Report of the Korean Society of Infectious Diseases Roundtable Discussion on Responses to the Measles Outbreaks in Korea in 2019

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than nonresponse considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions.Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

Report of the Korean Society of Infectious Diseases Roundtable Discussion on Responses to the Measles Outbreaks in Korea in 2019

During the 2019 domestic measles outbreak in Korea, measles occurred in healthcare workers with two doses of the measles, mumps and rubella vaccine, and the strict application of the Occupational Safety and Health Act required medical institutions to identify healthcare workers' immunity to measles and vaccinate the susceptible pockets. In response to the frontline medical institutions' request to review the measles recommendations and guidelines, the Korean Society of Infectious Diseases held a roundtable discussion on the causes of measles outbreak, timing of vaccinations, antibody tests, and booster vaccinations for healthcare workers, and financial support from the government and municipality as well as response strategies against the outbreak in healthcare settings. In Korea, the seroprevalence of measles is decreasing in the vaccine-induced immunity group during the maintenance of measles elimination over several years. The susceptible group against measles is in their 20s and 30s, and this may be because of waning immunity rather than nonresponse considering Korea's vaccine policy. The risk of measles nosocomial infection from community increases as these susceptible pockets actively engage in medical institutions.Thus, data on the immunity of low seroprevalence group in Korea are needed, further discussion is needed on the booster vaccination based on the data. Especially, antibody testing and vaccination in healthcare workers may be necessary to prevent the spread of measles in medical insutitutions, and further discussion is needed regarding specific testing methods, and the timing and frequency of test and vaccination.

Correlation between Reactogenicity and Immunogenicity after the ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccination

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

Comparison of Antibody and T Cell Responses Induced by Single Doses of ChAdOx1 nCoV-19 and BNT162b2Vaccines

There are limited data directly comparing humoral and T cell responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines. We compared Ab and T cell responses after first doses of ChAdOx1 nCoV-19 vs. BNT162b2 vaccines. We enrolled healthcare workers who received ChAdOx1 nCoV-19 or BNT162b2 vaccine in Seoul, Korea. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein-specific IgG Abs (S1-IgG), neutralizing Abs (NT Abs), and SARS-CoV-2-specific T cell response were evaluated before vaccination and at 1-wk intervals for 3 wks after vaccination. A total of 76 persons, comprising 40 injected with the ChAdOx1 vaccine and 36 injected with the BNT162b2 vaccine, participated in this study. At 3 wks after vaccination, the mean levels (±SD) of S1-IgG and NT Abs in the BNT162b2 participants were significantly higher than in the ChAdOx1 participants (S1-IgG, 14.03±7.20 vs. 6.28±8.87, p<0.0001; NT Ab, 183.1±155.6 vs. 116.6±116.2, p=0.035), respectively. However, the mean values of the T cell responses in the 2 groups were comparable after 2 wks. The humoral immune response after the 1st dose of BNT162b2 developed faster and was stronger than after the 1st dose of ChAdOx1. However, the T cell responses to BNT162b2 and ChAdOx1 were similar.

WHO International Health Regulations Emergency Committee for the COVID-19 outbreak / 한국역학회지

To discuss whether the coronavirus disease 2019 (COVID-19) outbreak constitutes a Public Health Emergency of International Concern (PHEIC), World Health Organization (WHO) organized the 15-member International Health Regulations Emergency Committee (EC). On January 22-23 and January 30, 2020, EC convened and discussed whether the situation in China and other countries would constitute PHEIC and issued recommendations for WHO, China and the international community. Based on the recommendations of EC, WHO declared the COVID-19 outbreak a PHEIC. One of the purposes of the declaration of PHEIC was to alarm countries with weak public health infrastructures to prepare promptly for emerging infectious diseases (EID) and provide WHO with a framework for proactively supporting those countries. On February 3, 2020, WHO proposed the 2019 COVID-19 Strategic Preparedness and Response Plan, which includes accelerating research and development (R&D) processes as one of three major strategies. On February 11-12, 2020, WHO held the Global Research and Innovation Forum: Towards a Research Roadmap for COVID-19. The fact that a COVID-19 R&D forum was the first meeting convened after the PHEIC declaration testifies to the importance of R&D in response to EID. Korea has demonstrated a remarkable capacity in its laboratory response by conducting high-throughput COVID-19 testing and utilizing innovative drive-through samplings. These measures for early detection and screening of cases should be followed by full efforts to produce research-based evidence by thoroughly analyzing epidemiological, clinical and immunological data, which will facilitate the development of vaccines and therapeutics for COVID-19. It is expected that Korea plays a global partner for COVID-19 research by actively participating in immediate and mid/long-term priorities jointly led by WHO and global partners.

Status of HPV vaccination among HPV-infected women aged 20–60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study / 부인종양

Objectives@#Since 2007, human papillomavirus (HPV) vaccines have been administered for the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination among HPV-infected adult women with abnormal cervical cytology before the introduction of National Immunization Program. @*Methods@#From 2010 to 2016, HPV-positive women (age, 20–60 years) with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women. @*Results@#Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women(adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29–0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13–0.96). @*Conclusion@#This study highlighted the status of HPV vaccination and the prevalence of HPV-16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women.

Status of HPV vaccination among HPV-infected women aged 20–60 years with abnormal cervical cytology in South Korea: a multicenter, retrospective study / 부인종양

WHO International Health Regulations Emergency Committee for the COVID-19 outbreak / 한국역학회지

To discuss whether the coronavirus disease 2019 (COVID-19) outbreak constitutes a Public Health Emergency of International Concern (PHEIC), World Health Organization (WHO) organized the 15-member International Health Regulations Emergency Committee (EC). On January 22-23 and January 30, 2020, EC convened and discussed whether the situation in China and other countries would constitute PHEIC and issued recommendations for WHO, China and the international community. Based on the recommendations of EC, WHO declared the COVID-19 outbreak a PHEIC. One of the purposes of the declaration of PHEIC was to alarm countries with weak public health infrastructures to prepare promptly for emerging infectious diseases (EID) and provide WHO with a framework for proactively supporting those countries. On February 3, 2020, WHO proposed the 2019 COVID-19 Strategic Preparedness and Response Plan, which includes accelerating research and development (R&D) processes as one of three major strategies. On February 11-12, 2020, WHO held the Global Research and Innovation Forum: Towards a Research Roadmap for COVID-19. The fact that a COVID-19 R&D forum was the first meeting convened after the PHEIC declaration testifies to the importance of R&D in response to EID. Korea has demonstrated a remarkable capacity in its laboratory response by conducting high-throughput COVID-19 testing and utilizing innovative drive-through samplings. These measures for early detection and screening of cases should be followed by full efforts to produce research-based evidence by thoroughly analyzing epidemiological, clinical and immunological data, which will facilitate the development of vaccines and therapeutics for COVID-19. It is expected that Korea plays a global partner for COVID-19 research by actively participating in immediate and mid/long-term priorities jointly led by WHO and global partners.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19–64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

Pathogenesis of coxsackievirus B2 in mice: characterization of clinical isolates of the coxsackievirus B2 from patients with myocarditis and aseptic meningitis in Korea

Group B coxsackieviruses (CVBs) are a group of common human pathogens producing various clinical symptoms. Although the virology of CVB is well known, there is limited information on viral pathogenesis and the relationship between clinical symptoms and viral phenotype, particularly for CVB type 2 (CVB2). In 2004 in Korea, two CVB2 strains were isolated: CB2/04/279 from stool of an acute myocarditis patient with heart failure and CB2/04/243 from an aseptic meningitis patient. In this study, a high degree of homology was observed between the CB2/04/279 and CB2/04/243 full genome sequences. The two Korean CVB2 isolates had 93.1% homology compared to 82.1%–82.5% nucleotide sequence identity with the cardiovirulence-associated reference CVB strain Ohio-1 (CVB/O). CVB2-induced pathogenesis was analyzed, focusing on virus-induced pathology of various tissues in 4-week-old BALB/c inbred male mice. Myocarditis developed and extensive pancreatic inflammation was observed in all mice infected with CB2/04/279 or CVB/O, but not in animals infected with CB2/04/243. This is the first report of the full-genomic sequence and pathogenesis of the CVB2 strain isolated from an acute myocarditis patient in Korea.

First Imported Case of Zika Virus Infection into Korea

Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

Engaging the international community during the 2015 Middle East respiratory syndrome outbreak in the Republic of Korea

The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea, which started with an imported case and spread throughout the country with a total of 186 cases, revealed the vulnerabilities of the health-care system of the country. The situation was compounded by the unique health-care settings in the Republic of Korea, including crowded emergency departments and large numbers of hospital visitors seeking care at multiple hospitals. To assist with the outbreak response, the Ministry of Health and Welfare of the Republic of Korea hosted several international joint missions that provided valuable information and recommendations for MERS control and prevention of future outbreaks. This report briefly summarizes the missions’ outcomes and discusses their positive impacts.

Measles Elimination Activities in the Western Pacific Region: Experience from the Republic of Korea

We describe the global status of measles control and elimination, including surveillance and vaccination coverage data provided by the World Health Organization (WHO). Since 2000, two doses of measles vaccine (MCV2) became recommended globally and the achievement of high vaccination coverage has led to dramatic decrease in the measles incidence. Our finding indicates that, in the Western Pacific Region (WPR), substantial progress has been made to control measles transmission in some countries; however, the measles virus continues to circulate, causing outbreaks. The Republic of Korea (ROK) experienced a series of resurgence of measles due to the importation and healthcare-associated transmission in infants, however overall incidence and surveillance indicators met the WHO criteria for measles elimination. The ROK was verified to be measles-free along with Australia, Mongolia, and Macau, China in 2014. One of the effective elimination activities was the establishment of solid keep-up vaccination system in school settings. The lessons learnt from the measles elimination activities in Korea may contribute to enhancing the surveillance schemes and strengthening of vaccination programs in member countries and areas of WPR.

Utility of RT-PCR-based Dot-blot Hybridization for Detecting and Genotyping Echoviruses

We attempted to detect and identify virus types quickly by improving an RT-PCR-based dot-blot hybridization test for echoviruses, important human pathogens mainly causing aseptic meningitis. This test was applied to reference viruses of seven echovirus serotypes prevalent in Korea (E6, 7, 9, 11, 13, 25, and 30) and seventy isolates of echovirus isolated in Korea between 2002 and 2004. The primers for target DNA and hybridization probes (25mer, 50mer, and 70mer) were designed within the VP1 region of the echovirus. In RT-PCR, a nonradioactive digoxigenin-DNA labeling mix was added instead of dNTP to initiate PCR. The PCR product was then hybridized against 25mer, 50mer, and 70mer probe DNA spotted on nylon membranes and the reaction was observed. To investigate the optimal conditions for hybridization, various concentrations of target DNA (0.1, 1, 10, and 100 ng/micron l), size of probe DNA (25mer, 50mer, and 70mer), concentrations of probe DNA (10~50 pM), and reaction time were included. In the test zone, the optimal condition in terms of time and cost was a reaction time of 1 h with 10 ng/micron l target DNA concentration and 10 pM of a 50mer probe. We found 100% diagnosis of the serotypes for seven reference echoviruses and 90% (63/70) sensitivity for clinical isolates. Also, tests with this probe for reactivity with seven reference echoviruses by using DNA chips showed that diagnostic identification was possible without other serotype cross-reactivity. Therefore, efficiency analysis of probe and target DNA on clinical specimens by using dot-blot analysis indicated that this system can be applied to the prestages of the DNA chip and that the dot blot analysis itself can be used in applications to develop a tool for diagnosing specific viral serotypes.

A Quantitative Comparison of Vaccinia Virus Shedding from Conventional Dressing Sites and Vaccination Lesions after Smallpox Vaccination

BACKGROUND: We compared vaccinia virus shedding from the vaccine inoculation site (vaccination lesion) and two sites of a dressing covering the vaccination site; the outer surface of the semipermeable dressing (outer surface) and the inner surface of the semipermeable dressing, that is, the surface of a folded gauze under the semipermeable membrane (gauze surface) MATERIAL AND METHODS: Subjects were recruited from the volunteers who participated in a clinical trial of the efficacy of a 1:10 dilution of Lancy-Vaxina? (Berna Biotech, Switzerland), and were seen every 2-3 days (days 6, 8, 10, 13, and 15 after smallpox vaccination) for scheduled dressing changes. Swab specimens were obtained from the vaccination lesion, the outer surface, and the gauze surface. Quantitative viral culture assays for these specimens were done. RESULTS: Vaccinia virus was recovered from 126 (81%) of the 156 vaccination lesion samples collected from the 40 participants. A high virus titer was recovered from the vaccination lesion (geometric mean titer (log10)=3.91 on day 8). Of the 39 swab samples obtained from the gauze surface of the gauze, 16 (41%) were positive for virus. An intermediate titer was recovered from the gauze surface (geometric mean titer (log10)=0.91 on day 8). Of the 133 swab samples obtained from the outer surface, only one (0.8%) was positive for vaccinia. No virus was recovered from the outer surface on day 8. CONCLUSION: Our findings suggest that the addition of a semipermeable dressing to the folded gauze further reduces viral shedding and therefore increases protection.

A Quantitative Comparison of Vaccinia Virus Shedding from Conventional Dressing Sites and Vaccination Lesions after Smallpox Vaccination

BACKGROUND: We compared vaccinia virus shedding from the vaccine inoculation site (vaccination lesion) and two sites of a dressing covering the vaccination site; the outer surface of the semipermeable dressing (outer surface) and the inner surface of the semipermeable dressing, that is, the surface of a folded gauze under the semipermeable membrane (gauze surface) MATERIAL AND METHODS: Subjects were recruited from the volunteers who participated in a clinical trial of the efficacy of a 1:10 dilution of Lancy-Vaxina? (Berna Biotech, Switzerland), and were seen every 2-3 days (days 6, 8, 10, 13, and 15 after smallpox vaccination) for scheduled dressing changes. Swab specimens were obtained from the vaccination lesion, the outer surface, and the gauze surface. Quantitative viral culture assays for these specimens were done. RESULTS: Vaccinia virus was recovered from 126 (81%) of the 156 vaccination lesion samples collected from the 40 participants. A high virus titer was recovered from the vaccination lesion (geometric mean titer (log10)=3.91 on day 8). Of the 39 swab samples obtained from the gauze surface of the gauze, 16 (41%) were positive for virus. An intermediate titer was recovered from the gauze surface (geometric mean titer (log10)=0.91 on day 8). Of the 133 swab samples obtained from the outer surface, only one (0.8%) was positive for vaccinia. No virus was recovered from the outer surface on day 8. CONCLUSION: Our findings suggest that the addition of a semipermeable dressing to the folded gauze further reduces viral shedding and therefore increases protection.

Updates on Enterovirus Surveillance in Korea

PURPOSE: We identified the causative viruses from patients with aseptic meningitis, acute hemorrhagic conjunctivitis and other enterovirus-related diseases to understand the epidemiological patterns and prevailing strains of enterovirus infections each year. MATERIALS AND METHODS: During 1999-2003, we examined 3,260 specimens from 2,939 patients with aseptic meningitis or other clinical manifestations for the presence of enteroviruses by using both cell culture/ neutralisation test and reverse transcription-polymerse chain reaction-sequencing. To investigate the etiological agents which caused an epidemic of acute haemorrhagic conjunctivitis, conjunctival swab samples from acute haemorrhagic conjunctivitis patients showing cytopathic effects in HEp2 cells were tested by enteroviral specific PCR. RESULTS: We identified 603 isolates of enteroviruses (20.5%) among 2,939 cases and 22 serotypes of human enteroviruses were isolated during this 5 year period. Echovirus 13 and coxsackievirus A24 in 2002 and coxsackievirus A9 in 2003 were the first enterovirus to be indentified in Korea since we began the enterovirus surveillance in 1993. While an epidemic of echovirus 13 infection in Korea began in Gwangju and Jeolla province in 2002 and spread to Seoul, Gyunggi, Busan, Ulsan and other regions, echovirus 6 isolates in 2002 were mainly detected in Busan specimens and some Gwangju samples. From the nucleotide sequencing of enteroviral PCR products of conjunctival swab specimens, we found 85% nucleotide homology to coxsackievirus A24 (D90457). CONCLUSIONS: We isolated 603 enteroviral isolates among 2939 cases during 1999-2003. Echovirus 13 and coxsackievirus A24 were the first enterovirus to be identified in Korea and caused nationwide epidemics in 2002.

Updates on Enterovirus Surveillance in Korea

PURPOSE: We identified the causative viruses from patients with aseptic meningitis, acute hemorrhagic conjunctivitis and other enterovirus-related diseases to understand the epidemiological patterns and prevailing strains of enterovirus infections each year. MATERIALS AND METHODS: During 1999-2003, we examined 3,260 specimens from 2,939 patients with aseptic meningitis or other clinical manifestations for the presence of enteroviruses by using both cell culture/ neutralisation test and reverse transcription-polymerse chain reaction-sequencing. To investigate the etiological agents which caused an epidemic of acute haemorrhagic conjunctivitis, conjunctival swab samples from acute haemorrhagic conjunctivitis patients showing cytopathic effects in HEp2 cells were tested by enteroviral specific PCR. RESULTS: We identified 603 isolates of enteroviruses (20.5%) among 2,939 cases and 22 serotypes of human enteroviruses were isolated during this 5 year period. Echovirus 13 and coxsackievirus A24 in 2002 and coxsackievirus A9 in 2003 were the first enterovirus to be indentified in Korea since we began the enterovirus surveillance in 1993. While an epidemic of echovirus 13 infection in Korea began in Gwangju and Jeolla province in 2002 and spread to Seoul, Gyunggi, Busan, Ulsan and other regions, echovirus 6 isolates in 2002 were mainly detected in Busan specimens and some Gwangju samples. From the nucleotide sequencing of enteroviral PCR products of conjunctival swab specimens, we found 85% nucleotide homology to coxsackievirus A24 (D90457). CONCLUSIONS: We isolated 603 enteroviral isolates among 2939 cases during 1999-2003. Echovirus 13 and coxsackievirus A24 were the first enterovirus to be identified in Korea and caused nationwide epidemics in 2002.

Small Round Structured Virus (SRSV) Outbreak Among Elementary School Students in Wonju Province / 감염

No abstract available.

Cloning and Sequence Analysis of the Full-length cDNA of Coxsackievirus B3 Isolated in Korea

We have determined and analyzed the full-length cDNA sequence of a coxsackievirus B3 (CVB3) Korean isolate (CVB3-Korea/97) which has been known as a general human pathogen. The whole genome contains 7,400 nucleotides and has a single large open reading frame with 6,555 nucleotides that encodes a potential polyprotein precursor of 2,185 amino acids. The genome also contains a 5' non-coding region (NCR) of 741 bases and a 3' NCR of 104 bases followed by poly(A) tail. Sequence homologies of nucleotides and deduced amino acids between the CVB3-Korea/97 strain and the prototype (Nancy strain) were 81.7% and 91.5%, respectively. The genes encoding the functional proteins including viral protease and RNA dependent RNA polymerase showed higher homology than those encoding the structural proteins. We have further analyzed the sequences of 5' NCR, VP1 and VP2 of CVB3-Korea/97, which are known as cardiovirulent determining factors at the nucleotide and amino acid levels. Although the CVB 3-Korea/97 strain was isolated from an aseptic meningitis patient without cardiomyopathy, its 234th nucleotide and 165th amino acid were uracil and Asn as same as those of other cardiovirulent strains one. However, the 155th amino acid of VR1, which closely associated with cardiovirulence, was replaced with Arg155 by single nucleoptide substitution from A2916 to T2916. Moreover, additional amino acid substitutions were observed in the flanking region of Asp155. Taken together, aminoacid(s) substitution in VP1 may play a critical role in determining cardiovirulence of the CVB3-Korea/97 strain rather than individual nucleotide replacements in the 5' NCR and/or an amino acid substitution in VP2.