2 제 8 권제 1 호 있는질환이다. 국내비만유병률에대한국민건강영양조사의결과보고서에따르면최근 3년간남녀각각 36% 및 26% 수준으로유지되고있으며, 이러한비만은단순한개인의신체적문제뿐아니라당뇨, 고혈압, 관상동맥등주요만성복합질환의위험요인이기때문에더욱위험한질환이라볼수있다.

Transcription

1 KOREA CENTER FOR KOREA CENTER FOR DISEASE DISEASE CONTROL&PERVENTION CONTROL&PREVENTION 주간건강과질병 KOREA CENTER FOR DISEASE CONTROL&PREVENTION ISSN: X 제 8 권제 1 호 공복혈당및당뇨, 비만관련형질에대한전장유전체연관성연구 Genomic Association Study on FPG, T2D and Obesity-Related Traits 질병관리본부국립보건연구원유전체센터형질연구과 황주연, 김봉조 1) Abstract BACKGROUND: Diabesity (diabetes and obesity) is a growing public health problem with an escalating global epidemic of overweight and obesity. Their apparent inseparability has led to multiple confounding effects on phenotypic variance. CURRENT STATUS: Majority of current GWAS have focused on individual genetic variation to a single trait or target phenotype. In fact, the results have been limited in terms of their ethnic difference and causal inference. However, some genes or loci might contain genetic pleiotropy that contributes to the overall disease susceptibility, despite the genetic heterogeneity between physiological and pathological entities. PROSPECTIVE FUTURE: However, it remains unclear whether the established obesity susceptibility loci have BMI-independent or mediated on T2D risk. This study is expected to broaden the understanding on the overall genetic architecture in metabolic and endocrine regulation. Ⅰ. 들어가는말 전세계성인인구 10 명중두명에해당하는비만은사회적인 심각한건강문제로서, 최근 글로비서티 (Globesity = global + obesity) 라는신조어가생기게될만큼성별, 인종, 사회적 신분이나교육수준과크게상관없이지속적으로증가추세에 CONTENTS 0001 공복혈당및당뇨, 비만관련형질에대한전장유전체연관성연구 년유럽항균제내성감시 0010 생물테러대비개인보호장비의적정비축방안 0013 주요통계 : 인플루엔자의사환자분율 / 호흡기바이러스발생환자분율 / 가을철발열성질환발생환자현황 1) 교신저자 (kbj6181@cdc.go.kr/ )

2 2 제 8 권제 1 호 있는질환이다. 국내비만유병률에대한국민건강영양조사의결과보고서에따르면최근 3년간남녀각각 36% 및 26% 수준으로유지되고있으며, 이러한비만은단순한개인의신체적문제뿐아니라당뇨, 고혈압, 관상동맥등주요만성복합질환의위험요인이기때문에더욱위험한질환이라볼수있다. 2002년국제햅맵프로젝트 (International HapMap Project) 및 2003년인간게놈프로젝트 (Human Genome Project) 와더불어 2008년에시작된 1000 지놈프로젝트 (The 1000 Genomes Project) 에이르기까지구축된대용량의인간참조유전체정보를이용하여다양한질환을대상으로유전체연구가이루어져왔으며, 대규모의데이터확장을위한각국가별코호트연구프로젝트간의컨소시엄이나네트워크구성을통한통합메타연구가활발히진행중이다. 이글에서는현재질병관리본부국립보건연구원유전체센터의형질연구과에서최근수행한공복혈당수치관련유전요인발굴을위한전장유전체연관분석연구를중심으로기술하고자한다 [1]. 즉비만인사람이당뇨위험에노출되어있는것은사실이지만당뇨환자라고해서반드시비만이거나반대로비만인사람이전부당뇨환자는아니라는것을보여준다. 또한 Y-Y paradox[2] 처럼같은체질량지수 (Body Mass Index, BMI) 를가진사람이라하더라도복부비만도에따라질환위험도양상이서로다르게나타나기도한다 (Figure 1). 마찬가지로, 당뇨병진단의주요변수로잘알려진공복혈당수치 (Fasting Plasma Glucose, FPG) 도당뇨에비의존적으로심혈관및대사질환과밀접하게연관되어있다. 최근유전체연구동향을살펴보면전장유전체연관분석 (Genome-Wide Association Study, GWAS) 및메타분석 (meta analysis) 을통해당뇨및비만관련각 70여개의유전변이가보고되었으나, 대부분이유럽인을대상으로연구가진행되었으며특히당뇨와의독립성이나다중연관성이규명된연구사례는아직부족한실정이다 [3](Table 1). 현재까지보고된당뇨관련유전변이 (genetic loci) 의대부분은당뇨에걸릴위험률이증가하는방향이지만상대적으로공복혈당수치도높게 나타나는경우는적다 (Table 2). 즉당뇨위험과공복혈당수치간에 유전영향방향성 (genetic effect direction) 이다른양상을 II. 몸말 비만은여러만성질환중특히제2형당뇨병 (type 2 diabetes mellitus) 발병과밀접한연관성을보이고있으나아직명확한원인규명은확립되어있지않은실정이다. 보이기때문에중간표현형 (intermediate phenotype) 인공복혈당수치가최종표현형 (end point phenotype) 인당뇨나다른대사질환발병위험단계로가기전의정상인혈중혈당수준 (overall glycemic status) 의기능조절에관여하는유전요인을발굴하는것은중요한의미가있다고볼수있다. 본연구에서는아시아인코호트기반으로구성된컨소시엄 (Asian Genetic Epidemiology Network, AGEN) 약 2만 6천명으로부터전장메타분석을통해혈당조절신규유전인자를발굴하고재현성검증연구를수행하였으며, 당뇨와의생리학적및병리학적차이 (physiological and pathological heterogeneity) 와인종특이적차이를보이는결과를보고하고자한다 [1]. 발굴단계 (discovery stage) 에서는 13개의전장유전체연관분석연구로부터구성된 2만 4천여명을대상으로메타분석 Figure 1. Y-Y Paradox [2] 수행하여총 14 개의후보유전변이를확보하였고, 그중 11 개는 유럽인종으로부터이미보고된유전인자로확인되었으며,

3 주간건강과질병 3 Table 1. Overview of european-based GWAS and meta-analysis Reference Study name Sample # Ancestry Phenotype Frayling et al. WTCCC 1924 Europeans BMI Scuteri et al. Sardinia 4741 Europeans BMI Chambers et al. LOLIPOP 2684 Indian Asians Insulin resistance Loos et al Northern European BMI Heard-Costa et al. The CHARGE Europeans WC Lindgren et al. The GIANT Europeans WHR Cotsapas et al Europeans BMI Meyre et al Europeans BMI Thorleifsson et al DeCODE Europeans BMI Wiler et al. The GIANT Europeans BMI Hinney et al Europeans BMI Scherag et al Europeans BMI Cho et al. KARE 8842 East Asians BMI Heid et al. MAGIC Europeans WHR Speliotes et al Europeans BMI Abbreviation: WTCCC= Wellcome Trust Case Control Consortium, CHARGE= Cohorts for Heart and Aging Research in Genomic Epidemiology, GIANT= Genetic Investigation of ANthropometric Traits, KARE= Korea Association REsource, MAGIC= Meta-Analsed of Glucose and Insulin-related triats Consortium, BMI= Body mass index, WHR= Waist Hip ratio, WC= Waist Circumference, IR= Insulin resistance Table 2. Genetic heterogeneity between FPG and T2D LOCUS FPG(fasting plasma glucose) T2D(type 2 diabetes) GCK UP NO G6PC2 UP DOWN MTNR1B UP UP T2D loci NO UP 재현성검증단계 (replication stage) 에서는나머지 3개의후보유전변이에대하여 5개연구과제로구성된 2만 2천여명을대상으로메타분석을수행하여최종적으로전장유전체연관유의수준 (genome-wide significant threshold, P<5 x 10-8) 을만족하는 3개의공복혈당수치관련신규유전자 (PDK1- RAPGEF4, KANK1, IGF1R) 를발굴하였다 (Figure 2-4). 이중 KANK1은유럽인종으로부터엑솜칩 (exome chip) 을통해발굴된인슐린분비연관성에대해이미보고된유전자로서 [4], 본연구에서새롭게발굴한인트론 (intron) 지역에위치한변이와기존엑손 (exon) 지역에위치한변이와는위험인자빈도 (risk allele frequency) 및연관불균형 (linkage disequilibrium) 등 두그룹간확연한유전적구조차이 (genetic heterogeneity) 를 Figure 2. Overall study work flow

4 4 제 8 권제 1 호 Figure 3. Association results of stage 1 meta-analysis for established FPG loci Abbreviation: FPG= fasting plasma glucose 연관연구를통해보고된변이들은실험에사용된유전변이칩 (SNP chip) 의프로브 (probe) 컨텐츠특성상대부분이인트론 (intron) 이나유전자간 (intergenic) 에위치한변이들로서기능적해석에대한한계가있었는데최근 ENCODE(The Encyclopedia of DNA Elements) 데이터 [5] 공개이후비번역변이 (non-coding variant) 에대한기능적역할에대해보고하였고 [6, 7] 본논문에서도다른염색체위치에존재하는혈당조절관련주요유전자들과장거리상호조절기작 (3D-long range interaction) 에관여하고있음을밝혔다. 비만에대한후속연구로서성인비만과달리소아비만의경우단기적문제일뿐아니라, 비만의 80-85% 가장기적으로당뇨, 고혈압, 지질, 당대사, 심혈관질환등으로발전할위험성에그대로노출되기때문에조기예측및예방을위한유전체연구가필요하다. 따라서한국인소아청소년기 Figure 4. Gene relationships among implicated loci of functional connections 확인하였다. 또한공복혈당수치는당뇨나인슐린저항성등과 서로연관성이높은것으로알려져있으나본연구에서발굴한 유전변이에대해의존도조건분석 (conditional analysis) 을 수행한결과공복혈당수치와인슐린저항성, 당뇨위험간 통계학적유의수준을만족하는표현형간차이 (phenotypic heterogeneity) 를확인하였다. 즉본연구에서발굴한변이는 당뇨에비의존적 (type 2 diabetes-independent) 으로아시아인 및공복혈당수치에특이적인연관성을보였다. 기존전장유전체 고도비만환자및정상인을대상으로비만원인유전변이를발굴하고성인코호트기반데이터와의비교분석을통해검증연구를수행하고자한다. 또한비만유전인자들중에서도단순과체중, 허리둘레등단순비만도에관여하는인자외에과식이나고도비만을유도하여식이조절이상에관여하는식탐유전자를발굴하여임상적으로좀더정확한유전적예측정보를제시할수있으리라본다 [8]. 이렇게밝혀진후보유전자를중심으로유전체-후성유전체- 대사체등멀티오믹스융합연구를통해기존염기서열정보만으로는부족했던질환발생기전및생물학적기능이해를높이고자한다 [9].

5 주간건강과질병 5 III. 맺는말 공복혈당및비만은당뇨, 고혈압등다양한복합만성질환과종합적으로발병되는밀접한상관관계가있으므로인구집단코호트기반의대규모유전체연구를통한다면발현성 (pleiotropy) 및다중질환연관성 (multi-association) 에대한정확한질환예측 (prediction) 및원인규명 (causal inference test) 에집중해야할것이다. 질환특이적인원인유전변이발굴과더불어비만을유발하는환경 (obesogenic environment) 을고려하여당뇨및비만의주요타겟조직세포 (islet, beta cell, pre-/adipocyte 등 ) 로부터의후보마커를발굴하고이에대한혈액시료에서의재현성 7. Sanyal A, Lajoie BR, Jain G, Dekker J The long-range interaction landscape of gene promoters. Nature. 489(7414): Hofker M, Wijmenga C A supersized list of obesity genes. Nat Genet (2): Bell CG, Finer S, Lindgren CM, Wilson GA, Rakyan VK, Teschendorff AE, Akan P, Stupka E, Down TA, Prokopenko I et al Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus. PLoS One. 5(11):e Dick KJ, Nelson CP, Tsaprouni L, Sandling JK, Aissi D, Wahl S, Meduri E, Morange PE, Gagnon F, Grallert H et al.. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 383(9933): 검증여부가뒷받침된다면 [10] 생물학적으로의미있는결과 도출이가능할것으로전망한다. IV. 참고문헌 1. Hwang JY, Sim X, Wu Y, Liang J, Tabara Y, Hu C, Hara K, Tam CH, Cai Q, Zhao Q et al Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. Diabetes. [Epub] 2. Yajnik CS, Yudkin JS The Y-Y paradox. Lancet. 363(9403): Herrera BM, Keildson S, Lindgren CM Genetics and epigenetics of obesity. Maturitas. 69(1): Huyghe JR, Jackson AU, Fogarty MP, Buchkovich ML, Stancakova A, Stringham HM, Sim X, Yang L, Fuchsberger C, Cederberg H et al Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat Genet. 45(2): Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T, Sandstrom R, Ma Z, Davis C, Pope BD et al.. A comparative encyclopedia of DNA elements in the mouse genome. Nature. 515(7527): Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gomez-Marin C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF et al.. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 507(7492):

6 6 제 8 권제 1 호 년유럽항균제내성감시 Antimicrobial Resistance Surveillance in European Union, 질병관리본부국립보건연구원감염병센터약제내성과 김종인, 김화수, 박찬 1) Abstract European Union sets a ' The day of Antimicrobial resistance care ' for November 8, 2008, and cope with increasing seriousness of the resistant bacteria through antimicrobial use monitoring and handwashing campaign. Antimicrobial resistance monitoring and new antimicrobial drug development can inhibit effective measures of spreading antimicrobial resistant bacteria. European Union has been operating for EARS-Net status monitoring through the use antimicrobials. Through this, showing a partial decrease antimicrobial resistance and antimicrobial management is in Belgium and France. The EARS-Net annually reported a trends of resistance rate to selected antimicrobial resistant strains of eight main species in the European Union. II. 몸말 유럽연합에서는유럽질병관리본부 (European Centre for Disease Prevention and Control, ECDC) 를통하여항균제내성감시를강화하고있다. 1998년에설치된유럽항균제내성감시시스템 (European Antimicrobial Resistance Surveillance system, EARSS) 은유럽감시시스템 (The European Surveillance System, TESSy) 의데이터베이스를활용하여 2010 년부터 EARS-Net 으로변경되어운영중이다. Ⅰ. 들어가는말 년영국경도상 ( 經度賞 Longitude Prize) 위원회는 6 대 난제 ( 친환경비행, 충분한식량공급방안, 신경재생치료법, 안전한식수확보, 치매극복, 항균제내성해결 ) 중항균제내성문제해결을인류최대의난제로선정하고 2015 년독일에서열리는 G7 정상회의에서항균제내성극복방안을논의하고자하는적극적인의지를보이고있다. 유럽연합에서는유럽항균제내성감시네트워크 (EARS-Net) 를구축하여적극적인내성균감시를시행하고있으며본글에서는 EARS-Net의운영방법과대표적인다제내성균의항균제내성률을소개하고자한다. AT Autria FI Finland MT Malta BE Belgium FR France NL Netherlands BG Bulgaria HR Croatia NO Norway Cy Cyprus HU Hungary PL Poland CZ Czech Republic IE Ireland PT Portugal DE Germany IS Iceland RO Romania DK Denmark IT Italy SE Sweden EE Estonia LT Lithuania SI Slovenia EL Greece LU Luxembourg SK Slovakia ES Spain LV Latvia UK United Kingdom Figure 1. Countries contributing AMR data to EARS-Net Abbreviation: AMR= Antimicrobial resistance, EARS-Net= European antimicrobial resistance surveillance network 1) 교신저자 (chanpark@nih.go.kr/ )

7 주간건강과질병 7 EARS-Net 은항균제감수성데이터를체계적으로수집할뿐아니라유럽항균제사용량감시네트워크 (European Surveillance Antimicrobial Consumption Network, ESAC-Net) 와의료관련감염감시네트워크 (Healthcareassociated Infections Surveillance Network, HAI-Net), 그리고유럽임상미생물학감염병학회 (European Society of Clinical Microbiology and Infectious Diseases, ESCMID) 와긴밀한협조체계를이루고있다. EARS-Net은 2012년 30개국이참여하여 8균종 (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aruginosa, Acinetobacter species, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium) 에대해항균제내성감시를 수행하였고, 2013년에는유럽연합에가입한크로아티아가 EARS-Net에참여하였다 (Figure 1). 각참여국가에서는항균제감수성시험결과관리담당자를배치하여매년유럽질병관리본부의 TESSy에업로드, 수집, 검증및크리닝절차를수행하고있지만참여국가별항균제내성판독기준과항균제내성판독가이드라인이다를수있기때문에, 최근에는 EUCAST(European Committee on Antimicrobial Susceptibility Testing) 지침에따라내성기준을판독있다. 항균제내성률은신뢰구간 95% 로서, 항균제감수성시험 (Antimicrobial Susceptibility Testing, AST) 의내성 (R;Resistant) 의퍼센트를통해내성률결과를산출하고특정한항균제조합이있는경우는중등도내성 (I;Intermediate) + 내성 (R;Resistant) 으로표현한다. EARS-Net 참여국가의실험실과의료기관데이터는해당 Table 1. Hospital denominator data for 2012 to EARS-net Country * Data for 2011 Total number of beds Annual occupancy rate (%) Country Total number of beds Annual occupancy rate (%) Austria 58, Latvia 5, Bulgaria 9, Lithuania 12, Cyprus 1, Malta* 1, Czech Republic* 38, Norway 5, Denmark* 3, Poland 18, Finland 9,528 - Portugal 8, France 127, Romania 5, Germany 18, Slovakia 13, Hungary 43, Slovenia 7, Iceland* Spain* 26, Ireland 12, Sweden 9, Italy 14, United Kingdom 18, Figure 2. Trends of invasive isolates with resistance to methicillin in Staphylococcus aureus

8 8 제 8 권제 1 호 국가의항균제내성현황을대표할수있도록검체를혈액으로 참여하는 30 개국의내성추이에대한분포를비교하였다. 지정하고, 병원의병상수, 병원의종별, 당해수집데이터의 비율등을정확하게수집하여신뢰도를높이도록하였다 (Table 1). EARS-Net 의주요목표는 4가지로첫째 정확히비교할수있는대표항균제내성데이터수집, 유럽의항균제내성현황에대한시공간적인경향분석, 둘째 정책결정을위한적시성있는항균제내성데이터제공, 셋째 참여국의항균제내성감시프로그램의구현, 유지, 발전을위한지원, 넷째 외부정도평가 (External Quality assessment, EQA) 를통해효율적이고효과적인참여국의항균제내성감시시스템을만들고자하는것이다. EQA를통해데이터를수집하고, 회원국의분석기준을표준화하여, 참여국가를대표할수있는항균제내성결과를보고할수있도록하였다. 유럽질병관리본부는 EARS-Net 을통하여보고된데이터를분석하여유럽항균제내성감시 (Antimicrobial resistance surveillance in Europe) 에보고하였다. 본문에서는주요감염병중그람양성균 2종과, 그람음성균 2종에대하여살펴보고, 그람양성균 (Gram-positive) 메티실린내성황색포도알균 (methicillin-resistant Staphylococcus aureus, MRSA) 일반적으로황색포도알균중 MRSA 비율은북유럽은낮고, 남유럽및동유럽은높은편이다. 2012년유럽 30개국 MRSA는 37,495 건이보고되었고국가별로 58-5,228 건의보고편차가있었다. MRSA 비율이가장낮은국가는스웨덴 0.7% 이며가장높은곳은루마니아 53.9% 이었다. 1개국이 1% 미만, 5개국이 1-5%, 3개국이 5-10%, 14개국이 10-25%, 5개국이 25-50%, 2개국이 50% 이상이었다. 증가하고있는나라는노르웨이, 폴란드, 포르투갈, 루마니아였다. 인구비율을고려하여분석한결과유럽연합의평균내성률은 2010년 17.4% 에서 2012년 17.8% 로증가하였다 (Figure 2). 반코마이신내성장알균 Figure 3. Trends of invasive isolates with resistance to vancomycin in Enterococcus faecium Figure 4. Trends of invasive isolates with resistance to third-generation cephalosporins in Escherichia coli

9 주간건강과질병 9 Figure 5. Trends of invasive isolates with resistance to third-generation cephalosporins in Klebsiella pneumoniae (vancomycin-resistant Enterococcus spp., VRE) 2012 년유럽의 29 개국에서수집한항균제감수성정보는 내성률은 2010 년 8.0% 에서 2012 년 6.2% 로다소감소하였다 (Figure 5). 7,171 건이며 건의수집건수차이가있었다. 아일랜드가 44.0% 로가장높았고, 불가리아, 크로아티아, 에스토니아, 아이슬란드, 룩셈부르크, 네덜란드, 슬로베니아, 스웨덴은 0% 였다. 인구비율을고려하여분석한결과유럽연합의평균내성률은 2010 년 7.4% 에서 2012 년 8.1% 로증가하였다 (Figure 3). III. 맺는말 세계보건기구의최근보고서에따르면세계 114 개국에서 수집한자료를분석한결과모든지역에서항균제내성증가 현상이확인되어서둘러대비하지않을시위험한결과를 그람음성균 (Gram-positive) 3세대세팔로스포린내성대장균 (3rd cephalosporin-resistant Escherichia coli) 2012년유럽 30개국에서는 EARS-Net 70,857건의항균제감수성정보를보고하였고, 보고된국가중스웨덴이 4.4% 로가장낮았고, 불가리아가 38.1% 로가장높았다. 전체적으로 19개국에서내성률이높아졌고, 유럽전체의내성률은 2010년 8.5% 였던것이 2012년 11.8% 로증가하는추세를보였다 (Figure 4). 카바페넴내성폐렴막대균 (carbapenem-resistant Klebsiella pneumoniae) 2012년유럽 29개국에서 16,285 건의내성정보를보고하였고국가별수집건수는 48-1,627 건으로편차가있었다. 2012년카바페넴내성률이 0% 인국가는 7개국이었으며, 가장높은곳은그리스로 60.5% 였다. 2012년에는프랑스, 그리스, 이탈리아, 노르웨이, 스페인이증가하였고, 유럽전체평균 가져올수있다고경고했다. 항균제내성균확산방지노력으로영국 (BSAC), 네덜란드 (NETHM AP), 스웨덴 (SW EDRES), 덴마크 (DANMAP) 등은자국의항균제내성감시시스템을운영할뿐만아니라, 유럽연합의 EARS-Net 을통하여가입국전체에대한내성균감시를하고있다. 우리나라에서도질병관리본부에서 2011년부터국가항균제내성정보시스템 (Korean Antimicrobial Resistance Monitoring System, KARMS) 을운영하여항균제내성을감시하고있으며, 유럽연합국가의체계화된항균제내성감시전략을참고하여항균제내성방지에이바지하도록노력해야할것이다. IV. 참고문헌 1. 고정애,. 170억경도상주제는항생제내성. 중앙일보 2면 Antimicrobial resistance surveillance in European report.. 3. World Health Organization.. Antimicrobial Resistance/ Global Report on Surveillance..

10 10 제 8 권제 1 호 생물테러대비개인보호장비의적정비축방안 Optimum Personal Protective Equipment (PPE) Stockpiling Plan against Bioterrorism 질병관리본부감염병관리센터생물테러대응과 최혁, 조광일 1) Abstract Since the 911 and Anthrax terror in the U.S., the countries around the world got interested in bioterrorism and started preparing measures against it. In Korea, preparation against such bioterrorism has been initiated. Compared to overseas cases, it is expected to create more casualties once bioterrorism occurs in Korea, owing to the distribution of population. In line with this, initial countermeasure and non-proliferation measures are considered to be very important when it comes to the characteristics of bioterrorism. In case of having bioterrorism or event that is suspicious of bioterrorism, the first responders work to rapidly cope with the situation and prevent further diffusion of hazardous chemicals. At that time, they are required to wear Personal Protective Equipment (PPE), and this PPE is considered to be very important. Thus, this study intends to examine the necessity of such equipment for personal protection. Also, it suggests assessment of the stocking plan of PPE so that the preparation for bioterrorism can be done in a rapid and safe manner. 2001년미국 9.11테러와연이어탄저균 ( 우편물 ) 을이용한생물테러발생이후전세계적으로생물테러에대한관심이커졌으며, 우리나라도이에대한대비를시작하게되었다. 생물테러는국가위기상안보위기및재난위기의사회적재난에해당하며, 보건복지부주관으로대응하도록되어있다. 이와관련하여보건복지부 ( 질병관리본부 ) 에서는생물테러대비및대응을위해종합계획을수립하고, 감시체계를운영하며, 역학조사수행및의약품장비등을비축관리하고있다. 또한, 초동대응요원을대상으로교육 훈련을수행 지원하고있으며, 생물테러와관련된한 미공동생물방어훈련을수행하는등국제적인협력체계도구축하여대비하고있다. 이글에서는생물테러대비대응방안중, 생물테러발생시추가확산을방지하고신속하게대응하는초동대응의중요성과초동대응요원용개인보호장비의필요성및적정비축방안에대해기술하고자한다. 생물테러는공포심을유발하고사회적혼란을야기하고자바이러스, 세균, 곰팡이, 독소등을사용하여살상을하거나사람, 동물혹은식물에질병을일으키는목적으로하는행위로서, 인구밀집지역에서의발생확률이높을수있다. 2001년미국에서발생한탄저테러의경우 22명이감염되고 5명이사망하였으며, 약 30,000여명이상이백신접종을하였는데, 이사건이우리나라에발생할경우를가정하면그피해는더커질것으로예상된다. 단순히인구수치를비교해보면, 우리나라가미국보다인구밀도가월등히높으며 (Table 1), Table 2에서알수있듯이수도권의인구밀도가특히높아실제로생물테러가수도권지역에서발생한다면많은인명피해가예상된다. 생물테러에이용되는무기는값이저렴하며쉽게은닉하여살포할수있고, 감염병이라는특성상잠복기가있어, 살포이후환자발생까지의시간차이로초기감지가어렵다. 또한소량으로도많은피해를입힐수있어, 생물테러발생시추가확산을방지하고신속하게대응하는것이무엇보다중요할수있다. 생물테러 ( 의심 ) 사건발생시출동하는초동대응요원은생물테러 ( 의심 ) 병원체로부터개인을보호하기위해개인보호장비를착용하게된다. 개인보호장비는감염성물질및위협으로부터개인을보호하도록고안된보호복이나호흡보호구등을의미하며, 미노동부산하 OSHA(Occupational Safety and 1) 교신저자 (anybody@korea.kr/ )

11 주간건강과질병 11 Table Global population-density by major country Nation Population-density(persons/km 2 ) Nation Population-density(persons/km 2 ) Korea* 499 Italy 202 India 381 China 144 Japan 336 France 117 England 260 USA 33 Germany 232 * 2013 Korea population-density is 499 persons. 20th level in global Table 2. Regional population and population density 2) Cities and Provinces Population (thousand) Populationdensity (persons/km 2 ) Population (thousand) Populationdensity (persons/km 2 ) Total 49, , Seoul 10,026 16,567 9,976 16,483 Busan 3,464 4,509 3,445 4,483 Daegu 2,477 2,803 2,475 2,801 Incheon 2,750 2,664 2,793 2,706 Gwangju 1,506 3,005 1,514 3,020 daejeon 1,527 2,827 1,540 2,852 Ulsan 1,105 1,043 1,116 1,053 Gyeonggi 11,788 1,159 11,937 1,174 Gangwon 1, , Chungbuk 1, , Chungnam 2, , Jeonbuk 1, , Jeonnam 1, , Gyeongbuk 2, , Gyeongnam 3, , Jeju metropolitan 24,564 2,080 24,706 2,092 Health Administration) 의분류기준에따라 Level A-D 로나뉘어진다. 가장높은보호단계인 Level A에서부터가장기본적인보호단계인 Level D로되어있는데, 생물테러대비를목적으로현장에서의미확인의심검체의확인및호흡기전파가가능한생물테러감염병으로부터보호를하기위한 Level A와 상대적저위험성생물테러감염병으로부터보호를하기위한 Level C를확보하여생물테러대비및대응을해야할필요성이있다. 생물테러대비초동대응요원은전국시 군 구보건소및국립검역소생물테러담당자들이역할을수행하고있으며, 2) 출처 : 통계청 장래인구추계시도편 : , 국도해양부 지적통계

12 12 제 8 권제 1 호 개인보호장비의최소적정수량을충족해야생물테러에신속하게대응할수있다. Level A는생물테러의심사건발생시혹은생물테러감염병에노출된지역에들어갈때착용하는보호복으로서 2인 1조로업무를수행하는특성상최소단위로 2세트가필요하며, Level C는초동대응요원및생물테러대책반에편성된모든인원이착용하는보호복으로지역별초동대응요원의편성에따라다르지만대개 6인에서 8인으로구성되며, 한번착용후에폐기를하는특성상최소 1인당 3세트이상이필요하므로초동대응요원편성지역당 세트가필요하다. 또한생물테러에쓰이는생물테러병원체는국내보다는해외를통해반입될가능성이더높기때문에검역구역에서의대비 대응이더철저하게이루어져야하며, 이와관련한장비또한시 군 구보건소의초동대응요원용장비보다더많은수의장비가필요하다. 실제로도대부분의의심사례가검역구역에서발생하고있어국외에서들어올수있는공 항만의신속한초동대응및대비를위해서는초동대응요원용개인보호장비는일반시 군 구보건소보다많은양이필요하다고할수 필요하며, 매년위와같은수량이비축되면내용연수가지나노후화되는장비들을순환적으로교체할수있어생물테러대비를위한장비의공백없이적절하게대처할수있을것이라고판단된다. 하지만국내에서는실제로발생하지않은생물테러에대한대비의성향상모든충족요건을갖춘상태로대비하기는힘들기때문에장비에대한유지보수및관리를좀더철저하게하여장비를좀더오래사용하고유지할수있도록하는것도중요하다. 앞에서기술한바와같이생물테러는생물테러감염병의특성상탐지가어려워신속한초동대응이얼마나잘되었느냐가확산방지및폭로자를최소화하는관건이된다. 신속한초동대응을위해서는적절한장비의관리와유지가필요하고, 이와동시에적정량의장비를확보하는것이중요한다. 또한인구밀집지역이나검역구역등에좀더신속하게대응할수있도록장비의확충에관련된유관기관과의논의도필요할것으로판단된다. 그리고초동대응요원들의역량강화를통해신속하고정확한생물테러대비 대응이이루어질수있기를기대해본다. 있다 (Table 3). 개인보호장비의내용연수는구성품마다다르나대개보호복의내용연수를기준으로판단을한다. 내용연수가지나서출동하는초동대응요원을보호하지못한다면개인보호장비의역할을하지못하는것이기에내용연수가지나기전에새로운장비로교체를해주어야할필요성이있는데, 보호복별로내용연수를확인하면 Level A 보호복의경우내용연수는 5년이고 Level C 보호복은 10년이다. 즉, Level A는 5년에한번, Level C는 10년에한번씩교체를해주어야한다. 이를적정비축량과대비하여연간필요수량으로추산하였을때, 최소필요수량으로 Level A 약 120세트, Level C 약 세트가 Table 3. Estimated of optimum stockpiling of PPE N Level A Level C Health center ,572-6,096 Quarantine station ,656-2,208 Total** ,228-8,304 * Estimation of optimum stockpiling of PPE for first responser, except holding optimum stockpiling of cities and provinces ** Based on 2013 Health and Quarantine station number

13 주간건강과질병 13 status of selected infectious diseases 1.Influenza, Republic of Korea, ending December 27, (52nd ) 년도제 52 주인플루엔자의사환자분율은외래환자 1,000 명당 8.9 명으로지난주 (7.2) 보다증가하였으나, 유행판단기준 (12.2/1,000 명 ) 보다낮은수준임 절기유행기준은 12.2 명 (/1,000) 으로변경 ILI per 1,000 (2013- season) baseline(12.2) ILI per 1,000 (Past seasons) Figure 1. The ly proportion of Influenza-Like Iliness per 1,000 outpatients, to seasons 2. Respiratory viruses, Republic of Korea, ending December 27, (52nd ) 년도제 52 주호흡기검체에대한유전자검사결과 62.6% 의호흡기바이러스가검출되었음. ( 최근 4 주평균 225 개의호흡기검체에대한유전자검사결과를나타내고있음 ) 주별통계는잠정통계이므로변동가능 () Weekly Total Detection rate (%) HAdV HPIV HRSV IFV HCoV HRV HBoV HMPV HAdV : human Adenovirus, HPIV : human Parainfluenza virus, HRSV : human Respiratory syncytial virus, IFV : Influenza virus, HCoV : human Coronavirus, HRV : human Rhinovirus, HBoV : human Bocavirus, HMPV : human Metapneumovirus : the rate of detected cases between Dec Dec. 13., (Average No. of detected cases is 227 in last 4 s) 2013 : the rate of detected cases between Dec Dec Scrub typhus, Leptospirosis, HFRS, Republic of Korea, ending December 27, (52nd )* 년도제52주쯔쯔가무시증환자는 27명이신고되었고, 금년발생누계는 8,292 명으로작년동기간대비 (10,357 명 ) 19.9% 감소하였음 렙토스피라증환자는 1명이신고되었고, 금년발생누계는 60명으로작년동기간대비 (50명 ) 20.0% 증가하였음 신증후군출혈열환자는 13명이신고되었고, 금년발생누계는 370명으로작년동기간대비 (528 명 ) 29.9% 감소하였음 Reported cases 1,800 1,600 1,400 1,200 1, Leptospirosis HFRS Reported cases 12,000 10,000 8,000 6,000 4, Leptospirosis HFRS , Scrub typhus Leptospirosis HFRS Scrub typhus Leptospirosis HFRS year Figure 1. The ly reported cases of Scrub typhus, Leptospirosis, HFRS through National Infectious Disease Surveillance System Figure 2. Cumulative reported cases of Scrub typhus, Leptospirosis, HFRS through National Infectious Disease Surveillance System

14 14 년제 52 주 ( ) Table 1. Reported cases of national infectious diseases in Republic of Korea, ending December 27, (52nd )* Group Ⅰ Group Ⅱ Group Ⅲ Group Ⅳ Classification of disease ly average Total no. of cases by year Imported cases of current : Country(no. of cases) Cholera Myanmar(1) Typhoid fever Paratyphoid fever Shigellosis Laos(1) EHEC Viral hepatitis A 9 1, ,197 5, China(1) Pertussis Tetanus Measles Mumps , ,024 7,492 6,137 6,094 6,399 Rubella Viral hepatitis B ** 81 4, ,394 2,753 1, Japanese encephalitis Varicella 1,919 44,314 1,022 37,361 27,763 36,249 24,400 25,197 United States(1) Streptococcus pneumoniae Malaria ,772 1,345 Indonesia(1) Scarlet fever 167 5, , Meningococcal meningitis Legionellosis Vibrio vulnificus sepsis Murine typhus Scrub typhus 27 8, ,365 8,604 5,151 5,671 4,995 Leptospirosis Brucellosis Rabies HFRS Syphilis 20 1, CJD/vCJD Tuberculosis , ,089 39,545 39,557 36,305 35,845 HIV/AIDS 19 1, , Dengue fever Indonesia(1) Q fever West Nile fever Lyme Borreliosis Melioidosis Chikungunya fever SFTS unit: no. of cases Abbreviation: EHEC= Enterohemorrhagic Escherichia coli, HFRS= Hemorrhagic fever with renal syndrome, CJD/vCJD= Creutzfeldt-Jacob Disease/variant Creutzfeldt-Jacob Disease, SFTS= Severe fever with thrombocytopenia syndrome. Cum: Cumulative counts from 1st to current in a year. * The reported data for year are provisional data but the data for years 2009, 2010, 2011, 2012 and 2013 are finalized data. According to surveillance data, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. The reported surveillance data excluded Hansen s disease and no incidence data such as Diphtheria, Poliomyelitis, Epidemic typhus, Anthrax, Plague, Yellow fever, Viral hemorrhagic fever, Smallpox, Botulism, Severe Acute Respiratory Syndrome, Animal influenza infection in humans, Novel Influenza, Tularemia, Newly emerging infectious disease syndrome and Tick-borne Encephalitis. Surveillance system for Viral hepatitis A, Viral hepatitis B, Syphilis, CJD/vCJD, West Nile fever was changed from Sentinel Surveillance System to National Infectious Disease Surveillance System as of December 30, Calculated by summing the incidence counts for the current, the 2 s preceding the current, and the 2 s following the current, for a total of 5 preceding years (For Viral hepatitis A, Viral hepatitis B, Syphilis, CJD/vCJD, West Nile fever, Lyme Borreliosis, Melioidosis, this calculation only used 3-year data (2011, 2012, 2013) because of being designated as of December 30, ** Data on viral hepatitis B included acute viral hepatitis B, HBsAg positive maternity and perinatal hepatitis B virus infection. Data on scarlet fever included both cases of confirmed and suspected since September 27, 2012.

15 주간건강과질병 15 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending December 27, (52nd )* unit: no. of cases Provinces Cholera Typhoid fever Paratyphoid fever Shigellosis Enterohemorrhagic Escherichia coli Viral hepatitis A Pertussis Tetanus 3-year average Total ,311 2, Seoul Busan Daegu Incheon Gwangju Daejeon Ulsan Sejong Gyonggi Gangwon Chungbuk Chungnam Jeonbuk Jeonnam Gyeongbuk Gyeongnam Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional data but the data for years 2009, 2010, 2011, 2012 and 2013 are finalized data. According to surveillance data, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. Viral hepatitis A data on sentinel surveillance system changed to National Infectious Disease Surveillance System as of December 30, average is mean value calculated by cumulative counts from 1st to current for 5 preceding years.

16 16 년제 52 주 ( ) Table 2. Reported cases of national infectious diseases in Republic of Korea, ending December 27, (52nd )* unit: no. of cases Measles Mumps Rubella Viral hepatitis B Japanese encephalitis Varicella Malaria Scarlet fever Provinces 3-year average Total ,578 8, ,784 2, ,919 44,314 30, ,875 1,057 Seoul ,302 1, ,609 2, Busan , ,415 2, Daegu ,944 2, Incheon ,551 2, Gwangju , Daejeon , Ulsan ,172 1, Sejong Gyonggi ,880 1, , ,502 7, , Gangwon ,142 2, Chungbuk Chungnam ,985 1, Jeonbuk , , Jeonnam , , Gyeongbuk ,578 1, Gyeongnam , ,358 1, Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional data but the data for years 2009, 2010, 2011, 2012 and 2013 are finalized data. According to survei, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. Viral hepatitis B data on sentinel surveillance system changed to National Infectious Disease Surveillance System as of December 30, average is mean value calculated by cumulative counts from 1st to current for 5 preceding years. Data on scarlet fever included both cases of confirmed and suspected since September 27, 2012.

17 주간건강과질병 17 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending December 27, (52nd )* unit: no. of cases Provinces Meningococcal meningitis Legionellosis Vibrio vulnificus sepsis Murine typhus Scrub typhus Leptospirosis Brucellosis Rabies Total ,292 7, Seoul Busan Daegu Incheon Gwangju Daejeon Ulsan Sejong Gyonggi Gangwon Chungbuk Chungnam Jeonbuk Jeonnam , Gyeongbuk Gyeongnam , Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional data but the data for years 2009, 2010, 2011, 2012 and 2013 are finalized data. According to surveillance data, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. Calculated by averaging the cumulative counts from 1st to current, for a total of 5 preceding years

18 18 년제 52 주 ( ) Table 2. Reported cases of national infectious diseases in Republic of Korea, ending December 27, (52nd )* unit: no. of cases Provinces Hemorrhagic fever with renal syndrome Syphilis CJD/vCJD Dengue fever Q fever Lyme Borreliosis Melioidosis Tuberculosis 3-year average 3-year average 3-year average 3-year average Total , ,536 37,138 Seoul ,881 7,715 Busan ,599 3,130 Daegu ,893 2,033 Incheon ,855 1,901 Gwangju Daejeon Ulsan Sejong Gyonggi ,477 7,016 Gangwon ,541 1,343 Chungbuk ,026 1,165 Chungnam ,523 1,504 Jeonbuk ,328 1,248 Jeonnam ,685 1,688 Gyeongbuk ,521 2,648 Gyeongnam ,315 2,556 Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional data but the data for years 2009, 2010, 2011, 2012 and 2013 are finalized data. According to surveillance data, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. Syphilis, CJD/vCJD data on sentinel surveillance system changed to National Infectious Disease Surveillance System as of December 30, 2010 average is mean value calculated by cumulative counts from 1st to current for 5 preceding years.

19 주간건강과질병 19 Table 3. Reported cases of national sentinel surveillance disease in Republic of Korea, ending December 20, (51st ) unit: no. of cases Viral hepatitis Sexually Transmitted Diseases Hepatitis C Gonorrhea Chlamydia Genital herpes Condyloma acuminata Total Cum: Cumulative counts from 1st to current in a year According to surveillance data, the reported cases may include all of the cases such as confirmed, suspected, and asymptomatic carrier in the group. average is mean value calculated by cumulative counts from 1st to current for 5 preceding years. 주요통계이해하기 <Table 1> 은지난 5년간발생한법정감염병과 년해당주발생현황을비교한표로, 는 년해당주의신고건수를나타내며, 은 년 1주부터해당주까지의누계건수, 그리고 ly average 는지난 5년 ( 년 ) 해당주의신고건수와이전 2주, 이후 2주의신고건수 ( 총 25주 ) 평균으로계산된다. 그러므로 과 ly average 의신고건수를비교하면해당주단위시점과예년의신고수준을비교해볼수있다. Total no. of cases by year 는지난 5년간해당감염병현황을나타내는확정통계이며연도별현황을비교해볼수있다. 예 ) 년 12 주의 ly average(5 년간주평균 ) 는 2009 년부터 2013 년의 10 주부터 14 주까지의신고건수를 총 25 주로나눈값으로구해진다. * ly average(5 년주평균 )=(X1 + X2 + + X25)/25 10주 11주 12주 13주 14주 년 해당주 2013년 X1 X2 X3 X4 X5 2012년 X6 X7 X8 X9 X 년 X11 X12 X13 X14 X 년 X16 X17 X18 X19 X 년 X21 X22 X23 X24 X25 <Table 2> 는 17 개시 도별로구분한법정감염병보고현황을보여주고있으며, 각감염병별로 Cum, average 와 Cum, 를비교해보면최근까지의누적신고건수에대한이전 5년동안해당주까지의평균신고건수와비교가가능하다. Cum, average 는지난 5년 ( 년 ) 동안의동기간신고누계평균으로계산된다. <Table 3> 은주요표본감시감염병에대한신고현황으로, 최근발생양상을신속하게파악하는데도움이된다.

20 발간등록번호 PUBLIC HEALTH WEEKLY REPORT, 주간건강과질병 PHWR ISSN: X PHWR Vol.8 NO.1 주간건강과질병, PHWR 은질병관리본부가보유한감시, 조사사업및연구자료에대한종합, 분석을통한근거에기반하여건강과질병관련정보를제공하고자최선을다할것이며, 제공되는원고의내용은질병관리본부의입장과는무관함을알립니다. 주간건강과질병에서제공되는감염병통계는 감염병의예방및관리에관한법률 에의거하여국가감염병감시체계를통해신고된자료를기반으로집계된것이며, 당해년도자료는의사환자단계에서신고된것으로확진결과가나오거나다른병으로확인된경우수정및변동가능한잠정통계입니다. 동간행물은인터넷 ( 에주간단위로게시되며이메일을통해정기적인구독을원하시는분은이름, 이메일, 주소, 연락처, 직업을간단히기입하여 주간건강과질병에대하여궁금하신사항은 창 발 간 : 2008 년 4 월 4 일 행 : 년 12 월 31 일 발행인 : 양병국편집인 : 정충현편집위원 : 윤승기, 최혜련, 박영준, 김윤아, 최영실, 김기순, 정경태, 최병선, 조신형, 조성범, 김봉조, 구수경, 김용우, 조은희, 박선희, 유석현, 조승희, 최수영 편 집 : 질병관리본부감염병관리센터감염병감시과 충북청원군오송읍오송생명 2 로 187 오송보건의료행정타운 ( 우 ) Tel. (043) , 7176 Fax. (043)