Mosaic genome of Human Coxsackievirus A4 associated with herpangina and HFMD in Yancheng, China, 2016 and 2018.

OBJECTIVES: To better understand the spectrums of pathogens causing herpangina and circulation of Coxsackievirus A4 in Yancheng, China. METHODS: Stool samples from herpangina and HFMD cases were collected. Real Time PCR Kits was used to identify Enterovirus 71, CV-A16 and CV-A6, and nested reverse transcription PCR (nRT-PCR) to detect the other enterovirus types. Complete VP1 and genome sequence of CV-A4 were amplified by using nRT-PCR. Genetic, phylogenetic and recombination analysis were performed. RESULTS: Co-circulation of three recombinant CV-A4 groups, including one novel (C2 lineage), was identified in Yancheng, China, 2016 and 2018. One was the major causative agent of herpangina, and another two were responsible for HFMD. Phylogenetic and recombination analysis indicated that the non-structural region of their genome originated from the same ancestry and subsequently adaptation. C2 lineage of CV-A4 group may be introduced from countries outside China and its genome occurred recombination in China. CONCLUSION: Novel recombinant CV-A4 was mainly associated with herpanginain in Yancheng, 2018, China. C2 lineage of CV-A4 group with recombinant non-structural region was also identified in HFMD patients.

Molecular epidemiology of enterovirus from children with herpangina or hand, foot, and mouth disease in Hangzhou, 2016.

Enteroviruses (EVs) are the major cause of hand, foot, and mouth disease (HFMD) and herpangina in children. In this study, we conducted a molecular investigation of EVs in throat swab samples from children in Hangzhou, China with a diagnosis of HFMD or herpangina. EVs were detected using one-step real-time RT-PCR, and their serotypes were determined based on partial VP1 gene sequences. The molecular typing results revealed the presence of six different EV serotypes in HFMD cases, including coxsackievirus (CV) A16 (20/30, 66.7%), CVA4 (3/30, 10.0%), CVA6 (3/30, 10.0%), EVA71 (2/30, 6.7%), CVB4 (1/30, 3.3%), and CVB5 (1/30, 3.3%). Eleven different EV serotypes were detected in herpangina cases, among which CVA4 was the most frequently detected serotype (105/170, 61.8%), followed by CVA16 (30/170, 17.6%), CVB4 (9/170, 5.3%), CVA6 (6/170, 3.5%), CVB3 (5/170, 2.9%), CVA10 (3/170, 1.8%), EVA71 (4/170, 2.4%), Echo9 (3/170, 1.8%), CVA9 (2/170, 1.2%), CVB1 (3/170, 1.8%) and CVA5 (1/170, 0.6%). The nucleotide sequence identity of EV strains from the same subtype ranged from 80.7% to 100%, and most of the EVs were closely related to virus strains found in Australia and mainland China. In conclusion, CVA 16 and CVA 4 were the main serotypes causing HFMD and herpangina, respectively, in children in Hangzhou in 2016. Most of these EVs were closely related to virus strains from Australia and mainland China.

Recombinant CV-A6 strains related to hand-foot-mouth disease and herpangina at primary care centers (Barcelona, Spain).

Aim: To describe the genetic diversity of enteroviruses (EV) causing hand, foot and mouth disease (HFMD) and herpangina, especially of coxsackievirus (CV)-A6, from patients attended at pediatric primary care centers during the 2017-2018 season. Methods: Phylogenetic analysis of partial VP1 region was performed for genetic characterization. The complete VP1 and 3Dpol proteins were sequenced for lineage determination and detection of recombination events. Results: An 80% of samples were EV laboratory-confirmed. CV-A6 was the most detected (70%) and associated with atypical HFMD (78%). The comparison of VP1 and 3Dpol phylogenies showed evidence of recombination in three strains, in which two shifted to CV-A16 3Dpol. Conclusion: The study provides recent information regarding the nonrecombinant and recombinant EVs related to HFMD at primary care centers.

Comparison of Nonpolio Enteroviruses in Children With Herpangina and Hand, Foot and Mouth Disease in Taiwan.

BACKGROUND: Nonpolio enterovirus (NPEV) infections are often present with herpangina (HA) and hand, foot and mouth disease (HFMD). Most countries sample NPEVs in HFMD cases, targeting enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) that are associated with outbreaks and severe complications. HA is also monitored in Taiwan and several other countries, but its viral characteristics are underreported. METHODS: Through Taiwan's National Virologic Surveillance, information regarding ~100,000 child respiratory samples (2002-2015) was linked to concurrent (0-6 days before the sampling date) outpatient records from the National Health Insurance databases, including ~15,000 HA-related and ~7000 HFMD-related samples. We assessed sample representation and NPEV positive rates, and estimated total numbers of EV-A71 and CV-A16. RESULTS: There were more HA events (4.0 millions) than HFMD events (1.2 millions) in Taiwan. In every 1000 events with HFMD and HA, 6.0 and 4.1, respectively, respiratory samples were collected. The NPEV positive rate in HFMD-related samples was 48%, consistent across most sampling seasons, and predominantly EV-A71 or CV-A16 (74%). By comparison, the HA-related samples had a lower positive rate overall (43%), occasionally EV-A71 or CV-A16 (13%), and the positive rate depended strongly on HA incidence (P < 10). Compared with sampling HFMD alone, inclusion of HA-related information predicted an earlier onset of EV-A71 outbreak in 2011, and predicted 30% more EV-A71 cases. CONCLUSIONS: This is the first representative report on viral characteristics of HA. Our findings confirm that HFMD monitoring is a reliable strategy, but there is a measurable additional benefit when HA is also monitored.

Hand, foot and mouth disease and herpangina caused by enterovirus A71 infections: a review of enterovirus A71 molecular epidemiology, pathogenesis, and current vaccine development.

Enterovirus A71 (EV-A71) infections are one of the main etiological agents of hand, foot and mouth disease (HFMD) and herpangina worldwide. EV-A71 infection is a life-threatening communicable disease and there is an urgent global need for the development of vaccines for its prevention and control. The morbidity rate of EV-A71 infection differs between countries. The pathogen's genetic lineages are undergoing rapid evolutionary changes. An association between the occurrence of EV-A71 infection and the circulation of different genetic strains of EV-A71 virus has been identified around the world. In this review, we present and discuss the molecular epidemiology and pathogenesis of the human disease caused by EV-A71 infection, as well as current prospects for the development of an EV-A71 vaccine.

Understanding physician antibiotic prescribing behavior for children with enterovirus infection.

BACKGROUND: Our previous study demonstrated that pediatricians prescribe antibiotics without proper clinical justification to patients with enterovirus infection, although antibiotics are not effective in treating the infections caused by these viruses. To improve the quality of healthcare, we aim to evaluate the association of clinical and demographic characteristics of patients and further to identify the determining factors for prescribing antibiotics to children experiencing enterovirus infection. METHODS: We retrospectively reviewed the medical records of children who were hospitalized between January 2008 and December 2016 with a diagnosis of herpangina or hand-foot-mouth disease (HFMD). We identified those children who were prescribed antibiotics for at least 24 hours during admission. We conducted a retrospective descriptive study to analyze data in order to determine the factors associated with pediatrician antibiotics prescribing for enterovirus infection. RESULTS: In the nine years of study period, the rate of antibiotics use was about 13% in these patients. A total of 3659 patients were enrolled during 2008~2012 and analyzed in detail. Elevated levels of C-reactive protein (CRP) and presence of leukocytosis in blood (WBC) were both significantly associated with pediatrician antibiotic prescribing for enterovirus infection (p<0.001). Between different specialistic devisions, there was significantly different proportion of antibiotics utilization for patients. In further analysis of antibiotics prescribing by Receiver operating characteristic (ROC) curve method, the level of CRP significantly had more the area under curve (0.708) compared with the count of WBC (p<0.05). CONCLUSIONS: The present study indicates that higher serum level of CRP is strongly associated with pediatricians prescribing antibiotics for children experiencing herpangina or HFMD. Antibiotic prescribing is a complex process. Pediatricians should be more judicious in decision-making time by their specialistics. Our findings would shed new light on process and allay the concern about inappropriate antibiotics.

Development of a pseudovirus based assay for measuring neutralizing antibodies against coxsackievirus B5.

Coxsackievirus B5 (CV-B5), an important Coxsackie B virus from genus Enteroviruse within the family Picornaviridae, has also been isolated from Hand, Foot, and Mouth Disease (HFMD) patients, and often associated with neurological manifestations. In this study, we found out that Coxsackievirus B3 (CV-B3) replicon RNA could be encapsidated with CV-B5 capsid to assemble infectious CV-B5 pseudovirus. We then utilized this single round infection system of CV-B5 to develop a neutralizing antibody quantification assay. This pseudovirus neutralization assay showed superiority in biosafety, sensibility, quantitativity, efficiency and high throughput, and would facilitate the epidemiological studies and vaccine development of CV-B5.

Large outbreak of herpangina in children caused by enterovirus in summer of 2015 in Hangzhou, China.

Herpangina, usually caused by coxsackie virus A, is prevalent in children spreading through the fecal-oral transmission and the respiratory droplets dissemination. Also, it is mostly asymptomatic and self-limiting. In our study, we found that large outbreak of herpangina in children occurred in the summer of 2015 in Hangzhou, China. From May 1th to August 31th, a total of 10 210 children were diagnosed with herpangina in Children's Hospital of Zhejiang University School of Medicine. 2 310 throat swabs were collected and tested for enterovirus detection by real-time RT-PCR, while 1 651 cases were positive with the rate of 71.5%. Based on VP1 gene or 5'UTR region sequences, Coxsackievirus A2, A4, A6, A10, B2, B4 and echovirus 30 were detected in these cases. More importantly, Coxsackievirus A2 may be the major subtype of enterovirus resulting in children with herpangina in hangzhou, China.

Molecular epidemiology of the enteroviruses associated with hand, foot and mouth disease/herpangina in Dongguan, China, 2015.

Enteroviruses (EVs) are the etiological agents involved in most cases of hand, foot and mouth disease (HFMD) and herpangina (HA). Information on the epidemiology profiles of EVs in China is very limited, as the present surveillance system of China focuses on CAV16 and EV71, and no published data are available in Dongguan. The aim of this study is to determine the prevalence of EVs among patients with HFMD and HA in Dongguan, China, during 2015. A total of 271 clinical stool specimens that were clinically determined to be positive for enteroviruses were genotyped by semi-nested polymerase chain reaction (PCR) for the VP1 genes of EVs. The results showed that a total of 14 enterovirus genotypes were identified among HFMD and HA patients in this study. CVA6 was the most common genotype for HFMD, and CVA2 accounted for the majority of HA cases in this study. Sequence and phylogenetic analysis showed that all of the CVA6 and CVA2 strains identified in our study displayed a close genetic relationship to strains identified in other cities in China. This study also demonstrates that there are associations between particular causative enterovirus genotypes and some clinical symptoms, which may provide useful information for improving case prevention, diagnosis and treatment of HFMD and HA.

Changes in enterovirus serotype constituent ratios altered the clinical features of infected children in Guangdong Province, China, from 2010 to 2013.

BACKGROUND: Enterovirus (EV)-related hand, foot, and mouth disease/herpangina (HFMD/HA) has been prevalent in Guangdong Province, China, since 2010. METHODS: Clinical data for EV-related HFMD/HA inpatients admitted to the Department of Paediatrics of Zhujiang Hospital from 2010 to 2013 were retrospectively reviewed. The corresponding EV serotypes were also determined by reverse transcription-polymerase chain reaction or BLAST analysis of the sequenced partial lengths of the viral protein1/5'-untranslated region. RESULTS: A total of 867 eligible inpatients admitted during 2010-2013 were included in the study. Of these, the serotype of the responsible EV was successfully identified in 824 cases. The incidence of enterovirus 71 (EV71) infection amongst pediatric HFMD/HA inpatients decreased dramatically from 55.5 % in 2010 to 8.1 % in 2013, with a similar decrease recorded for coxsackievirus A16 (CVA16). However, the incidence of non-EV71/CVA16 infection increased from 30.0 % in 2010 to 83.8 % in 2013. We noted that the types of infection caused by different EV serotypes varied: EV71 was responsible for 100 % of the paralysis cases (26/26), 84.6 % of the deaths (11/13), and 84.1 % of cases with severe central nervous system involvement (SCNSI) (74/88); echovirus contributed to 16.4 % of the deaths (2/13) and 4.4 % of the SCNSI cases; and coxsackievirus accounted for only 2.2 % of the SCNSI cases (2/90). The clinical features of HFMD/HA cases varied greatly during the time period examined, with drastic changes in the hospitalization rates (45.1, 63.7, 36.4, and 19.1 % for 2010, 2011, 2012, and 21013, respectively), mortality rates (2.3, 0.9, 2.5, and 0.0 %, respectively), paralysis (5.1, 1.2, 5.4, and 0.0 %, respectively), SCNSI (16.8, 7.1, 12.7, and 2.2 %, respectively), and acute respiratory infection (21.1, 22.0, 45.9, and 59.0 %, respectively). CONCLUSIONS: The incidences of infection caused by different EV serotypes, along with the clinical features of HFMD/HA cases, changed drastically in Guangdong Province, China, from 2010 to 2013, with the biggest changes observed in 2013. The changed constituent ratios of the different EV serotypes might therefore be responsible for the differences in the observed clinical features of HFMD/HA during this period.

Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

BACKGROUND: A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. METHODS: We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. RESULTS: There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. CONCLUSIONS: Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

Genomic characteristics of coxsackievirus A8 strains associated with hand, foot, and mouth disease and herpangina.

Coxsackievirus A8 (CV-A8), a member of the genus Enterovirus of the family Picornaviridae, can cause a variety of infectious diseases, such as hand, foot and mouth disease (HFMD), herpangina (HA), encephalitis, paralysis, myelitis, and meningitis. This is a first report of complete genome sequences of CV-A8 strains associated with HFMD/HA since the prototype strain Donovan was identified in 1949. The complete genome sequences of eight new CV-A8 strains showed 19.2 %-20.6 % nucleotide differences when compared to the prototype strain Donovan, and 81.5 %-99.9 % similarity to each other. The topology of a polyphyletic tree based on complete capsid protein gene sequences indicated that the new CV-A8 strains and Donovan are monophyletic. However, seven CV-A8 strains clustered with CV-A10 and CV-A2 in the 5'UTR and P2 region, respectively. In the P3 region, three and four CV-A8 strains grouped with CV-A6 and CV-A2, respectively. Seven CV-A8 strains segregated from Donovan and grouped in a separate lineage in the 3'UTR. The strain CVA8/SZ266/CHN/2014 was most similar to EV71 in the nonstructural proteins regions. Phylogenetic analysis classified worldwide CV-A8 isolates into four distinct clusters, and almost all Chinese and Thai CV-A8 strains evolved independently in their respective lineages, which indicated geographical evolution of CV-A8.

Diagnostic uncertainty of herpangina and hand-foot-and-mouth disease and its impact on national enterovirus syndromic monitoring.

The community burden of enterovirus is often monitored through syndromic monitoring systems based on reported cases of enterovirus-related infection (EVI) diagnoses. The extent to which this is affected by under- and over-diagnosis has not been reported. In Taiwan, children often make more than one healthcare visit during an episode of infection. We used change of diagnosis within an episode of infection as a guide of diagnostic uncertainty in a nationally representative cohort of Taiwanese children (n = 13 284) followed from birth to the 9th birthday through electronic health records. We conducted a nested case-control analysis and estimated cross-diagnosis ratios (CDRs) as the observed proportion of acute respiratory infection (ARI) diagnoses following an EVI diagnosis in excess of background ARI burdens. With 19 357 EVI diagnoses in this cohort, the CDR within 7 days was 1·51 (95% confidence interval 1·45-1·57), confirming a significant excess of ARI diagnoses within the week following an EVI diagnosis. We used age-specific CDRs to calibrate the weekly EVI burden in children aged 3-5 years in 2008, and the difference between observed and calibrated weekly EVI burdens was small. Therefore, there was evidence suggesting a small uncertainty in EVI diagnosis, but the observed EVI burdens through syndromic monitoring were not substantially affected by the small uncertainty.

Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study.

BACKGROUND: The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed to assess the risk of leukaemia after enterovirus infection in children. METHODS: We did a nationwide retrospective cohort study by analysing data from the National Health Insurance Research Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years were identified. With use of computer-generated random numbers, children not infected with enterovirus were randomly selected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parental occupation, and index year of enterovirus infection. We only included children with complete baseline data for age and sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of the first clinic visit for the enterovirus infection was defined as the index date for initiation of follow-up person-year measurement and participants. All study patients were followed up until they developed leukaemia, were lost to follow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Our primary endpoint was a diagnosis of leukaemia during follow-up. FINDINGS: Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insured children in the NHIRD. We identified 282 360 children infected with enterovirus and 282 355 children not infected with enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3·26 per 100 000 person-years for the enterovirus-infected and 5·84 per 100 000 person-years for the non-enterovirus-infected cohorts. The risk of leukaemia was significantly lower in the enterovirus-infected cohort than in the non-enterovirus-infected cohort (adjusted subhazard ratio [SHR] 0·44, 95% CI 0·31-0·60; p<0·0001). Children infected with enterovirus have a reduced risk of both lymphocytic leukaemia (adjusted SHR 0·44, 0·30-0·65; p<0·0001) and acute myeloid leukaemia (adjusted SHR 0·40, 0·17-0·97; p=0·04). Herpangina and hand-foot-and-mouth disease were the main diseases associated with the reduced risk of leukaemia. INTERPRETATION: The association between enterovirus infection and the reduced risk of developing leukaemia supports Greaves' delayed infection hypothesis for the cause of childhood leukaemia.

PREVALENCE OF HUMAN ENTEROVIRUS AMONG PATIENTS WITH HAND, FOOT, AND MOUTH DISEASE AND HERPANGINA IN THAILAND, 2013.

Human enterovirus (EV) infection causes hand, foot, and mouth disease (HFMD) and herpangina (HA). We studied the prevalence of enterovirus (EV) among patients with HFMD and HA in Thailand during 2013. We conducted a study in archived specimens of patients sent for screening for enterovirus. A total of 203 clinical specimens from 184 individuals with painful blister in the oropharynx and on the palms, soles, knees, elbows or buttock were examined by semi-nested polymerase chain reaction (PCR) for the 5'UTR and VP1 genes of EV. Eighty-six samples were positive: EV71 was detected in 14 (30%), CV-A8 in 12 (26%) and CV-A16 in 10 (21%). Classification of EV species detected revealed that 46 specimens were EV-A, 14 specimens were EV-B, 1 specimen was EV-D, and 16 specimens were positive for unclassified enterovirus. The majority of individuals with EV infection were aged 2-6 years. Multiple EV-A serotypes were detected among HFMD and HA patients in our study.

Prevalence and characterization of enterovirus infections among pediatric patients with hand foot mouth disease, herpangina and influenza like illness in Thailand, 2012.

Hand, foot, and mouth disease (HFMD) and herpangina are common infectious diseases caused by several genotypes of human enterovirus species A and frequently occurring in young children. This study was aimed at analyzing enteroviruses from patients with these diseases in Thailand in 2012. Detection and genotype determination of enteroviruses were accomplished by reverse transcription-polymerase chain reaction and sequencing of the VP1 region. Enterovirus-positive samples were differentiated into 17 genotypes (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5, echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8 (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus infections were most prevalent during July with 34.4% in HFMD, 39.8% in herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD and herpangina occurred in infants over one year-old. This represents the first report describing the circulation of multiple enteroviruses in Thailand.

Outbreak of herpangina in the Brazilian Amazon in 2009 caused by Enterovirus B.

In October 2009, our laboratory was contacted by a Brazilian Public Health organization regarding a severe community outbreak of an acute exanthematic and febrile disease in the Brazilian Amazon that primarily affected children. A total of 44 patients with febrile disease were identified by the local public health system, 37 of whom were children between 1 and 9 years of age. Molecular virological and phylogenetic characterization revealed that enterovirus B was the etiological agent of this outbreak, which was characterized by a clinical presentation known as herpangina.

Hand, foot, and mouth disease caused by coxsackievirus A6, Thailand, 2012.

In Thailand, hand, foot, and mouth disease (HFMD) is usually caused by enterovirus 71 or coxsackievirus A16. To determine the cause of a large outbreak of HFMD in Thailand during June-August 2012, we examined patient specimens. Coxsackievirus A6 was the causative agent. To improve prevention and control, causes of HFMD should be monitored.

Risk factors for neurologic complications of hand, foot and mouth disease in the Republic of Korea, 2009.

In 2009, the first outbreak of hand, foot and mouth disease (HFMD) or herpangina (HP) caused by enterovirus 71 occurred in the Republic of Korea. This study inquired into risk factors associated with complications of HFMD or HP. A retrospective medical records review was conducted on HFMD or HP patients for whom etiologic viruses had been verified in 2009. One hundred sixty-eight patients were examined for this investigation. Eighty patients were without complications while 88 were accompanied by complications, and 2 had expired. Enterovirus 71 subgenotype C4a was the most prevalent in number with 67 cases (54.9%). In the univariate analysis, the disease patterns of HFMD rather than HP, fever longer than 4 days, peak body temperature over 39℃, vomiting, headache, neurologic signs, serum glucose over 100 mg/dL, and having an enterovirus 71 as a causative virus were significant risk factors of the complications. After multiple logistic analysis, headache (Odds ratio [OR], 10.75; P < 0.001) and neurologic signs (OR, 42.76; P < 0.001) were found to be the most significant factors. Early detection and proper management of patients with aforementioned risk factors would be necessary in order to attain a better clinical outcome.

Enteroviruses isolated from herpangina and hand-foot-and-mouth disease in Korean children.

Hand-foot-and-mouth disease (HFMD) and herpangina are commonly prevalent illness in young children. They are similarly characterized by lesions on the skin and oral mucosa. Both diseases are associated with various enterovirus serotypes. In this study, enteroviruses from patients with these diseases in Korea in 2009 were isolated and analyzed. Demographic data for patients with HFMD and herpangina were compared and all enterovirus isolates were amplified in the VP1 region by reverse transcription-polymerase chain reaction and sequenced. Among the enterovirus isolates, prevalent agents were coxsackievirus A16 in HFMD and coxsackievirus A5 in herpangina. More prevalent months for HFMD were June (69.2%) and May (11.5%), and June (40.0%) and July (24.0%) for herpangina. Age prevalence of HFMD patients with enterovirus infection was 1 year (23.1%), 4 years (19.2%), and over 5 years (19.2%). However, the dominant age group of herpangina patients with enterovirus infection was 1 year (48.0%) followed by 2 years (28.0%). Comparison of pairwise VP1 nucleotide sequence alignment of all isolates within the same serotypes revealed high intra-type variation of CVA2 isolates (84.6-99.3% nucleotide identity). HFMD and herpangina showed differences in demographic data and serotypes of isolated enteroviruses, but there was no notable difference in amino acid sequences by clinical syndromes in multiple comparison of the partial VP1 gene sequence.