Real-World Safety and Effectiveness of Fluticasone Furoate/Vilanterol in Patients with Asthma and/or Chronic Obstructive Pulmonary Disease: A Post-Marketing Study in Korea.

BACKGROUND AND OBJECTIVE: Fluticasone furoate/vilanterol (FF/VI; RELVAR ELLIPTA) is approved in Korea for patients with asthma or chronic obstructive pulmonary disease (COPD). This study evaluated the effectiveness and safety of FF/VI in Korean patients with asthma and/or COPD over a 6-year period. METHODS: This was an open-label, multicentre, observational, post-marketing surveillance study in patients newly treated with FF/VI (100 or 200 µg/25 µg once daily). Safety endpoints were the incidence of adverse events (AEs), including unexpected AEs/adverse drug reactions (ADRs) and serious AEs/ADRs. Effectiveness was assessed after 24 weeks by Global Physician Assessment (logistic regression) and forced expiratory volume in 1 s (FEV1; paired t-tests). RESULTS: Of the 3426 patients enrolled across 45 hospitals between July 2014 and June 2020, 3216 were included in the safety analysis (50.5% female; mean age ± standard deviation [SD]: 58.6 ± 16.3 years). Overall incidence of AEs was 30.9% (n = 992); 4.1% (n = 132) were ADRs. Serious AEs were reported in 4.1% (n = 132) of patients; 0.1% (n = 4) were ADRs. Of 1543 patients analysed for symptomatic improvement, 89.2% (n = 1377) improved, 9.4% (n = 145) were unchanged, and 1.4% (n = 21) worsened. Mean FEV1 (difference ± SD) increased significantly in patients with asthma (0.09 ± 0.29 L; p < 0.0001), COPD (0.11 ± 0.24 L; p = 0.0011), or both (0.05 ± 0.18 L; p = 0.0399), indicating improved lung function. CONCLUSION: In this real-world study, FF/VI administered to Korean patients was well tolerated and effective for the treatment of asthma and COPD. These results were consistent with other studies in Asian and global populations.

A Korean Post-Marketing Study of Abacavir/Dolutegravir/Lamivudine in Patients with HIV-1.

BACKGROUND: Abacavir/dolutegravir/lamivudine has been indicated in Korea since 2015 for treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination. This regulatory post-marketing surveillance (PMS) study evaluated the real-life safety and effectiveness of abacavir/dolutegravir/lamivudine in patients with HIV-1 in clinical practice in Korea. MATERIALS AND METHODS: This open-label post-marketing surveillance examined data from consecutive patients (aged ≥12 years) with HIV-1 infection receiving abacavir/dolutegravir/lamivudine according to locally approved prescribing information; treatment-naïve and treatment-experienced patients were permitted. Data regarding patient demographics, medical history, clinical characteristics, medications (HIV-1 related and concomitant), resource utilization and comorbidities were extracted from patient records over a 1-year treatment period. Outcomes included safety of abacavir/dolutegravir/lamivudine (primary endpoint) and real-life effectiveness according to physician's global assessment and the proportion of patients with plasma HIV-1 RNA count <50 copies/mL at 48 weeks. RESULTS: Of 663 patients treated with abacavir/dolutegravir/lamivudine at 27 centers in Korea (June 2015 - June 2021), 656 were eligible for the safety analyses and 484 for effectiveness analyses. Patients were mostly male (94.8%) mean age was 42.2 ± 14.0 years and mean weight was 68.1 ± 11.0 kg. Adverse events (AEs, n = 656 in total) were mostly mild in severity, with the most common being nasopharyngitis (7.9%), retching (7.5%), headache (4.9%). Of 121 adverse drug reactions (ADRs), the most frequent were retching (4.4%), headache (1.8%) and dizziness (1.7%). Of 55 serious AEs, the most frequent were anogenital warts (1.1%). Of 2 serious ADRs, nothing was unexpected, and both resolved. The risk of experiencing an AE while receiving abacavir/dolutegravir/lamivudine appeared to be especially increased in patients receiving concomitant medications for other conditions. Abacavir/dolutegravir/lamivudine effectively suppressed HIV-1 (96.1% of patients had plasma HIV-1 RNA <50 copies/mL), and 99.0% of patients showed symptom improvement based on physician assessment. CONCLUSION: Results of this PMS study showed that abacavir/dolutegravir/lamivudine administered as highly active antiretroviral therapy was well tolerated and effective in patients with HIV-1 infection.

Novel SARS-CoV-2 entry inhibitors, 2-anilinoquinazolin-4(3H)-one derivatives, show potency as SARS-CoV-2 antivirals in a human ACE2 transgenic mouse model.

The ongoing COVID-19 has not only caused millions of deaths worldwide, but it has also led to economic recession and the collapse of public health systems. The vaccines and antivirals developed in response to the pandemic have improved the situation markedly; however, the pandemic is still not under control with recurring surges. Thus, it is still necessary to develop therapeutic agents. In our previous studies, we designed and synthesized a series of novel 2-anilinoquinazolin-4(3H)-one derivatives, and demonstrated inhibitory activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and MERS-CoV in vitro. We then conducted in vivo studies using modified compounds that are suitable for oral administration. These compounds demonstrated no toxicity in rats and inhibited viral entry. Here, we investigated the in vivo efficacy of these drug candidates against SARS-CoV-2. Three candidate drugs, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (1), N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-dichlorophenyl)acetamide (2), and N-(7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-N-(3,5-difluorophenyl)acetamide (3) were administered orally to hACE2 transgenic mice at a dose of 100 mg/kg. All three drugs improved survival rate and reduced the viral load in the lungs. These results show that the derivatives possess in vivo antiviral efficacy similar to that of molnupiravir, which is currently being used to treat COVID-19. Overall, our data suggest that 2-anilinoquinazolin-4(3H)-one derivatives are promising as potential oral antiviral drug candidates against SARS-CoV-2 infection.

An Open-Label, Multicentre, Observational, Post-Marketing Study to Monitor the Safety and Effectiveness of Umeclidinium/Vilanterol in Korean Patients.

BACKGROUND: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period. METHODS: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 µg/25 µg) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician's evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement. RESULTS: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (<0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment. CONCLUSION: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

Identification of 3-Oxindole Derivatives as Small Molecule HIV-1 Inhibitors Targeting Tat-Mediated Viral Transcription.

The heterocyclic indole structure has been shown to be one of the most promising scaffolds, offering various medicinal advantages from its wide range of biological activity. Nonetheless, the significance of 3-oxindole has been less known. In this study, a series of novel 3-oxindole-2-carboxylates were synthesized and their antiviral activity against human immunodeficiency virus-1 (HIV-1) infection was evaluated. Among these, methyl (E)-2-(3-chloroallyl)-4,6-dimethyl-one (6f) exhibited the most potent inhibitory effect on HIV-1 infection, with a half-maximal inhibitory concentration (IC50) of 0.4578 µM but without severe cytotoxicity (selectivity index (SI) = 111.37). The inhibitory effect of these compounds on HIV-1 infection was concordant with their inhibitory effect on the viral replication cycle. Mode-of-action studies have shown that these prominent derivatives specifically inhibited the Tat-mediated viral transcription on the HIV-1 LTR promoter instead of reverse transcription or integration. Overall, our findings indicate that 3-oxindole derivatives could be useful as a potent scaffold for the development of a new class of anti-HIV-1 agents.

Optimization of 2-Aminoquinazolin-4-(3H)-one Derivatives as Potent Inhibitors of SARS-CoV-2: Improved Synthesis and Pharmacokinetic Properties.

We previously reported the potent antiviral effect of the 2-aminoquinazolin-4-(3H)-one 1, which shows significant activity (IC50 = 0.23 µM) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with no cytotoxicity. However, it is necessary to improve the in vivo pharmacokinetics of compound 1 because its area under the curve (AUC) and maximum plasma concentration are low. Here, we designed and synthesized N-substituted quinazolinone derivatives that had good pharmacokinetics and that retained their inhibitory activity against SARS-CoV-2. These compounds were conveniently prepared on a large scale through a one-pot reaction using Dimroth rearrangement as a key step. The synthesized compounds showed potent inhibitory activity, low binding to hERG channels, and good microsomal stability. In vivo pharmacokinetic studies showed that compound 2b had the highest exposure (AUC24h = 41.57 µg∙h/mL) of the synthesized compounds. An in vivo single-dose toxicity evaluation of compound 2b at 250 and 500 mg/kg in rats resulted in no deaths and an approximate lethal dose greater than 500 mg/kg. This study shows that N-acetyl 2-aminoquinazolin-4-(3H)-one 2b is a promising lead compound for developing anti-SARS-CoV-2 agents.

Synthesis and biological evaluation of 2-benzylaminoquinazolin-4(3H)-one derivatives as a potential treatment for SARS-CoV-2.

Despite the continuing global crisis caused by coronavirus disease 2019 (COVID-19), there is still no effective treatment. Therefore, we designed and synthesized a novel series of 2-benzylaminoquinazolin-4(3H)-one derivatives and demonstrated that they are effective against SARS-CoV-2. Among the synthesized derivatives, 7-chloro-2-(((4-chlorophenyl)(phenyl)methyl)amino)quinazolin-4(3H)-one (Compound 39) showed highest anti-SARS-CoV-2 activity, with a half-maximal inhibitory concentration value greater than that of remdesivir (IC50 = 4.2 µM vs. 7.6 µM, respectively), which gained urgent approval from the U.S. Food and Drug Administration. In addition, Compound 39 showed good results in various assays measuring metabolic stability, human ether a-go-go, Cytochromes P450 (CYPs) inhibition, and plasma protein binding (PPB), and showed better solubility and pharmacokinetics than our previous work.

A Korean Post-Marketing Surveillance Study of Dolutegravir Single-Agent Tablets in Patients with HIV-1.

BACKGROUND: The integrase strand transfer inhibitor dolutegravir has been indicated in Korea since 2014 for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. This regulatory post-marketing surveillance (PMS) study evaluated the real-life safety and effectiveness of dolutegravir in patients with HIV-1 in clinical practice in Korea. MATERIALS AND METHODS: This open-label PMS study examined data from consecutive patients (aged ≥12 years) with HIV-1 infection receiving dolutegravir according to locally approved prescribing information; treatment-naïve and treatment-experienced patients were permitted. Data regarding patient demographics, medical history, clinical characteristics, medications (HIV-related and concomitant), and comorbidities were extracted from patient records over a 1-year treatment period. Outcomes included the safety of dolutegravir (primary endpoint) and real-life effectiveness according to the Physician Global Assessment (PGA) and the proportion of patients with plasma HIV-1 RNA count <50 copies/mL at 48 weeks. RESULTS: Of 147 patients treated with dolutegravir at 18 centers in Korea (August 2014 - August 2020), 139 were eligible for the safety analyses and 75 for effectiveness analyses. Patients (mean age 47 years) were mostly male (92.8%) and received dolutegravir in combination with nucleoside reverse transcriptase inhibitor (70.5%) or protease inhibitors (21.6%). Adverse events (AEs) (n = 179 in total) were mostly mild in severity, with the most common being nasopharyngitis (5.0%), dyspepsia (5.0%), pruritus (4.3%), and rash (4.3%). Of 16 adverse drug reactions (ADRs), the most frequent were rash, diarrhea, headache, insomnia, and somnolence (1.4% each). Of 2 serious ADRs, only 1 (gastroenteritis) was unexpected, and both resolved. The risk of experiencing an AE while receiving dolutegravir appeared to be especially increased in patients receiving concomitant medications for other conditions. Dolutegravir effectively suppressed HIV-1 (93.3% of patients had plasma HIV-1 RNA <50 copies/mL), and 100% of patients showed symptom improvement based on physician global assessment. CONCLUSION: Results of this PMS study showed that dolutegravir administered as highly active antiretroviral therapy was well tolerated and effective in patients with HIV-1 infection.

Risk factors for unplanned extubation in ventilated neonates in South Korea.

PURPOSE: Although unplanned extubation (UE) is a common occurrence in neonatal intensive care units (NICUs), the factors influencing UE have not been clearly identified in South Korea. Therefore, we investigated the incidence of UE along with its risk factors among neonates in the NICU. DESIGN AND METHODS: This retrospective cohort study was conducted in a single NICU in B city. The electronic medical records of 137 ventilated neonates admitted between January 2017 and June 2018 were analyzed using an audit tool on extubation. Kaplan-Meier estimation and univariate and multivariate Cox proportional hazards models were used for statistical analyses. RESULTS: The rate of UE was 32.1%, with an incidence of 6.56 per 100 ventilation days during the 18-month study period. Risk factors for UE were the use of sedatives or analgesics; no re-fixation of the endotracheal tube (ETT); suction frequency; a high nurse-patient ratio; and working night shifts (weekdays 5 p.m. to 8 a.m.), weekends, or holidays. CONCLUSIONS: The rate of UE among neonates was found to be considerably higher than that of other countries. Among the various factors, nursing-related factors were most commonly associated with the risk of UE. APPLICATION TO PRACTICE: Various prevention strategies, including complete ETT fixation, maintaining ETT placement, a low nurse-patient ratio, and close observation of the ETT may help reduce UE in the NICU.

Design, synthesis and biological evaluation of 2-aminoquinazolin-4(3H)-one derivatives as potential SARS-CoV-2 and MERS-CoV treatments.

Despite the rising threat of fatal coronaviruses, there are no general proven effective antivirals to treat them. 2-Aminoquinazolin-4(3H)-one derivatives were newly designed, synthesized, and investigated to show the inhibitory effects on SARS-CoV-2 and MERS-CoV. Among the synthesized derivatives, 7-chloro-2-((3,5-dichlorophenyl)amino)quinazolin-4(3H)-one (9g) and 2-((3,5-dichlorophenyl)amino)-5-hydroxyquinazolin-4 (3H)-one (11e) showed the most potent anti-SARS-CoV-2 activities (IC50 < 0.25 µM) and anti-MERS-CoV activities (IC50 < 1.1 µM) with no cytotoxicity (CC50 > 25 µM). In addition, both compounds showed acceptable results in metabolic stabilities, hERG binding affinities, CYP inhibitions, and preliminary PK studies.

Viral and serological kinetics in Zika virus-infected patients in South Korea.

Zika virus is a mosquito-borne flavivirus that causes clinical symptoms similar to those observed in dengue and chikungunya virus infections. The Korea Centers for Disease Control and Prevention initiated laboratory testing using a real-time reverse transcription-polymerase chain reaction in January 2016. More than 1,000 suspected cases of infection were tested and nine were confirmed as imported cases of Zika virus infection from January to July 2016. The travel destinations of the infected individuals were Brazil, Philippines, Viet Nam, Guatemala, Puerto Rico, and the Dominican Republic. Phylogenetic analysis based on the partial envelope gene indicated that the viruses belonged to the Asian genotype circulating in South America. We further investigated the duration for which the viral RNA and virus-specific antibodies were detectable after the symptom onset. After the day of symptom onset, Zika virus was detectable until 6 days in serum, 14 days in urine and saliva, and 58 days in semen. Immunoglobulin M against Zika virus was detected as early as 2 days after the symptom onset and was maintained at these levels until 41 days, whereas Immunoglobulin G was detectable from 8 days after the symptom onset and was maintained until 52 days. These findings would help diagnostic laboratories improve their testing programs for Zika virus infection.

Comparison of the Epidemiological Aspects of Imported Dengue Cases between Korea and Japan, 2006-2010.

To compare the epidemiological characteristics of dengue cases imported by travelers or immigration in both Korea and Japan, we determined dengue incidence and related risk factors. During 2006-2010, 367 and 589 imported dengue cases were reported in Korea and Japan, respectively. In Korea, the presumptive origins for the dengue infections were Southeast Asia (82.6%), Southern Asia (13.9%), Eastern Asia (1.1%), South America (0.3%), Central America (0.3%), Africa (0.3%), and other countries (1.6%). In Japan, the origins of the infections were Southeast Asia (69.8%), Southern Asia (20.0%), Eastern Asia (1.7%), South America (2.5%), Central America (1.2%), Africa (1.2%), Oceania (2.4%), and other countries (1.2%). In both countries, more dengue cases were reported for men than for women (p < 0.01), and those aged 20-30 years accounted for > 60% of the total cases. The frequency of imported cases in summer and autumn (∼70% of total cases) was similar in both countries. This study demonstrates that there is a similar pattern of imported dengue cases in Korea and Japan. Therefore, there is a risk of an autochthonous dengue outbreak in Korea, as indicated by the recent outbreak in Japan in 2014.

Comparison of four serological tests for detecting antibodies to Japanese encephalitis virus after vaccination in children.

OBJECTIVES: Several different methods are currently used to detect antibodies to Japanese encephalitis virus (JEV) in serum samples or cerebrospinal fluid. These methods include the plaque reduction neutralization test (PRNT), the hemagglutination inhibition (HI) test, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA). The purpose of this study was to compare the performance of each method in detecting vaccine-induced antibodies to JEV. METHODS: The study included 29 children who had completed a primary immunization schedule with an inactivated vaccine against JEV derived from mouse brain (n = 15) or a live attenuated SA14-14-2 vaccine (n = 14). Serum samples were collected between 3 months and 47 months after the last immunization. The serum samples were tested by performing the PRNT, HI test, in-house IFA, and commercial ELISA. The antibody detection rates were compared between tests. RESULTS: All 29 serum samples were positive with the PRNT, showing antibody titers from 1:20 to 1:2560. The HI test showed positive rates of 86.7% (13/15) and 71.4% (10/14) in the inactivated and live attenuated vaccine groups, respectively. The results of the IFA for immunoglobulin (Ig)G were positive in 53.3% (8/15) of children in the inactivated vaccine group and 35.7% (5/14) in the live attenuated vaccine group. Neither the IFA nor ELISA detected JEV IgM antibodies in any of the 29 children. CONCLUSION: These results show that detection rates of vaccine-induced antibodies to JEV have a wide range (0-100%) depending on the testing method as well as the time since immunization and individual differences between children. These findings are helpful in interpreting serological test results for the diagnosis of Japanese encephalitis in situations where vaccines are widely administered.

Travel-Associated Chikungunya Cases in South Korea during 2009-2010.

OBJECTIVES: Chikungunya (CHIK) has been classified as a communicable disease group IV in South Korea since late 2010. Based on this, we investigated the extent of imported cases of CHIK in dengue-suspected individuals returning from dengue-endemic regions. METHODS: A total of 486 dengue-suspected serum samples were screened for CHIK by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Further RT-PCR-positive samples were used for the viral culture, and CHIK was subsequently confirmed by sequence analysis of the culture samples. RESULTS: Five out of 107 dengue-positive samples were found to be positive for CHIK and 15 out of 379 dengue-negative samples were found to be positive for CHIK by immunoglobulin M ELISA. Further, a CHIK virus was isolated from one of the two RT-PCR-positive sera by cell culture and confirmed by sequence analysis. CONCLUSION: The present study documents the first evidence of travel-associated CHIK infection in South Korea. Considering the intense international traffic between countries, our finding emphasizes the urgent need for active patient and vector surveillance for timely response to reduce the introduction of CHIK in Korea.

Epidemiologic features of animal bite cases occurring in rabies-endemic areas of Korea, 2005 to 2009.

OBJECTIVES: Human rabies is a reemerging infectious disease in Korea. There was no human rabies case for 14 years until the disease had reoccurred in 1999. To prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in Korea was conducted since 2005 as a part of a human rabies control program. The animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (PEP) guideline of the Korea Centers for Disease Control and Prevention. METHODS: Information of animal bite cases that occurred from 2005 to 2009 in rabies high-risk regions were collected by cooperation with Regional Public Health Centers in 18 cities/districts of rabies endemic areas. RESULTS: A total of 2458 animal bite cases were reported. Dogs accounted for 86% of animal bites and 67% of the animals were not vaccinated against rabies virus. For PEP, among rabies-vaccinated animals, 92.7% were observed for clinical signs and 1.4% underwent necropsy. Among unvaccinated animals, 72.7% were observed for clinical signs and 4.1% underwent necropsy. The remaining animals were not available for examination. Of the animal bite patients, 32.5% received PEP and 51.6% were treated by first aid or by washing the wound. CONCLUSIONS: Given that no human rabies cases were reported since 2005 and animal rabies was continuously reported in endemic areas of Korea, the human rabies control program implemented in 2005 appears to have a significant role in the prevention and control of human rabies.

Recent approaches targeting beta-amyloid for therapeutic intervention of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuropathological features comprising amyloid deposits and neuronal losses in brain. In AD, aggregation of a ß amyloid peptide (Aß), produced from proteolytic cleavage of amyloid precursor protein, is believed to be implicated in the pathophysiological cascade leading to neuronal death. Most AD drugs currently available can only alleviate symptoms rather than modify the underlying molecular cause of AD. In this review, we describe and discuss the recent patents issued within the past two years focusing on therapeutic interventions targeting at various Aß-associated pathological mechanisms of AD. The described therapeutic strategies include 1) reduction of synthesis of Aß, 2) inhibition of Aß aggregation, 3) immunotherapeutic/enzymatic clearance of Aß, 4) targeting other amyloidogenic proteins interacting with Aß and 5) amelioration of Aß downstream toxic effects. Important issues to be considered for further improvement of therapeutic efficacy of these approaches are also discussed.

Development and field evaluation of a nested RT-PCR kit for detecting Japanese encephalitis virus in mosquitoes.

A novel nested reverse transcription-polymerase chain reaction (RT-PCR)-based kit is described for detecting Japanese encephalitis virus (JEV), especially for genotype 1 and 3 strains. The assay consists of a first round RT-PCR and a subsequent nested PCR amplification. It has unique features such as the use of a premix system in which all reagents are lyophilized in reaction tubes and the inclusion of control RNA in each reaction to monitor false negative results. In addition, an automatic tissue homogenizer and a RNA extraction system are used concurrently for assay standardization and increasing throughput. The assay using the kit proved specific for JEV with no amplification of other JEV-related flaviviruses. The detection limits were approximately 0.1 PFU/ml and 1 PFU/ml for JEV genotypes 1 and 3, respectively. The assay protocol has been validated in large-scale field trials in South Korea during the 2008-2009 surveillance seasons. Nineteen of 1136 pools of mosquitoes (54,583 mosquitoes total) were identified as JEV positive. This nested RT-PCR kit combined with control RNA and an automatic RNA extraction system should be suitable for routine JEV surveillance programs.

Identification of Dengue Type 1 Virus (DENV-1) in Koreans Traveling Abroad.

OBJECTIVES: To date, no indigenous dengue virus (DENV) transmissions have been reported in Korea. However, imported dengue infections have been diagnosed in travelers returning from endemic areas. This study presents the first virological evidence of travel-associated DENV importation into South Korea. METHODS: From January 2004 to June 2006, a total of 278 serum samples from 245 patients with suspected dengue fever were tested using the Panbio Dengue Duo IgM/IgG Rapid Strip Test. We selected 11 of the early symptomatic-phase sera that were negative for IgM and retrospectively studied them by virus isolation and reverse transcription-polymerase chain reaction. RESULTS: All 11 serum samples were found to be DENV positive by reverse transcription-polymerase chain reaction and viruses were successfully isolated from seven of the 11 serum samples. All the isolates were identified as DENV serotype-1. CONCLUSION: We successfully isolated seven DENV serotype-1 strains for the first time in South Korea from imported infections. Considering that the vector mosquito, Aedes albopictus, already exists in South Korea, we propose that a vector surveillance program for dengue is urgently needed.

Serum MicroRNA Expression Profiling in Mice Infected with Rabies Virus.

OBJECTIVES: Serum or plasma microRNAs (miRNAs) are potential biomarkers for the diagnosis for cancer and prenatal diseases. This study was conducted to investigate whether rabies virus causes a change in serum miRNA expression. METHODS: ICR mice were intramuscularly inoculated with rabies virus and were sacrificed weekly to collect serum and brain tissue for 4 weeks postinoculation. Mice were assigned to four groups based on the results of indirect immunofluorescent assays, enzyme-linked immunosorbent assay, and nested reverse transcription-polymerase chain reaction and the expression profiles of serum miRNAs were compared using a commercial mouse miRNA expression profiling assay. RESULTS: The expression levels of miRNAs changed significantly with the different stages of the disease. The expression level of 94 serum miRNAs in infected mice changed at least twofold. Seven microRNAs of them were significantly upregulated or downregulated in all infected mice regardless of disease status. The number of miRNAs with an expression level change decreased with the progression of the disease. In a hierarchical cluster analysis, infected mice clustered into a group separate from uninfected control mice. CONCLUSIONS: Based on the relationship of miRNAs to gene expression regulation, miRNAs may be candidates for the study of viral pathogenesis and could have potential as biomarkers.

Molecular epidemiology of Japanese encephalitis virus circulating in South Korea, 1983-2005.

We sequenced the envelope (E) gene of 17 strains of the Japanese encephalitis virus (JEV) isolated in South Korea in 1983-2005 and compared the sequences with those from previously reported strains. Our results show the remarkable genetic stability of the E gene sequence in Korean JEV strains. Five pairs of E gene sequences from 10 Korean strains were identical, despite geographical differences and a maximum five-year time span. Sequence comparisons with other Asian strains revealed that the Korean strains are closely related to those from China, Japan, and Vietnam. Genotype 3 strains were predominant in Korea before 1993, when genotype 1 strain K93A07 was first isolated. The two genotypes were detected simultaneously in 1994 but since then, only genotype 1 has been isolated in South Korea. Thus, the genotype change occurred according to the year of isolation rather than the geographical origin.