연구논문, Research article 2017 년국내메르스의심환자감시및대응결과 질병관리본부메르스대책반김은경, 류보영, 이지아, 김세원, 김지아, 김지연, 김정연, 김효진, 신희영, 이기용, 최선아, 최초로, 최한샘, 이정헌, 이아경, 김희정, 문상준, 홍정익 * * 교신저자 : hongji3755@korea.kr, 043-719-7190 Results of national surveillance and response in patients with Middle East respiratory syndrome coronavirus infection under investigation in Korea in 2017 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 2012, 2,127 confirmed cases have been reported globally, with a high mortality rate of 35.6% (as of December 31, 2017). 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, 2017. Current status: A total of 220 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%). 40 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
들어가는말 중동호흡기증후군 (Middle East respiratory syndrome, MERS; 이하메르스 ) 은 2012년 4월사우디아라비아에서처음보고후 2017년 12월 31일까지전세계적으로 27개국에서 2,127 명이확진되고 757명이사망하여치사율 35.6% 를보이는급성호흡기질환이다. 확진환자는주로사우디아라비아에서발생하고있으며 ( 확진 1,753 명, 사망 683명 ), 대부분낙타와직접접촉에의한 1차감염이다. 1차감염자와가족과의접촉또는의료기관내감염등으로인한 2차감염은소규모유행으로지속적으로발생하고있다. 2017년의메르스발생양상도예년과같이대부분사우디아라비아 ( 확진 238명, 사망 74명 ) 를중심으로지속적이고산발적으로발생하였고 신고 보고대상으로정하고있으며, 메르스대응지침 에따라역학조사및메르스검사를시행하는대상자를메르스의심환자까지확대하여신고하도록하고있다. 신고대상을메르스의심환자까지확대한것은의심증상이있는본인의자발적신고또는진료시인지한의사등누구나신고가능하도록하여메르스를조기에인지하고대응하기위함으로 증상발생 14일이내중동지역의방문력이있고발열과호흡기증상이있는경우 의심환자에해당한다 [5-7]. 이와관련하여질병관리본부는중동지역 ( 아라비안반도및인근 13개국 ) 방문 여행객을대상으로메르스의심환자발생감시체계를 2016년에이어 2017년에도유지하고있으며, 이와관련된 2017년메르스의심환자감시및대응결과를정리하여공유하고자한다. 네차례의료기관중심유행도발생하여해외로부터메르스국내 유입을차단하고조기대응하기위한체계적이고지속적인감시및대응관리가매우중요하다 [1-4]. 국내에서는메르스를 감염병의예방및관리에관한법률 에근거하여제4군감염병으로지정하여환자및의사환자를 몸말 방법및대상 60 50 MERS-suspect patients in 2017 Non-MERS patients in 2017 MERS-suspect patients in 2016 Non-MERS patients in 2016 No. of patients 40 30 20 10 0 37 18 40 33 20 26 24 33 26 27 17 26 24 25 11 17 16 20 19 21 27 15 21 23 23 14 19 22 10 11 11 17 12 14 17 17 24 28 19 23 20 18 18 22 15 13 11 9 18 10 9 15 7 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 0 2 3 3 4 4 4 4 2 3 2 5 8 5 2 4 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 week 29 Figure 1. Trends of notification and response on suspect patients of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by week, 2016 and 2017 www.cdc.go.kr 122
Table 1. Reporting entities or pathways of MERS-related cases between 2016 and 2017 N (%) Reporting entities or pathways MERS-suspect patients Non-MERS suspect patients 2016 2017 2016 2017 Via KCDC call center 1339 / Community health center 70 (35.0) 81 (36.8) 542 (83.4) 869 (84.5) At healthcare facilities 81 (40.5) 99 (45.0) 79 (12.2) 19 (1.8) At the port of entry (mainly airport quarantine stations) 49 (24.5) 40 (18.2) 29 (4.5) 140 (13.6) Total 200 220 650 1,028 MERS-suspect patients in 2016 MERS-suspect patients in 2017 24.5% 35.0% 18.2% 36.8% Via KCDC call center 1339 / Community health center 40.5% 45.0% At healthcare facilities At the port of entry (mainly airport quarantine stations) (N = 200) (N = 220) Figure 2. Comparison of MERS-suspect patients by reporting entities, 2016 and 2017 격리하고검사를실시한다. 질병관리본부긴급상황실과중앙 2017년 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 2017년 1월 1일부터 12월 31일까지질병관리본부콜센터 (1339) 또는지자체보건소등을통해인지 신고된사례는총 1,248건, 월평균 104건으로월최소 78건, 최대 156건이신고되었다. 5월, 10월과 12월에월 120건이상신고되어월별신고가가장많았으며 2016년에는 1월과 5월에신고가많았으나 2017년에는이슬람하지성지순례기간이후인 10월과국내급성호흡기감염증이유행하는 12월에의심환자신고가많았다. 메르스의심환자신고는 2017년에총 1,248건으로 2016년 www.cdc.go.kr 123
Table 2. Demographical, epidemiological and clinical characteristics of suspected patients of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, 2017 Variables Characteristics N (%) Nationality Korean 170 (77.3) Foreigners 50 (22.7) Sex Male 124 (56.4) Female 96 (43.6) Age (years) 0-9 23 (10.5) Visiting or stopping-over countries in the Middle East * 10-19 7 (3.2) 20-29 52 (23.6) 30-39 56 (25.5) 40-49 31 (14.1) 50-59 26 (11.8) 60+ 25 (11.4) UAE 136 (61.8) Saudi Arabia 39 (17.7) Israel 17 (7.7) Qatar 13 (5.9) Iran 10 (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 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 (0.5) Clinical Body temperature over 37.5 193 (87.7) characteristics Masked fever due to medication (analgesic, common cold, antimicrobial) 23 (10.5) Fever and symptoms of respiratory illness 156 (70.9) 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) Symptoms at Fever 186 (84.5) presentation 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 (5.0) GI symptoms 4 (1.8) Others 4 (1.8) Close contact Close contact since symptom onset per one suspected case, median (range) 25 (0-247) *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
Table 3. Comparison of respiratory viruses isolated from suspect patients for MERS-CoV infection under investigation by reverse transcription polymerase chain reaction (RT-PCR), 2016 and 2017 N (%) Respiratory pathogens 2016 2017 Negative 102 (51.0) 75 (34.1) Positive 98 (49.0) 145 (65.9) Single pathogen 92 (46.0) 128 (58.2) Influenza A(H3N2) 21 (10.5) 41 (18.6) Influenza A(H1N1)pdm09 28 (14.0) 14 (6.4) Rhinovirus 11 (5.5) 25 (11.4) Influenza B 16 (8.0) 18 (8.2) Human metapneumovirus 5 (2.5) 11 (5.0) Human adenovirus 2 (1.0) 7 (3.2) Human coronavirus 4 (2.0) 7 (3.2) Human parainfluenzavirus 3 (1.5) 5 (2.3) Repiratory syncytial virus 2 (1.0) - Multi-pathogens 6 (3.0) 17 (7.7) Influenza B, Human metapneumovirus 1 (0.5) 1 (0.5) Influenza B, parainfluenza virus - 1 (0.5) Influenza A, Human coronavirus - 1 (0.5) Influenza A, parainfluenza virus - 1 (0.5) Influenza A(H1N1), Rhinovirus - 2 (0.9) Influenza A(H3N2), Rhinovirus 1 (0.5) 1 (0.5) Influenza A, Influenza B - 1 (0.5) Influenza B, Rhinovirus 1 (0.5) 1 (0.5) Bocavirus, parainfluenza virus - 1 (0.5) Bocavirus, RSV 1 (0.5) 1 (0.5) Adenovirus, Human metapneumovirus - 1 (0.5) Adenovirus, Rhinovirus - 2 (0.9) Adenovirus, Bocavirus 1 (0.5) 1 (0.5) Rhinovirus, Bocavirus - 1 (0.5) Rhinovirus, RSV - 1 (0.5) Adenovirus, Rhinovirus, Human coronavirus 1 (0.5) - 850명과비교시 46.8% 가량증가하였고메르스의심환자분류는 2017년총 220건으로 2016년 200건과비교시 10.0% 가량증가하였다. 월평균의심환자분류는 18.3명으로주별의심환자신고및분류현황은그림 1에나타내었다 (Figure 1). 2017년메르스의심환자신고경로를보면, 의료기관에서진료시의사등의료진에의해보고된경우가 99건 (45.0%) 으로가장많았고의심환자본인이메르스의심증상으로 1339로신고하거나보건소를통해신고한경우가 81건 (36.8%) 이었다. 2016년신고경로와 비교시의료기관을통한신고와질병관리본부콜센터및보건소를통한신고모두증가하였다. 공항등출입국시설의검역과정에서의심환자로분류된경우가 40건 (18.2%) 이었다 (Figure 2, Table 1). 지자체별메르스의심환자분류및대응은검역소대응을제외하고경기 64건 (29.1%), 서울 43건 (19.5%), 인천 10건 (4.5%) 순으로많았고, 그외시 도에서의심환자대응건수는연간 1 9 건이었다. 검역소에서신고한의심환자는이송거리를고려하여서울 (19건) 과인천 (21건 ) 에소재한국가지정격리병원을이용하였으며이를반영한 www.cdc.go.kr 125
시 도별대응빈도는서울 64건 (29.1%), 경기 62건 (28.2%), 인천 31건 (14.1%) 순이었다. 의심환자로분류된경우지체없이음압격리병상에입원하여검사를실시하였고 220명모두메르스바이러스유전자검사에서음성으로확인되었다. 의심환자의일반적, 역학적및임상적특성 의심환자의인구학적특성을보면평균연령은 36세이고, 내국인이 170명 (77.3%), 외국인이 50명 (22.7%) 이었다. 성별은남성이 124명 (56.4%) 으로여성보다많았으며, 연령대는 20대와 30대가 108명 (49.1%) 으로높은빈도를보였다. 의심환자의중동 메르스의심환자에게확진검사를실시할때, 다른호흡기바이러스에의한감염을배제하기위해급성호흡기바이러스감염증 8종에대한유전자검사를동시에실시하였다. 2017년메르스의심환자에게급성호흡기바이러스감염증이확인된경우는 145명 (65.9%) 으로 2016년 98명 (49.0%) 에비하여바이러스검출이증가하였고, 2016년과 2017년모두 Influenza A 검출이가장많은것으로나타났다 (2016년 24.5%, 2017년 25.0%). 2017년메르스의심환자의급성호흡기바이러스감염증은 Influenza A 55건 (25.0%), Rhinovirus 25건 (11.4%), Influenza B 18건 (8.2%) 순으로확인되었고, 의심환자의 7.7%(17건 ) 는 2개이상의호흡기바이러스에중복감염된것으로확인되었는데 2016년에비해다중병원체검출도증가하였다 (Table 3). 지역방문력은 2017 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 (70.9%), 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 4,280명으로의심환자 1인당평균 25명이었으며최소 0명에서최대 247명을접촉한것으로확인되었다 (Table 2). 의심환자의호흡기바이러스감염원 맺는말 국내 감염병위기경보수준대응체계 에따라현재는메르스환자의국내유입이없는 관심 단계이나, 질병관리본부에서는메르스대책반을운영하고국외발생동향을면밀히파악하고중동지역방문 경유후국내에입국하는여행객에의한메르스국내유입을조기에인지하여대응하기위해메르스의심환자연중감시체계를유지하고있다. 2017년메르스의심환자감시결과, 의심환자의 85.5% 는 2017년메르스발생국가를방문 경유하였다. 낙타접촉, 현지의료기관방문등역학적연관성이높아위험노출을고려할수있는사례는 38건 (17.3%) 이었고대부분은역학적연관성이낮거나경증사례였다. 2015년국내메르스유행시대부분중증급성하기도질환 ( 폐렴 ) 이있었던것과달리 2016년과 2017년모두대부분경증의호흡기증상을보였고폐렴이의심또는확인된경우는 2016년 8.0%, 2017년 14.1% 에불과하였다. 메르스의심환자에대한사례정의및기준은국가별로다르나국외감시체계운영결과를보면메르스의심환자의인플루엔자양성률이방글라데시의경우 40% 로보고되었고, 싱가포르의경우 27% 로보고되어 [3] 2017년국내인플루엔자양성률 28% 와비슷한 www.cdc.go.kr 126
수준으로나타나해외여행전인플루엔자예방접종과여행시감염예방수칙을지키도록적극권장할필요가있다. 2017년메르스의심환자감시결과, 의심환자가의료기관을통해신고되는경우가 45% 로 2016년 (40%) 과비슷한수준으로조사되어메르스의심환자가의료기관방문을자제하고먼저질병관리본부콜센터또는보건소에신고후안내에따르도록대국민홍보를강화시킬필요가있다. 또한, 의심환자의 82.7% 는메르스위험노출 ( 낙타접촉, 현지의료기관방문등 ) 없이중동지역을단순방문 경유하였고, 메르스가아닌급성호흡기바이러스에의한감염이 65.9% 를차지하고있어향후주요역학적, 임상적특성을고려한메르스의심환자사례정의및대응방안개선에대한검토가필요하다. 이번분석결과는 2016년과 2017년메르스의심환자의감시및대응결과를토대로메르스대응 대비를지속적으로보완하는근거로활용할것을기대한다. 참고문헌 1. Abdulaziz A, Bin Saeed, Glen R. AbediSurveillance and Testing for Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, April 2015-February 2016. Emerging Infectious disease 2017 Apr;23(4):682-85 2. World Health Organization. http://www.who.int/emergencies/merscov/en/ retrieved on 24, Jan. 2018. 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 2013-2016. PLoS ONE 13(1):e01899914 Jan 16, 2018:1-8. 4. Korea Centers for Disease Control and Prevention. Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015. Osong Public Health Res Perspect. 2015;6(4):269-78. 5. 보건복지부질병관리본부, 2016 메르스 (MERS) 대응지침 4-1판, 2016.11. 6. 보건복지부질병관리본부, 2016 메르스 (MERS) 대응지침 4-2판, 2017.3.20. 7. 보건복지부질병관리본부, 2016 메르스 (MERS) 대응지침 5판, 2017.7.10. www.cdc.go.kr 127