주간건강과질병 제 1 권제 31 호 연구논문 1, Research article 1 갱년기여성의만성질환위험요인규명을위한전향적추적관찰연구 성균관대학교강북삼성병원종합건진센터코호트연구소김유진, 조아라, 장유수, 조주희, 유승호 질병관리본부국립보건연구원생명의과학센터심혈관질환과

Transcription

1 pissn X eissn PUBLIC HEALTH WEEKLY REPORT, PHWR Vol.1 No.31 CONTENTS 814 갱년기여성의만성질환위험요인규명을위한전향적추적관찰연구 821 단백체기반데이터베이스확보를통한병원체자원동정고도화 826 당뇨병극복을위한정밀의료적용 831 주요감염병통계환자감시 : 전수감시, 표본감시 병원체감시 : 인플루엔자및호흡기바이러스 급성설사질환, 엔테로바이러스 매개체감시 : 말라리아매개모기, 일본뇌염매개모기

2 주간건강과질병 제 1 권제 31 호 연구논문 1, Research article 1 갱년기여성의만성질환위험요인규명을위한전향적추적관찰연구 성균관대학교강북삼성병원종합건진센터코호트연구소김유진, 조아라, 장유수, 조주희, 유승호 질병관리본부국립보건연구원생명의과학센터심혈관질환과구슬, 박현영 * * 교신저자 : hypark65@korea.kr Prospective observational study on the risk factors for chronic disease in menopausal transition women Kim Yoo Jin, Cho Ara, Chang Yoosoo, Cho Juhee, Ryu Seungho Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine Seul Koo, Park Hyun-Young* Division of Cardiovascular Diseases, Center for Biomedical Sciences, KNIH, KCDC Background: The influence of the menopausal transition period on chronic disease remains largely unexplored. The aim of the present study was to investigate prevalence and incidence rate of physical and psychological outcomes, to establish risk factors which influence disease occurrence, and to examine sequential change of physical and psychological health according to menopausal status. Methodology/results: Menopausal stages were defined according to the criteria of the Stages of Reproductive Aging Workshop (STRAW +1). We recruited 4,328 women, aged years in the pre-menopause or the early menopausal transition stage, who underwent a comprehensive health examination at the Kangbuk Samsung Hospital Total Healthcare Center from August 214 to December 216. Among 4,328 women, 2,418 women were followed until December 216. The higher prevalence of obesity and hypercholesterolemia was observed in the early menopausal transition. Women in the early menopausal transition had higher scores of Menopause-specific quality-of-life (MENQoL) than pre-menopause women. Over time, body mass index, LDL-cholesterol, glucose, insulin and free T4 showed significantly increased per visit. Further longitudinal studies are necessary to confirm the findings of this study. Conclusion: The association between menopausal stages and chronic disease has implications for public health and clinical research, as a better understanding of chronic disease and its relation to menopausal stages may help in recognizing women at risk, allowing for appropriate interventions. 들어가는말 폐경은여성의월경이중단되는상태로난소호르몬인 에스트로겐과프로게스테론의분비가줄어들면서나타난다 [1]. 여성에서폐경은나이가들면서자연스럽게경험하게되는 과정이지만, 폐경이행기 (menopause transition) 및폐경후기 814

3 주간건강과질병 제 1 권제 31 호 (postmenopausal) 에걸쳐동반되는증상이나질환이일상생활의유지를방해하고삶의질을저하시킬수있다 [1]. 최근많은연구에서폐경이행기여성들이혈관운동증상, 신경적증상, 수면장애, 우울등단기적인정신건강변화뿐만아니라여성의삶의질등장기적인건강에도영향을줄수있다고보고하였다 [2]. 질병관리본부국립보건연구원에서 212~213년수행한단면연구인 폐경기증상에대한행동양식과여성건강관련실태조사 에따르면, 폐경으로인한삶의질을혈관운동성, 심리사회적, 신체적, 성적영역으로나누어평가하였을때, 폐경후여성들은전영역에서삶의질저하를경험하고있었다 [3]. 또한폐경후여성에서폐경전에비해비만및주요만성질환 ( 당뇨병, 고혈압, 고콜레스테롤혈증 ) 의유병률이높았다. 이와같이폐경이행에따른삶의질저하와다양한질병상태의변화에도불구하고현재까지국내에서이와관련된전향적연구는거의없어만성질환과위험인자사이의인과관계를추론하기에는한계가있다. 국외에서는 SWAN(Study of Women s Health Across the Nation) 연구를포함하여갱년기여성건강과관련된많은연구가이루어져왔다. SWAN 연구는미국내다민족 (multi-ethnic) 을대상으로폐경이행기동안발생하는생리학적, 정신적변화를관찰하는종단 (longitudinal) 연구로, 1995년부터 216년까지최대 15번의추적조사를시행하였으며갱년기관련심혈관질환, 여성호르몬, 심리질환, 바이오마커등다양한영역에서많은연구결과가발표되고있다. 연구대상자는주로백인여성 (46%) 이며, 중국계미국인과일본계미국인여성도각각 8%, 9% 포함되어있다. 연구결과는인종별로상이하게나타나는경우가많았는데, 중국계와일본계는조기폐경 ( 약물복용및자궁적출술을제외한 4세이전의자연적폐경 ) 을거의경험하지않았다 [4]. 열성홍조 (hot flash) 또는야간발한 (night sweat) 증상은히스패닉계와아프리카계미국인에게서더자주경험했다고보고되었다 [5]. 아시아에서는 5개국폐경여성 1,명을대상으로단면조사 (Asian Menopause Survey) 가수행되었으며각국가별 ( 중국, 말레이시아, 대만, 태국, 홍콩 ) 폐경증상, 호르몬대체요법에 Health Study) 는여성의만성질환및생활습관에대한조사를실시하였다 [7]. 그러나한국인을대상으로진행된연구는매우미비한실정이며인종, 생활양식및식습관등이다른국외대상자연구결과를한국인에게그대로적용하기에무리가있다. 또한선행연구들은소규모로진행된단면조사이거나, 단순폐경여부에국한된조사만을실시하여폐경진행상태에따른신체 정신건강지표및삶의질의시계열적변화와만성질환발생의차이에대한결과를제시하기에제한점이있다. 따라서이러한선행연구의제한점을보완하여우리나라에서도갱년기여성건강상태를파악하고위험요인에대한과학적근거를뒷받침하기위한여성건강코호트의구축이필요하다. 또한우리나라에서수행한기존단면연구결과의재현여부와폐경이행에따른건강상태변화에대한인과관계분석을위하여일정규모이상의대상자, 폐경이행기전단계부터폐경후까지의추적기간, 폐경관련고유인자등을고려한연구결과도출이필요하다. 특히일련의폐경단계를거치면서관찰되는임상적인특징, 신체및정신건강의변화와위험인자의인과관계를규명하기위해생식노화시스템을고려한표준화지표로널리여겨지고있는폐경단계정의 (Executive summary of the Stage of Reproductive Aging Workshop +1, STRAW +1) 를적용한갱년기추적관찰연구를수행하여야한다. 질병관리본부국립보건연구원은학술연구개발용역과제를통해 214년부터현재까지강북삼성병원서울종합검진센터를방문한만 42~52 세여성중폐경전및폐경이행기전기여성을대상으로갱년기여성건강코호트를구축해오고있다. 본연구는표준화된폐경단계정의를적용하여일련의폐경단계진행상태에따른주요임상적지표변화와신체및정신적건강상태변화를조사하고있다. 폐경이진행되는단계별로신체및정신적질환의유병률과발생률을조사하고, 질환발생에영향을주는위험요인을규명함으로써과학적인근거를제시할수있을것이다. 또한향후한국여성건강관리정책을수립하기위한기초자료로활용될수있을것이다. 대한이득, 성생활실태에결과를제시하고있다 [6]. 또다른 연구로중국에서진행한상하이여성건강연구 (Shanghai Women s 815

4 주간건강과질병 제 1 권제 31 호 몸말 조사설계및방법 갱년기여성건강코호트는국내중년여성이폐경단계를거치면서발생하는신체및정신건강지표변화를관찰하고만성질환의발생과위험인자를규명하여향후갱년기여성의건강관리대책을수립하기위한목적으로 214년부터강북삼성병원서울종합건진센터코호트연구소에서연구를진행하고있다. 214년 4월부터국내외문헌고찰및동향조사와전문가자문회의를통해측정변수및 폐경증상및삶의질에관한설문 (Menopause-specific quality of life, MENQoL) 으로폐경기관련설문도구를선정하였고, 대규모장기간지속되고있는갱년기여성연구중가장대표적인미국 SWAN의연구프로토콜을기반으로국내실정에맞는프로토콜을설정하였다. 214년 8월예비연구 (pilot study) 를시행하였고, 발견된문제점을수정 보완한후본격적인코호트를구축하여현재까지추적조사하고있다. 211년발표된 STRAW +1 Expert Report의최신폐경단계정의를반영하여대상자는월경주기패턴에따라폐경단계를폐경전 (pre-menopause; 규칙적인월경 ), 폐경이행기전기 (early transition; 최근월경 1주기이내에월경주기간격이 7일이상차이나는주기가적어도 2번이상있었던경우 ), 폐경이행기후기 (late transition; 최근 6일이상지속되는무월경경험 ), 폐경 (post menopause; 1년이상무월경 ) 4단계로구분하였다. 연구대상자선정기준은강북삼성병원서울종합건진센터를방문한만 42~52 세사이의중년여성중최근 3개월이내에월경이있는폐경전, 폐경이행기전기여성이다. 기저시점에서최근 6일이상지속되는무월경경험시 ( 폐경이행기후기 ), 호르몬대체요법을받은여성, 최근월경 1주기이내에경구피임약을복용한적이있는경우, 자궁절제술또는양측난소절제술을받은경우, 암과거력이있는경우, 최근 1년이내에갑상선기능저하또는기능항진으로약물복용경력이있는경우, 신부전증이있는경우, 반복조사나연구동의를거부한여성은제외하였다. 연구참여시점이후부터는참여자의월경주기에맞추어매월문자및전화연락을통해월경력 데이터를수집하고, STRAW +1의정의에따라개발된월경주기추적로직을이용해연구참여자의월경주기상태를파악하여폐경단계가변화하는특정시점인폐경이행기전기, 폐경이행기후기, 폐경경험시반복조사를시행하고있다. 총 5,명을목표로기저시점에서건강검진문진표를통해인구사회학적특징, 생활습관, 신체계측, 식이조사, 질병력, 여성력, 정신건강관련자료를수집하고폐경증상및삶의질 (MENQoL) 설문지를조사하여폐경기에특화된설문자료를추가로확보하고있다. 그리고건강검진을통해신체계측, 혈청지질, 혈당대사, 갑상선호르몬, 상복부초음파, 골밀도등의검진자료도수집하고있다. 특히, SWAN Study 등기존유사연구에서포함하지못한 HbA1c, Free T4, 지방간변수를추가로조사하였으며향후유전 환경적요인발굴등연구를위해생체시료 ( 혈액, 소변 ) 를추가수집하여국립보건연구원에기탁하고있다. 구체적인조사시기및항목은표 1과같다 (Table 1). 조사결과 214년 8월부터 216년 12월까지총 4,519 명의연구대상자를모집하였으며, 연구동의철회및자궁적출등으로인해중도탈락된 191명을제외하고총 4,328명누적등록되었다 (Table 2). 이들중 2,418명이재방문하였고, 현재까지누적된 1차추적조사율은 55.9% 이었다. 기저시점에서의연구참여자폐경단계를살펴보았을때폐경전여성이 3,97명 (9.%), 폐경이행기전기단계여성이 421명 (1.%) 이었다. 인구학적특성분석결과, 참여자들의평균나이는 44.5 ± 2.5세였고, 41~45 세까지는폐경전단계의비율이높았지만 46세이후부터는폐경이행기전기에해당하는비율이더높게나타났다 (Figure 1). 연구참여자의 79.2%(n = 3,213) 가전문대학졸업이상의교육을받았고, 68.8%(n = 2,874) 의연구참여자가월가구소득이 4만원이상이라고응답하여고학력, 고소득에해당하는연구참여자의비율이높았다 (Table 3). 폐경상태에따른갱년기증상및삶의질을물어보는설문으로혈관운동증상, 심리사회증상, 육체적증상, 비뇨생식기증상 4개 816

5 주간건강과질병 제 1 권제 31 호 Table 1. Summary of variables and point of visit Method Category Contents Baseline Early transition Late transition Post menopause Demographics Marital status, Education, Household income Lifestyle Smoking, Drinking, Physical activity, etc Nutrition Food Frequency Questionnaires(FFQ) Questionnaires Disease history Morbidity, Surgical, Family history, etc Femininity Menarche age, Menstrual cycle, Gynecologic surgery, etc Mental health Sleep habit, Stress, Depression Menopause Menopause Specific Quality of Life Questionnaire (MENQoL) Menstrual cycle Menstrual date, Period, Amount, etc. Anthropometry Height, Weight, Waist circumference, Blood pressure, etc. Serum lipid 1 Total-, HDL-, LDL-Cholestero, Triglyceride Serum lipid 2 Apo A1, Apo B Physical examination Glucose metabolismglucose, HbA1c, Insulin Thyroid hormone Free T4, TSH Inflammation hs-crp - - Bone density DXA - - Ultrasonography, Endoscopy, Breast ultrasonic Abbreviation: HDL-: High density lipoprotein; LDL-: Low density lipoprotein; TSH: Thyroid stimulating hormone; hs-crp: High sensitivity C-reactive protein; DXA: Dual-energy X-ray absorptiometry. Table 2. Number of study participants Year Target number of study participants New registration Cumulative registration Final number of participants (Excluding drop-out) 214 1,5 1,68 1,68 1, , 2,32 3,388 3, ,5 1,131 4,519 4,328 Total 5, 4,519-4,328 영역의질을평가해보았을때, 모든영역에서폐경전여성보다폐경이행기전기여성의삶의질점수가낮게나타났다 (Table 4). 흡연, 음주, 신체활동등생활습관에있어서폐경이행단계에따라통계적으로유의한차이는보이지않았으나폐경이행기전기단계의여성들이주관적인건강상태가좋지않다고응답하는경향이 있었다. 추가적으로체질량지수 (BMI) 기준에따른비만정도를분석한결과, 폐경이행기전기단계여성들에서비만이많았으나 ( 폐경전 17.2%, 폐경이행기전기 2.6%) 유의한차이가없었고, 허리둘레 / 신장비 (Waist to height ratio >.5) 에따른복부비만유병률은 817

6 주간건강과질병 제 1 권제 31 호 Menopausal stage (%) Pre-menopause Early transition Age Figure 1. Age distribution according to menopausal stage Table 3. Demographic characteristics of participants Characteristics Age(year) Total Pre-menopause Early transition n(%) n(%) n(%) P-value Mean(SD) 44.5(2.5) 44.4(2.5) 45.4(2.9) <.1 Education High school 842(2.8) 751(2.6) 91(22.7) College/University 3,213(79.2) 2,93(79.4) 31(77.3).316 Household income < 4,, 314(7.5) 284(7.6) 3(7.2) 4,, 2,874(68.8) 2,6(69.2) 274(65.7).991 No answer 987(23.6) 874(23.3) 113(27.1) 폐경이행기전기단계여성이 25.7% 로폐경전여성 21.2% 보다높았으며통계적으로유의한차이가있었다. 폐경전여성에비해폐경이행기전기단계의여성에서주요만성질환 ( 당뇨병, 고혈압, 고콜레스테롤혈증, 고중성지방혈증, 저HDL콜레스테롤혈증, 대사증후군 ) 유병률이증가하는경향을보였고, 특히폐경이행단계에따라고콜레스테롤혈증이통계적으로유의하게 증가하였다. 지방간, 골다공증은폐경단계에따라유의한차이는없었다. 연구참여자의수면시간은평균 6.6 ± 1.3시간이었으며, 수면의질을평가했을때 23.9% 가수면문제를경험하고있는것으로나타났다. 수면문제는폐경이행단계에따라통계적으로유의한차이가있었으며폐경이행기전기단계의여성들이수면문제를 818

7 주간건강과질병 제 1 권제 31 호 Table 4. Menopause-specific quality-of-life(menqol) scores across menopausal stages MENQoL domains Pre-menopause Early transition P-value Vasomotor 1.5 ± ± Psychosocial 2.4 ± ± 1.4 <.1 Physical 2.8 ± ± 1.2 <.1 Sexual 2.3 ± ± 1.6 <.1 Total score 2.2 ± ± 1.4 <.1 Table 5. Metabolic profiles at baseline and during follow-up Metabolic profiles 1 st visit(baseline) 2 nd visit n Mean ± SD n Mean ± SD Paired t-test P-value Glucose 1, ± , ± 13.9 <.1 Total cholesterol 1, ± 3.6 1, ± Triglyceride 1, ± , ± 5. <.1 HDL-cholesterol 1, ± , ± LDL-cholesterol 1, ± 28. 1, ± 29.8 <.1 HbA1c 1, ±.4 1, ±.5 <.1 Free T4 1,1 1.2 ±.2 1,1 1.2 ±.2.16 TSH 1,5 2.3 ± 1.6 1,5 2.3 ± Insulin 1,1 5.4 ± 3.4 1,1 5.8 ± 3.6 <.1 HOMA-IR 1,1 1.3 ±.9 1,1 1.4 ± 1. <.1 Abbreviation: HDL-: High density lipoprotein; LDL-: Low density lipoprotein; TSH: Thyroid stimulating hormone; HOMA-IR: Homeostatic model assessment for insulin resistance. 경험하는것으로나타났다. 그러나스트레스, 우울증상은폐경이행단계에따라통계적으로유의한차이가없었다. 폐경단계의변화를경험한대상자에한해반복조사자료를분석한결과에서도폐경이행단계변화에따라체중, 체질량지수, 허리둘레, 체지방량이유의한증가추세를보였고, 혈당, 중성지방, 저밀도콜레스테롤, 당화혈색소, Free T4, 인슐린, HOMA-IR 이폐경이행단계변화에따라유의하게증가하였다 (Table 5). 맺는말 지난 3년간약 4천명의연구참여자들을통해살펴본우리나라폐경이행기전기단계의여성은폐경전단계의여성보다주요만성질환 ( 당뇨병, 고혈압, 고콜레스테롤혈증, 고중성지방혈증, 저HDL콜레스테롤혈증, 대사증후군 ) 유병률이증가하는경향을보였고, 특히폐경이행단계에따라고콜레스테롤혈증이통계적으로 유의하게증가하였다. 반복추적조사에서도체질량지수, 허리둘레, 혈당, 중성지방, 저밀도콜레스테롤, 당화혈색소, Free T4, 인슐린농도및인슐린저항성, 폐경기삶의질점수가폐경이행단계에따라유의하게증가하는경향을보였다. 이는상대적으로근거가 819

8 주간건강과질병 제 1 권제 31 호 부족했던폐경이행에따른여성의신체및정신건강상태변화추이에대한결과로제시할수있으며, 여성의기대수명이증가하고여성의사회적지위가높아지는사회적인측면에서도갱년기건강관리가절실하게필요함을시사한다. 본연구는서울지역의단일건강검진센터에서수행하고있어연구참여자의응답률과충실도가높아추적률이좋은반면사회경제적수준이높은연구참여자들로구성되어있다. 따라서우리나라전체여성을대표한다고보기는어렵다는제한점이있다. 향후다기관연구네트워크를구성하는등연구를확장하여지역사회전반에걸친전향적연구가필요하다. 최근통계에따르면 216년연령대별여성인구는 4대 (16.3%), 5대 (16.1%) 순으로가장높았고최근 1년간여성의고용률이전반적으로상승하는동시에 45~54세의여성고용률이상대적으로높아졌다 [8]. 이처럼활발한경제활동을하며사회적으로중요한역할을담당하고있는중년여성들의삶의질을결정하는갱년기증상에대한관리는점차더중요해지고있으나아직까지관련연구는미흡한실정이다. 본연구에서구축된갱년기여성건강코호트는폐경전 1.116/j.fertnstert PubMed PMID: ; PubMed Central PMCID: PMCPMC 질병관리본부 폐경기증상에대한행동양식과여성건강관련실태조사학술연구용역과제최종결과보고서. 4. Huang KE, Xu L, I NN, Jaisamrarn U. The Asian Menopause Survey: knowledge, perceptions, hormone treatment and sexual function. Maturitas. 21;65(3): Epub 29/12/19. doi: 1.116/j.maturitas PubMed PMID: Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N. Premature menopause in a multi-ethnic population study of the menopause transition. Human reproduction (Oxford, England). 23;18(1): Epub 23/1/15. PubMed PMID: Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, et al. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 4-55 years of age. American journal of epidemiology. 2;152(5): Epub 2/9/12. PubMed PMID: Zheng W, Chow WH, Yang G, Jin F, Rothman N, Blair A, et al. The Shanghai Women s Health Study: rationale, study design, and baseline characteristics. American journal of epidemiology. 25;162(11): Epub 25/1/21. doi: 1.193/aje/kwi322. PubMed PMID: 통계청 통계로보는여성의삶. 시점부터폐경시점까지의장기간반복추적조사를통해어떤단계에서공중보건학적예방조치가필요한지보여주는자료를제공할것으로기대된다. 이는폐경이임박한시점에증상이심해진후진단및치료를하는것이아니라, 폐경이행기초기단계부터예방적차원에서관리가이루어질수있도록여성건강관리대책수립을위한기초자료로활용할수있을것이다. 참고문헌 1. Nelson HD. Menopause. Lancet (London, England). 28;371(9614): Epub 28/3/4. doi: 1.116/s (8) PubMed PMID: Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the Stages of Reproductive Aging Workshop + 1: addressing the unfinished agenda of staging reproductive aging. Fertility and sterility. 212;97(4): Epub 212/2/22. doi: 82

9 주간건강과질병 제 1 권제 31 호 연구단신 1, Brief report 1 단백체기반데이터베이스확보를통한병원체자원동정고도화 질병관리본부감염병연구센터병원체자원관리 TF 유원선, 이경민, 황규잠 * * 교신저자 : kyuhwang61@korea.kr, Improved identification for pathogen resources using MALDI-TOF MS Yu Won-Seon, Lee Kyeong-Min and Hwang Kyu-Jam Pathogen Resource Management TF, Center for Infectious Disease Research, KCDC Although pathogens are threats to public health as causative agents of infectious diseases, a recent trend is emerging where pathogen resources are being recognized as important elements for enabling research and development in the biotechnology industry. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is a method of measuring the constituent material based on the time it takes to ionize and reach the detector in a vacuum tube. Up to now, 1 proteome-based MS profiles has been obtained using MALDI-TOF MS, producing a database of clinical isolate pathogen resources in Korea. It is expected that this project will contribute to the improvement in the identification rate through continual addition to a proteome-based database. 세균, 바이러스, 진균등과같은병원체자원은인간에게질병을일으키는위험성을동반하면서한편으로는백신후보주의개발, 진단마커의탐색, 관련질병기전연구등에귀중한자원으로활용될수있는잠재적가치성을보유하고있다 [1]. 생물다양성협약 (Convention on Biological Diversity) 의부속협약에따른유전자원접근및이익공유에관한나고야의정서 (Nagoya Protocol) 가 214년에발효된후생물자원으로써병원체자원의가치가높아지고있다. 이를근거로다른나라의병원체자원을이용하여진단제, 백신, 치료제등을개발할경우그소유권과이익을제공한나라와공유해야된다. 따라서 세계각국은자국의병원체자원에대한주권확보에주력하고있으며국가간병원체자원의이동또한제한하고있다 [2]. 질병관리본부국립보건연구원병원체자원관리TF에서는국가병원체자원은행 (National Culture Collection for Pathogens; NCCP, 의운영을통하여인체에감염을일으키는병원성미생물을국가차원에서수집하고자원화하여이를질병의예방, 진단, 백신및신약개발등을수행하는보건의료연구자들에게제공하고있다. 국가병원체자원은행은국제사회변화에대처하고자지난 년 2월4일에병원체자원의수집, 관리및활용촉진에관한법률을시행하는등병원체자원관리의역량을 821

10 주간건강과질병 제 1 권제 31 호 강화하고있다 [3]. 병원체자원을보존관리함에있어미생물동정은병원체의특성을구분하는데기본이되는매우중요한항목이다. 현미경을이용한형태학적특성과생화학적특성을이용한전통적인미생물동정법은시간이많이소요되고, 실험자의숙련도에따라결과의판정에오류가다소발생할수있다는단점이있다. 이러한문제를해결하고자지방산의비율을분석하는 Microbial Identification System(MIDI, Inc., Wilmington, North Carolina, USA), 생화학적특성을이용한 VITEK2(BioMeriux, Inc., Marcy_l Eltoile, France), 그리고 Matrix-Assisted Laser Desorption/Ionization Time of Flight(MALDI-TOF) 질량분석기 (Bruker Daltonics, Inc., Bremen, Germany) 등미생물자동화동정기기가개발되어연구및산업적인곳에널리활용되고있다. 특히이러한자동화동정시스템들은분석에상대적으로시간이걸리는 16S rrna의계통진화분석과비교하여다수의균주를신속하고간편하게분석할수있다는장점이있으며, 미생물의생화학적분석결과를기존에연구된결과와비교하여결과를판정하는데시간소요가짧은장점과더불어분석이가능한병원체가한정되어있다는한계도갖고있다 [4]. Matrix-Assisted Laser Desorption/Ionization Time Of Flight Mass Spectrometer(MALDI-TOF MS) 는검체를이온화하여 진공관에서검출기에도달하는시간을근거로구성물질의질량을측정하는방법이다. MALDI-TOF MS를이용한세균및진균의동정방법과분석원리에대한모식도는다음과같다 (Figure 1). MALDI-TOF MS를이용한미생물동정의일반적인과정은다음과같다. 세균및진균의집락샘플을 MALDI plate에점적한후 matrix를첨가하고완전히건조시킨다 (Figure 1A). 혼합물이올려진 plate를진공조건을만들어주면유기용매는기화되고시료는 matrix 와함께균질하게결정화된다. 이때 laser를조사하면에너지가 matrix를통해샘플로전달되어약한이온화가발생한다. 전기장을사용하여이온들을질량대전하비 (mass-to-charge ratio, m/z) 에따라분리시킨후, MS 소프트웨어를사용하여분석해 MS profile 을생성한다. 이프로파일은질량대전하비 (mass-to-charge ratio, m/z; X축 ) 에대한폴리펩타이드의양 (intensity value; y축 ) 에해당하는점으로표시한다 (Figure 1B). 생성된단백체프로파일은내재되어있는참조스펙트럼데이터베이스의스펙트럼과샘플의단백체프로파일패턴을비교하는핑커프린팅방법을적용하여미생물동정결과를얻는다. 최근개발된 MALDI Biotyper 3. (Bruker Daltonics, Bremen, Germany) 은 MALDI-TOF MS 기법을이용하여얻은세균의단백질정보를이미구축된각균종의정보와비교분석하여균종을동정하는방법이다 [5, 6]. MALDI-TOF MS는균체에서의단백발현에대한대표 (A) (B) Figure 1. General schematic for the identification of bacteria and yeast by MALDI-TOF MS (A) and for MS analysis of ionized microbiological isolates and clinical material (B) 822

11 주간건강과질병 제 1 권제 31 호 프로파일을만들수있어다양한바이오마커개발연구에사용되고있다. 또한 MALDI-TOF MS의장점은특정기술이나비싼시약의사용없이최소시간내에미확인세균집락을동정할수있다는점이다. Seng 등 (29) 의연구에의하면 MALDI-TOF MS 동정시간은균주당평균 6분이며, 산출된동정비용은상품화키트를포함한전통적동정방법의 22~32% 로미생물실험실에서이용하기에간편하고동정에소요되는시간이매우짧으며소모비용이적음을제시하였다 [7]. MALDI-TOF MS분석은일반실험실에서의분자유전학적방법과비교했을때시간을크게단축시켜주기때문에미생물동정에있어서진일보된동정방법으로서의잠재력을 가지고있다. MALDI-TOF MS의대표적인분석소프트웨어인 SARAMIS(BioMeriux, Inc., Marcy_l Eltoile, France) 나 Biotyper (Bruker Daltonics Inc., Bremen, Germany) 는세균동정에서매우뛰어난기능을보이는것으로보고되고있다. 그러나각균주별특성을단백질수준으로만비교하여구분하는것에는제한이있는것으로알려져있다. 최근에는다양한임상분리주의수집을통하여대표프로파일을확보하고이에대한단백체데이터베이스를강화하여 16S rrna 유전자염기서열분석및전통적인생화학적분석만으로동정하기어려운세균의동정과관련된보고가증가하고있다. Benagli(212) 및 Lista(211) 등은 Aeromonas 속, Brucella 속의균주간유전자적상관관계에근거하여종동정이가능한참조 (A) (B) (C) (D) (E) (F) Figure 2. Representative spectra from Bacillus and E. coli strains supplemented in the database by MALDI-TOF MS. The intensity is shown as a percentage of the total intensity on the y-axis, and the mass to charge ration (m/z) is shown on the x-axis. (A) B. cereus NCCP14796 entfm, CER, (B) B. cereus NCCP1599 entfm,nhea,cytk, (C) B. thuringiensis NCCP11234, (D) B. licheniformis NCCP11231, (E) B. subtillis NCCP 198, (F) E. coli NCCP 1637 CTX-M-14, ST

12 주간건강과질병 제 1 권제 31 호 Figure 3. Major spectrum profile (MSP) dendrogram of Bacillus strains supplemented in the database 라이브러리를만들었다고보고하였다 [8, 9]. 또한세균및진균과다르게바이러스동정에 MALDI-TOF MS를사용한보고는없었으나최근에바이러스단백체프로파일을확보하여바이러스에감염된세포와비감염세포를구분하는실험에활용한보고가있었다 [1]. 있는신규분자지표탐색을진행할예정이다. 이연구를통하여국내임상분리병원체자원의단백체기반데이터베이스를지속적으로확보함으로써병원체자원동정및분석기술향상에크게기여할수있을것으로기대하고있다. 병원체자원관리 TF 에서는병원체자원동정및특성확인 방법으로 MALDI-TOF MS를사용하고있다. 국가병원체자원은행에등록되어있는병원체자원중 Bacillus, Escherichia 속 6종 1주에대한단백체프로파일 1건을확보하였다. 5종의 Bacillus, E. coli 균종의대표적인단백체프로파일은다음과같다 (Figure 2). 확보된단백체프로파일을이용하여국내임상분리병원체자원데이터베이스를제작하였고단백체프로파일기반 major spectrum profile(msp) 계통도를제작하여 Bacillus strain 간의상관관계를확인한결과각각의종들은단일계통군에속하는것을확인하였다 (Figure 3). 향후유전자기반 DNA 핑거프린팅방법과의비교분석을수행하고병원체자원동정과특성확인에활용할수 참고문헌 1. 유원선, 이경민, 황규잠. 자동화동정시스템으로미동정된인체유래병원체의자원화. 주간건강과질병. 215;8(42): Greiber T, Moreno SP, Ahren M et al An explanatory guide to the Nagoya Protocol on access and benefit-sharing. ICUN. 3. 송수진, 이경민, 황규잠. 국가병원체자원의수집, 관리및활용촉진을위한법률제정의필요성. 주간건강과질병. 215;8(45): Funke G, Monnet D, Bernardis C, von Graevenitz A, Freney J. Evaluation of the VITEK 2 system for rapid identification of medically relevant gram-negative rods. J Clin Microbiol. 1998;36, 824

13 주간건강과질병 제 1 권제 31 호 Clark AE, Kaleta EJ, Arota A, Wolk DM. Matrix-Assisted Laser Desorption Ionization- Time of Flight Mass Spectrometry: a Fundamntal Shift in the Routine Practice of Clinical Microbiology. Clinical Microbiology Reviews. 213;26(3): Yu WS, Lee KM, Hwang KJ. Taxonomic Identification of Bacillus Species Using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry. Ann Clin Microbiol. 216;19(4): Seng P, Drancourt M, Gouriet F, Fournier PE, Rolain JM, et al. Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Clin Infect Dis. 29;49: Benagli C, Demarta A, Caminada AP, Ziegler D, Petrini O, Tonolla M. A rapid MALDI-TOF MS identification database at genospecies level for clinical and environmental Aeromonas strains. PLoS One. 212;7, e Lista F, Reubsaet FA, De Santis, Parchen RR, Kieboom J et al. Reliable identification at the species level of Brucella isolates with MALDI-TOF-MS. BMC Microbiol. 211;11(December (1)), Calderaro A, Arcangeletti MC, Rodighiero I, Buttrini M, Montecchini S, Simone RV et al. Identification of different respiratory viruses, after a cell culture step, by matrix assisted laser desorption/isonization time of flight mass spectrometry (MALDI-TOF MS). Sci Rep. 216;27(6):

14 주간건강과질병 제 1 권제 31 호 연구단신 2, Brief report 2 당뇨병극복을위한정밀의료적용 질병관리본부국립보건연구원유전체센터유전체연구과김정민, 윤준호, 김봉조 * * 교신저자 : kbj6181@korea.kr/ Applications of precision medicine to overcome diabetes Kim Jeong-Min, Yun Jun Ho, Kim Bong-Jo Division of Genome Research, Center for Genome Science, KNIH, KCDC Diabetes is one of the prevalent chronic diseases affecting the quality of patient s life seriously. According to the World Health Organization (WHO) report, the prevalence rate of diabetes patients in the worldwide population over 18 years old was estimated at 8.5% in 214. In Korea, that of Korean population aged >= 3 years old was reported as 13.7% in 216, together with prevalence of impaired fasting glucose of 24.8% that is a precursor stage of diabetes. Precision Medicine (PM) is a field of medicine that manages patient-driven omics data, electronic medical records (EMRs) and life-style data to provides treatment tailored to each person. To overcome the lack of actionable genomic findings in diabetes research, several approaches based on PM, such as enlargement of sample size and increase of study power, phenotype with EMRs, analysis of omics data, and machine-learning with various patient-driven data such as microbiome, were suggested and has been in progress. Because wearable devices is also valuable in PM, the development of non-invasive continuous glucose meter is ongoing to help diabetes patients. Following trends in PM on chronic diseases, Division of Genome Research, KNIH has been producing, analyzing, and curating several omics data, including genomics, transcriptomics, epigenomics, and metabolomics for more sophisticated analysis. As a part of PM projects, it is expected that the integrative analysis of omics data, EMRs and life log data by artificial intelligence with deep learning technics would make us possible to predict, prevent and treat the diabetes in the precise manner. 당뇨병은췌장에서인슐린을더이상만들수없거나생산된인슐린을우리몸이효과적으로사용할수없게되어혈중당농도를조절하지못하게되어혈당이높아지고궁극적으로는신체여러기관에다발적인문제를유발하는대표적인만성질환이다. 많이알려진당뇨의합병증으로는시력상실, 신장기능상실, 심장병등이있다. 최근국제보건기구 (WHO) 보고에의하면당뇨환자는 198년 1억8백만명에서 214년 4억2천2백만명으로증가하여 18세이상에서 8.5% 유병률을나타내고있다 [1]. 우리나라에서도생활습관및식생활의서구화로인하여당뇨병환자가증가되어, 216년보고에따르면 3세이상의 826

15 주간건강과질병 제 1 권제 31 호 성인에서 13.7% 의높은유병률을보인다 [2]. 더욱이당뇨전단계인 공복혈당장애 (impaired fasting glucose, IFG) 1) 의유병률이 24.8% 로높게보고되어혈중당농도에대한적절한관리가없다면향후폭발적인당뇨유병률이예상되고개인및국가차원의경제적부담이예상된다 [2]. 정밀의료는오믹스정보 ( 유전체, 전사체, 에피유전체, 대사체등 ), 의료 임상정보, 생활습관정보등을통합분석하는개인별최적의맞춤형의료서비스이다. 215년미국오바마행정부는개인유전자, 환경및생활양식등의개인별차이가질병예방및치료에중요함을인식하고 정밀의료이니셔티브 (Precision Medicine Initiative, PMI) 시행을발표하였다. 216년 2억1천5백만달러의예산을투입하여 1만명의참여자로부터다양한정밀의료정보들을모으는 정밀의료코호트프로그램 (PMI-Cohort Program) 을비롯한암유전체발굴및임상적용, 그리고상호운용성및표준개발등을수행하여 P4 Medicine(Predict, Prevent, Personalize, Participate) 을조기에정착시켜치료중심에서예방중심으로의료시스템을전환하고궁극적으로국민의건강권신장및과도한의료비증가를경감하고자하였다 [3]. 년현재는 PMI-Cohort Program 을 All of Us Research Program 으로변경하여정밀의료참여자의적극적이고능동적인참여와다양한정밀의료데이터의활용을추진하고있다 [4]. 이글에서는당뇨병극복을위한정밀의료관련선행연구결과를소개하고앞으로정밀의료적용이진행될방향성에대해기술하고자한다. 지난십여년동안유전체연구는당뇨병발생과관련높은후보유전인자들을발굴하여당뇨병과유전인자의연관성을밝히는데많은도움을주었다 [5]. 하지만, 당뇨병발생과치료에도움이되는 실제역할을하는유전인자 (actionable genomic finding) 를규명하는데여전히어려움이있다. 이러한점을극복하기위해서유전체연구를수행하는연구대상자수의크기와연구파워 (study power) 를키우는방법, 전자의무기록 (Electronic medical record, EMR) 과같은정보를이용한표현형분석 (phenotying), 그리고 전사체, 에피유전체, 대사체등오믹스정보를활용하여당뇨환자를세분화하고표적치료에활용하는방법등이제시되었다 [6]. 이런다양한방법들을기반으로당뇨병에대한정밀의료적용을위한기초연구들이진행되었고향후나아가야할방향이제시되었다. 먼저 1형당뇨병, 2형당뇨병으로구분되어지는기존의단순한분류법을벗어나서당뇨병자체가상당히상호이질적인 (heterogeneous) 질병이라는사실을인식하고, 당뇨환자의약 9% 를차지하는 2형당뇨병의경우에는 EMR과유전체정보를바탕으로보다세분화할필요가있다. 그리고다양한정밀의료정보들과의통합분석이필요하고, 세분화된연구또는임상시험에다양한당뇨연구그룹들의적극적인참여가요구된다. 이러한취지로미국에서는여러가지접근법에기초한당뇨관련다양한연구들이진행중이다 (Table 1)[7]. 그결과, EMR과유전체정보를이용하여 2형당뇨환자들을 3가지유형의세부그룹으로나누고, 각각의유형과관련성이높은유전변이와표현형을분류하였다. 그리고기존의 2형당뇨병치료법대신다양하고세밀한치료방법을설정하는데도움을주어서 2형당뇨병에대한정밀의료적용가능성을보여주었다 [8]. 당뇨병관련정밀의료에서가장먼저본격적으로적용될분야인 약물유전체학 (pharmacogenomics) 에서는여러가지당뇨병치료약들의효과및부작용과관련된유전변이들에대한데이터가축적되어서기존의시나리오인, 일차적인당뇨병치료제인메트포민 (metformin) 처방을통해혈중당농도를측정하여약물효과가나타나면계속적인처방을진행하고, 약물효과가나타나지않으면약물조합 (drug-combination) 을투여하는것과는달리, 앞으로정밀의료에서는환자의유전체분석 (genotyping) 을수행한후에환자들을약물의부작용, 약물반응이좋은그룹, 그리고약물반응이좋지않은그룹으로나눈후각각에적합한약물을투여하는방향으로진행하여약물부작용을줄이고또한약물에의한효과를증진시키는방향으로나아갈것이다. 또한, 당뇨병합병증과관련되는유전변이들에대한데이터가축적되면이를바탕으로당뇨병약물치료시합병증발생유무와기간을 1 ) 공복혈당장애 (Impaired Fasting Glucose, IFG): 공복시혈당이 mg /dl 인경우로써당뇨병전단계를나타내는지표임. 출처 : 질병관리본부국가정보포털 (health.cdc.go.kr/ health) 827

16 주간건강과질병 제 1 권제 31 호 Table 1. List of research programs for diabetes in the United States Research name Topics & data for diabetes Reference TEDDY Finding T1D genetic risks and other factors in children Accelerating Medicines Partnership Developing a portal providing access to comprehensive results from large genetic association studies of T2D Framingham Heart Study Cohorts studying cardiovascular disease -study.org/ Insulin Resistance Atherosclerosis Study Cohorts for heart and aging research in genomic epidemiology NCT5135 CHARGE initiative Providing the opportunity to study biomarkers associated with incident diabetes TOPMed Supporting the trans-omics for precision medicine nhlbi-precision-medicine-initiavtive-tipmed GRADE Comparing long-term benefits and risks of four diabetes drug with metformin in T2D patients Joslin Diabetes Center Finding factors protecting against complications New Sensor Technology Monitoring the health of PMI cohort Adapted contents from Fradkin et al.[7] and tabulated 미리예측하여환자의삶의질을향상시킬수있다 [9]. 그리고기계학습 (machine-learning) 을이용하여혈액지표, 식습관, 신체계측, 물리적활동량및장내미생물등의지표를통합분석하여식후당지수 (glycemic index, GI) 반응을예측하는기술을개발하고개인에게적합한식습관을통하여식후혈당수치를조절할수있는가능성을제시하였다 [1]. 마지막으로, 정밀의료정보중하나인생활습관정보를수집하는웨어러블디바이스 (wearable device) 에대한중요성이제기되고있는가운데, 당뇨환자들의혈당체크의어려움을해결할수있는 비침습혈당계 (noninvasive glucose meter) 에대한개발도진행되고있다. 그예로써, 환자의복부에센서를삽입하여지속적으로혈당을측정하는연속혈당계는손가락에서피를내는표준적혈당측정법인자가혈당측정계를대체해나갈것으로예상된다. 최근에는환자로부터분비되는땀을분석하여혈당을측정하는방식뿐만아니라아직은비공개이지만애플사는애플워치에들어갈 무채혈연속혈당측정 기능을개발 중이라는헬스케어전문가의의견이제시되었다 [11]. 이와같이당뇨병과같은만성질환에대한정밀의료적용이서서히진행되고있는가운데, 질병관리본부국립보건연구원유전체센터유전체연구과에서는지난수년간한국인만성질환 ( 당뇨병, 심혈관질환등 ) 관련오믹스정보생산및분석사업을추진하여정밀의료적용에대비하고자하였다. 214년부터형질분석연구사업, 포스트게놈다부처유전체사업의일환으로한국인칩 2) 사업을수행하여 년말까지약 13만명의한국인유전체정보를확보할예정이며정밀의료를위한핵심인프라로활용할예정이다. 또한, IHEC 3) 에회원국으로참여하여약 1,종의주요만성질환참조에피유전체지도작성및공개를진행하고있으며, 특히이중에는한국인을대상으로생산된 5종의에피유전체정보를포함하고있다. 또한대사체분석을통해 2형당뇨병관련대사체마커및연관유전변이를발굴하였다. 그리고 오믹스데이터정도관리가이드라인 을작성하고공개하였으며분석 2) 질병관리본부국립보건연구원에서개발한한국인질병유전체연구에최적화된유전체칩 ( 한국인칩, Korea Biobank Array: KCHIP) 으로약 83만개의유전변이를가지고있으며이중 2만개는단백질기능영향유전변이로구성되어있다. ( 주간건강과질병제8권, 215.7,16) 3) IHEC(International Human Epigenome Consortium): 211년부터전세계 8개국이참여한 국제인간에피지놈컨소시엄 ( 인체유래세포 25종대상 1,개에피지놈유전체지도확보및국제공동연구추진. 한국은질병관리본부국립보건연구원참여 828

17 주간건강과질병 제 1 권제 31 호 관련교육과홍보를통해국내연구자를지원하였다. 그외유전적다양성정보, 복제수변이및유전체분석툴관련 DB 구축을통하여다양한유전체정보를서비스하고있다. 향후오믹스정보와 EMR 등보건의료빅데이터와의연계분석을위한가이드라인작성방안을마련하여오믹스정보기반의보건의료빅데이터, EMR 및생활습관정보등의정밀의료정보들과의통합연계분석을진행하여한국인만성질환에대한정밀의료적용기반을구축하고자한다. Sci. Transl. Med. 215;7(311): 311ra Singh S, Usman K and Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World Journal of Diabetes, 216;7(15): Zeevi D, Korem T, Zmora N. et al. Personalized nutrition by prediction of glycemic responses, Cell. 215;163(5): 최윤섭의 Healthcare Innovation ( com/216/1/4/artificial-pancreas-with-watson/). 유전자이상에의해주로발생하는암, 희귀병등에대한정밀의료적용분야는기술발전과관련정보의증가로인해빠른속도로진행되고있지만, 당뇨병과같은만성질환의경우에는정밀의료적용이쉽지만은않다. 하지만, 위에서언급한것처럼유전체정보를중심으로한다양한오믹스정보의생산및분석과 EMR 정보와의연계통합분석수행을통한당뇨환자의세부그룹화, 유전자정보를기반으로한약물치료효율성증대및부작용최소화, 그리고웨어러블디바이스를통해수집되는여러가지정밀의료정보들을인공지능 / 딥러닝으로분석한결과등을활용하면당뇨병발생의예측, 예방그리고표적치료가머지않아실현될전망이다. 참고문헌 1. WHO(World Health Organization) Fact Sheets Diabetes ( fs312/en/), WHO, Reviewed November 대한당뇨병학회, 216. Diabetes Fact Sheet in Korea 년도예비타당성조사보고서- 유전체 Health-ICT 융합기반정밀의료기술개발 KISTEP( 한국과학기술기획평가원 ),.1월. 4. 미국 NIH Precision Medicine Cohort Program(All of Us Research Program) 5. GWAS Catalog, 6. Floyd JS, Pasty BM. The application of genomics in diabetes: barriers to discovery and implementation. Diabetes Care. 216;39: Fradkin JE, Hanlon MC and Rodgers GP. NIH Precision Medicine Initiative: Implication for diabetes research. Diabetes Care. 216;39: Li L, Cheng WY, Glicksberg BS. et al. Identification of type 2 diabetes subgroups through topological analysis of patient similarity

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19 status of selected infectious diseases 1.1 환자감시 : 전수감시감염병주간발생현황 (3th ) Table 1. Reported cases of national infectious diseases in Republic of Korea, ending July 29, (3th )* Group Ⅰ Group Ⅱ Group Ⅲ Group Ⅳ Classification of disease ly average Total no. of cases by year 216* Unit: No. of cases Imported cases of current : Country(no. of cases) Cholera Typhoid fever Paratyphoid fever Shigellosis EHEC Philippines(1) Viral hepatitis A 73 3, ,679 1,84 1, ,197 Laos(1) Pertussis Tetanus Measles Italy(1) Mumps 352 1, ,57 23,448 25,286 17,24 7,492 Rubella Viral hepatitis B (Acute) Japanese encephalitis Varicella 1,23 42, ,6 46,33 44,45 37,361 27,763 Streptococcus pneumoniae Malaria Nigeria(1), South Sudan(1) Scarlet fever , ,911 7,2 5,89 3, Meningococcal meningitis Legionellosis Vibrio vulnificus sepsis Murine typhus Scrub typhus ,15 9,513 8,13 1,365 8,64 Leptospirosis Brucellosis Rabies HFRS Syphilis 38 1, ,569 1,6 1, CJD/vCJD Tuberculosis , ,892 32,181 34,869 36,89 39,545 HIV/AIDS ,62 1,18 1,81 1, Viral hepatitis C 24 2, VRSA CRE 19 1, Vietnam(6), Laos(3), Dengue fever Thailand(3), Philippines(2), 149 Malaysia(1), Maldives(1), Myanmar(1), Nigeria(1) Q fever West Nile fever 1 Lyme Borreliosis Melioidosis Chikungunya fever Nigeria(1), Philippines(1) SFTS MERS Zika virus infection Abbreviation: EHEC= Enterohemorrhagic Escherichia coli, HFRS= Hemorrhagic fever with renal syndrome, CJD/vCJD= Creutzfeldt-Jacob Disease / variant Creutzfeldt-Jacob Disease, VRSA= Vancomycin-resistant Staphylococcus aureus, CRE= Carbapenem-resistant Enterobacteriaceae, SFTS= Severe fever with thrombocytopenia syndrome, MERS-CoV= Middle East Respiratory Syndrome Coronavirus. Cum: Cumulative counts from 1st to current in a year. * The reported data for year are provisional but the data from 212 to 216 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, Haemophilus influenzae type b, Epidemic typhus, Anthrax, Plague, Yellow fever, Viral hemorrhagic fever, Smallpox, Severe Acute Respiratory Syndrome, Animal influenza infection in humans, Novel Influenza, Tularemia, Newly emerging infectious disease syndrome and Tick-borne Encephalitis. Data on scarlet fever included both cases of confirmed and suspected since September 27, 212. 문의 : (43)

20 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending July 29, (3th )* Unit: No. of cases Provinces Cholera Typhoid fever Paratyphoid fever Shigellosis Enterohemorrhagic Escherichia coli Viral hepatitis A Pertussis Tetanus Total ,63 1, 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 but the data from 212 to 216 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. average is mean value calculated by cumulative counts from 1st to current for 5 preceding years

21 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending July 29, (3th )* Unit: No. of cases Provinces Measles Mumps Rubella Viral hepatitis B (Acute) Japanese encephalitis Varicella Malaria Scarlet fever Total ,313 9, ,23 42,149 23, ,852 3,338 Seoul , ,535 2, , Busan ,41 1, Daegu ,342 1, Incheon ,576 1, Gwangju , Daejeon , Ulsan , Sejong Gyonggi ,777 2, ,967 6, , Gangwon ,6 1, Chungbuk Chungnam , Jeonbuk , Jeonnam , Gyeongbuk , Gyeongnam , ,217 1, , Jeju , Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional but the data from 212 to 216 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. 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,

22 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending July 29, (3th )* Unit: No. of cases Provinces Meningococcal meningitis Legionellosis Vibrio vulnificus sepsis Murine typhus Scrub typhus Leptospirosis Brucellosis Hemorrhagic fever with renal syndrome Total 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 but the data from 212 to 216 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 834

23 Table 2. Reported cases of national infectious diseases in Republic of Korea, ending July 29, (3th )* Unit: No. of cases Syphilis CJD/vCJD Dengue fever Q fever Lyme Borreliosis SFTS Zika virus infection Tuberculosis Provinces 3-year 3-year Total 38 1, ,237 2,591 Seoul ,122 4,13 Busan ,155 1,584 Daegu ,63 Incheon ,61 Gwangju Daejeon Ulsan Sejong Gyonggi ,71 4,22 Gangwon Chungbuk Chungnam Jeonbuk Jeonnam Gyeongbuk ,2 1,443 Gyeongnam ,143 1,353 Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year are provisional but the data from 212 to 216 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. 5(3)-year average is mean value calculated by cumulative counts from 1st to current for 5(3) preceding years

24 1.2 환자감시 : 표본감시감염병주간발생현황 (3th ) 1. Influenza, Republic of Korea, ending July 29, (3th ) 년도제 3 주인플루엔자의사환자분율은외래환자 1, 명당 3.9 명으로지난주 (6.3 명 ) 대비감소 잠정통계로변동가능함 216- 절기유행기준은 8.9 명 (/1,) 인플루엔자유행주의보해제 : 년 6 월 2 일 ( 발령 : 216 년 12 월 8 일 ) ILI per 1, Figure 1. Weekly proportion of influenza-like illness per 1, outpatients, to 216- flu seasons 2. Hand, Foot and Mouth Disease(HFMD), Republic of Korea, ending July 29, (3th ) 년도제 3 주수족구병의사환자분율은외래환자 1, 명당 26.8 명으로지난주 (29.6 명 ) 대비감소 수족구병은 29 년 6 월법정감염병으로지정되어표본감시체계로운영 No. of outpatients / 1, Figure 2. Status of HFMD sentinel surveillance,

25 3. Ophthalmologic infectious disease, Republic of Korea, ending July 29, (3th ) 년도제 3 주유행성각결막염의외래환자 1, 명당분율은 24. 명으로지난주 24. 명과동일 동기간급성출혈성결막염의환자분율은.6 명으로지난주.5 명대비증가 6 5 No. of outpatients / 1, Figure 3. Weekly proportion of epidemic keratoconjunctivitis per 1, outpatients 5 4 No. of outpatients / 1, Figure 4. Weekly proportion of acute hemorrhagic conjunctivitis per 1, outpatients 837

26 4. Sexually Transmitted Diseases, Republic of Korea, ending July 29, (3th ) 년도제 29 주보고기관 (586 개 ) 당성기단순포진 2.8 명, 클라미디아 2.3 명, 임질 2.1 명, 첨규콘틸롬 1.7 명발생함. Unit: No. of cases/sentinels Sexually Transmitted Diseases 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. 문의 : (43) , 7132 자세히보기 : 질병관리본부 정책 / 사업 감염병감시 표본감시주간소식지 1.3 수인성및식품매개감염병집단발생주간현황 (3th ) Waterborne & Foodborne disease outbreaks, Republic of Korea, ending July 29, (3th ) 년도제 3 주에집단발생이 6 건이발생하였으며누적발생건수는 37 건 ( 환례수 3,84 명 ) 이발생함 No. of outbreaks Average no. of cases in last 4 years( ) Figure 5. Number of waterborne & foodborne disease outbreaks reported by,

27 2.1 병원체감시 : 인플루엔자및호흡기바이러스주간감시현황 (3th ) 1. Influenza viruses, Republic of Korea, ending July 29, (3th ) 제 3 주에의뢰된호흡기검체 19 건중인플루엔자바이러스 2 건 (1.%)[A/H3N2 2 건 ] 검출되었음. No. of positives Percent positives (%) A/H3N2 A(not subtyped) A/H1N1pdm9 B percent positive Figure 6. Number of specimens positive for influenza by subtype, 216- season 2. Respiratory viruses, Republic of Korea, ending July 29, (3th ) 년도제3주호흡기검체에대한유전자검사결과 36.8% 의호흡기바이러스가검출되었음. ( 최근 4주평균 19개의호흡기검체에대한유전자검사결과를나타내고있음 ) 주별통계는잠정통계이므로변동가능 216- () 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 Jan. 1. July. 29., (Average No. of detected cases is 19 in last 4 s) 216 : the rate of detected cases between Dec Dec 자세히보기 : 질병관리본부 알림 주간질병감시정보 839

28 2.2 병원체감시 : 급성설사질환실험실표본주간감시현황 (29th ) Detection rate of acute gastroenteritis causing virus and bacteria, Republic of Korea, ending July 22, (29th ) 년도제29주실험실표본감시급성설사질환유발바이러스검출건수는 7건 (1.6%), 세균검출건수는 48건 (2.3%) 이었음. Acute gastroenteritis-causing viruses No. of sample No. of detection (Detection rate, %) Group A Rotavirus Norovirus Enteric Adenovirus Astrovirus Total (1.4) 3 (4.2) 2 (2.8) 6 (8.5) 12 (16.9) (2.4) 1 (1.2) 4 (4.8) 5 (6.) 12 (14.3) (1.2) 4 (4.8) 3 (3.6) 2 (2.4) 1 (12.) (.) 4 (6.1) 2 (3.) 1 (1.5) 7 (1.6) 2,5 39 (15.1) 367 (17.9) 51 (2.5) 68 (3.3) 795 (38.8) Acute gastroenteritis-causing bacteria Week No. of Sample Salmonella Pathogenic spp. E.coli Shigella spp. No. of isolation (Isolation rate, %) V.parahaem V. cholerae Campylobacter C.perfringens S. aureus B. cereus Total olyticus spp (5.3) 15 (5.68) () () () 3 (1.14) 1 (.38) 9 (3.41) 8 (3.3) 5 (18.94) (6.22) 11 (5.26) () 1 (.48) () 3 (1.44) 2 (.96) 1 (.48) 7 (3.35) 38 (18.18) (5.88) 29 (13.12) () () () 7 (3.17) 3 (1.36) 11 (4.98) 8 (3.62) 71 (32.13) (3.38) 14 (5.91) () () () 13 (5.49) () 9 (3.8) 4 (1.69) 48 (2.25) 5, (2.58) 137 (2.7) 3 (.6) 2 (.4) () 59 (1.16) 66 (1.3) 93 (1.83) 99 (1.95) 593 (11.68) * Bacterial Pathogens ; Salmonella spp., E. coli (EHEC, ETEC, EPEC, EIEC), Shigella spp., Vibrio parahaemolyticus, Vibrio cholerae, Campylobacter spp., Clostridium perfringens, Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Yersinia enterocolitica. * hospital participating in Laboratory surveillance in 216 (7 hospitals) 자세히보기 : 질병관리본부 알림 주간질병감시정보 84

29 2.3 병원체감시 : 엔테로바이러스실험실주간감시현황 (29th ) Detection rate of enterovirus in enterovirus sentinel surveillance, Republic of Korea, ending July 22, (29th ) 년도제 29 주실험실표본감시결과엔테로바이러스검출건수는 26 건이며, 년도누적발생건수는 21 건임. Aseptic meningitis 8 Detection rate (%) Enterovirus detection rate (%) Enterovirus detection rate (%) Figure 7. Detection rate of enterovirus in aseptic meningitis patients from 216 to HFMD and Herpangina 25 Detection rate (%) Enterovirus detection rate (%) Enterovirus detection rate (%) HFMD with Complications Figure 8. Detection rate of enterovirus in HFMD and herpangina patients from 216 to Detection rate (%) Enterovirus detection rate (%) Enterovirus detection rate (%) Figure 9. Detection rate of enterovirus in HFMD with complications patients from 216 to 841

30 3.1 매개체감시 : 말라리아매개모기주간감시현황 (29th ) Vector surveillance : Malaria vector mosquitoes, Republic of Korea, ending July 22, (29th ) 년도제 29 주말라리아매개모기수는평균 8 개체로평년 15 개체대비 7 개체 (46.7%) 감소 ( 전년 8 개체대비동일 ) 년도제 29 주전체모기수는평균 16 개체로평년 36 개체대비 2 개체 (55.6%) 감소 ( 전년 21 개체대비 5 개체 (23.8%) 감소 ) 7 6 No. of mosquitoes Total Mosquitoes(Average) Malaria Vector Mosquitoes(Average) Total Mosquitoes Malaria Vector Mosquitoes Total Mosquitoes Malaria Vector Mosquitoes Week Figure 1. Weekly incidences of malaria vector mosquitoes in 3.2 매개체감시 : 일본뇌염매개모기주간감시현황 (29th ) Vector surveillance : Japanese encephalitis vector mosquitoes, Republic of Korea, ending July 22, (29th ) 년 29 주일본뇌염매개모기주간발생현황 - 29 주전체모기수 : 평균 75 개체로평년 1,9 개체대비 385 개체 (35.3%) 감소 ( 전년 871 개체대비 166 개체 (19.1%) 감소 ) - 29 주일본뇌염매개모기 ( 작은빨간집모기, C.t*) 수 : 평균 64 개체로평년 61 개체대비 3 개체 (4.9%) 증가 ( 전년 9 개체대비 55 개체 (611%) 증가 ) No. of mosquitoes 2, 1,8 1,6 1,4 1,2 1, Year Total Year C.t* Total C.t* Total C.t* Week Figure 11. Weekly incidences of Japanese encephalitis vector mosquitoes in 자세히보기 : 질병관리본부 민원 / 정부 3. 사전정보공개

31 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 211 년부터 215 년의 1 주부터 14 주까지의신고건수를 총 25 주로나눈값으로구해진다. * ly average(5 년주평균 )=(X1 + X2 + + X25)/25 1주 11주 12주 13주 14주 215년 해당주 214년 X1 X2 X3 X4 X5 213년 X6 X7 X8 X9 X1 212년 X11 X12 X13 X14 X15 211년 X16 X17 X18 X19 X2 21년 X21 X22 X23 X24 X25 <Table 2> 는 17 개시 도별로구분한법정감염병보고현황을보여주고있으며, 각감염병별로 Cum, average 와 Cum, 을비교해보면최근까지의누적신고건수에대한이전 5년동안해당주까지의평균신고건수와비교가가능하다. Cum, average 는지난 5년 ( 년 ) 동안의동기간신고누계평균으로계산된다. <Table 3> 은표본감시감염병에대한신고현황으로, 최근발생양상을신속하게파악하는데도움이된다.

32 발간등록번호 주간건강과질병, PHWR 은질병관리본부에서시행되는조사사업을통해생성된감시및연구자료를기반으로근거중심의건강및질병관련정보를제공하고자최선을다할것이며, 제공되는정보는질병관리본부의특정의사와는무관함을알립니다. 본간행물에서제공되는감염병통계는 감염병의예방및관리에관한법률 에의거, 국가감염병감시체계를통해신고된자료를기반으로집계된것으로집계된당해년도자료는의사환자단계에서신고된것이며확진결과시혹은다른병으로확인될경우수정될수있는잠정통계임을알립니다. 주간건강과질병, PHWR 은질병관리본부홈페이지를통해주간단위로게시되고있으며, 정기적구독을원하시는분은 이메일을통해보내지는본간행물의정기적구독요청시구독자의성명, 연락처, 직업및이메일주소가요구됨을알려드립니다. 주간건강과질병 발간관련문의 : kcdc215@korea.kr/ /33 창 발 간 : 28 년 4 월 4 일 행 : 년 8 월 3 일 발행인 : 정은경 편집인 : 박도준 편집위원 : 최영실, 김기순, 최병선, 조신형, 조성범, 김봉조, 구수경, 김용우, 이동한, 조은희, 이은규, 신영림, 김청식, 권효진, 김호용 편 집 : 질병관리본부유전체센터의과학지식관리과 충북청주시흥덕구오송읍오송생명 2 로 187 오송보건의료행정타운 ( 우 )28159 Tel. (43) /33 Fax. (43)