1995~2000년 예방접종 후 이상반응 사례 분석 - 국가보상 신청 사례와 예방접종 후 이상반응 감시체계 보고 사례를 중심으로 -

이홍주,손영모,김정순,김영택,이종구,최보율,Lee, Hong Jue,Sohn, Young Mo,Kim, Joung Soon,Kim, Young Taek,Lee, Jong Gu,Choi, Bo Youl 대한소아감염학회 2001 Pediatric Infection and Vaccine Vol.8 No.2

목 적 : 예방접종 사업의 안정화를 위해서는 발생된 이상반응이 적절하게 보고되고, 발견된 이상반응에 대하여 신속하고 정확한 원인 규명을 위한 역학조사를 시행하여 조사된 결과에 따라 적절하게 대응하는 것이 필요하다. 이에 연구자들은 1995년부터 2000년까지 국가 보상을 신청하거나 보고된 예방접종 후 이상반응 감시체계를 통해 보고된 이상반응 사례들을 수집하여 보고 사례와 국가 보상의 변화 양상과 사례의 역학적 특성을 파악하여 이상반응 감시체계의 개선 방향을 제시할 수 있는 기반을 마련하고자 하였다. 방 법 : 1995년부터 1996년까지 예방접종 후 이상반응에 대하여 국가보상신청을 하거나 국립보건원 방역과로 보고된 61건을 대상으로 국가보상 신청시 제출한 자료와 역학조사와 관련된 모든 자료들을 수집, 정리하여 사례들의 역학적 특성들을 파악하였으며, 역학조사 방법과 보상과 관련된 사항들에 대하여 정리 분석하였다. 결 과 : 연도별 보고 건수는 1995년 12명, 1996년 3명, 1998년 12명, 1999년 5명, 2000년 29명으로 총 61명이었으며, 이 중 사망자는 24명(39.3%)이고, 이 중 16명(66.7%)에서 부검이 시행되었다. 보상 심의를 신청한 경우는 36건(59.0%)이었는데, 이 중 17건(47.2%)이 보상받았고, 역학조사를 실시한 경우는 49건(80.3%)이었다. 보고 사례 중 보상 신청 사례는 1995~1998년에는 17건 중 15건(88.2%), 1999~2000년에는 38건 중 15건(76.3%)으로 감소하였으나, 심의 결과 보상을 받는 비율은 1995~1998년 26.6%에서 1999~2000년 53.3%로 증가하였다. 보고 사례 중 역학조사가 이루어진 경우는 1995~1998년에는 17건 중 14건(82.4%), 1999~2000년에는 38건 중 29건(76.3%)으로 역학조사를 실시하는 비율은 감소하였으나 반드시 역학조사가 필요하나 누락되는 경우는 개선되었다. 이상반응 발생을 인지한 후 역학조사에 착수하기까지의 소요시간이 1일 이내인 경우가 1995~1998년에는 전체의 25%에 불과하던 것이 1999년 이후에는 전체의 43.5%로 증가하였다. 전체 이상반응 발생에 있어 남녀간 차이는 보이지 않지만 사망자 21명만을 살펴보면 남자가 14명(66.7%), 여자가 7명(33.3%)으로 남자가 2배나 많았다. 연령별 분포는 정기예방접종이 집중되어 있는 생후 2개월부터 24개월까지가 전체의 75.4%를 차지하고 있다. 접종에서 발병까지의 기간은 전체의 78.4%가 접종 후 일주일 이내에 발생하였다. 결 론 : 보고체계 도입 이후 역학조사가 필요한 경우 대부분에서 조사가 시행되었고, 보고를 받고 신속하게 조사를 착수하는 비율이 증가한 것은 긍정적인 변화로 평가된다. 그러나, 전체적으로 보았을 때 외국에 비하여 감시체계를 통해 보고되는 사례 수가 매우 적어 이상반응의 역학적 양상을 파악함에는 제한점이 있다. 예방접종 사업의 안정성 확보라는 목표를 달성하기 위해서는 무엇보다 보고율 향상을 위한 노력이 경주되어야 할 것으로 생각된다. Purpose : To describe the characteristics of the claims for compensation and the methodology of investigations concerning adverse events following immunization(AEFI) and epidemiologic characteristics of the AEFI. From these results, to give a suggestion for improving AEFI surveillance system, consequently to stabilize National Immunization Program. Methods : Totally 61 cases were reported to the National Compensation Program and surveillance system of AEFI from 1995 to 2000. Documents from National Compensation Program, medical records and epidemiologic investigation reports of the cases were collected and analyzed. Results : The number of reported cases was 12 in 1995, 3 in 1996, 12 in 1998, 5 in 1999, and 29 in 2000, respectively. That of deaths was 24(39.3%) and 16 cases among them were autopsied(66.7%). That of claims for compensation was 36 and 17 cases among them were compensated(47.2%). The proportion of claim was lower in 1999~2000 than in 1995~1998, but proportion of compensation increased. Although proportion of investigation was lower in 1999~2000 than in 1995~1998, cases which were not epidemiologically investigated, decreased. The epidemiologic investigation launched within 24 hours after report increased from 25% in 1995~1998 to 48.3% in 1999~2000. Among reported cases, the number of boys was 31(50.8%), and 75.4% of subjects were from 2 months to 24 months old. 78.4% of adverse events occurred within one week after immunization. Conclusion : We can find that surveillance system of AEFI and quality of epidemiologic investigation has been somewhat improved. But, it seems that severe cases were more frequently reported than moderate or mild cases, and reporting rate was lower than that of other developed countries. We could not identify the detailed epidemiologic characteristics of AEFI due to these limitation of data. To achieve the stabilization of National Immunization Program, reporting rate and the quality of investigation should be improved.

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans

( Sujeong Kwon ),( Eun Ji E. Kim ),( Seung-jae V. Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.6

Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response (UPR^mt), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of C. elegans are usually conserved across phyla. Thus, understanding the mechanisms of mitochondria-mediated defense responses in C. elegans may provide insights into similar mechanisms in complex organisms, including mammals. [BMB Reports 2018; 51(6): 274-279]

Impact of COVID-19 Pandemic on Tuberculosis Preventive Services and Their Post-Pandemic Recovery Strategies: A Rapid Review of Literature

Jeong Yoolwon,민진수 대한의학회 2023 Journal of Korean medical science Vol.38 No.5

Background: Coronavirus disease 2019 (COVID-19) pandemic has disrupted tuberculosis (TB) care and prevention around the world. The aim of this study is to review literature on the impact of COVID-19 on TB preventive services and discuss their policy options during and after the pandemic. Methods: We conducted a rapid review of scientific literature on the impact of COVID-19 on TB preventive services and their recovery strategies. After conducting a line-by-line open coding, their codes were applied in the descriptive theme building process, which was guided by the End TB strategy. TB preventive measures were selected and classified into five analytical categories: 1) vaccination against TB, 2) detection and treatment of latent TB infection (LTBI), 3) screening and diagnostics, 4) active case finding and contact tracing, and 5) surveillance. Results: We identified 93 articles, of which 65 were research articles. During the pandemic, we observed decrease in Bacillus Calmette-Guérin (BCG) coverage, TB diagnostic services, case finding activities, and LTBI management. TB case detection was declined, which was not resumed to the pre-pandemic level after loosening the lock-down. Several recommendations were highlighted: 1) secure BCG stocks and its supply chains, 2) consider catch-up activities of routine immunization and LTBI screening, 3) maintain minimal TB health services, infection prevention and control, and surveillance, 4) leverage laboratory capacity and contact tracing mechanisms, 5) consider simultaneous testing for TB and COVID-19, and 6) Incorporate digital health technologies. Conclusions: Our findings and lessons learnt from the pandemic can aid in the development of future national TB control program.

The imitator of immune-tolerant chronic hepatitis B: A killer in disguise

Moon Haeng Hur,Jeong-Hoon Lee 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2

두경부암에서 면역회피 기전과 면역항암제 치료

장현(Hyun Chang) 대한두경부종양학회 2017 대한두경부 종양학회지 Vol.33 No.1

두경부 편평상피세포암은 전세계적으로 6번째로 흔하며 예후가 불량한 암종이다. 면역 감시는 두경부암의 발생과 진행을 억제하는 중요한 기전으로 알려져 있다. 두경부암세포는 면역 감시를 T세포의 관용을 유도하거나 체크포인트를 통한 T세포 기능을 억제하는 등의 방법으로 회피할 수 있다. 한편 진행성 두경부암 임상연구에서 체크포인트 억제제는 명확한 항종양효과를 입증하였다. 이처럼 면역항암제가 중요한 암치료 방법으로 떠오르는 이때에 본 종설은 두경부암의 면회회피 기전 및 임상적용근거에 대한 최근 지식을 정리하였다. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally with high morbidity and mortality. Immune surveillance is well recognized as an important mechanism to prevent development or progression of HNSCC. HNSCC can escape the immune system through multiple mechanisms including development of tolerance in T cells and inhibition of T-cell-related pathways, generally referred to as checkpoint inhibitors. Recent clinical trials have demonstrated a clear advantage in advanced HNSCC patients treated with immune checkpoint blockade. Right at the front of the new era of immunotherapy, we will review current knowledge of immune escape mechanisms and clinical implication for HNSCC.

Mesenchymal stem cells and cancer: Friends or enemies?

Hong, I.S.,Lee, H.Y.,Kang, K.S. Elsevier Science Publishers 2014 Mutation research Vol.768 No.-

<P>There is increasing evidence that mesenchymal stem cells (MSCs) have the ability to migrate and engraft into tumor sites and exert stimulatory effects on cancer cell growth, invasion and even metastasis through direct and/or indirect interaction with tumor cells. However, these pro-tumorigenic effects of MSCs are still being discovered and may even involve opposing effects. MSCs can be friends or enemies of cancer cells: they may stimulate tumor development by regulating immune surveillance, growth, and angiogenesis. On the other hand, they may inhibit tumor growth by inhibiting survival signaling such as Wnt and Akt pathway. MSCs have also been proposed as an attractive candidate for the delivery of anti-tumor agents, owing to their ability to home into tumor sites and to secrete cytokines. Detailed information about the mutual interactions between tumor cells and MSCs will undoubtedly lead to safer and more effective clinical therapy for tumors. In this article, we summarize a number of findings to provide current information on the potential roles of MSCs in tumor development; we then discuss the therapeutic potential of engineered MSCs to reveal any meaningful clinical applications. (C) 2014 Elsevier B.V. All rights reserved.</P>

Investigation of adverse events following bacille Calmette-Guérin immunization using immunization safety surveillance system in Korea Centers for Disease Control and Prevention

Eui Jeong Roh,Youn-Kyung Lee,이미희,Min-Kyoung Kim,Tae Eun Kim,이석구,정은희 대한백신학회 2020 Clinical and Experimental Vaccine Research Vol.9 No.2

Purpose: The report of adverse events following immunization (AEFI) in Korea has continued since 1994, and the most frequently reported cases of AEFI of Korea Centers for Disease Control and Prevention (KCDC) is bacille Calmette-Guérin (BCG). Meanwhile, various inoculation methods and strains have been used in the past 6 years in Korea. Therefore, we investigated AEFI of BCG by strain types and inoculation methods using immunization safety surveillance of KCDC. Materials and Methods: We reviewed BCG AEFIs registered in the KCDC from January 2013 to June 2018. Results: There were 336 AEFI cases during the period, and average time interval from vaccination to symptom onset was within 2 months. AEFI proportion was 6.4 cases per 100,000 doses for BCG percutaneous Tokyo strain, 41.6 cases per 100,000 doses of BCG intradermal Danish strain, and 25.9 cases per 100,000 doses of BCG intradermal Tokyo strain. Intradermal type was more reported AEFI than percutaneous type in the same strain. The most common adverse events were local reaction like BCG lymphadenitis and severe adverse reactions such as osteomyelitis or disseminated BCG disease were 0.1 to 0.2 cases per 100,000 doses which are correlated with the range of World Health Organization published AEFI rates. Conclusion: The AEFI reporting rate does not equal the actual proportion of AEFI occurrence. Because AEFI monitoring is a passive surveillance system, various factors might influence the number of events reported. Nevertheless, it is important to analyze BCG AEFI by vaccine strains and inoculation method using surveillance data of KCDC.

Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines

Kochhar, Sonali,Excler, Jean-Louis,Bok, Karin,Gurwith, Marc,McNeil, Michael M.,Seligman, Stephen J.,Khuri-Bulos, Najwa,Klug, Bettina,Laderoute, Marian,Robertson, James S.,Singh, Vidisha,Chen, Robert T Elsevier Ltd. 2019 Vaccine Vol. No.

<P><B>Abstract</B></P> <P>Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely <I>potential or known</I> AEFI and establish the optimal risk window(s); and (3) conducting “near real-time“ prospective monitoring for <I>unknown</I> clustering’s of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators.</P>

국가정보와 법의 지배 - 스파이 활동에 대한 국제법적 규율의 동향과 그 한계 -

한희원 동국대학교 비교법문화연구원 2021 比較法硏究 Vol.21 No.2