirus; one of norovirus, rotavirus, and adenovirus; one of norovirus, rotavirus, and sapovirus; and one of rotavirus, enteric adenovirus, and astrovirus.

Table 1. Detection rates (%) of viral acute gastroenteritis by viruses and co-infections, 2019–2023.

Virus	NoV	RoV	E.AdV	AstV	SaV
NoV	69.2	0.6	0.4	0.6	0.1
RoV	-	9.2	0.4	0.1	0.1
E.AdV	-	-	7.8	0.1	0.1
AstV	-	-	-	9.5	0.1
SaV	-	-	-	-	4.4

NoV=norovirus; RoV=group A rotavirus; E.AdV=enteric adenovirus; AstV=astrovirus; SaV=sapovirus; –=not available.

The detection rates by time period and virus were further analyzed for children under the age of 5, who exhibited high detection rates. Seasonally, the detection rates of the 5 viruses causing gastroenteritis were higher in the winter months (December through February) and lower in the summer months (July through September) (Figure 2). The average monthly detection rate peaked in January at 44.2% and was lowest in October at 9.1%. However, in 2022, the detection rates were unusually high during the summer months. In 2023, the pattern returned to one similar to 2019, with higher detection rates in the winter and lower in the summer.

Figure 2. Detection rates of viral acute gastroenteritis by monthly: under 5 years of age, 2019–2023.

An examination of the detection rates by virus indicates that norovirus, which had the highest detection rate among the 5 viruses, aligned closely with the overall detection trends. Rotaviruses experienced a peak in the spring of 2019–2020, followed by a lower detection rate in 2021–2022. In 2023, a similar spring peak was observed, akin to that of 2019. Enteric adenoviruses, astroviruses, and sapoviruses consistently showed low annual detection rates, generally below 10%. Notably, sapoviruses were seldom detected in 2020–2021. However, the detection rates for these three viruses saw an increase from spring 2021 through winter 2022 compared to other years.

2. Genotyping

Over the past 5 years (2019–2023), the most prevalent genotypes for each pathogen in ROK are as follows: Noroviruses were predominantly detected in the GII genogroup (Figure 3A), with the GII.4 genotype being the most prevalent within this group for 5 consecutive years, averaging a detection rate of 55.2%. This was followed by GII.2, which was consistently detected except in 2022. For rotavirus, seven genotypes exhibited detection rates of 5% or more throughout the period in ROK, with G8P[8] consistently being the most predominant (Figure 3B). This was followed by G3P[8], which has been consistently detected until recently, while the detection rates for G2P[4] and G9P[8] have declined since 2022.

Figure 3. Detection rates of viral acute gastroenteritis by genotype: under 5 years of age, 2019–2023.

Detection rates of 5% or higher are shown as graph lines. NoV=norovirus; RoV=group A rotavirus; AstV=astrovirus; E.AdV=enteric adenovirus; SaV=sapovirus.

Astroviruses showed the highest detection rate for type 1a, averaging 71.2%. In contrast, type 4c, which previously had a low detection rate of 5% or less in both 2021 and 2022, experienced a significant increase to 12.0% in 2023 (Figure 3C). Enteric adenoviruses were most frequently detected, with an average rate of 82.8%, predominantly of the F41 type, which is associated with gastroenteritis. Additionally, genotypes from groups B and C, typically associated with respiratory adenoviruses, were also detected (Figure 3D). For sapoviruses, groups GI, GII, and GV were mainly detected (Figure 3D). However, due to the low prevalence of sapoviruses as a cause of gastroenteritis, the statistical analysis for primary genotyping has been limited.

Discussion

This study examined the prevalence of viruses that cause gastroenteritis over the past 5 years. Out of the specimens collected, 6,415 cases (11.8%) tested positive for one or more pathogens. The average detection rate over 5 years was 11.7% (ranging from 7.7 to 14.4%). Viral acute gastroenteritis showed varying susceptibility by age, with higher detection rates in children under 5 years old [1,2]. Notably, among the positive samples, the highest detection rate occurred in children under 5 (68.1%), with norovirus exhibiting the highest detection rate among the viruses at 69.2%. As previously reported [10,11], noroviruses have shown a significant increase in detection during the winter months, with a decline in the summer and fall, over the last 5 years. However, the data from 2022 displayed a unique pattern, showing elevated detection rates in both summer and winter. Rotaviruses typically manifest with springtime outbreaks [11] and had relatively low detection rates in 2021–2022. Enteric adenoviruses, astroviruses, and sapoviruses, which are generally found year-round without clear seasonality [10,11], exhibited unusually high detection rates in 2021–2022. The exact reasons for this timing of pathogen detection remain unclear but are thought to be influenced by the coronavirus disease 2019 pandemic and the subsequent lifting of social distancing measures, which may have impacted the prevalence of these diseases.

Globally, norovirus type GII.4 has been identified as the most predominant [3,4], and this study confirms that GII.4 has also been the most prevalent in ROK over the past 5 years. Group A rotaviruses come in various genotypes, with types G1–4 and P[4 or 8] primarily causing disease in humans, as well as combinations of these genotypes [6,10]. In this study, type G8P[8] was identified as the most predominant genotype, with several other genotypes detected at a frequency of 5% or greater. Unlike noroviruses and rotaviruses, which display a range of genotypes, enteric adenovirus type F41 and astrovirus type 1a were identified as the dominant genotypes, with detection rates exceeding 70%. These types, 1a and F41, are the most widely detected genotypes both domestically and globally [10]. The genes that cause human infection of sapoviruses are known as GI to GV [9], with types GI, GII, and GV identified in ROK. However, identifying a particularly dominant genotype was challenging due to the low overall number of positives.

From 2019 to 2023, pathogen detection rates paralleled the actual incidences of viral acute gastroenteritis [12]. Notably, the summer of 2022 was characterized by high detection rates and a corresponding increase in patient cases. However, detailed patient data were unavailable, except for the aggregate numbers across all age groups, which limited further comparative analysis. In the future, integrating pathogen surveillance results with detailed patient information, such as the genotypes of pathogens detected and demographic specifics like region and age, could enhance the efficiency of the surveillance system for gastroenteritis.

This study focused on the results of sentinel surveillance for individual outbreaks of pathogens causing viral acute gastroenteritis. Gastroenteritis, known for their rapid transmission through direct or indirect contact with carriers, contaminated food, or environments, are highly contagious and often lead to outbreaks [10]. Yet, the lack of reported analyses on domestic outbreaks in the literature constrains further comparative studies. Expanding the analysis to include epidemiological factors, such as the location and progression of an outbreak, along with pathogen details like virus type and genotype, will provide a valuable scientific foundation for response strategies and preparedness for gastroenteritis.

Gastroenteritis is among the most common diseases globally, transmitted through contaminated food or person-to-person contact. The factors influencing the epidemiology of these diseases are diversifying, with climate change, international travel, and advances in transportation and logistics reducing regional barriers. Gastroenteritis continues to pose significant health challenges each year, necessitating ongoing pathogen surveillance as no definitive cure or vaccine exists. The EnterNet enhances national prevention and control of infectious diseases by analyzing the prevalence and characteristics of pathogens causing waterborne and foodborne diseases. Additionally, accumulating data through pathogen surveillance, linked with actual disease incidences and outbreaks, will aid in developing a more robust gastroenteritis management system. This underscores the need for a coordinated surveillance framework involving the KDCA, Provincial and City Health and Environmental Research Institutes, and private healthcare providers for pathogen diagnosis, analysis, and information sharing.