pissn X eissn PUBLIC HEALTH WEEKLY REPORT, PHWR Vol.11 No CONTENTS 년국내메르스의심환자감시및대응결과 0128 탄저균 poly-γ-

pissn 25-811X eissn 2586-86 www.cdc.go.kr PUBLIC HEALTH WEEKLY REPORT, PHWR Vol.11 No.5 218 CONTENTS 121 217 년국내메르스의심환자감시및대응결과 128 탄저균 poly-γ-d-glutamic acid 캡슐에의한자연살해세포의인터페론감마생산기전 134 주요감염병통계환자감시 : 전수감시, 표본감시 병원체감시 : 인플루엔자및호흡기바이러스 급성설사질환, 엔테로바이러스

주간건강과질병 제 11 권제 5 호 연구논문, Research article 217 년국내메르스의심환자감시및대응결과 질병관리본부메르스대책반김은경, 류보영, 이지아, 김세원, 김지아, 김지연, 김정연, 김효진, 신희영, 이기용, 최선아, 최초로, 최한샘, 이정헌, 이아경, 김희정, 문상준, 홍정익 * * 교신저자 : hongji3755@korea.kr, 43-719-719 Results of national surveillance and response in patients with Middle East respiratory syndrome coronavirus infection under investigation in Korea in 217 Kim Eun Kyoung, Ryu Boyoung, Lee Jia, Kim Sewon, Kim Jia, Kim Ji Yeon, Kim Jeong Yeon Kim Hyo Jin, Shin Hee Yeong, Lee Ki Yong, Choi Seona, Choi Choro, Choe Han Saem, Lee Jeong Heon, Lee Ah Kyung, Kim Hee Jung, Moon Sangjun, Hong Jeongik Task Force Team for MERS-CoV Preparedness and Response, KCDC Background: Since Middle East respiratory syndrome (MERS) infection in humans was reported for the first time in Saudi Arabia in 212, 2,127 confirmed cases have been reported globally, with a high mortality rate of 35.6% (as of December 31, 217). Sporadic outbreaks of primary infections, including those associated with direct camel contact and small-scale epidemics in hospitals, have been continuously reported in Saudi Arabia, suggesting the requirement for sustained implementation of strengthened surveillance. This article aims to describe the results of national surveillance and response in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection under investigation in Korea from January 1 to December 31, 217. status: A total of 22 cases were classified as MERS-suspect cases, with confirmed case of zero. Of the suspect cases, more cases were notified by healthcare providers (99 cases, 45%) than through self-reporting by calling the Korea Centers for Disease Control and Prevention (KCDC) call center (#1339) or the public health center (81 cases, 36.8%). 4 cases (18.2%) were identified at the port of entry. More cases occurred in men (77.3%) than in women, and 22.7% cases occurred in foreigners. One hundred and thirty-six cases (55.1%) included patients with a history of travelling to the United Arab Emirates (UAE), followed by Saudi Arabia (39 cases, 15.8%) and Qatar (13 cases, 5.3%). Most of the suspect cases were classified as exhibiting a low epidemiologic risk. The most common symptoms were fever (186 cases, 84.5%) and cough (162 cases, 73.6%), whereas pneumonia was observed in 31 cases (14.1%). Respiratory viral infections, such as influenza (63 cases, 28.6%) and rhinovirus (25 cases, 11.4%) were found. Prospective future: It is suggested that individuals who develop flu-like symptoms within 14 days after travelling to the Middle East should refrain from visiting healthcare facilities, and instead call #1339 or the public health center and then follow the guidance provided. Adminstration of seasonal influenza vaccinations is also strongly recommended before traveling abroad. Considering the major epidemiological and clinical characteristics of the suspect cases, it is necessary to continuously review and clarify the case definition and counter measures. Keywords: Middle East respiratory syndrome coronavirus, Middle East respiratory syndrome, Camelus, Influenza, Rhinovirus www.cdc.go.kr 121

주간건강과질병 제 11 권제 5 호 들어가는말 중동호흡기증후군 (Middle East respiratory syndrome, MERS; 이하메르스 ) 은 212년 4월사우디아라비아에서처음보고후 217년 12월 31일까지전세계적으로 27개국에서 2,127 명이확진되고 757명이사망하여치사율 35.6% 를보이는급성호흡기질환이다. 확진환자는주로사우디아라비아에서발생하고있으며 ( 확진 1,753 명, 사망 683명 ), 대부분낙타와직접접촉에의한 1차감염이다. 1차감염자와가족과의접촉또는의료기관내감염등으로인한 2차감염은소규모유행으로지속적으로발생하고있다. 217년의메르스발생양상도예년과같이대부분사우디아라비아 ( 확진 238명, 사망 74명 ) 를중심으로지속적이고산발적으로발생하였고 신고 보고대상으로정하고있으며, 메르스대응지침 에따라역학조사및메르스검사를시행하는대상자를메르스의심환자까지확대하여신고하도록하고있다. 신고대상을메르스의심환자까지확대한것은의심증상이있는본인의자발적신고또는진료시인지한의사등누구나신고가능하도록하여메르스를조기에인지하고대응하기위함으로 증상발생 14일이내중동지역의방문력이있고발열과호흡기증상이있는경우 의심환자에해당한다 [5-7]. 이와관련하여질병관리본부는중동지역 ( 아라비안반도및인근 13개국 ) 방문 여행객을대상으로메르스의심환자발생감시체계를 216년에이어 217년에도유지하고있으며, 이와관련된 217년메르스의심환자감시및대응결과를정리하여공유하고자한다. 네차례의료기관중심유행도발생하여해외로부터메르스국내 유입을차단하고조기대응하기위한체계적이고지속적인감시및대응관리가매우중요하다 [1-4]. 국내에서는메르스를 감염병의예방및관리에관한법률 에근거하여제4군감염병으로지정하여환자및의사환자를 몸말 방법및대상 6 5 MERS-suspect patients in 217 Non-MERS patients in 217 MERS-suspect patients in 216 Non-MERS patients in 216 No. of patients 4 3 2 1 2 9 7 11 24 17 16 19 1 11 9 1 2 19 15 11 26 21 23 33 17 24 33 21 23 14 22 12 14 17 17 24 18 22 15 13 9 7 3 4 4 5 5 4 5 2 3 4 5 5 5 4 4 5 5 5 6 9 2 2 2 2 2 1 3 3 3 1 3 2 3 3 4 4 4 4 2 3 2 5 8 5 2 4 18 15 26 25 11 4 28 19 27 18 17 23 26 27 2 1 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17 18 19 2 21 22 23 24 25 26 27 28 29 3 31 32 33 34 35 36 37 38 39 4 41 42 43 44 45 46 47 48 49 5 51 52 37 29 18 Figure 1. Trends of notification and response on suspect patients of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by, 216 and 217 www.cdc.go.kr 122

주간건강과질병 제 11 권제 5 호 Table 1. Reporting entities or pathways of MERS-related cases between 216 and 217 N (%) Reporting entities or pathways MERS-suspect patients Non-MERS suspect patients 216 217 216 217 Via KCDC call center 1339 / Community health center 7 (35.) 81 (36.8) 542 (83.4) 869 (84.5) At healthcare facilities 81 (4.5) 99 (45.) 79 (12.2) 19 (1.8) At the port of entry (mainly airport quarantine stations) 49 (24.5) 4 (18.2) 29 (4.5) 14 (13.6) Total 2 22 65 1,28 MERS-suspect patients in 216 MERS-suspect patients in 217 24.5% 35.% 18.2% 36.8% Via KCDC call center 1339 / Community health center 4.5% 45.% At healthcare facilities At the port of entry (mainly airport quarantine stations) (N = 2) (N = 22) Figure 2. Comparison of MERS-suspect patients by reporting entities, 216 and 217 격리하고검사를실시한다. 질병관리본부긴급상황실과중앙 217년 1월 1일부터 12월 31일까지메르스로의심되어질병관리본부콜센터 (1339) 또는지자체보건소등으로신고된사례를대상으로역학조사를실시하였다. 메르스의심환자신고기준및의심환자분류기준은 메르스대응지침 (4-1판 16년 12월개정, 4-2판 17년 3월개정, 5판 17년 7월개정 ) 에따라시행하였으며중동지역및인근국가즉바레인, 이라크, 이란, 이스라엘, 요르단, 쿠웨이트, 레바논, 오만, 카타르, 사우디아라비아, 시리아, 아랍에미리트, 예멘 13개국방문자중신고대상의심환자를대상으로한다. 메르스의심환자를최초인지한보건소에서는역학조사서를이용하여각의심사례의인적사항, 중동지역여행력, 임상증상, 신고경위등필요정보를수집하여시 도역학조사관에게보고하고, 역학조사관이의심환자로분류하면의심환자를국가지정격리병원에 역학조사관은각사례에대해실시간자료수집과동시에대응단계별조치사항을검토하고필요조치를취하였다. 의심환자신고및대응현황 217년 1월 1일부터 12월 31일까지질병관리본부콜센터 (1339) 또는지자체보건소등을통해인지 신고된사례는총 1,248건, 월평균 14건으로월최소 78건, 최대 156건이신고되었다. 5월, 1월과 12월에월 12건이상신고되어월별신고가가장많았으며 216년에는 1월과 5월에신고가많았으나 217년에는이슬람하지성지순례기간이후인 1월과국내급성호흡기감염증이유행하는 12월에의심환자신고가많았다. 메르스의심환자신고는 217년에총 1,248건으로 216년 www.cdc.go.kr 123

주간건강과질병 제 11 권제 5 호 Table 2. Demographical, epidemiological and clinical characteristics of suspected patients of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, 217 Variables Characteristics N (%) Nationality Korean 17 (77.3) Foreigners 5 (22.7) Sex Male 124 (56.4) Female 96 (43.6) Age (years) -9 23 (1.5) Visiting or stopping-over countries in the Middle East * 1-19 7 (3.2) 2-29 52 (23.6) 3-39 56 (25.5) 4-49 31 (14.1) 5-59 26 (11.8) 6+ 25 (11.4) UAE 136 (61.8) Saudi Arabia 39 (17.7) Israel 17 (7.7) Qatar 13 (5.9) Iran 1 (4.5) Oman 8 (3.2) Kuwait 7 (3.2) Jordan 7 (3.6) Iraq 4 (1.8) Bahrain 3 (1.4) Lebanon 3 (1.4) Epidemiological History of traveling/stopping-over without any other exposure at risk 182 (82.7) characteristics History of any exposure one or more among the following risks Clinical characteristics Symptoms at presentation Visiting in a healthcare facility 29 (13.2) Direct contact of camel 8 (3.6) Visiting in a healthcare facility and camel meat intake 1 (.5) Body temperature over 37.5 193 (87.7) Masked fever due to medication (analgesic, common cold, antimicrobial) 23 (1.5) Fever and symptoms of respiratory illness 156 (7.9) Pneumonia with fever and symptoms of respiratory illness 14 (6.4) Pneumonia with fever 17 (7.7) Fever 16 (7.3) Symptoms of respiratory illness 17 (7.7) Fever 186 (84.5) Cough 162 (73.6) Sputum 79 (35.9) Sore throat 49 (22.3) Myalgia 38 (17.3) Runny nose, rhinorrhea 38 (17.3) Chills 36 (16.4) Headache 18 (8.2) Short of breath/dyspnea 11 (5.) GI symptoms 4 (1.8) Others 4 (1.8) Close contact Close contact since symptom onset per one suspected case, median (range) 25 (-247) *Multiple responses; Epidemiological risk from countries in the Middle East within 14 days before symptom onset; body temperature over 37.5 or under 37.5 by medication; Any one or more among the following symptoms: cough, chills, sputum, myalgia, sore throat, nasal discharge/congestion, short of breath, dyspnea; Any one or more among the following symptoms: nausea, diarrhea, gastric discomfort; Including chest pain, eye pain, diaphragm pain www.cdc.go.kr 124

주간건강과질병 제 11 권제 5 호 Table 3. Comparison of respiratory viruses isolated from suspect patients for MERS-CoV infection under investigation by reverse transcription polymerase chain reaction (RT-PCR), 216 and 217 N (%) Respiratory pathogens 216 217 Negative 12 (51.) 75 (34.1) Positive 98 (49.) 145 (65.9) Single pathogen 92 (46.) 128 (58.2) Influenza A(H3N2) 21 (1.5) 41 (18.6) Influenza A(H1N1)pdm9 28 (14.) 14 (6.4) Rhinovirus 11 (5.5) 25 (11.4) Influenza B 16 (8.) 18 (8.2) Human metapneumovirus 5 (2.5) 11 (5.) Human adenovirus 2 (1.) 7 (3.2) Human coronavirus 4 (2.) 7 (3.2) Human parainfluenzavirus 3 (1.5) 5 (2.3) Repiratory syncytial virus 2 (1.) - Multi-pathogens 6 (3.) 17 (7.7) Influenza B, Human metapneumovirus 1 (.5) 1 (.5) Influenza B, parainfluenza virus - 1 (.5) Influenza A, Human coronavirus - 1 (.5) Influenza A, parainfluenza virus - 1 (.5) Influenza A(H1N1), Rhinovirus - 2 (.9) Influenza A(H3N2), Rhinovirus 1 (.5) 1 (.5) Influenza A, Influenza B - 1 (.5) Influenza B, Rhinovirus 1 (.5) 1 (.5) Bocavirus, parainfluenza virus - 1 (.5) Bocavirus, RSV 1 (.5) 1 (.5) Adenovirus, Human metapneumovirus - 1 (.5) Adenovirus, Rhinovirus - 2 (.9) Adenovirus, Bocavirus 1 (.5) 1 (.5) Rhinovirus, Bocavirus - 1 (.5) Rhinovirus, RSV - 1 (.5) Adenovirus, Rhinovirus, Human coronavirus 1 (.5) - 85명과비교시 46.8% 가량증가하였고메르스의심환자분류는 217년총 22건으로 216년 2건과비교시 1.% 가량증가하였다. 월평균의심환자분류는 18.3명으로주별의심환자신고및분류현황은그림 1에나타내었다 (Figure 1). 217년메르스의심환자신고경로를보면, 의료기관에서진료시의사등의료진에의해보고된경우가 99건 (45.%) 으로가장많았고의심환자본인이메르스의심증상으로 1339로신고하거나보건소를통해신고한경우가 81건 (36.8%) 이었다. 216년신고경로와 비교시의료기관을통한신고와질병관리본부콜센터및보건소를통한신고모두증가하였다. 공항등출입국시설의검역과정에서의심환자로분류된경우가 4건 (18.2%) 이었다 (Figure 2, Table 1). 지자체별메르스의심환자분류및대응은검역소대응을제외하고경기 64건 (29.1%), 서울 43건 (19.5%), 인천 1건 (4.5%) 순으로많았고, 그외시 도에서의심환자대응건수는연간 1 9 건이었다. 검역소에서신고한의심환자는이송거리를고려하여서울 (19건) 과인천 (21건 ) 에소재한국가지정격리병원을이용하였으며이를반영한 www.cdc.go.kr 125

주간건강과질병 제 11 권제 5 호 시 도별대응빈도는서울 64건 (29.1%), 경기 62건 (28.2%), 인천 31건 (14.1%) 순이었다. 의심환자로분류된경우지체없이음압격리병상에입원하여검사를실시하였고 22명모두메르스바이러스유전자검사에서음성으로확인되었다. 의심환자의일반적, 역학적및임상적특성 의심환자의인구학적특성을보면평균연령은 36세이고, 내국인이 17명 (77.3%), 외국인이 5명 (22.7%) 이었다. 성별은남성이 124명 (56.4%) 으로여성보다많았으며, 연령대는 2대와 3대가 18명 (49.1%) 으로높은빈도를보였다. 의심환자의중동 메르스의심환자에게확진검사를실시할때, 다른호흡기바이러스에의한감염을배제하기위해급성호흡기바이러스감염증 8종에대한유전자검사를동시에실시하였다. 217년메르스의심환자에게급성호흡기바이러스감염증이확인된경우는 145명 (65.9%) 으로 216년 98명 (49.%) 에비하여바이러스검출이증가하였고, 216년과 217년모두 Influenza A 검출이가장많은것으로나타났다 (216년 24.5%, 217년 25.%). 217년메르스의심환자의급성호흡기바이러스감염증은 Influenza A 55건 (25.%), Rhinovirus 25건 (11.4%), Influenza B 18건 (8.2%) 순으로확인되었고, 의심환자의 7.7%(17건 ) 는 2개이상의호흡기바이러스에중복감염된것으로확인되었는데 216년에비해다중병원체검출도증가하였다 (Table 3). 지역방문력은 217 년메르스발생국가 4 개국 ( 사우디아라비아, 아랍에미리트, 카타르, 오만 ) 을방문한경우가전체의심환자중 85.5%(188건 ) 를차지하였다. 의심환자가방문 경유한중동국가는 2개이상의중동국가방문 경유를포함하여아랍에미리트 136건 (55.1%), 사우디아라비아 39건 (15.8%), 이스라엘 17건 (6.9%) 순으로나타났다. 메르스위험요인이있는의심환자는총 38명 (17.3%) 이었으며이중현지의료기관방문은 29명 (13.2%), 낙타접촉은 8명 (3.6%) 이었고그외위험요인이없는중동국가를단순방문 경유후분류된사례는 182명 (82.7%) 이었다 (Table 2). 의심환자의임상적특성을보면, 평균체온은 38.2 이었으며, 발열과호흡기증상이있는경우가 156명 (7.9%), 폐렴이있는경우가 31명 (14.1%) 이었다. 의심환자의주호소증상은발열 186건 (84.5%), 기침 162건 (73.6%), 가래 79건 (35.9%), 인후통 49건 (22.3%), 근육통 38건 (17.3%), 콧물 38건 (17.3%), 오한 36건 (16.4%), 두통 18건 (8.2%) 등으로확인되었다. 의심환자가증상발현시부터격리입원전까지접촉한밀접접촉자규모는총 4,28명으로의심환자 1인당평균 25명이었으며최소 명에서최대 247명을접촉한것으로확인되었다 (Table 2). 의심환자의호흡기바이러스감염원 맺는말 국내 감염병위기경보수준대응체계 에따라현재는메르스환자의국내유입이없는 관심 단계이나, 질병관리본부에서는메르스대책반을운영하고국외발생동향을면밀히파악하고중동지역방문 경유후국내에입국하는여행객에의한메르스국내유입을조기에인지하여대응하기위해메르스의심환자연중감시체계를유지하고있다. 217년메르스의심환자감시결과, 의심환자의 85.5% 는 217년메르스발생국가를방문 경유하였다. 낙타접촉, 현지의료기관방문등역학적연관성이높아위험노출을고려할수있는사례는 38건 (17.3%) 이었고대부분은역학적연관성이낮거나경증사례였다. 215년국내메르스유행시대부분중증급성하기도질환 ( 폐렴 ) 이있었던것과달리 216년과 217년모두대부분경증의호흡기증상을보였고폐렴이의심또는확인된경우는 216년 8.%, 217년 14.1% 에불과하였다. 메르스의심환자에대한사례정의및기준은국가별로다르나국외감시체계운영결과를보면메르스의심환자의인플루엔자양성률이방글라데시의경우 4% 로보고되었고, 싱가포르의경우 27% 로보고되어 [3] 217년국내인플루엔자양성률 28% 와비슷한 www.cdc.go.kr 126

주간건강과질병 제 11 권제 5 호 수준으로나타나해외여행전인플루엔자예방접종과여행시감염예방수칙을지키도록적극권장할필요가있다. 217년메르스의심환자감시결과, 의심환자가의료기관을통해신고되는경우가 45% 로 216년 (4%) 과비슷한수준으로조사되어메르스의심환자가의료기관방문을자제하고먼저질병관리본부콜센터또는보건소에신고후안내에따르도록대국민홍보를강화시킬필요가있다. 또한, 의심환자의 82.7% 는메르스위험노출 ( 낙타접촉, 현지의료기관방문등 ) 없이중동지역을단순방문 경유하였고, 메르스가아닌급성호흡기바이러스에의한감염이 65.9% 를차지하고있어향후주요역학적, 임상적특성을고려한메르스의심환자사례정의및대응방안개선에대한검토가필요하다. 이번분석결과는 216년과 217년메르스의심환자의감시및대응결과를토대로메르스대응 대비를지속적으로보완하는근거로활용할것을기대한다. 참고문헌 1. Abdulaziz A, Bin Saeed, Glen R. AbediSurveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, April 215-February 216. Emerging Infectious disease 217 Apr;23(4):682-85 2. World Health Organization. http://www.who.int/emergencies/merscov/en/ retrieved on 24, Jan. 218. 3. Muraduzzaman AKM, Khan MH, Parveen R, et al., Event based surveillance of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Bangladesh among pilgrims and travelers frome the Middle East: An update for the period 213-216. PLoS ONE 13(1):e1899914 Jan 16, 218:1-8. 4. Korea Centers for Disease Control and Prevention. Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 215. Osong Public Health Res Perspect. 215;6(4):269-78. 5. 보건복지부질병관리본부, 216 메르스 (MERS) 대응지침 4-1판, 216.11. 6. 보건복지부질병관리본부, 216 메르스 (MERS) 대응지침 4-2판, 217.3.2. 7. 보건복지부질병관리본부, 216 메르스 (MERS) 대응지침 5판, 217.7.1. www.cdc.go.kr 127

주간건강과질병 제 11 권제 5 호 연구단신, Brief report 탄저균 poly-γ-d-glutamic acid 캡슐에의한자연살해세포의인터페론감마생산기전 질병관리본부감염병분석센터고위험병원체분석과전준호, 이해리, 이기은 * * 교신저자 : gerhie@korea.kr, 43-719-827 Poly-γ-d-glutamic acid capsule of Bacillus licheniformis, a surrogate of Bacillus anthracis capsule induces interferon-gamma production in natural killer cells through interaction with macrophages Jeon Jun Ho, Lee Hae-Ri, Rhie Gi-eun Division of High-risk Pathogens, Center for Laboratory Control of Infectious Diseases, KCDC The poly-γ-d-glutamic acid (PGA) capsule, a major virulence factor of Bacillus anthracis, provides protection to the bacterium from phagocytosis, thereby facilitating unimpeded bacterial growth in the host. We investigated the crosstalk between murine natural killer (NK) cells and macrophages stimulated with the PGA capsule of Bacillus licheniformis, a surrogate of B. anthracis capsule. PGA induced interferon-gamma (IFN-γ) production from NK cells cultured with macrophages. This effect was dependent on macrophage-derived interleukin (IL)-12 and cell-cell contact between NK cells and macrophages through NK cell receptor NKG2D and its ligand RAE-1. Thus, PGA may enhance NK cell activation by inducing IL-12 production in macrophages and facilitating a contact-dependent crosstalk with macrophages. Keywords: NK cells, Poly-r-d-glutamic acid, Interferon gamma, Bacillus anthracis 들어가는말 탄저균 (Bacillus anthracis) 은아포를형성하는그람양성균으로미국질병관리본부 (Centers for Disease Control and Prevention, CDC) 에서생물무기화가능성에따라지정한위험단계중최상위인 Tier1 select agent에속하는고위험병원체이다 [1, 2]. 탄저균은부종독소 (edema toxin) 와치사독소 (lethal toxin) 와같은외독소를 분비하며이들은탄저균의숙주감염시각각부종과세포사멸을유도하는주요병독력인자로알려져있다 [3]. 또한탄저균의외막을구성하는 poly-γ-d-glutamic acid (PGA) 캡슐은숙주면역세포의포식작용을억제하여탄저균을보호하는역할을한다 [4]. 자연살해세포 (natural killer cells) 는병원성미생물감염시최전방에서방어를수행하며세포독성및사이토카인분비를통하여미생물의침입및확산을억제하는주요면역세포 www.cdc.go.kr 128

주간건강과질병 제 11 권제 5 호 A B Stimulation SPL NK-depleted SPL NK PGA Medium BMDMs ND NK+BMDMs PGA 2 4 6 8 1 IFN-γ (pg/ ml ) NK1.1 IFN-γ Merge Figure 1. PGA induces IFN-γ production in murine NK cells (A) Splenocytes (SPL), NK-depleted SPL, BMDMs, and purified NK cells with or without BMDMs were stimulated with 1 μg / ml PGA for 48 h. Levels of IFN-γ in culture supernatants were measured by ELISA. *, P <.5, compared with the untreated control group. ND, not detected. (B) SPL were stimulated with 25 μg / ml PGA for 3 h and then stained with Alexa Fluor 647-conjugated anti-nk 1.1 and FITC-conjugated anti-ifn-γ antibodies. Fluorescence images were obtained by confocal microscopy (Source: Lee et al., Journal of Microbiology and Biotechnology. 217;27(5):132-7). 중하나이다. 미생물감염시자연살해세포의활성화를 위해서는단핵구 (monocytes), 대식세포 (macrophages) 또는 이글에서는 PGA 캡슐에의한자연살해세포의활성화와이에 대한기전에대하여기술하고자한다. 수지상세포 (dendritic cells) 와같은다른면역세포와의상호작용이 필요하다. 이러한상호작용에는다른면역세포와의직접적인접촉또는인터루킨 (IL)-12, IL-18 과같은사이토카인을통한간접적인자극이포함될수있다 [6]. 자연살해세포로부터분비되는인터페론 (interferon, IFN) 은미생물감염시숙주의방어기전에중요한역할을수행한다 [7]. 예를들면 Mycobacterium tuberculosis와 Francisella tularensis와같은세포내침입미생물감염시 Type I 인터페론 (IFN-α, IFNβ) 과 Type II 인터페론 (IFN-γ) 이숙주방어면역반응에중요한역할을함이알려져왔다 [8, 9]. 탄저균포자는자연살해세포에서 IFNγ의생산을유도하는것으로알려졌으며, 흡입탄저모델및탄저균세포감염실험에서 IFN-γ를처리한마우스와대식세포의생존율을증가시킬수있음이알려져왔다. 또한자연살해세포에서분비된 IFN-γ는탄저균감염시숙주의방어기전에중요한역할을함이보고되었다 [1-12]. 하지만탄저균의 PGA 캡슐이자연살해세포를활성화시켜탄저균에대한숙주의방어면역반응을유도하는지에대해서는아직까지알려져있지않다. 몸말 PGA 캡슐이마우스의비장세포 (splenocyte) 에서 IFNγ의분비를유도하는지를알아보기위하여 1 μg / ml의 PGA를비장세포에 48시간동안처리한후배양액에존재하는 IFNγ의양을면역효소분석법 (Enzyme-Linked Immunosorbent Assay, ELISA) 을이용하여확인하였다. Figure 1A에서보는바와같이 PGA가처리된비장세포에서 IFN-γ 단백질이발현되었다. 자연살해세포는 IFN-γ를생산하는주요세포로알려져있으므로자연살해세포를제거한비장세포에 PGA를처리하여 IFN-γ의생산이유도되는지조사하였다. Figure 1A에서와같이 PGA에의한 IFN-γ 생산은자연살해세포를제거한비장세포에서현저히감소하였다 (P =.9). 자연살해세포와대식세포의상호작용이미생물감염에의한 IFN-γ 생산에중요한역할을함이알려져있으므로골수유래 www.cdc.go.kr 129

주간건강과질병 제 11 권제 5 호 A IL-12p7 (pg/ ml ) 6 4 2 PGA Medium SPL BMDMs B IL-12p7 (pg/ ml ) 8 6 4 2 NS PGA - + + + αil-12 - - + - Control lgg - - - + C IFN-γ (pg/ ml ) 12 8 2 αil-12 Control lgg 24 h 48 h NS NS PGA - - + + + + + + - - - - + + - - - - - - - - + + Figure 2. IL-12 secreted by PGA-stimulated macrophages is involved in NK cells activation to produce IFN-γ (A) SPL and BMDMs were stimulated with 1 μg / ml PGA for 48 h. IL-12 p7 concentrations were determined by ELISA. NK cells with BMDMs (B) or SPL (C) were pretreated with anti-il-12 neutralizing antibody (2.5 μg / ml ) or control IgG (2.5 μg / ml ) for 1h, followed by stimulation with 1 μg / ml PGA for an additional 48h. IFN-γ concentrations were measured by ELISA. *P <.5. NS denotes not significant (Source: Lee et al., Journal of Microbiology and Biotechnology. 217;27(5):132-7). 대식세포 (Bone marrow-derived macrophages, BMDMs), 자연살해세포단독또는골수유래대식세포와자연살해세포를혼합하여배양시 PGA가 IFN-γ의생산을유도할수있는지조사하였다. Figure 1A에서보는바와같이 PGA는자연살해세포에서 IFN-γ의생산을유도하였으며골수유래대식세포에서는유도하지못하였다. 또한자연살해세포와골수유래대식세포를동시배양한세포에 PGA를처리할경우자연살해세포단독에비하여 PGA에의한 IFN-γ 생산이통계적으로유의하게증가되었다 (P <.5). PGA로자극한비장세포에서분비되는 IFN-γ의주된생산자가자연살해세포임을추가로확인하기위하여자연살해세포특이형광항체및공초점현미경 (confocal microscope) 을이용하여조사하였다. Figure 1B에서보는바와같이 PGA는자연살해세포특이마커인 NK1.1 표면항원을보유하고있는세포에서만 IFNγ의생산을유도함을확인할수있었다. 따라서비장세포중에서자연살해세포가 PGA 자극시 IFN-γ를생산하는주된세포임을확인할수있었다. 자연살해세포가 IFN-γ를분비하기위해서는다른사이토카인의자극또는수용체를통하여이웃세포와의직접적인접촉이필요하며, 특히탄저균감염시자연살해세포에의한 IFN-γ 분비에대식세포가생산하는 IL-12 가중요한역할을한다고알려져있다. 따라서 PGA가비장세포와골수유래대식세포를자극하여 IL-12 의분비를유도하는지조사하였다. 그결과, Figure 2A에서보는바와같이 PGA는통계적으로유의하게비장세포와골수유래대식세포에서 IL-12 의분비를유도하였다 (P <.5). PGA 자극에의하여자연살해세포에서유도되는 IFN-γ 생산에대식세포가분비하는 IL-12의역할을알아보기위하여자연살해세포와대식세포를동시배양한세포 (Figure 2B) 와비장세포 (Figure 2C) 에각각대조군항체와 IL-12 중화항체를 1시간전처리한후 PGA를 24시간또는 48시간동안처리하였다. 그결과자연살해세포와대식세포를동시배양한세포그리고비장세포모두에서대조군항체를처리한그룹에비해 IL-12 중화항체를처리한그룹에서 PGA에의한 IFN-γ 분비가통계적으로유의하게감소되는것을확인하였다 (P <.5). 이러한결과들을종합해볼때 PGA 자극에의해대식세포에서생산되는 IL-12 가자연살해세포의 IFN-γ 분비에중요함을확인할수있었다. 다음으로 PGA에의한 IFN-γ 생산에자연살해세포와대식세포사이의세포간접촉의필요성을자연살해세포와대식세포간의직접적인접촉을막을수있는 transwell을 www.cdc.go.kr 13

주간건강과질병 제 11 권제 5 호 A 8 B 8 NS IFN-γ (pg/ ml ) 6 4 2 Transwell - + + + PGA+BMDMs sup. - + - - PGA - - + + IFN-γ (pg/ ml ) 6 4 2 PGA - + + + + αnkg2d - - + - - αrae-1 - - - + - Control lgg - - - - + Figure 3. NK cell activation by PGA requires cell-cell contact-dependent co-stimulation by macrophages (A) Purified NK cells with bone marrow-derived macrophages (BMDMs) were stimulated with 1 μg/ ml PGA for 48 h in the different conditions as indicated. (B) Purified NK cells with BMDMs were pretreated with control IgG, anti-nkg2d (5 μg/ ml ) or anti-rae1 (5 μg/ ml ) neutralizing antibodies for 1 h and then the cells were stimulated with 1 μg/ ml PGA for 48h. IFN-γ concentrations in the culture supernatants were determined by ELISA. *P <.5. NS denotes not significant (Source: Lee et al., Journal of Microbiology and Biotechnology. 217;27(5):132-7). 사용하여조사하였다. Figure 3A에서보는바와같이 PGA를처리한골수유래대식세포의배양액은 transwell을이용하여대식세포와자연살해세포간접촉을막았을경우에 IFN-γ의분비를거의유도하지못하였다. 따라서세포간접촉이 IFN-γ의분비에중요함을확인할수있었다. 자연살해세포활성화유도수용체인 NKG2D가자연살해세포의 IFN-γ 분비에중요함이알려져있으므로자연살해세포와 PGA로자극한대식세포간상호작용에의한 IFN-γ 분비에 NKG2D 수용체가관여하는지를조사하였다. NKG2D 수용체에대한중화항체를처리할경우 PGA에의한 IFN-γ 분비가약 55%(P =.1) 감소하였으며, 또한 NKG2D 수용체의리간드 (ligand) 들중하나인 RAE-1에대한중화항체를처리한경우에도 PGA에의한 IFN-γ 분비가약 57%(P =.1) 감소하였다 (Figure 3B). 이러한결과들을종합해볼때 PGA에의한자연살해세포의활성화와 IFN-γ 분비에 NKG2D와 RAE-1 결합을 맺는말 이연구에서는 PGA에의해활성화된대식세포와자연살해세포간의상호작용을통한자연살해세포의활성화기전에대하여조사하였다. 그결과활성화된대식세포에서분비되는 IL- 12와 NKG2D-RAE-1 결합을통한대식세포와자연살해세포간상호작용이 PGA에의한 IFN-γ 분비에필요함을확인할수있었다. 그러나보다더자세한기전을밝히기위하여 IL-18, IL-15 그리고 type I IFNs와같은 soluble factor 뿐만아니라 NKp3, NKp46과같은자연살해세포활성화수용체가자연살해세포에서의 IFN-γ 분비에관여하는지에대한추가연구가필요하다. 이연구결과는탄저균캡슐에의한탄저병기전을이해하고, 백신과치료제개발을위한주요자료로활용될수있을것으로기대된다. 통한대식세포와의세포간접촉이중요함을확인할수있었다. 이연구단신은 Journal of Microbiology and Biotechnology 217;27(5):132-7 에게재된논문의재편집을통해작성되었습니다. www.cdc.go.kr 131

주간건강과질병 제 11 권제 5 호 참고문헌 1. Inglesby TV, O Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, et al. Anthrax as a biological weapon: updated recommendations for management. JAMA. 22;287:2236-52. 2. Morse SA Pathogen security-help or hindrance? Front Bioeng Biotechnol. 215;2:83 3. Guichard A, Nizet V, Bier E. New insights into the biological effects of anthrax toxins:linking cellular to organismal responses. Microbes Infect. 212;14:97-118. 4. Leppla SH, Robbins JB, Schneerson R, Shiloach J. Development of an improved vaccine for anthrax. J Clin Invest. 22;11:141-4. 5. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 28;9:53-1. 6. Newman KC, Riley EM. Whatever turns you on: accessory-celldependent activation of NK cells by pathogens. Nat Rev Immunol. 27;7:279-91. 7. Schoenborn JR, Wilson CB. Regulation of interferon gamma during innate and adaptive immune responses. Adv Immunol. 27;96:41-11. 8. Roberts LM, Davies JS, Sempowski GD, Frelinger JA. IFN-gamma, but not IL-17A, is required for survival during secondary pulmonary Francisella tularensis Live Vaccine Strain infection. Vaccine. 214;32:3595-63. 9. Walberg K, Baron S, Poast J, Schwartz B, Izotova L, Pestka S, et al. Interferon protects mice against inhalation anthrax. J Interferon Cytokine Res. 28;28:597-61. 1. Gold JA, Hoshino Y, Hoshino S, Jones MB, Nolan A, Weiden MD. Exogenous gamma and alpha/beta interferon rescues human macrophages from cell death induced by Bacillus anthracis. Infect Immun. 24;72:1291-7 11. Gonzales CM, Williams CB, Calderon VE, Huante MB, Moen S T, P opov V L, et al. Antibacterial role for natural killer cells in host defense to Bacillus anthracis. Infect Immun. 212;8:234-42. 12. Klezovich-Benard M, Corre JP, Jusforgues-Saklani H, Fiole D, Burjek N, Tournier JN, et al. Mechanisms of NK cell-macrophage Bacillus anthracis crosstalk: a balance between stimulation by spores and differential disruption by toxins. PLoS Pathog. 212;8:e12481. www.cdc.go.kr 132

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주요감염병통계, Statistics of selected infectious diseases 1.1 환자감시 : 전수감시감염병주간발생현황 (4th Week) Table 1. Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Category Ⅰ Category Ⅱ Category Ⅲ Category Ⅳ Classification of disease 218 ly average www.cdc.go.kr 134 Total no. of cases by year 217 216 215 214 213 Cholera 5 4 3 Typhoid fever 9 28 3 128 121 121 251 156 Paratyphoid fever 3 1 73 56 44 37 54 Imported cases of current : Country (no. of cases) Shigellosis 1 58 3 111 113 88 11 294 Philippines(4), Vietnam(1) EHEC 1 4 1 139 14 71 111 61 Vietnam(1) Viral hepatitis A 55 254 39 4,429 4,679 1,84 1,37 867 Pertussis 14 64 2 326 129 25 88 36 Tetanus 2 34 24 22 23 22 Measles 3 9 11 18 7 442 17 Mumps 258 972 283 16,921 17,57 23,448 25,286 17,24 Rubella 1 1 11 11 11 11 18 Viral hepatitis B (Acute) 7 32 4 393 359 155 173 117 Japanese encephalitis 9 28 4 26 14 Varicella 1,22 6,41 1,74 8,71 54,6 46,33 44,45 37,361 Streptococcus pneumoniae 22 12 6 518 441 228 36 - Malaria 5 2 515 673 699 638 445 Scarlet fever 417 1,611 171 22,862 11,911 7,2 5,89 3,678 Meningococcal meningitis 1 18 6 6 5 6 Legionellosis 7 23 1 197 128 45 3 21 Vibrio vulnificus sepsis 47 56 37 61 56 Murine typhus 1 2 18 15 9 19 Scrub typhus 17 1 1 1,592 11,15 9,513 8,13 1,365 Leptospirosis 13 1 134 117 14 58 5 Brucellosis 2 9 26 4 5 8 16 Rabies HFRS 3 34 6 599 575 384 344 527 Syphilis 42 187 2 2,152 1,569 1,6 1,15 799 CJD/vCJD 4 11 1 68 42 33 65 34 Tuberculosis 64 2,378 594 28,577 3,892 32,181 34,869 36,89 HIV/AIDS 15 36 14 1,5 1,62 1,18 1,81 1,13 Viral hepatitis C 257 983-6,411 - - - - Russia(1), China(1) VRSA - - - - - CRE 172 645-5,373 - - - - Dengue fever 5 15 4 177 313 255 165 252 Philippines(2), Taiwan(1), Vietnam(1), Cambodia(1) Q fever 6 42 1 126 81 27 8 11 West Nile fever Lyme Borreliosis 2 12 4 27 9 13 11 United Kingdom(1) Melioidosis 2 4 4 2 2 Chikungunya fever 5 1 2 1 2 SFTS 272 165 79 55 36 MERS - 185 - - Zika virus infection - 11 16 - - - Unit: No. of cases 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 217, 218 are provisional but the data from 213 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) 719-7112

Table 2. Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅰ Reporting area Cholera Typhoid fever Paratyphoid fever Shigellosis 218 218 218 218 Overall 9 28 1 3 2 1 58 9 Seoul 1 4 2 2 2 9 2 Busan 2 4 3 Daegu 1 1 3 Incheon 3 1 1 1 5 3 Gwangju 1 1 Daejeon 1 1 2 Ulsan 2 2 Sejong 2 2 Gyonggi 4 2 1 3 11 3 Gangwon 2 2 Chungbuk 1 Chungnam 1 1 1 5 Jeonbuk 1 1 Jeonnam 1 1 2 1 Gyeongbuk 1 1 2 Gyeongnam 2 4 1 1 Jeju Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 135

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅰ Diseases of Category Ⅱ Reporting area Enterohemorrhagic Escherichia coli 218 Viral hepatitis A Pertussis Tetanus 218 218 218 Overall 1 4 55 254 131 14 64 7 2 Seoul 7 37 24 4 9 2 Busan 3 6 2 1 Daegu 1 1 2 8 3 1 1 Incheon 1 18 11 1 4 Gwangju 1 3 3 1 1 1 Daejeon 5 13 6 Ulsan 1 2 2 Sejong 1 1 2 2 Gyonggi 1 16 76 43 1 39 1 Gangwon 1 5 4 Chungbuk 5 11 5 1 2 1 Chungnam 1 5 32 8 Jeonbuk 2 2 8 1 2 Jeonnam 4 4 1 Gyeongbuk 5 11 3 1 Gyeongnam 1 1 7 3 3 3 1 Jeju 1 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 136

Table 2. Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅱ Reporting area Measles Mumps Rubella 218 218 218 Viral hepatitis B (Acute) 218 Overall 3 9 258 972 1,25 1 1 7 32 1 Seoul 2 38 116 119 1 1 5 2 Busan 13 61 97 1 3 1 Daegu 1 1 9 42 27 2 Incheon 1 15 55 4 1 Gwangju 8 26 19 Daejeon 5 3 49 1 1 Ulsan 7 38 37 2 1 Sejong 2 5 5 1 2 Gyonggi 1 3 71 243 24 3 8 4 Gangwon 11 36 51 1 Chungbuk 8 25 21 1 Chungnam 11 54 4 2 1 Jeonbuk 7 3 132 2 1 Jeonnam 1 1 14 41 74 1 Gyeongbuk 9 45 36 1 1 2 Gyeongnam 1 21 11 18 1 6 Jeju 9 24 2 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 137

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅱ Diseases of Category Ⅲ Reporting area Japanese encephalitis Varicella Malaria Scarlet fever 218 218 218 218 Overall 1,22 6,41 4,97 5 5 417 1,611 611 Seoul 145 876 52 2 61 224 64 Busan 82 279 323 43 132 46 Daegu 53 34 296 16 49 24 Incheon 61 385 294 2 1 26 82 24 Gwangju 45 28 131 1 2 75 3 Daejeon 34 176 13 14 56 18 Ulsan 5 177 164 27 76 25 Sejong 9 28 28 3 12 1 Gyonggi 362 1,915 1,43 1 1 96 419 185 Gangwon 17 155 198 4 27 8 Chungbuk 47 238 12 1 1 9 45 11 Chungnam 43 26 231 18 57 28 Jeonbuk 33 244 233 13 7 24 Jeonnam 65 262 231 22 86 22 Gyeongbuk 46 267 26 1 6 41 Gyeongnam 67 35 362 3 118 52 Jeju 43 214 19 5 23 8 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 138

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅲ Reporting area Meningococcal meningitis Legionellosis Vibrio vulnificus sepsis Murine typhus 218 218 218 218 Overall 1 7 23 3 1 Seoul 5 2 1 Busan 2 Daegu 1 1 Incheon 1 1 Gwangju Daejeon 1 2 Ulsan 1 1 Sejong Gyonggi 2 6 1 Gangwon Chungbuk 1 Chungnam 1 Jeonbuk 1 Jeonnam Gyeongbuk 1 1 Gyeongnam 1 Jeju 1 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 139

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅲ Reporting area Scrub typhus Leptospirosis Brucellosis 218 218 218 Hemorrhagic fever with renal syndrome 218 Overall 17 1 45 13 1 2 9 3 34 23 Seoul 2 2 1 1 2 4 1 Busan 1 2 Daegu 2 Incheon 1 2 1 1 1 Gwangju 1 Daejeon 1 2 Ulsan 1 4 2 Sejong Gyonggi 2 4 5 1 1 1 3 1 6 1 Gangwon 1 1 1 3 Chungbuk 1 4 1 1 1 Chungnam 1 1 2 2 2 1 Jeonbuk 2 5 4 2 Jeonnam 6 15 1 3 1 Gyeongbuk 6 2 3 2 Gyeongnam 3 41 9 12 13 1 Jeju 4 2 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 14

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅲ Diseases of Category Ⅳ Reporting area Syphilis CJD/vCJD Tuberculosis Dengue fever 218 218 218 218 Overall 42 187 74 4 11 1 64 2,378 2,418 5 15 14 Seoul 1 54 13 2 113 41 494 2 5 5 Busan 3 9 4 1 39 166 183 3 Daegu 1 7 4 26 11 121 1 2 Incheon 8 17 7 34 115 13 1 1 1 Gwangju 5 2 1 1 17 49 64 Daejeon 1 8 2 18 55 61 1 Ulsan 2 2 1 16 51 47 Sejong 8 16 4 Gyonggi 8 42 19 2 3 1 128 522 52 2 3 3 Gangwon 1 5 4 36 118 96 Chungbuk 2 6 2 2 75 69 Chungnam 2 7 1 2 29 118 95 Jeonbuk 3 23 99 93 Jeonnam 4 2 1 1 37 123 113 1 Gyeongbuk 3 9 3 1 48 178 162 1 1 Gyeongnam 8 4 43 16 158 1 Jeju 1 4 3 5 31 25 Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 141

Table 2. (Continued) Reported cases of national infectious diseases in Republic of Korea, ending January 27, 218 (4th Week)* Unit: No. of cases Diseases of Category Ⅳ Reporting area Q fever Lyme Borreliosis SFTS Zika virus infection 218 218 218 3-year 218 3-year Overall 6 42 1 2 12 - Seoul 2 6 - Busan 2 1 - Daegu 2 - Incheon - Gwangju - Daejeon 2 - Ulsan 3 1 - Sejong - Gyonggi 2 14 3 - Gangwon - Chungbuk 2 6 - Chungnam 5 - Jeonbuk - Jeonnam 2 - Gyeongbuk 1 2 1 - Gyeongnam 1 4 1 - Jeju - Cum: Cumulative counts from 1st to current in a year * The reported data for year 217, 218 are provisional but the data from 213 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. www.cdc.go.kr 142

1.2 환자감시 : 표본감시감염병주간발생현황 (4th ) 1. Influenza, Republic of Korea, s ending January 27, 218 (4th ) 218 년도제 4 주인플루엔자표본감시 ( 전국 2 개표본감시기관 ) 결과, 의사환자분율은외래환자 1, 명당 43.6 명으로지난주 (59.6 명 ) 대비감소 217-218 절기유행기준은 6.6 명 (/1,) 1 9 8 7 ILI per 1, 6 5 4 3 2 1 36 38 4 42 44 46 48 5 52 2 4 6 8 1 12 14 16 18 2 22 24 26 28 3 32 34 217-218 216-217 215-216 214-215 213-214 Figure 1. Weekly proportion of influenza-like illness per 1, outpatients, 213-214 to 217-218 flu seasons 2. Hand, Foot and Mouth Disease(HFMD), Republic of Korea, s ending January 27, 218 (4th ) 218 년도 4 주차수족구병표본감시 ( 전국 95 개의료기관 ) 결과, 의사환자분율은외래환자 1, 명당.3 명으로전주 (.4 명 ) 대비감소 수족구병은 29 년 6 월법정감염병으로지정되어표본감시체계로운영 No. of outpatients / 1, 55. 5. 45. 4. 35. 3. 25. 2. 15. 1. 5. 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 218 217 216 215 214 213 Figure 2. Weekly proportion of hand, foot and mouth disease per 1, outpatients, 213-218 www.cdc.go.kr 143

3. Ophthalmologic infectious disease, Republic of Korea, s ending January 27, 218 (4th ) 218 년도제 4 주유행성각결막염의표본감시 ( 전국 92 개의료기관 ) 결과, 외래환자 1, 명당분율은 15. 명으로전주 12.5 명대비증가 동기간급성출혈성결막염의환자분율은 1. 명으로지난주.8 명대비증가 6 5 No. of outpatients / 1, 4 3 2 1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 218 217 216 215 214 Figure 3. Weekly proportion of epidemic keratoconjunctivitis per 1, outpatients 5 4 No. of outpatients / 1, 3 2 1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 218 217 216 215 214 Figure 4. Weekly proportion of acute hemorrhagic conjunctivitis per 1, outpatients www.cdc.go.kr 144

4. Sexually Transmitted Diseases, Republic of Korea, ending January 27, 218 (4th ) 218 년도제 4 주성매개감염병표본감시기관 ( 전국보건소및의료기관 584 개참여 ) 에서성기단순포진 2.6 건, 첨규콘딜롬 2.1 건, 클라미디아감염증 1.9 건, 임질 1.2 건발생을신고함. 제 4 주차신고의료기관수 : 임질 19 개, 클라미디아 59 개, 성기단순포진 51 개, 첨규콘딜롬 31 개 Unit: No. of cases/sentinels Gonorrhea Chlamydia Genital herpes Condyloma acuminata 218 218 218 218 Total 1.2 2.1 2.5 1.9 4.4 4. 2.6 5.6 4.6 2.1 3.6 2.9 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)719-7118, 7132 자세히보기 : 질병관리본부 정책 / 사업 감염병감시 표본감시주간소식지 1.3 수인성및식품매개감염병집단발생주간현황 (4th ) Waterborne and foodborne disease outbreaks, Republic of Korea, s ending January 27, 218 (4th ) 218 년도제 4 주보고기관 ( 전국 254 개보건소 ) 에서집단발생이 4 건이발생하였으며누적발생건수는 24 건 ( 사례수 167 명 ) 이발생함. 35 3 25 No. of outbreaks 2 15 1 5 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 218 217 Average no. of cases in last 5 years(212-216) Figure 5. Number of waterborne and foodborne disease outbreaks reported by, 217-218 www.cdc.go.kr 145

2.1 병원체감시 : 인플루엔자및호흡기바이러스주간감시현황 (4th ) 1. Influenza viruses, Republic of Korea, s ending January 27, 218 (4th ) 218 년도 4 주에 17 개시 도보건환경연구원및 52 개의료기관에서의뢰된호흡기검체 35 건중 164 건양성 [A(H1N1)pdm9 1 건, A(H3N2) 63 건, B 형 1 건 ] No. of positives 2 18 16 14 12 1 8 6 4 2 36 37 38 39 4 41 42 43 44 45 46 47 48 49 5 51 52 1 2 3 4 5 6 7 8 9 1 11 12 13 14 15 16 17 18 19 2 21 22 23 24 25 26 27 28 29 3 31 32 33 34 35 A(H3N2) A(not subtyped) A(H1N1)pdm9 B Percent positive 12. 1. 9. 8. 7. 6. 5. 4. 3. 2. 1. Percent positives (%) Figure 6. Number of specimens positive for influenza by subtype, 216-217 to 217-218 flu season 2. Respiratory viruses, Republic of Korea, s ending January 27, 218 (4th ) 218 년도제 4 주호흡기검체에대한유전자검사 (17 개시 도보건환경연구원및전국 52 개참여의료기관 ) 결과, 75.1% 의호흡기바이러스가 검출되었음. ( 최근 4 주평균 38 개의호흡기검체에대한유전자검사결과를나타내고있음 ) 주별통계는잠정통계이므로변동가능 217-218 () Weekly total Detection rate (%) HAdV HPIV HRSV IFV HCoV HRV HBoV HMPV 1 87.5 3.2. 8.2 67.7 5.7 2.5.. 2 71.3 2.1.6 4.5 57.3 5.7.6..6 3 8.2 2.2 1.6 2.2 64.2 6.7 1.9.3 1. 4 75.1 2.3 1. 4.3 53.8 8.2 3.9.3 1.3 78.2 2.4.8 4.7 6.6 6.6 2.2.2.7 217 56.6 3.7 6.3 4.6 1.9 4.4 19.4 2. 5.3 - 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 December. 24. 217. January. 2. 218, (Average No. of detected cases is 32 in last 4 s) 217 : the rate of detected cases between January. 1. 217. - December. 3. 217. 자세히보기 : 질병관리본부 알림 주간질병감시정보 www.cdc.go.kr 146

2.2 병원체감시 : 급성설사질환실험실표본주간감시현황 (3rd ) Detection rate of acute gastroenteritis causing virus and bacteria, Republic of Korea, Republic of Korea, s ending January 2, 218 (3rd ) 218 년도제 3 주실험실표본감시 (17 개시 도보건환경연구원및 7 개의료기관 ) 급성설사질환유발바이러스검출건수는 19 건 (43.2%), 세균 검출건수는 12 건 (6.%) 이었음. Acute gastroenteritis-causing viruses Week No. of sample No. of detection (Detection rate, %) Group A Rotavirus Norovirus Enteric Adenovirus Astrovirus Total 217 52 82 9 (11.) 26 (31.7) (.) 3 (3.7) 38 (46.3) 218 1 64 3 (4.7) 17 (26.6) 3 (4.7) 1 (1.6) 24 (37.5) 2 7 1 (14.3) 23 (32.9) 3 (4.3) 1 (1.4) 37 (52.9) 3 44 6 (13.6) 11 (25.) 1 (2.3) 1 (2.3) 19 (43.2) 178 19 (1.7) 51 (28.7) 7 (3.9) 3 (1.7) 8 (44.9) * The samples were collected from children 5 years of sporadic acute gastroenteritis in Korea. 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. 217 52 225 3 (1.3) 3 (1.3) () () () 1 (.4) 2 (.9) 4 (1.8) 3 (1.3) 16 (7.1) 218 1 139 2 (1.4) () () () () 1 (.7) 2 (1.4) 2 (1.4) 1 (.7) 8 (5.8) 2 193 1 (.5) 2 (1.) () () () 1 (.5) 4 (2.) 1 (.5) 1 (.5) 1 (5.2) 3 21 (.) 4 (2.) 1 (.5) () () 3 (1.5) 2 (1.) 2 (1.) () 12 (6.) 533 3 (.6) 6 (1.1) 1 (.2) () () 5 (.9) 8 (1.5) 5 (.9) 2 (.6) 3 (5.6) * 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 218 (7 hospitals) 자세히보기 : 질병관리본부 알림 주간질병감시정보 www.cdc.go.kr 147

2.3 병원체감시 : 엔테로바이러스실험실주간감시현황 (3rd ) Detection rate of enterovirus in enterovirus sentinel surveillance, Republic of Korea, s ending January 2, 218 (3rd ) 218 년도제 3 주실험실표본감시 (8 개시 도보건환경연구원, 전국 6 개참여병원 ) 결과, 새로검출된엔테로바이러스 건 (218 년누적 2 건, 양성률 4.3%) 중무균성수막염 건 (218 년누적 건 ), 수족구병및포진성구협염 건 (218 년누적 1 건 ), 합병증동반수족구 건 (218 년누적 건 ), 기타 건 (218 년누적 1 건 ) 임. Aseptic meningitis 8 Detection rate (%) 6 4 2 1 5 9 13 17 21 25 29 33 37 41 45 49 53 218 Enterovirus detection rate (%) 217 Enterovirus detection rate (%) Figure 7. Detection rate of enterovirus in aseptic meningitis patients from 217 to 218 HFMD and Herpangina 25 Detection rate (%) 2 15 1 5 1 5 9 13 17 21 25 29 33 37 41 45 49 53 218 Enterovirus detection rate (%) 217 Enterovirus detection rate (%) Figure 8. Detection rate of enterovirus in HFMD and herpangina patients from 217 to 218 HFMD with Complications Detection rate (%) 1 9 8 7 6 5 4 3 2 1 1 5 9 13 17 21 25 29 33 37 41 45 49 53 218 Enterovirus detection rate (%) 217 Enterovirus detection rate (%) Figure 9. Detection rate of enterovirus in HFMD with complications patients from 217 to 218 www.cdc.go.kr 148

주요통계이해하기 < 통계표 1> 은지난 5년간발생한법정감염병과 218 년해당주발생현황을비교한표로, 금주환자수 ( ) 는 218 년해당주의신고건수를나타내며, 218 년누계환자수 ( 218) 는 218년 1주부터해당주까지의누계건수, 그리고 5년주평균환자수 ( ly average) 는지난 5년 (213-217 년 ) 해당주의신고건수와이전 2주, 이후 2주의신고건수 ( 총 25주 ) 평균으로계산된다. 그러므로금주환자수 ( ) 와 5년주평균환자수 ( ly average) 의신고건수를비교하면해당주단위시점과예년의신고수준을비교해볼수있다. 연도별환자수 (Total no. of cases by year) 는지난 5년간해당감염병현황을나타내는확정통계이며연도별현황을비교해볼수있다. 예 ) 218 년 12 주의 5 년주평균환자수 ( ly average) 는 213 년부터 217 년의 1 주부터 14 주까지의신고건수를 총 25 주로나눈값으로구해진다. * 5 년주평균환자수 ( ly average)=(x1 + X2 + + X25)/25 1주 11주 12주 13주 14주 218년 해당주 217년 X1 X2 X3 X4 X5 216년 X6 X7 X8 X9 X1 215년 X11 X12 X13 X14 X15 214년 X16 X17 X18 X19 X2 213년 X21 X22 X23 X24 X25 < 통계표 2> 는 17 개시 도별로구분한법정감염병보고현황을보여주고있으며, 각감염병별로최근 5년누계평균환자수 (Cum, average) 와 218년누계환자수 (Cum, 218) 를비교해보면최근까지의누적신고건수에대한이전 5년동안해당주까지의평균신고건수와비교가가능하다. 최근 5년누계평균환자수 (Cum, average) 는지난 5년 (213-217 년 ) 동안의동기간신고누계평균으로계산된다. 기타표본감시감염병에대한신고현황그림과통계는최근발생양상을신속하게파악하는데도움이된다.

발간등록번호 11-1351159-2-3 주간건강과질병, PHWR 은질병관리본부에서시행되는조사사업을통해생성된감시및연구자료를기반으로근거중심의건강및질병관련정보를제공하고자최선을다할것이며, 제공되는정보는질병관리본부의특정의사와는무관함을알립니다. 본간행물에서제공되는감염병통계는 감염병의예방및관리에관한법률 에의거, 국가감염병감시체계를통해신고된자료를기반으로집계된것으로집계된당해년도자료는의사환자단계에서신고된것이며확진결과시혹은다른병으로확인될경우수정될수있는잠정통계임을알립니다. 주간건강과질병, PHWR 은질병관리본부홈페이지를통해주간단위로게시되고있으며, 정기적구독을원하시는분은 kcdc215@korea.kr로신청가능합니다. 이메일을통해보내지는본간행물의정기적구독요청시구독자의성명, 연락처, 직업및이메일주소가요구됨을알려드립니다. 주간건강과질병 발간관련문의 : kcdc215@korea.kr/ 43-249-328/33 창 발 간 : 28 년 4 월 4 일 행 : 218 년 2 월 1 일 발행인 : 정은경 편집인 : 박도준 편집위원 : 최영실, 김기순, 최병선, 조신형, 조성범, 김봉조, 구수경, 김용우, 이동한, 조은희, 이은규, 신영림, 김청식, 전경아, 권효진 편 집 : 질병관리본부유전체센터의과학지식관리과 충북청주시흥덕구오송읍오송생명 2 로 187 오송보건의료행정타운 ( 우 )28159 Tel. (43) 249-328/33 Fax. (43) 249-334