The impact of discontinuing single-room isolation of patients with vancomycin-resistant enterococci: a quasi-experimental single-centre study in South Korea.

OBJECTIVES: There is limited data on the effects of discontinuing single-room isolation while maintaining contact precautions, such as the use of gowns and gloves. In April 2021, our hospital ceased single-room isolation for patients with vancomycin-resistant enterococci (VRE) because of single-room unavailability. This study assessed the impact of this policy by examining the incidence of hospital-acquired VRE bloodstream infections (HA-VRE BSI). METHODS: This retrospective quasi-experimental study was conducted at a tertiary-care hospital in Seoul, South Korea. Time-series analysis was used to evaluate HA-VRE BSI incidence at the hospital level and in the haematology unit before (phase 1) and after (phase 2) the policy change. RESULTS: At the hospital level, HA-VRE BSI incidence level (VRE BSI per 1000 patient-days per month) and trend did not change significantly between phase 1 and phase 2 (coefficient -0.015, 95% confidence interval (CI): -0.053 to 0.023, P=0.45 and 0.000, 95% CI: -0.002 to 0.002, P=0.84, respectively). Similarly, HA-VRE BSI incidence level and trend in the haematology unit (-0.285, 95% CI: -0.618 to 0.048, P=0.09 and -0.018, 95% CI: -0.036 to 0.000, P = 0.054, respectively) did not change significantly across the two phases. CONCLUSIONS: Discontinuing single-room isolation of VRE-colonized or infected patients was not associated with an increase in the incidence of VRE BSI at the hospital level or among high-risk patients in the haematology unit. Horizontal intervention for multi-drug-resistant organisms, including measures such as enhanced hand hygiene and environmental cleaning, may be more effective at preventing VRE transmission.

Impact of carbapenem-targeted antimicrobial stewardship interventions: an interrupted time-series analysis.

BACKGROUND: The development of carbapenem-resistant Gram-negative bacilli (CR-GNB) is largely favoured by indiscriminate and prolonged carbapenem use, which is a significant contributing factor. AIM: To evaluate the impact of two carbapenem antibiotic stewardship programme interventions on both carbapenem prescriptions and the clinical isolation rates of CR-GNBs, using interrupted time-series analysis. METHODS: A time-series analysis was performed using data for carbapenem usage from a tertiary hospital in South Korea from January 2017 to July 2022. Two carbapenem antibiotic stewardship programme interventions were implemented sequentially: (i) a prospective audit and feedback (PAF) from November 2018 to April 2020 (intervention 1), and (ii) preauthorization from May 2020 to August 2020 (intervention 2). Monthly carbapenem usage and incidence of CR-GNB before and after each intervention were compared using an autoregressive integrated moving average model. FINDINGS: Implementation of PAF resulted in a significant reduction in carbapenem consumption, followed by an additional decrease after the preauthorization was implemented. The incidence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae increased after intervention 1, but there was a significant change from an increasing trend to a stationary trend after intervention 2. The incidence of carbapenem-resistant Pseudomonas aeruginosa, which had increased during the baseline period, became stationary after intervention 1. A significant decrease was observed in the incidence of carbapenem-resistant Acinetobacter baumannii during the implementation of intervention 1 and 2. CONCLUSION: This study emphasizes the importance of adopting comprehensive antibiotic management and rigorous infection control to prevent infections caused by antibiotic-resistant bacteria.

Risk of transmission of COVID-19 from healthcare workers returning to work after a 5-day isolation, and kinetics of shedding of viable SARS-CoV-2 variant B.1.1.529 (Omicron).

BACKGROUND: There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation. AIM: To evaluate the risk of transmission from healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable-virus shedding kinetics. METHODS: This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14th to April 3rd, 2022 in units with five or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022. FINDINGS: Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1-5 days after their return. Of these, nine (4%) had an epidemiologic link other than with the returning HCW, and nine (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (N = 32), the median time from symptom onset to negative conversion of viable virus was four days (95% confidence interval: 3-5). CONCLUSION: Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.

Protective effects of the phytogenic feed additive "comfort" on growth performance via modulation of hypothalamic feeding- and drinking-related neuropeptides in cyclic heat-stressed broilers.

Identification of alternatives to antibiotics in livestock and poultry is necessary. Fueled by consumer preferences, phytogenic feed additives are increasingly used in the food system; however, their mode of action is not well defined. Here, we used broiler chickens, in which appetite and feeding behavior regulation are controlled by complex mechanisms, to determine the effect of the phytogenic feed additive "comfort" (PFA-C) as well as its underlying molecular mechanisms on growth performance in heat-stressed broiler chickens. Heat stress significantly increased birds' core body temperature, water intake, and the hypothalamic expression of heat shock protein (HSP) 70, whereas it decreased feed intake, BW, and woody breast incidence. Phytogenic feed additive "comfort" supplementation downregulated the hypothalamic expression of HSP70, reduced core body temperature, increased feed and water intake, and improved BW in HS broilers. At molecular levels, the effect of PFA-C on growth performance seemed to be mediated by modulation of hypothalamic expression of melanocortin receptor 2, arginine vasopressin, aquaporin 2, and sodium and potassium-transporting ATPase subunit beta 1 polypeptides. In summary, PFA-C supplementation ameliorates heat stress productivity losses via a potential cytoprotective effect, reduction of hypothalamic intracellular stress, and modulation of hypothalamic feeding- and drinking-related polypeptide expression.

Identifi cation of the Underlying Genetic Factors of Skin Aging in a Korean Population Study.

Genetic polymorphisms may affect the molecular mechanisms underlying determination of skin type. So far, several genetic studies have been reported; however, very few studies have been conducted to examine the relationship between genotype and skin phenotypes. In this study, the genome sequences of individuals tested for five cosmetic characteristics (wrinkles, moisture content, pigmentation, oil content, and ensitivity) were determined, and we also conducted five genome-wide association studies (GWASs) to identify predictive markers. Some single-nucleotide polymorphisms (SNPs) within those genes were more frequent in individuals exhibiting stronger traits. GWASs revealed that two genome-wide significant SNPs within FCRL5 and OCA2 genes were associated with wrinkles and pigmentation, respectively (p < 5 × 10-8), and that genomewide SNPs in 21 genes (wrinkles: FCRL5, REEP3, ADSS, and SPTLC1; moisture: TBX4, TRPM3, CEMIP2, CTSH, and TTC39C; pigmentation: OCA2, NCLN, TNS1, CDC42BPA, HS3ST4, and UNCX; oil: SYN2, CNDP1, GAS6, INSR, and TNFRSF19; and sensitivity: CREB5) might be associated with five skin phenotypes. Among these, a genome-wide significant SNP (rs117381658) and the SNP located downstream of FCRL5, which encodes a member of the immunoglobulin receptor family, were associated with an increased risk of wrinkles (p = 1.52 × 10-8). The other genome-wide significant SNP (rs74653330) was associated with a decreased risk of pigmentation (p = 1.04 × 10-8), which is located in the coding region of OCA2 that encodes for a transporter of melanin. Our study reports genetic factors associated with skin cosmetology parameters in the Korean population. We hope our findings will provide a foundation for further genetic and molecular studies related to custom cosmetics. Based on these findings, the industry will be able to provide consumers with ingredients capable of palliating the lack of function associated in genes with SNPs.

An IFN-γ and TNF-α dual release fluorospot assay for diagnosing active tuberculosis.

OBJECTIVES: Currently available interferon (IFN)-γ-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-α-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-γ- and/or TNF-α-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-γ and TNF-α dual release fluorospot assay for active TB. METHODS: Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-γ- and TNF-α-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. RESULTS: A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70-93) and 70% (95% CI 61-79), respectively. The IFN-γ/TNF-α dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-γ single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). CONCLUSIONS: The fluorospot-based IFN-γ/TNF-α dual release assay appears to be a simple and useful test for diagnosing active TB.

Long-term performance of the IGRA to predict and prevent active tuberculosis development in HIV-infected patients.

To estimate the long-term performance of the interferon-gamma release assay (IGRA) in predicting active tuberculosis (ATB) development among human immunodeficiency virus (HIV) infected patients in an intermediate TB burden country. A retrospective cohort study was conducted. HIV-infected patients with 1 IGRA result but no current or previous ATB who had been retained in care for 1 year were enrolled and observed for ATB development from 2006 to 2016. Sixty-two IGRA-positive and 354 IGRA-negative patients were observed for a median period of 4.03 years. ATB incidence in IGRA-positive vs. negative patients was respectively 15.24/1000 person-years (py) (95%CI 4.15-39.02) vs. 0.67/1000 py (95%CI 0.01-3.68) (P = 0.001). The sensitivity, specificity and positive and negative predictive values of the IGRA were respectively 80.0% (28.4-99.5%), 85.9% (82.1-89.1%), 6.5% (4.0-10.2%) and 99.7% (98.4-99.9%). Among the 62 IGRA-positive patients, 25 were treated for latent tuberculous infection (LTBI) and 37 were not. Patients with LTBI treatment did not develop ATB, while four cases of ATB occurred among patients without LTBI treatment. Among the 257 IGRA-negative patients who received a follow-up IGRA, 34 (12.9%) patients converted to positive. No ATB developed in IGRA converters. Screening for LTBI using IGRAs and LTBI treatment can be useful to prevent ATB in an intermediate TB burden country. .

Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease in Korea and China. Although there is previous evidence of person-to-person transmission via direct contact with body fluids, the role of environmental contamination by SFTS virus (SFTSV) in healthcare settings has not been established. We therefore investigated the contamination of the healthcare environment by SFTSV. METHODS: We investigated the possible contamination of hospital air and surfaces with SFTSV transmission by collecting air and swabbing environmental surface samples in two hospitals treating six SFTS patients between March and September 2017. The samples were tested using real-time RT-PCR for SFTS M and S segments. RESULTS: Of the six SFTS patients, four received mechanical ventilation and three died. Five rooms were occupied by those using mechanical ventilation or total plasma exchange therapy in isolation rooms without negative pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained from fomites including stethoscopes, and 9 of 43 were obtained from fixed structures including doorknobs and bed guardrails. Some samples from fixed structures such as television monitors and sink tables were obtained in areas remote from the patients. SFTSV RNA was not detected in five air samples from three patients' rooms. CONCLUSIONS: Our data suggest that SFTSV contamination was extensive in surrounding environments in SFTS patients' rooms. Therefore, more strict isolation methods and disinfecting procedures should be considered when managing SFTS patients.

Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) virus has a variety of central nervous system (CNS) manifestations. However, there are limited data regarding SFTS-associated encephalopathy/encephalitis (SFTSAE) and its mechanism. METHODS: All patients with confirmed SFTS who underwent cerebrospinal fluid (CSF) examination due to suspected acute encephalopathy were enrolled in three referral hospitals between January 2013 and October 2016. Real-time RT-PCR for SFTS virus and chemokine/cytokines levels from blood and CSF were analysed. RESULTS: Of 41 patients with confirmed SFTS by RT-PCR for SFTS virus using blood samples, 14 (34%) underwent CSF examination due to suspected SFTSAE. All 14 patients with SFTSE revealed normal protein and glucose levels in CSF, and CSF pleocytosis was uncommon (29%, 4/14). Of the eight patients whose CSF was available for further analysis, six (75%) yielded positive results for SFTS virus. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) level in CSF were significantly higher than those in serum (geometric mean 1889 pg/mL in CSF versus 264 pg/mL in serum for MCP-1, p = 0.01, and geometric mean 340 pg/mL in CSF versus 71 pg/mL in serum for IL-8, p = 0.004). CONCLUSIONS: The CNS manifestation of SFTS as acute encephalopathy/encephalitis is a common complication of SFTS. Although meningeal inflammation was infrequent in patients with SFTSAE, SFTS virus was frequently detected in CSF with elevated MCP-1 and IL-8. These findings indicate that possible direct invasion of the CNS by SFTS virus with the associated elevated cytokine levels in CSF may play an important role in the pathogenesis of SFTSAE.

Molecular epidemiology and environmental contamination during an outbreak of parainfluenza virus 3 in a haematology ward.

BACKGROUND: Although fomites or contaminated surfaces have been considered as transmission routes, the role of environmental contamination by human parainfluenza virus type 3 (hPIV-3) in healthcare settings is not established. AIM: To describe an hPIV-3 nosocomial outbreak and the results of environmental sampling to elucidate the source of nosocomial transmission and the role of environmental contamination. METHODS: During an hPIV-3 outbreak between May and June 2016, environmental surfaces in contact with clustered patients were swabbed and respiratory specimens used from infected patients and epidemiologically unlinked controls. The epidemiologic relatedness of hPIV-3 strains was investigated by sequencing of the haemagglutinin-neuraminidase and fusion protein genes. FINDINGS: Of 19 hPIV-3-infected patients, eight were haematopoietic stem cell recipients and one was a healthcare worker. In addition, four had upper and 12 had lower respiratory tract infections. Of the 19 patients, six (32%) were community-onset infections (symptom onset within <7 days of hospitalization) and 13 (68%) were hospital-onset infections (≥7 days of hospitalization). Phylogenetic analysis identified two major clusters: five patients, and three patients plus one healthcare worker. Therefore, seven (37%) were classified as nosocomial transmissions. hPIV-3 was detected in 21 (43%) of 49 environmental swabs up to 12 days after negative respiratory polymerase chain reaction conversion. CONCLUSION: At least one-third of a peak season nosocomial hPIV-3 outbreak originated from nosocomial transmission, with multiple importations of hPIV-3 from the community, providing experimental evidence for extensive environmental hPIV-3 contamination. Direct contact with the contaminated surfaces and fomites or indirect transmission from infected healthcare workers could be responsible for nosocomial transmission.

MicroRNA-30a-5p (miR-30a) regulates cell motility and EMT by directly targeting oncogenic TM4SF1 in colorectal cancer.

PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, and many oncogenes and tumor suppressor genes are involved in CRC. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate gene expression. Previous studies have revealed that miRNAs regulate the development and progression of many cancers. In this study, we investigated the role of microRNA-30a-5p (miR-30a) in CRC and its unknown mechanisms. METHODS: qRT-PCR was used to detect miR-30a and TM4SF1 mRNA expression in CRC specimens and cell lines. CRC cell migration and invasion were assessed after transfection with miR-30a or TM4SF1 using wound healing and trans-well migration and invasion assays. Transmembrane-4-L-six-family protein (TM4SF1) was validated as a target of miR-30a in CRC through luciferase reporter assay and bioinformatics algorithms. Moreover, two EMT regulators, E-cadherin and VEGF, were also identified using Western blotting and immunohistochemistry. RESULTS: We found that miR-30a was down-regulated in CRC tumor tissues and cell lines, and miR-30a was inversely associated with advanced stage and lymph node metastatic status compared with normal tissues. miR-30a decreased migration and invasion in CRC cell lines, and miR-30a overexpression not only down-regulated TM4SF1 mRNA and protein expression, but also inhibited the expression of VEGF and enhanced expression of E-cadherin. We also showed that TM4SF1 was up-regulated in CRC tumor specimens compared with adjacent normal tissues, and TM4SF1 expression was significantly associated with advanced stage and lymph node status compared with adjacent normal tissues. CONCLUSIONS: These results suggest that miR-30a is an important regulator of TM4SF1, VEGF, and E-cadherin for CRC lymph node metastasis, a potential new therapeutic target in CRC.

Validation of the Korean National Healthcare-associated Infections Surveillance System (KONIS): an intensive care unit module report.

BACKGROUND: National surveillance data should be validated to identify methodological problems within the surveillance programme and data quality issues. AIM: To test the validity of healthcare-associated infection (HAI) rate data from the Korean National Healthcare-associated Infections Surveillance System (KONIS). METHODS: Records from intensive care units of 12 (14.8%) of 81 participating hospitals for January-March 2014 were examined. The validation team reviewed 406 medical records of 110 patients with 114 reported HAIs - including 34 urinary tract infections (UTIs), 57 bloodstream infections (BSIs) and 23 cases of pneumonia (PNEU) - and 296 patients with no reported HAIs during one-day visits conducted in August and September 2014. The reviewers' diagnosis of HAI was regarded as the reference standard; in ambiguous cases, the KONIS Steering Committee confirmed the diagnosis of HAI. FINDINGS: Sensitivity values for UTIs, BSIs and PNEU were 85.3%, 74.0% and 66.7%, and specificity values were 98.7%, 99.1% and 98.7%, respectively. Positive predictive values were 85.3%, 94.7% and 78.3%, and negative predictive values were 98.7%, 94.6% and 97.7%, respectively. Sensitivity for PNEU was lower than that for UTIs and BSIs. The hospitals participating in KONIS infrequently reported conditions that were not HAIs. Sensitivity for BSIs was lower in this study than in KONIS validation studies conducted in 2008 and 2010. CONCLUSIONS: KONIS data are generally reliable; however, sensitivity for BSIs exhibited a decrease. This study shows the need for ongoing validation and continuous training of surveillance personnel to maintain the accuracy of surveillance data.

Phenotypic changes of methicillin-resistant Staphylococcus aureus during vancomycin therapy for persistent bacteraemia and related clinical outcome.

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.

Incidence and differential characteristics of culture-negative fever following pancreas transplantation with anti-thymocyte globulin induction.

BACKGROUND: Limited data are available on the incidence and characteristics of culture-negative fever following pancreas transplantation (PTx) with anti-thymocyte globulin (ATG) induction. Our study aims to better define the features of culture-negative fever, so it can be delineated from infectious fever, hopefully helping clinicians to guide antibiotic therapy in this high-risk patient population. METHODS: We performed a retrospective cohort study of postoperative fever among 198 consecutive patients undergoing PTx at our center between August 1, 2004 and December 31, 2014. Fever was classified as culture-negative if there was neither a positive culture nor a documented clinical diagnosis of infection. RESULTS: Fever was identified in 113 patients; 66 were deemed to be infectious, 39 were culture-negative, and 8 were indeterminate. High body mass index of recipient (odds ratio 1.87, 95% confidence interval: 1.15-3.03, P = 0.011) was a significant factor associated with culture-negative fever in multivariate analysis. No patients with culture-negative fever were diagnosed with infiltrates or effusion on chest radiography. In addition, an increase in white blood cell count, C-reactive protein, and serum amylase was less prominent in culture-negative fever. Culture-negative fever developed most frequently at postoperative 7 or 14 days, showing a biphasic curve. CONCLUSION: Culture-negative fever develops in a substantial proportion of patients early after PTx. The awareness of the possibility and clinical features of post-transplant culture-negative fever might help clinicians to guide antibiotic therapy in this high-risk patient population, especially following ATG induction and early steroid withdrawal.

Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country.

Risk of stroke and transient ischaemic attack after herpes zoster.

We assessed the association of herpes zoster (HZ) with stroke/transient ischaemic attack (TIA) in the general population according to age with controlling risk factors for stroke, using a nationwide representative cohort. The study was based on a prospective dynamic cohort consisting of 1 million Koreans representing all age groups, genders and geographical areas in the Korea Health Insurance Database. New events of stroke/TIA and HZ were identified using the diagnostic codes in the International Classification of Diseases, tenth revision. The risk for stroke/TIA after HZ was compared with HZ-free stroke/TIA individuals according to age group. A total of 766 179 adults were followed up for 11 years from 2003. The incidence of the first-diagnosed HZ cases was 9.40 per 1000 person-years, and that of the first-diagnosed stroke/TIA cases was 9.77 per 1000 person-years. The risk for stroke/TIA was higher in patients who had previous HZ episodes than in those who had never experienced HZ (incidence rate ratio 1.90; 95% CI 1.85-1.95). In addition, this risk persisted for several years after HZ. The risk of stroke/TIA after HZ gradually decreased with age; adjusted hazard ratio (HR) 2.04 in 18- to 30-year-olds, HR 1.74 in 30- to 40-year-olds, HR 1.43 in 40- to 50-year-olds, HR 1.23 in 50- to 60-year-olds, HR 1.24 in 60- to 70-year-olds, and HR 1.29 in those >70 years old, after controlling risk factors for stroke/TIA. Our findings provide evidence that HZ carries an increased risk of stroke or TIA and that the effect of HZ on stroke decreases with increasing age.