Journal of Bacteriology and Virology 2014. Vol. 44, No. 3 p.274 282 http://dx.doi.org/10.4167/jbv.2014.44.3.274 Communication Infection Frequency and Mixed infection on Eight Viruses from Patients with Acute Respiratory Syndromes in Seoul Heejin Ham 1*, Jungim Jang 1, Sukju Jo 1, Younghee Oh 1 and Sonil Pak 2 1 Microbiology Department, Seoul Metropolitan Government Research Institute of Public Health and Environment, Gwacheon; 2 College of Veterinary Medicine, Kangwon National University, Chuncheon, Korea For our survey of the infection frequency and mixed infection of the viruses causing acute respiratory syndromes, we analyzed those viruses from acute respiratory patients in Seoul. Total 1,038 specimens of oropharyngeal swab were tested by the real-time polymerase chain reaction (PCR) kit (Kogenebiotech, Korea) from Jan. to Dec. in 2013. Virus detection rate causing acute respiratory infection was 46% (476/1,038). The most frequently isolated virus was only hrv (21.6%, 103/476), followed by only ADV (8.96%, 93/476), only IFV A (H3N2) (18.1%, 86/476), and only hcov (7.8%, 37/ 476) etc. Most of acute respiratory viruses had severe fever. Infection frequency information and mixed infection status on respiratory viruses circulating in Seoul will be helpful for the management of acute respiratory infection and for epidemiological continuous studies. Key Words: Mixed infection, Respiratory viruses, Seoul INTRODUCTION 호흡기질환은유행시기에따라서다르지만일반적으로 influenza virus (IFV) 가호흡기질환환자에서높은비율로분리되고, rhinovirus (hrv), parainfluenza virus (PIV) 등이호흡기질환의주요원인으로알려져있다 (1). 인플루엔자바이러스를비롯한급성호흡기질환을일으키는바이러스들은임상증상이비슷하여증상만으로병원체를감별하기가어렵고, 증상도가볍게스쳐가는감기증세에서부터폐렴이나기관지염과같은중증감염으로이어지는경우가많다 (2). 호흡기바이러스의증상은바이러스가주로감염을일으키는부위에따라서전신증상의유무가크게달라지게됨으로상기도와하기도증상을구 분하게되는데, 해부학적으로각부위를감염하는바이러스가어느정도구분되기도한다. Rhinovirus, coronavirus 등은상기도감염을일으키면서도하기도감염을일으키고, influenza virus는주로하기도감염을, parainfluenza, metapneumovirus, adenovirus, respiratory syncytial virus (RSV) 등은하기도감염바이러스이면서도상기도감염을일으키는것으로각각알려져있다. 또한, 상기도감염은열이나전신증상이하기도감염에비하여약하다고표현하지만, 상기도감염에서 fever는성인은없으나소아에서는있을수있으므로, 바이러스이외에나이가증상을결정하는주요인자이다. 급성호흡기질환환자관련검체를, 서울지역에소재하는병의원으로부터채취하여, 그원인바이러스들에대한분포를조사함으로써질병치료와예방에대한기초자료를확보하고자한다. Received: July 11, 2014/ Revised: August 22, 2014/ Accepted: August 26, 2014 * Corresponding author: Heejin Ham. Microbiology Department, Seoul Metropolitan Government Research Institute of Public Health and Environment, 30, Janggunmaeul 3-gil, Gwacheon 427-070, Korea. Phone: +82-2-570-3426, Fax: +82-2-570-3275, e-mail: hhj3814@seoul.go.kr ** This study was supported by KINRESS (Korea Influenza and Respiratory Viruses Surveillance System) project of the Korean CDC. We are grateful for this support. CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/license/by-nc/3.0/). 274
Infection Frequency and Mixed Infection on Eight Viruses 275 MATERIALS AND METHODS 검체수집과가검물처리서울시내 11개병의원으로부터 1,038명의급성호흡기감염증환자의인후도말가검물 (oropharyngeal swabs) 검체 1,038건을멸균된면봉으로수집하였고 (A병원 322건, G병원 127건, K병원 122건, S병원 105건, 기타병원들 362건등 ), 급성호흡기감염증에대한감염을일으키는원인바이러스들에대해서울시보건환경연구원에서분석하였다. 환자의인후도말가검물을사용한본사업은임상시험심사위원회 (Institutional Review Board) 의심의를거쳤고, 검체채취는피험자들의동의를받아진행하였으며, 환자의임상적정보는기록지를통해각병원들에서통합적으로얻었다. 임상적정보와증상에대한기록지를포함하여 11개병원모두에서동일한프로토콜을사용하였다. 환자의인후도말가검물은바이러스수송용배지 (viral transport medium, Becton Dickinson, Ireland) 에넣은후냉장, 운반하여즉시또는 -70 이하에보관하였다가, 멸균된 0.1 M phosphate buffered saline (PBS, ph 7.4, Sigma, USA) 9 ml에넣어 4, 3,000 rpm에서 30분간원심분리하였으며상층액을사용하였다. 바이러스핵산추출및유전자확인수집된가검물은진탕하여원심분리한상층액을 viral RNA mini kit (QIAgen, Hilden, Germany) 를사용하여 RNA를추출하였다. 검체 140 μl에 AVL buffer (guanidine thiocyanate 함유 ) 560 μl를 15초간혼합하여실온에서 10분동안방치하였고, 95~100% 에탄올 560 μl을넣어혼합후 10초간 voltexing 하였으며, 이용액 630 μl을 spin column tube에옮긴후 8,000 rpm에서 1분간원심분리하였고, spin column tube 아래수집된용액을제거후위의과정을 1회더반복하였다. 또한 AW1 Buffer (guanidine hydrochloride 함유 ) 500 μl를첨가후 8,000 rpm에서 1분간원심분리하였고, spin column tube 하단에수집된용액을제거후 AW2 Buffer 를 500 μl를첨가후 13,000 rpm에서 2분원심분리하였으며, spin column을새 spin column tube에꽂은후 Buffer AVE (sodium azide 함유 ) 50 μl를첨가하고실온에서 1분간정치한후 8,000 rpm에서 1분간원심분리, real time-pcr을위한 template로사용하였다. Real-time PCR test Real-time PCR을위해추출한 RNA 5 μl을 real-time PCR 진단 kit (Kogenebiotech, Seoul, Korea) 에각각넣은후반응액이완전히섞이도록하였다. 대상바이러스별 real-time PCR 진단 kit들은 PowerChek parainfluenza virus 1/2/3 real time kit (Kogenebiotech, Seoul, Korea), PowerChek influenza virus A/B real time kit (Kogenebiotech), PowerChek pandemic H1N1/H3N2/H5N1 real time kit (Kogenebiotech), PowerChek adenovirus/bocavirus real time kit (Kogenebiotech), PowerChek rhinovirus real time kit (Kogenebiotech), PowerChek influenza RT-premix with BNA, BHA, Uni-R real time kit (Kogenebiotech), PowerChek RSV/A&B/HMV real time kit (Kogenebiotech), PowerChek coronavirus 229E/OC43/NL63 real time kit (Kogenebiotech) 이었다. 유전자증폭을위해 real-time PCR 기기인 7500 fast thermal cycler (Applied Bio-systems, Foster city, CA, USA) 를이용하여 RNA virus (IFV, hrv, PIV, RSV, hcov, hmpv) 의경우 50 에서 30분, 95 에서 15분처리후 RNA를변성시키고, DNA virus (ADV, hbov) 의경우유전자증폭을위해 50 에서 2분, 95 에서 15분 DNA를변성시킨다. 그후각각 95 15초, 60 1분을 1회로하여 40회반응시킨후, Ct값과 curve를확인하였다. RESULTS AND DISCUSSION 월별급성호흡기바이러스검출양상 2013년채취한총 1,038건의검체검사결과, 호흡기바이러스 45.9% (476/1,038) 가운데, 가장많은검출율을보인바이러스들로는라이노바이러스 21.6% (103/476), 아데노바이러스 8.96% (93/476), 인플루엔자 A형 (H3N2) 바이러스 18.1% (86/476), 그리고코로나바이러스 7.8% (37/ 476) 등으로각각나타났다. 12건이상검출된경우에한하여월별급성호흡기바이러스검출양상을살펴보면, ADV와 hrv 는연중모든달에걸쳐골고루나타나는특징을보였다. ADV+hRV 중복감염의경우 4월 6월, 12월을제외한나머지모든달에걸쳐나타났고, hcov 단독감염의경우, 6, 7, 8, 9월을제외한모든달에걸쳐서나타났으며, IFV A (H1N1) pdm09 바이러스단독감염의경우는 1월부터 4월까지 4개월간만나타났고, IFV A (H3N2) 바이러스단독감염의경우는 1월부터 5월까지 5개월간그리고 7월에 1건나타나는특징을각각보였다. PIV의
276 H Ham, et al. Table 1. Distributions of viruses detected from patients with acute respiratory infection in 2013 in Seoul by periodic surveillance Viral agents Months Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Total Human rhinovirus 6 5 7 24 7 4 8 5 8 14 14 03 Adenovirus 3 3 2 6 8 3 12 12 8 13 12 93 Adenovirus+human bocavirus 1 2 1 4 Adenovirus+human coronavirus 2 Adenovirus+ 1 2 2 1 4 14 Adenovirus+parainfluenza virus 1 2 1 6 Adenovirus+respiratory syncytial virus A(H1N1)pdm09 3 6 4 4 A(H3N2) 31 29 15 9 86 A(H3N2)+ adenovirus A(H3N2)+ human coronavirus 2 A(H3N2)+ 1 3 B 3 1 2 3 9 B+ respiratory syncytial virus Human bocavirus 2 4 Human bocavirus+ 2 4 Human bocavirus+parainfluenza virus Human bocavirus+ respiratory syncytial virus Human coronavirus 6 2 2 2 1 2 3 19 37 Human coronavirus+ 3 1 4 Human coronavirus+parainfluenza virus Human coronavirus+ respiratory syncytial virus Human metapneumovirus 2 6 Human metapneumovirus+ Parainfluenza virus 2 3 6 8 11 2 2 36 Parainfluenza virus+ 1 3 Respiratory syncytial virus 7 3 2 1 2 6 6 7 36 Respiratory syncytial virus+ 2 Total detected numbers (%) 67 (53.6) 55 (56.1) 38 (38.8) 50 (53.8) 35 (40.2) 19 (31.7) 37 (50.7) 21 (51.2) 24 (47.1) 44 (49.4) 41 (39.4) 45 (37.8) 476 (45.9) Sample numbers 125 98 98 93 87 60 73 41 51 89 104 119 1,038
Infection Frequency and Mixed Infection on Eight Viruses 277 경우 2월, 3월, 11월을제외한모든달에걸쳐나타났고, RSV의경우 6월과 7월을제외한모든달에걸쳐나타났다 (Table 1, Fig. 1). Kim 등 (1) 에의하면 2010년에서 2011 년까지부산대학병원과양산부산대학교어린이병원에서급성하기도염으로입원한소아환자들의비인두흡인물을채취하여검사한결과, RSV는 9월에서 2월까지유행하였고, 12월에가장많이검출되었다고하였다. 또한 hrv 는 10월에서 11월에유행하다가 1월에서 3월발현이떨어지는추세를보이다가 4월부터다시발현이증가하고, PIV 4월에서 9월까지유행하였고, ADV는 8월에서 12월까지빈도가높았다고하였으며, hmpv는 4월에서 6월까지높은빈도를보였고, IFV A는 12월과 1월에유행하다가 2월에급격히감소되었다고보고하여본결과와다소차이가있었다. Park 등 (3) 은 2008년부터 2011년까지부산지역병의원에서급성호흡기감염증환자들의비강세척액과인후도찰물에서검사한결과, 라이노바이러스 와아데노바이러스는년중검출되었고, 보카바이러스는 4-8월까지, 코로나바이러스 3월부터 6월까지, 엔테로바이러스는 3월부터시작하여봄과여름에주로검출되었으며, 호흡기세포융합바이러스 (RSV) 는매년 9-10월인가을에서겨울에걸쳐검출되었으며파라인플루엔자는주로날씨가높아지는 6-8월에많이검출되었다고보고하였다. 검출된호흡기바이러스 476건가운데 hrv 단독감염이 21.6% (103/476) 로가장많이검출되었는데검체수를대비하면 9.92% (103/1,038) 로 Ham 등 (4) 이서울지역병의원들에서호흡기환자들의인후도말에서조사한결과, hrv는상기도감염의매우흔한원인으로널리알려져있다고보고한것과동일하였다. 그다음으로 ADV 단독감염이 19.5% (93/476) 로검출되었는데, 검체수대비 8.96% (93/1038) 로나타났고 IFV (H3N2) 단독감염이 18.1% (86/476) 로검출되었는데, 검체수대비 8.29% (86/1038) 로각각나타났다. Figure 1. Distributions of viruses detected from patients with acute respiratory infection in 2013 in Seoul by periodic surveillance
278 H Ham, et al. Table 2. Each age viral detection distribution from patients with acute respiratory infection in 2013 in Seoul by periodic surveillance Viral agents Ages' interval Detected numbers 0~13 years 14~83 years Total Male Female Total Male Female Human rhinovirus 103 69 34 35 34 9 25 Adenovirus 93 83 44 39 10 7 3 Adenovirus+human bocavirus 4 4 1 3 Adenovirus+human coronavirus 2 2 Adenovirus+ 14 13 5 8 Adenovirus+parainfluenza virus 6 6 3 3 Adenovirus+respiratory syncytial virus 1 A(H1N1)pdm09 14 5 4 1 9 4 5 A(H3N2) 86 27 12 15 59 35 24 A(H3N2)+adenovirus 1 A(H3N2)+human coronavirus 2 A(H3N2)+ 3 3 1 2 B 9 6 4 2 3 3 B+respiratory syncytial virus 1 Human bocavirus 4 4 3 1 Human bocavirus+ 4 4 4 Human bocavirus+parainfluenza virus 1 Human bocavirus+respiratory syncytial virus 1 Human coronavirus 37 28 12 16 9 4 5 Human coronavirus+ 4 4 2 2 Human coronavirus+parainfluenza virus 1 Human coronavirus+respiratory syncytial virus 1 Human metapneumovirus 6 5 1 4 Human metapneumovirus+ 1 Parainfluenza virus 36 24 12 12 12 3 9 Parainfluenza virus+ 3 3 1 2 Respiratory syncytial virus 36 26 14 12 10 4 6 Respiratory syncytial virus+ 2 2 Total detected numbers (%) 476 (45.9) 324 (54.0) 163 (52.5) 161 (56.2) 152 (34.7) 70 (33.9) Sample numbers 1,038 600 314 286 438 206 232 82 (35.3) 호흡기바이러스단독감염과중복감염분포 2013년채취한총 1,038건의검체검사결과, 호흡기바이러스 45.9% (476/1038) 를검출하였고, 검출된호흡기 바이러스 476건가운데 ADV의경우, ADV 단독감염이 93건, ADV+hBoV 4건, ADV+hCoV 2건, ADV+hRV 14건, ADV+PIV 6건, ADV+RSV 1건등이었고, hbov의경우 hbov 단독감염이 4건 hbov+hrv 4건, hbov+piv 1건,
Infection Frequency and Mixed Infection on Eight Viruses 279 Table 3. Clinical symptoms from patients with acute respiratory infection in 2013 in Seoul by periodic surveillance Viral agents Symptoms or diseases Detected numbers Fever Cough Pharyngitis Chill Muscle pain Clinical symptoms Snot Headache Stuffiness Hoarse Fineness sound Sputum Vomitting Loss of appetite Asthma Human rhinovirus 103 69 46 35 20 20 50 22 7 30 3 8 2 Adenovirus 93 81 29 38 11 25 17 42 25 2 22 11 9 2 Adenovirus+ human bocavirus Adenovirus+ human coronavirus Adenovirus+ Adenovirus+ parainfluenza virus Adenovirus+respiratory syncytial virus A(H1N1)pdm09 A(H3N2) A(H3N2)+adenovirus A(H3N2)+human coronavirus A(H3N2)+human rhinovirus Human influenza virus B Human influenza virus B+respiratory syncytial virus 4 4 3 1 3 2 2 2 1 2 1 2 14 10 6 3 1 2 5 4 4 1 6 6 5 4 1 4 2 1 2 14 14 8 6 6 6 6 5 2 86 75 62 51 41 39 48 50 20 5 1 34 4 4 2 2 2 3 3 3 2 9 8 5 6 7 4 7 6 2 3 1 Human bocavirus 4 4 2 2 1 3 2 1 Human bocavirus+ Human bocavirus+ parainfluenza virus Human bocavirus+ respiratory syncytial virus 4 3 2 Human coronavirus 37 33 23 10 3 6 4 19 11 9 Human coronavirus+ Human coronavirus+ parainfluenza virus Human coronavirus+ respiratory syncytial virus 4 3 1 1 1
280 H Ham, et al. Table 3. Clinical symptoms from patients with acute respiratory infection in 2013 in Seoul by periodic surveillance (Continued) Viral agents Symptoms or diseases Human metapneumovirus Human metapneumovirus+ Detected numbers Fever Cough Pharyngitis Chill Muscle pain Clinical symptoms Snot Headache Stuffiness Hoarse Fineness sound Sputum Vomitting Loss of appetite 6 4 3 2 1 3 1 Asthma Parainfluenza virus 36 22 15 16 10 12 10 15 8 4 12 Parainfluenza virus+ Respiratory syncytial virus Respiratory syncytial virus+human rhinovirus 3 2 36 19 20 8 5 5 7 17 10 3 16 1 2 2 Total detected numbers (%) 476 (45.9) 372 (46.7) 240 (49.2) 180 (41.4) 101 (37.5) 121 (38.7) 124 (38.3) 235 (50.2) 112 (48.1) 24 (53.3) 3 (37.5) 144 (51.1) 22 (44.9) 27 (45.8) 9 (60.0) Sample numbers 1,038 797 488 435 269 313 324 468 233 45 8 282 49 59 15 hbov+rsv 1건등이었으며, hcov의경우 hcov+hrv 가 4건, hcov+piv 1건, hcov++rsv 1건등이었고, hmpv의경우, hmpv 단독감염이 6건 hmpv+hrv 1건이었으며, hrv 단독감염은 103건이나타났다. IFV의경우는 IFV A (H1N1) pdm09의경우 14건이었고, IFV A (H3N2) 단독감염의경우 86건이었으며, IFV A (H3N2) 중복감염으로는 IFV A (H3N2)+ADV 1건, IFV A (H3N2)+hCoV 2건, IFV A (H3N2)+hRV 3건등이었고, IFV A (H5N1) 의경우나타나지않았으며, IFV B의경우 IFV B 단독감염은 9건, 중복감염은 IFV B+RSV 1건으로나타났다. PIV의경우, PIV 단독감염은 36건, 중복감염은 PIV+hRVs 3건이었다. 그리고 RSV의경우단독감염은 36 건중복감염은 RSV+hRV 2건으로각각나타났다 (Table 2). Seo 등 (5) 에의하면 2005년부터 2007년까지전남대학교병원등광주지역병원들에서입원또는내원한호흡기감염증이의심되는환자들의인후부, 비강등에서채취한검체를검사한결과, 2개의바이러스에혼합감염의경우가운데 hrv, hbov, hcov, IFV 혼합감염의주를이루었다고보고하여본결과와유사하였고. 세가지의바이러스가혼합감염된 3건이있었고주로 hrv 와함께감염되었다고보고하였으나본결과에서는 3가지이상의혼합감 염은없었다. 호흡기바이러스감염을성별및연령별로조사하여소아와성인에서의차이를살펴본결과, 일반적으로소아 (0~13세) 의경우에중복감염이빈번하였고, 성인 (14~ 84세 ) 의경우는소아에비해상대적으로중복감염이드물게나타났으며, 성별에따른차이는없는것으로나타났다 (Table 2). 바이러스별임상증상임상증상은인플루엔자및급성호흡기감염증기록지에의해병원들에서조사된것을근거로사용하였다. 동일바이러스감염자가운데 50% 이상에서동일증상을나타낸경우를살펴보면아데노바이러스의경우 87.1% (81/93) 에서발열증세를나타내었고, 코로나바이러스의경우 89.2% (33/37) 에서발열증세를, 62.2% (23/37) 에서기침, 그리고 51.4% (19/37) 에서콧물증세를나타내었으며, 라이노바이러스는 67.0% (69/103) 에서발열증세를나타내었고, 인플루엔자바이러스 (H1N1pdm09) 의경우발열증세는 100% (14/14) 에서, 기침은 57.1% (8/14) 에서나타냈으며, 인플루엔자 (H3N2) 바이러스의경우발열증세는 87.2% (75/86) 에서, 기침은 72.1% (62/86), 인후염 59.3%
Infection Frequency and Mixed Infection on Eight Viruses 281 (51/86), 근육통 55.8% (48/86), 콧물 58.1% (50/86) 에서각각나타났고, 파라인플루엔자바이러스의경우 61.1% (22/36) 에서발열증상이, 호흡기세포융합바이러스 (RSV) 는 52.8% (19/36) 에서발열과 55.6% (20/36) 에서기침증세를보였다 (Table 3). Park 등 (3) 은 2008년부터 2011년까지부산지역병의원에서급성호흡기감염증환자들의비강세척액과인후도찰물에서검사한결과, 호흡기세포융합바이러스 (RSV) 를제외한 6종의바이러스감염자 50% 이상에서발열증상을나타내었다고하였고, 아데노바이러스의경우 83.9% 에서발열증상을나타내었다고하여본결과와동일하였다. 또한 Park 등 (3) 에의하면부산지역병의원급성호흡기감염증환자들에서기침은보카바이러스감염자의 74.3% 가증상을나타내어 7종의바이러스감염자중가장빈번한증상으로나타났으며그다음호흡기세포융합바이러스 (RSV) 71.4% 순이었고, 콧물은라이노바이러스감염자 55.1% 에서그다음코로나바이러스감염자 52.4% 순으로증상이나타났다고보고하였으며, 파라인플루엔자는발열 (75.0%) 과기침 (60.0%) 이많이나타났다고보고하여본결과와유사하였다. Kim 등 (1) 에의하면 2010년에서 2011년까지부산대학병원과양산부산대학교어린이병원에서급성하기도염으로입원한소아환자들의비인두흡인물을채취하여검사한결과, 폐렴은 RSV가 67.7% 로주된원인이었고, 세기관지염도 RSV가 49.8% 로가장많았다고보고하였고, 크루프 (croup, 급성폐쇄성후두염, acute obstructive laryngitis) 는 PIV가 40.7% 등으로보고하였다. 만성폐렴은한건도없었고, 천식 (asthma) 은 ADV 단독감염 93건중 2건에서, hcov 단독감염 37건가운데 1건, hmpv 단독감염 6건중 1건, hrv 단독감염 103건가운데 2건, 그리고 IFV A (H1N1) pdm09 바이러스단독감염 14건가운데 1건, IFV A (H3N2) 바이러스단독감염 86건가운데 2건에서각각나타나는등모두단독감염의경우에만나타나는특징을보였다 (Table 3). Lee 등 (2) 은 2010 년부터 2011년까지영남대학교병원소아청소년과에입원한환자에서조사한결과, 급성세기관지염은 RSV가가장많았고, 크루프 (croup) 는 PIV가가장많았으며, 호흡기외질환으로열성경련은거의모든호흡기바이러스에서비슷하게발생하였고, 뇌수막염은 ADV가많았으며, 간염은 RSV가가장많았다고하여차이를보였다. 호흡기바이러스의증상은감염을일으키는부위와그증상에따라콧물, 재채기, 목아픔, 인후염, 편도선염등 의상기도감염과기관지염, 폐렴, 기관지천식등의하기도감염으로구분되는데, 연구결과 rhinovirus와 coronavirus는발열증세가각각 67.0% 와 89.2% 에서나타나상기도감염을일으키면서도하기도감염까지는가지않음을나타내었고, influenza virus는 H1N1pdm09의경우발열증세 100%, 기침 57.1% 에서, H3N2의경우발열증세 87.2%, 기침 72.1%, 인후염 59.3%, 근육통 55.8%, 콧물 58.1% 에서각각나타나주로하기도감염을나타내었으며, parainfluenza virus는 61.1% 에서발열증세를, adenovirus 는 87.1% 에서발열증세를각각보임으로 rhinovirus 및 coronavirus과크게다르지않음을나타내었고, respiratory syncytial virus (RSV) 는 52.8% 에서발열과 55.6% 에서기침증세를보임으로하기도감염과상기도감염이동시에나타남을알수있었다. 서울시내 11개병의원의선정이대표성이있는지의여부는참여도와지역별분포등을고려하여자체엄정히선정한지정병원들이기는하나, 실제참여병의원들이 K병원은송파구에, A병원은강남구에, S의원은동작구에, 그리고 G의원은노원구에각각소재하는등서울시내 25개자치구가운데지역별분포가고려되는과정에서참여도가고려되지않을수없는부분등으로인한충분한대표성이확보하지는못한제한점이있기는하나전체적인경향과흐름파악에는의미있는결과들로사료된다. 11개병의원가운데종합병원이나대형병원은없었으며, 중소규모의 1차병원들이었고, 소아과 2개소, 소아청소년과 5개소, 가정의학과 1개소, 내과 3개소등으로운영하는개인병원들이었으며, 모두외래환자들의가검물로분석하였다. REFERENCES 1) Kim HY, Kim KM, Kim SH, Son SK, Park HJ. Clinical manifestations of respiratory viruses in hospitalized children with acute viral lower respiratory tract infections from 2010 to 2011 in Busan and Gyeongsangnam-do, Korea. Pediatr Allergy Respir Dis 2012;22:265-72. 2) Lee EK, Lee YY, Choi KH. Epidemiology and clinical features of respiratory viruses in pediatric inpatients in a single medical center in Daegu from 2010 to 2012. Yeungnam Univ J Med 2013;30:95-100. 3) Park YK, Park SH, Kim NH, Park EH, Hwang SJ, Jin SH.
282 H Ham, et al. Isolated respiratory virus and clinical features analysis of acute respiratory illness in Busan. The Annual Report of Busan Metropolitan city Institute of Health & Environment 2011;20: 16-26. http://www.google.co.kr/search?hl=ko&source=hp&q=isolated+ respiratory+virus+and+clinical+features+analysis+of+acute+ respiratory+illness+in+busan (Updated on Feb 2014). 4) Ham HJ, Jang JI, Choi SS, Oh SA, Jo SJ, Choi SM, et al. Epidemoilogical characterization of respiratory viruses detected from acute respiratory patients in Seoul. Ann Clin Microbiol 2013;16:188-95. 5) Seo JJ, Kim MJ, Kim SH, Kee HY, Chung JK, Kim ES, et al. Characterization of respiratory viral infection in children in Gwangju. Infection and Chemotherapy 2008;40:218-29.