Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

개선된 사람 혈장중 세파클러 농도 정량법을 이용한 세파클러 캡슐의 생체이용률 측정

김태완,송옥경,한선영,Cao, Qing-Ri,박미진,강성화,신관석,Cui, Jing-Hao,이범진 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2

After establishing improved HPLC analytical method ofcefaclor in human plasma samples, a bioavailability study of cefaclor capsules was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). The standard calibration curve using an HPLC with UV detector was constructed in a range of 0.0324--16 μg/m1. The 6% perchloric acid instead of 6% trichloroacetic acid was used to precipitate plasma protein. The HPLC chromatograms were precisely and accurately resolved when spiked with human plasma spiked with cefaclor and cephalexin (internal standard). Twenty healthy male Korean volunteers received two commercial cefaclor capsules, Neocef ' capsule (Jinyang Pharm. Co., Ltd) or Ceclor" capsule {Lilly Korea. Co., Ltd.) at the 250 mg cefaclor in a 2 x 2 crossover study. There was a one-week washout period between the doses. Plasma concentrations of cefaclor were monitored for 8 hours after oral drug administration. AUC, the area under the plasma concentration-time curve from time zero to 8 hr (13 points), was calculated by the linear trapezoidal rule method. C,,,a" (maximum plasma drug concentration) and Tmax (time to reach Cma,) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC, and Cmax. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the AUC, ratio and the Cmax ratio for Neocer/Ceclor" were 0.9049 S S < 1.0304 and 0.9776 5 S 1.226, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of Neocef"/Ceclor" with respect to the extent of absorption.

인간 면역부전 바이러스(HIV) 감염자 사이에서의 1기 및 2기 매독의 유행

장희창,조재현,박완범,이기덕,이창섭,김홍빈,오명돈,최강원 대한감염학회 2004 감염과 화학요법 Vol.36 No.6

목적 : 국내 HIV 감염자 사이에서 발생한 매독의 유행을 보고하고, 그 역학적 특성을 규명하고자 하였다. 재료 및 방법 : 1999년 7월부터 2003년 9월까지 서울대학교 병원에서 추적 관찰을 받아온 HIV 감염자를 대상으로 하여 1기 및 2기 매독의 발생을 조사하였다. 발생률을 정확히 구하기 위해 추적 관찰을 받은 모든 HIV 감염자의 인년을 6개월 간격으로 구하였다. 결과 : 51개월 동안, 465명의 HIV 감염자가 서울대학교 병원에서 추적 관찰을 받았다. 이중 38명이 1기 및 2기 매독으로 진단되었다. 1기 및 2기 매독의 발생률은 이기간 동안 100인년 당 4.1명이었다. 1999년 7월부터 2001년 12월 사이에는 발생자가 없었으나, 이후 발생률은 꾸준히 증가하여 2003년 9월에는 100인년 당 18.8명이 되었다. 1기 및 2기 매독의 발생률은 동성애자 및 양성애자에서 이성애자에서보다 4.3배 높았고, HAART로 치료를 받지 않은 환자에서 HAART로 치료를 받고 있던 환자에서 보다 10.9배 높았다. 결론 : 2002년부터 국내 HIV 감염자 사이에서 1기 및 2기 매독이 유행하기 시작하였고, 이러한 유행은 동성애자와 양성애자 및 HAART로 치료를 받고 있지 않던 사람 사이에서 발생하였다. Background : This study was performed to characterize the epidemiologic and clinical features of outbreak of syphilis among HIV sero-positive patients in Korea. Materials and Methods : A retrospective case review of patients diagnosed with primary and secondary syphilis from July 1999 to September 2003 was carried out at Seoul National University Hospital in Korea. To estimate the incidence, person-years (PYs) of all HIV sero-positive patients, who visited the hospital in the same period, were calculated every 6 months. Results : In a 51 month period, 465 HIV-positive patients were followed up at Seoul National University Hospital. 38 cases of primary and secondary syphilis were diagnosed. The incidence of primary and secondary syphilis was 4.1 per 100 PYs during the study period. There was no case from July 1999 to December 2001, and then the incidence rose until September 2003 from 5.5 per 100 PYs in 1999 to 18.8 per 100 PYs in 2003. The rate of primary and secondary syphilis was 4.3 times higher among homosexual and bisexual men than heterosexual men (95% CI 1.87 to 11.17), and 10.9 times higher among patients who did not receive HAART than patients who were receiving HAART (95% CI 5.47 to 21.79). Conclusion : The outbreak of primary and secondary syphilis among HIV-positive patients started in 2002 and has been escalating, especially among homosexual/bisexual men and in patients who did not receive HAART.

국내 의료기관의 항생제 사용 실태와 규제 시스템 조사

방지환,송경호,박완범,김성한,조재현,김홍빈,김남중,오명돈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

목적 : 이전 연구들에 따르면 아직까지 국내에서 불필요한 항생제 사용은 무시할 수 없는 수준이며, 특히, 수술환자들에 대한 예방적 항생제 투여가 문제로 지적되고 있다. 많은 병원에서 불필요한 항생제 처방을 제한하려는 노력을 하고 있지만 구체적인 현황에 대한 자료는 적은 실정이다. 이에 본 연구자 등은 국내 의료기관의 항생제 규제 시스템의 현황과 수술시 예방적 항생제 사용의 적정성을 알아보고자 한다. 재료 및 방법 : 전임 감염내과 전문의가 근무하는 의료기관 55곳에 대해 설문조사를 시행하였다. 설문의 내용은 적정한 항생제 사용을 유도하기 위한 정책 및 규제 프로그램, 실제 각 의료기관의 예방적 항생제 사용 현황 등으로 이루어져 있다. 결과 : 55개의 의료기관에 보낸 설문 중 44개가 회수되었다. 회신한 의료기관에서 항생제 처방 관리는 제한항생제 시스템을 가장 많이 이용하고 있었고(95.5%), 항생제에 대한 교육(79.5%), 전산시스템에서 관리(59.1%), 감염내과에 의뢰(54.5%), 항생제 사용 실적 검토(52.3%) 등의 순이었다. 대개의 병원에서 glycopeptides (100.0%), carbapenems (93.0%), quinupristin/dalfopristin 또는 linezolid(93.0%), 4세대 cephalosporin (74.4%), caspofungin 또는 voriconazole (62.8%), liposomal amphotericin B (60.5%) 등을 제한항생제로 분류하여 관리하고 있었다. 모든 의료기관에서 위절제술 및 유방절제술시에 불필요하게 예방적 항생제를 사용하고 있었다. 슬관절치환술의 경우 2세대 cephalosporin을 예방적으로 사용하는 경우가 가장 많았으며(30.2%), 관상동맥우회술의 경우 3세대 cephalosporin을 예방적으로 사용하는 경우가 가장 많았다(47.2%). 예방적 항생제의 투여 기간을 살펴보면 위절제술시 70.5%에서 4일을 초과하여 사용하고 있었고, 유방절제술시에는 63.6%에서, 슬관절치환술시에는 81.8%에서, 관동맥우회술시에는 81.1%에서 4일을 초과하여 장기간 예방적 항생제를 투여하고 있었다. 한편, 예방적 항생제 투여시 aminoglycoside계 항생제를 병용하는 경우도 많았다. 결론 : 아직까지 국내 의료기관에서 항생제 오남용을 막기 위한 노력이 더 필요할 것으로 생각되며, 특히 수술시 예방적 항생제의 올바른 투여에 많은 관심이 필요하다. Background : Previous studies in Korea showed that unnecessary antibiotic use could not be neglected, especially in prophylactic use. Currently many hospitals employ diverse antibiotic stewardship programs, but there are few studies on surveillance of such programs. So, we planned this study to evaluate current status of antimicrobial stewardship and adequacy of antimicrobial prophylaxis in surgery. Materials and Methods : We sent questionnaires about policy on antibiotic usage, control program for adequate antibiotic prescription, and actual status of prophylactic antibiotic usage to 55 infectious disease physicians in each hospital. Results : Of 55 contacted infectious diseases clinicians, 44 answered the questionnaire. Majority of hospitals employed restricted antimicrobial system (95.5%), education (79.5%), control by order communicating system (59.1%), consult to infectious disease physicians (59.1%), and review of cumulative antimicrobial usage (52.3%) to prevent inadequate antibiotic use. Glycopeptides were designated as a restricted antimicrobial agent in 100.0% of hospitals; carbapenems, 93.0%; quinupristin/ dalfopristin or linezolid, 93.0%; the 4th generation cephalosporins, 74.4%; caspofungin or voriconazole, 62.8%; liposomal amphotericin B, 60.5%, and so on. Unnecessary perioperative prophylactic antimicrobial agents were prescribed in gastrectomy and mastectomy in all the hospitals. The second generation cephalosporins and the third generation cephalosporins were the most commonly prescribed prophylactic antimicrobial agents in total knee replacement arthroplasty (TKRA) and coronary artery bypass graft surgery (CABG) respectively. In 70.5% of institutes they use prophylactic antimicrobial agents more than four days in gastrectomy; 63.6% in mastectomy; 81.8% in TKRA; 81.1% in CABG. Unnecessary combination of aminoglycosides with other antimicrobial agents for prophylactic use was another common problem. Conclusion : This study shows that more effort is required to diminish antimicrobial misuse or overuse, especially in prophylactic use for surgical patients.

철근 콘크리트 전단벽과 강재 보 전단접합부의 내진거동

이원호,윤현도,강대언,송한범,태경훈,박완신 대한건축학회 2004 대한건축학회 학술발표대회 논문집 - 계획계/구조계 Vol.24 No.1(구조계)

Ductile coupled flexural wall is the primary seismic load resisting system of buildings. In these systems, connections are generally headed stud bolt connection. The purpose of experimental study is to evaluate the seismic behavior of these connection under cyclic loading. A comprehensive experimental test involving 4 specimens has been performed and this program is used to study the effect of value of moment and edge distance. Through experimental test, the seismic behavior of typical headed stud bolt connections was established.

골수구성 백혈병 환자에게 발생한 결핵성 림프절염

이창섭,송진수,최평균,조재현,방지환,박경화,박완범,김홍빈,김남중,윤성수,박선양,김병국,오명돈,최강원 대한감염학회 2006 감염과 화학요법 Vol.38 No.5

혈액질환 가운데 결핵 발생이 증가한다고 알려진 것은 호지킨 림프종을 포함한 림프증식성질환 그리고 모양세포성 백혈병 등이 있다. 또한 동종 골수이식을 받은 환자에서도 결핵은 증가한다고 알려져있다. Kaplan 등은 골수구성 백혈병 환자에서 결핵 발생이 증가한다고 보고하였다. 그러나 골수구성 백혈병 환자에서 결핵의 발생이 증가하는 이유에 대해서는 아직까지 정확하게 밝혀지지 않았다. 저자들이 2년 동안 후향적으로 조사한 180명의 성인 골수구성 백혈병 환자들 가운데 결핵이 발생한 환자는 4명이었고, 발생 부위는 모두 림프절이었다. 결핵은 골수구성 백혈병의 특정 아형에만 국한되어 발생하지 않았지만, 50%에서 FAB 분류에 의한 M4였다. 림프절이 종대된 골수구성 백혈병 환자에서 특히, 결핵의 유병율이 높은 나라에서는 결핵성 림프절염도 감별진단에 포함시켜야 한다. During the neutropenic phase, leukemia patients receiving chemotherapy are prone to bacterial and, fungal infections; occasionally mycobacterial, viral and protozoal organisms may also cause infections. Mycobacterium tuberculosis infection was reported very rarely in these patients. This report describes four patients with M. tuberculosis infection identified from 185 adult patients who were diagnosed myelogenous leukemia between January 2003, and December 2004. There was no patient with M. tuberculosis infection from 44 lymphoid leukemia and 11 acute biphenotypic leukemia patients. Sites of infection were all lymph nodes. Three among four patients were presented with lymphadenopathy at initial diagnosis of leukemia, and the other one presented with lymphadenopathy after induction chemotherapy. There was no patient presented with lymphadenopathy during the neutropenic phase. Tuberculous lymphadenitis was presented in a patient with three acute myelogenous leukemia (FAB class 2 M4, 1 M2) and a chronic myelogenous leukemia, accelerated phase. An acute myelogenous leukemia patient had a leukemic cell and tubercle bacilli in the same lymph node. Tuberculosis should also be included as a differential diagnosis in myelogenous leukemia patient with lymphadenopathy, especially in the countries in which the disease is endemic.

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19

Park Do Hyeon,Lee Eunyoung,Jung Jongtak,Kang Chang Kyung,Song Kyoung-Ho,Choe Pyoeng Gyun,Park Wan Beom,Bang Ji Hwan,Kim Eu Suk,Kim Hong Bin,Park Sang-Won,Kim Nam Joong,Oh Myoung-don 대한의학회 2022 Journal of Korean medical science Vol.37 No.16

Background: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). Methods: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. Results: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. Conclusion: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.

Replicative virus shedding in the respiratory tract of patients with Middle East respiratory syndrome coronavirus infection

Park, Wan Beom,Poon, Leo L.M.,Choi, Su-Jin,Choe, Pyoeng Gyun,Song, Kyoung-Ho,Bang, Ji Hwan,Kim, Eu Suk,Kim, Hong Bin,Park, Sang Won,Kim, Nam Joong,Peiris, Malik,Oh, Myoung-don Elsevier 2018 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Vol.72 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Information on the duration of replicative Middle East respiratory syndrome coronavirus (MERS-CoV) shedding is important for infection control. The detection of MERS-CoV sub-genomic mRNAs indicates that the virus is replicative. This study examined the duration for detecting MERS-CoV sub-genomic mRNA compared with genomic RNA in diverse respiratory specimens.</P> <P><B>Methods</B></P> <P>Upper and lower respiratory samples were obtained from 17 MERS-CoV-infected patients. MERS-CoV sub-genomic mRNA was detected by reverse transcription PCR (RT-PCR) and MERS-CoV genomic RNA by real-time RT-PCR.</P> <P><B>Results</B></P> <P>In sputum and transtracheal aspirate, sub-genomic mRNA was detected for up to 4 weeks after symptoms developed, which correlated with the detection of genomic RNA. In oropharyngeal and nasopharyngeal swab specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate.</P> <P><B>Conclusions</B></P> <P>These findings suggest that MERS-CoV does not replicate well in the upper respiratory tract.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Middle East respiratory syndrome coronavirus (MERS-CoV) sub-genomic mRNAs indicates that the virus is replicative. </LI> <LI> Sub-genomic mRNA was detected in lower respiratory tract specimens for up to 4 weeks after symptoms developed. </LI> <LI> In upper respiratory tract specimens, the detection of sub-genomic mRNA and genomic RNA did not correlate. </LI> </UL> </P>

Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak

Park, Wan Beom,Kwon, Nak-Jung,Choe, Pyoeng Gyun,Choi, Su-Jin,Oh, Hong Sang,Lee, Sang Min,Chong, Hyonyong,Kim, Jong-Il,Song, Kyoung-Ho,Bang, Ji Hwan,Kim, Eu Suk,Kim, Hong-Bin,Park, Sang Won,Kim, Nam Jo The Korean Academy of Medical Sciences 2016 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.31 No.2

<P>During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.</P>

COVID-19 Vaccination in Korea

Park Wan Beom,Hwang Young Hoon,Cheong Hee Jin 대한감염학회 2023 Infection and Chemotherapy Vol.55 No.1

Since December 2020, various coronavirus disease 2019 (COVID-19) vaccines have been developed and approved. As of February 2023, mRNA vaccines including bivalent vaccines (Pfizer/BioNTech, Moderna), recombinant protein vaccines (Novavax, SK Bioscience), and viral vector vaccines (AstraZeneca, Janssen) have been approved in Korea. COVID-19 vaccination can effectively reduce hospitalization and deaths due to symptomatic COVID-19, especially severe and critical COVID-19. The primary series vaccination against COVID-19 is recommended for all adults aged ≥18 years in Korea. Booster vaccination with the bivalent mRNA vaccine is available for those ≥12 years who have completed the primary series vaccination, regardless of the type of vaccine previously received, and is recommended for all adults. Booster vaccination can be administered since 90 days after the last dose. Localized and systemic adverse events following COVID-19 vaccination are relatively common and more frequently documented in younger age groups. Rare but potentially serious specialized adverse reactions include anaphylaxis, thrombosis with thrombocytopenia syndrome, myocarditis, and Guillain-Barré syndrome. Previous severe allergic reactions, such as anaphylaxis, to any COVID19 vaccine or vaccine component are considered a contraindication for vaccination. The indications and schedule for COVID-19 vaccination are subject to change based on further research results and the COVID-19 pandemic.