Trends in acute viral gastroenteritis among children aged ≤5 years through the national surveillance system in South Korea, 2013-2019.

Acute gastroenteritis is a global public health concern. This study aimed to analyze the trend and characteristics of acute viral gastroenteritis through a national surveillance network. Enteric viruses were detected in 9510 of 31,750 (30.1%) cases assessed from 2013 to 2019 by EnterNet. The most prevalent pathogens were norovirus (15.2%) and group A rotavirus (9.7%); most infections were reported in 2017 (34.0%). Norovirus and rotavirus coinfections were the most common. Norovirus infections were prevalent among 1-year-old children (1835 out of 9510 cases) during winter, and group A rotavirus infections were common during spring. Seasonality was not observed among enteric adenovirus, astrovirus, and sapovirus. The prevalent viral genotypes detected included norovirus GII.4, enteric adenovirus F41, astrovirus genotype 1, and sapovirus GI.1. However, changes in enteric virus trends were noted during the study period. Norovirus prevalence extended into spring, and new genotypes of enteric adenovirus, astrovirus, and sapovirus were identified. These surveillance data elucidate enteric virus epidemiological characteristics.

Pooling Upper Respiratory Specimens for Rapid Mass Screening of COVID-19 by Real-Time RT-PCR.

To validate the specimen-pooling strategy for real-time reverse transcription PCR detection of severe acute respiratory syndrome coronavirus 2, we generated different pools including positive specimens, reflecting the distribution of cycle threshold values at initial diagnosis. Cumulative sensitivities of tested pool sizes suggest pooling of <6 specimens for surveillance by this method.

Nationwide External Quality Assessment of SARS-CoV-2 Molecular Testing, South Korea.

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future.

Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea.

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.

Influence of anonymous HIV testing on national HIV surveillance in the Republic of Korea (2000 to 2015): a retrospective analysis.

BACKGROUND: Owing to the continuous increase in the number of new human immunodeficiency virus (HIV) infection in Korea, public health centers (PHCs) have performed anonymous tests since 1989. No study has examined the patterns of anonymous HIV testing performed at PHCs and the characteristics of HIV infection detected in those tests. We aimed to assess the influence of anonymous HIV testing on Korea's national HIV surveillance. METHODS: HIV screening test data from 253 PHCs over a 16-year period were classified into 13 groups based on reason for testing. For anonymous HIV test takers (Anonymous), the HIV positivity per 10,000 tests was calculated, as repetitions could not be distinguished. Those with suspected HIV infection voluntarily underwent HIV testing and revealed their identity (Suspected). HIV prevalence was calculated as the number of HIV-positive persons per 10,000 test takers. Analyses were performed using chi-square and Cochran-Armitage trend test with SAS 9.4. RESULTS: Approximately 400,000 HIV screening tests were performed at PHCs annually, which remained unchanged in the past 10 years. The proportion of anonymous testing increased from < 3.0% before 2014 to 4.8% in 2014 and 6.1% in 2015. While the number of HIV cases increased, the number of anonymous HIV-positive test results per 10,000 tests decreased from 68.8 in 2010 to 41.8 in 2015. The HIV prevalence among the suspected was approximately 20.0 per 10,000 test takers before 2014, which steeply increased to 71.6 in 2015. Those with suspected HIV were predominantly men, aged 20 years, foreigners, and metropolitan city dwellers in the last 6 years. The high prevalence of persons with suspected HIV resulted in a doubling of HIV prevalence at PHCs between 2014 and 2015. CONCLUSIONS: Anonymous and Suspected, which were driven by similar motives, impacted each other. Increase in HIV prevalence among the suspected led to a higher HIV prevalence among all test takers in PHCs and higher proportions of HIV infection nationwide, which could be attributed to the increase in the number of anonymous tests performed in PHCs. HIV positivity among the anonymous and HIV prevalence among the suspected are key indexes of the national HIV surveillance in Korea.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Antibodies in Rural Areas, South Korea.

We investigated 1,228 residents of 3 rural areas in South Korea and determined that 50 (4.1%) were positive for severe fever with thrombocytopenia syndrome virus antibodies. Fever and gastrointestinal symptoms in the previous 3 years and career duration were associated with virus seropositivity.

Metabolic Complications among Korean Patients with HIV Infection: The Korea HIV/AIDS Cohort Study.

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.

Severe fever with thrombocytopenia syndrome virus, South Korea, 2013.

During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.

Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013.

We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May-October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

Retrospective serosurveillance of bovine norovirus (GIII.2) and nebovirus in cattle from selected feedlots and a veal calf farm in 1999 to 2001 in the United States.

There is a dearth of information on the seroprevalence of bovine norovirus (BoNoV) and nebovirus in cattle of the US. In this retrospective study, serum IgG antibodies to two bovine enteric caliciviruses, GIII.2 BoNoV (Bo/CV186-OH/00/US) and genetically and antigenically distinct nebovirus (Bo/NB/80/US), were evaluated in feedlot and veal calves from different regions of the US during 1999-2001. Three groups of 6- to 7-month-old feedlot calves from New Mexico (NM) (n=103), Arkansas (AR) (n=100) and Ohio (OH) (n=140) and a group of 7- to 10-day-old Ohio veal calves (n=47) were studied. Serum samples were collected pre-arrival or at arrival to the farms for the NM, AR and OH calves and 35 days after arrival for all groups for monitoring seroconversion rates during the period. Virus-like particles of Bo/CV186-OH/00/US and Bo/NB/80/US were expressed using the baculovirus expression system and were used in ELISA to measure antibodies. A high seroprevalence of 94-100 % and 78-100 % was observed for antibodies to GIII.2 BoNoV and nebovirus, respectively, in the feedlot calves tested. In the Ohio veal farm, an antibody seroprevalence of 94-100 % and 40-66 % was found for GIII.2 BoNoV and nebovirus, respectively. Increased seropositive rates of 38-85 % for GIII.2 BoNoV and 26-83 % for nebovirus were observed at 35 days after arrival and commingling on farms for all groups. Infection of calves with either GIII.2 BoNoV or nebovirus, or both viruses, appeared to be common in the regions studied in the US during 1999-2001. These two viruses likely remain endemic because no commercial vaccines are available.

Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation.

Apoptosis has been shown to be induced and downregulated by the Hantaan virus (HTNV) nucleocapsid (N) protein. To address these conflicting data, expression of the p53 protein, one of the key molecules involved in apoptosis, was assessed in the presence of the N protein in A549 and HeLa cells. The amount of p53, increased by drug treatment, was reduced when cells were infected with HTNV or transfected with an expression vector of the HTNV N protein. When cells were treated with a proteasome inhibitor (MG132) or an MDM2 antagonist (Nutlin-3), p53 expression was not reduced in N protein-overexpressed cells. We concluded that the HTNV N protein ubiquitinates and degrades p53 MDM2-dependently. Here we report downregulation of p53 expression through a post-translational mechanism: MDM2-dependent ubiquitination and degradation by the HTNV N protein. These results indicate that N protein-dependent p53 degradation through the ubiquitin proteasome system is one of the anti-apoptotic mechanisms employed by HTNV.

The first reported hepatitis E outbreak in a food manufacturing factory: Korea, 2022.

OBJECTIVES: On February 16, 2022, 12 cases of hepatitis E virus (HEV) infection were reported in a food manufacturing factory in Korea. The aim of this study was to identify additional cases and to determine the source of this HEV outbreak. METHODS: This study was an in-depth investigation of 12 HEV immunoglobulin M (IgM)-positive cases and their demographic, clinical, and epidemiological characteristics. On-site specimens were collected from the environment and from humans, and a follow-up investigation was conducted 2 to 3 months after the outbreak. RESULTS: Among 80 production workers in the factory, 12 (15.0%) had acute HEV infection, all of whom were asymptomatic. The follow-up investigation showed that 3 cases were HEV IgMpositive, while 6 were HEV IgG-positive. HEV genes were not detected in the HEV IgM-positive specimens. HEV genes were not detected in the food products or environmental specimens collected on-site. HEV was presumed to be the causative pathogen. However, it could not be confirmed that the source of infection was common consumption inside the factory. CONCLUSIONS: This was the first domestic case of an HEV infection outbreak in a food manufacturing factory in Korea. Our results provide information for the future control of outbreaks and for the preparation of measures to prevent domestic outbreaks of HEV infection.

Characteristics of recent HIV infection among individuals newly diagnosed as HIV-positive in South Korea (2008-2015).

Most HIV-positive individuals diagnosed in Korea are infected through sexual contact, with the time of HIV infection therefore often being unknown. The aim of this study was to investigate the characteristics of diagnosed patients near the time of HIV seroconversion to establish useful HIV intervention strategies. Cross-sectional study. Newly diagnosed HIV cases based on the national HIV surveillance system in South Korea, 2008-2015. To distinguish recent from long-standing HIV infection among 5898 nationwide HIV-positive specimens, limiting antigen avidity assays (Sedia HIV-1 LAg-Avidity EIA, cut-off = 1.5) were performed. Data on CD4+ T cell count at HIV diagnosis and death from AIDS within one year after first HIV diagnosis were used to distinguish recent HIV infections. Acute HIV infection is characterized by detectable HIV RNA or HIV p24 antigen levels, along with a negative or indeterminate antibody western blot result, but with the subject subsequently testing positive after a predetermined period. We analyzed the characteristics of recent and acute HIV infections by sex, age, nationality, HIV testing site, region, and reason for HIV testing. Recent and acute HIV infections were described as the proportion of recent and acute HIV infections among newly-diagnosed cases in a given year. Recent and acute HIV infections over the 8-year study period were 20.5% (1210/5898) and 9.5% (562/5898), respectively. Both infections were generally higher in the following groups: males, younger age, Koreans, individuals who were tested due to disease, residents of smaller city or rural area, and individuals diagnosed in recent calendar years. Acute infections were significantly higher among individuals tested in hospitals and due to suspected HIV infection. The recent and acute HIV infection in younger age groups (< 30 years) has been increasing in a given year. There was an increase in the proportion of young individuals with recent HIV infection, and we identified risk groups more at risk of HIV infection recently in Korea. Therefore, our results could prove useful for the development and assessment of national HIV prevention strategies in Korea and provide valuable data for further HIV research.

First complete genomic characterization of two tick-borne encephalitis virus isolates obtained from wild rodents in South Korea.

We determined for the first time the complete genome sequences of two Korean strains of the tick-borne encephalitis virus (TBEV), designated KrM 93 and KrM 213, isolated from the lung tissues of wild rodents in 2006. The genomes are 11,097 nucleotides (nt) in length and consist of a 132 nt 5'-noncoding region (NCR), a 10,245 nt open reading frame (ORF) containing 10 viral protein-coding regions (3,415 amino acids), and a 720 nt 3'-NCR. Compared with the 31 fully sequenced TBEV strains currently available, KrM 93 and KrM 213 show genomic nucleotide (and deduced amino acid) sequence divergences ranging from 1.8 (0.7) to 19.2 (26.6)% and 1.9 (0.8) to 19.3 (26.7)%, respectively. Phylogenetic and recombination analyses based on the complete genome sequence were performed to identify genetic variations and relationships between the TBEV strains. These showed that the Korean TBEV strains clustered with the Western subtype rather than with Far-Eastern or Siberian subtypes, and phylogenetic trees derived from capsid (C), envelope (E), nonstructural (NS) 4B and NS5 regions represented the same branching pattern shown by the complete genome-based tree. Although no recombination events were identified in these two Korean strains, 11 putative recombination events were identified within the NS5 regions or in the 3'-NCRs of TBEV strains in general. The results provide insight into the genetics of TBEV strains to understand the molecular epidemiology, genetic diversity, and evolution of TBEV.

The laboratory test procedure to confirm rotavirus vaccine infection in severe complex immunodeficiency patients.

The rotavirus vaccine is a live vaccine, and there is a possibility of infection by the virus strain used in the vaccine. We investigated the process of determining whether an infection was caused by the vaccine strain in a severe complex immunodeficiency (SCID) patient with rotavirus infection. The patient was vaccinated with RotaTeq prior to being diagnosed with SCID. The testing process was conducted in the following order: confirming rotavirus infection, determining its genotype, and confirming the vaccine strain. Rotavirus infection was confirmed through enzyme immunoassay and VP6 gene detection. G1 and P[8] were identified by multiplex polymerase chain reaction for the genotype, and G3 was further identified using a single primer. By detecting the fingerprint gene (WC3) of RotaTeq, it was confirmed that the detected virus was the vaccine strain. Genotypes G1 and P[8] were identified, and the infection was suspected of having been caused by rotavirus G1P[8]. G1P[8] is the most commonly detected genotype worldwide and is not included in the recombinant strains used in vaccines. Therefore, the infection was confirmed to have been caused by the vaccine strain by analyzing the genetic relationship between VP4 and VP7. Rotavirus infection by the vaccine strain can be identified through genotyping and fingerprint gene detection. However, genetic linkage analysis will also help to identify vaccine strains.

Nationwide seroprevalence of hepatitis A in South Korea from 2009 to 2019.

Hepatitis A, an acute type of hepatitis caused by the hepatitis A virus, occurs worldwide. Following the 2009 hepatitis A epidemic in South Korea, patient outbreak reports were collectively converted to an "all-patient report" in 2011, and national immunization programs were introduced for children in 2015. In this study, we aimed to analyze the changes and characteristics of hepatitis A antibody titers in South Korea following the epidemic. The results of hepatitis A antibody tests performed at clinical laboratories from 2009 to 2019 were analyzed based on year, age, region, sex, and medical institution. The average 2009-2018 positive anti-hepatitis A virus immunoglobulin G rate was 51.8%, but it increased (56.06%) in 2019. Significantly different antibody-positive rates were observed based on age: <10 years, 54.5%; 20-29 years, 19.5%; ≥50 years, almost 100%. The positive rate of individuals in their teens and 20s gradually increased, whereas that of those in their 30s and 40s gradually decreased. Males had higher antibody-positive rates than females, and samples from higher-level general hospitals exhibited higher antibody rates. The positive anti-hepatitis A virus immunoglobulin M rates gradually decreased after 2009 and were <1% after 2012. However, a high positive rate of 3.69% was observed in 2019 when there was an epidemic. Anti-hepatitis A virus immunoglobulin G-positive rates were similar throughout the year, but the anti-hepatitis A virus immunoglobulin M-positive rates increased from January, peaked in April, and decreased from July, exhibiting distinct seasonality. This is considered to be related to groundwater pollution during the spring drought season. The introduction of the "all-patient report" and national vaccination program for children has had an effective influence on hepatitis A management. However, for hepatitis A prevention, policy considerations for high-risk age groups with low antibody-positive rates will be necessary.

Validation of real-time RT-PCR for detection of SARS-CoV-2 in the early stages of the COVID-19 outbreak in the Republic of Korea.

A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay that does not require Emergency Use Authorization (EUA) reagents was tested and validated for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. Early diagnosis of COVID-19 enables timely treatment and the implementation of public health measures. We validated the sensitivity, specificity, precision, linearity, accuracy, and robustness of the RT-qPCR assay for SARS-CoV-2 detection and compared its performance with that of several EUA-approved kits. Our RT-qPCR assay was highly specific for SARS-CoV-2 as demonstrated by not amplifying 13 other viruses that cause respiratory diseases. The assay showed high linearity using a viral isolate from a patient with known COVID-19 as well as plasmids containing target SARS-CoV-2 genes as templates. The assay showed good repeatability and reproducibility with a coefficient of variation of 3%, and a SARS-CoV-2 limit of detection of 1 PFU/mL. The RT-qPCR-based assay is highly effective and can facilitate the early diagnosis of COVID-19 without the use of EUA-approved kits or reagents in the Republic of Korea.

Non-Polio Enteroviruses from Acute Flaccid Paralysis Surveillance in Korea, 2012-2019.

The risk of polio importation and re-emergence persists since epidemic polio still occurs in some countries, and the resurgence of polio occurring almost 20 years after polio eradication was declared in Asia has been reported. We analyzed the results of acute flaccid paralysis (AFP) surveillance in Korea to assess the quality of AFP surveillance and understand the etiology of non-polio enterovirus (NPEV)-associated central nervous system diseases in a polio-free area. We investigated 637 AFP patients under 15 years of age whose cases were confirmed during 2012-2019 by virus isolation, real-time reverse transcription polymerase chain reaction, and VP1 gene sequencing. Among the 637 AFP cases, NPEV was detected in 213 (33.4%) patients, with the majority observed in EV-A71, with 54.9% of NPEV positives. EV-A71 has been shown to play a role as a major causative agent in most neurological diseases except for Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM), and meningitis. This study provides information on the AFP surveillance situation in Korea and highlights the polio eradication stage in the monitoring and characterization of NPEV against the outbreak of neurological infectious diseases such as polio.