대한수혈학회지 : 제 26 권제 3 호, 2015 The Korean Journal of Blood Transfusion Vol. 26, No. 3, 235-248, December 2015 http://dx.doi.org/10.17945/kjbt.2015.26.3.235 pissn 1226-9336 eissn 2383-6881 Review Article 신종감염병과혈액제제안전 오덕자 1 ㆍ강재원 1 ㆍ허광 2 ㆍ조덕 3 ㆍ임채승 4 대한적십자사혈액수혈연구원 1, 혈액관리본부 2, 삼성서울병원진단검사의학과 3, 고려대학교병원진단검사의학과 4 Emerging Infectious Disease and Safety of Blood Components Deok Ja Oh 1, Jae-Won Kang 1, Kwang Huh 2, Duck Cho 3, Chae-Seung Lim 4 Blood Transfusion Research Institute 1, Blood Services Headquarters 2, Korean Red Cross, Wonju, Department of Laboratory Medicine, Samsung Medical Center 3, Department of Laboratory Medicine, Korea University Medical Center 4, Seoul, Korea Recently, the emergency of Middle East Respiratory Syndrome in Korea raised public concern regarding emerging infectious disease (EID) and affected the strategy for blood safety. Although some cases of EID such as West Nile virus in the and hepatitis E virus in Japan emerged in a restricted area, the emergence can rapidly affect the situation in other countries in a globalized society with advancements in transportation and international exchange. Because the risk of transfusion-mediated infection may occur by the agent of EID which can be transmitted through blood, the strategy for safety must be considered for agents that were not tested in the stage of blood donor screening. We reviewed the characteristics of transfusion-transmissible EIDs raising concerns worldwide and the strategies which had been adopted. (Korean J Blood Transfus 2015;26:235-248) Key words: Emerging infectious disease, Blood safety, Transfusion 서론 2015년 5월중동지역에서감염된사람을통해국내로유입되어온나라를떠들썩하게만들었던중동호흡기증후군코로나바이러스 (Middle east respiratory syndrome-corona virus, MERS-CoV) 에의한소위 메르스사태 가이제는진정되었다. 이신종감염병 (emerging infectious disease, EID) 확산사태는첫번째감염자로부터의료기관을중심으로확산되어 2015년 11월 27일현재총 186명의확진자와 38명의사망자를발생시키고막을내렸다. 20.4% 의사망률 (mortality) 을보이며온국민을공포로몰아넣고관광산업을비롯한국내여러분야에심각한영향을끼쳤다. 이와같은 EID의국내유행사례는이번뿐아니라 2002년중증급성호흡기증후군 (severe acute respiratory syndrome, SARS), 2009년신종인플루엔자 A (Swine Flu, influenza A virus subtype H1N1) 때도유사한영향을끼쳤었고, 2015년 4월세계보건기구 (World Health Organization, WHO) Received on November 23, 2015. Revised on December 15, 2015. Accepted on December 16, 2015 Correspondence to: Deok Ja Oh Blood Transfusion Research Institute, Korean Red Cross, 50 Hyeoksin-ro, Wonju 26465, Korea Tel: 82-33-811-0201, Fax: 82-33-811-0209, E-mail: dj57_2000@redcross.or.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright C 2015 The Korean Society of Blood Transfusion - 235 -
Korean J Blood Transfus Vol. 26, No. 3, 235-248, Dec. 2015 는홍콩을중심으로다시유행기미를보이고있는홍콩독감 (Hong Kong Flu, influenza A virus subtype H3N2) 에대한경고를내리고있는상황이다. 인간으로부터채혈된혈액제제를환자에게공급하는혈액관리측면에서볼때새로운감염병의발생은혈액의안전성을가장크게위협하는요소가된다. 전파경로가불확실하고, 질병의경과및세균이나바이러스의혈중내잔여여부를확인할검사법이개발되지않은경우에는혈액제제의안전성을보증할수가없기때문이다. EID 에대한헌혈보류기간이나혈액제제안전관리대책은나라마다상황에따라다르게적용하고있는데, 분명한것은향후에도효율적인진단법은제한될것이고특정지을수없는미생물에의한 EID는계속발생하고, 유행될것이라는점이다. 저자들은최근경험한 MERS 사태를통하여국내유입및향후유입가능성이있는대표적인 EID에대하여문헌및자료를통하여정리하고, 다른나라에서의상황과해당국가에서시행하고있는혈액제제안전성확보방안을알아보았다. 국내에서그동안유행했던 EID에대한대책과유행가능성이있는 EID에대한안전성확보방안도함께정리해보았다. 문헌및정보자료는국내질병관리본부, 1) WHO, 2,3) 미국 FDA, 4-10) 일본의후생노동성자료를 11-13) 참조하였다. 본론 1. EID의정의및발생원인 WHO에서는 EID를과거 20년동안에발생률이꾸준히증가되고있거나, 발생후감소추세를보이다어느시점부터갑자기유행하고확산되는질환들로정의하고있다. 14) 이러한 EID의등장과 확산에는신체적, 환경적, 유전적, 생물학적, 사회학적, 정치학적, 경제학적요소와같이여러가지요인이관련되는데 1992년미국 Emory 대학의 Institute of Medicine의보고서에서는이러한 EID 의등장요인으로인구의변화및인간행동방식의변화, 산업기술의진보, 경제적성장및대지활용방식의변화, 국제적교류의활성화, 미생물학적적응및변화, 현실만족에의한공공의료정책의붕괴의 6가지요인을들었다. 15) 2003년에는이에추가된 7가지증가요인으로, 감염에대한감수성, 기후및날씨, 생태계의변화, 빈곤및사회적불평등, 전쟁과기근, 정치적의지의결여, 생물학적테러를제시하였다. 15) 2. 수혈감염가능 EID 의해외현황및혈액안전대책 특히혈액을매개로전파되는 EID는수혈에의한감염의가능성이존재하기때문에, 안전한혈액제제확보를위해서는이에대한대비책을사전에강구해두는것이중요한일일것이다. 2009년미국혈액은행협회 (American Association of Blood Bank, AABB) 에서는혈액안전성에영향을끼칠수있는 EID로 68종의병원체에대하여 Fact Sheet를발행하였으며, 과학적 / 역학적근거, 대중의인지도및규제기관의관심정도, 대중의관심도에따라등급을구분하였으며, 과학적 / 역학적근거는 낮음 에서 높음 까지로다양하지만규제기관의관심도가큰경우 Red, 과학적 / 역학적근거가충분한경우 Orange, 과학적 / 역학적근거가 없음 에서 낮음 정도이면서규제기관의관심도가조금이라도있는경우 Yellow, 위험도를지니고있으나, 현상황에서는우선적인고려가되지않는경우 White 로구분하였다 (Table 1). 14) 또한 2011년에황열바이러스 (Yellow Fever Virus) 와홍역바이러스 (Measles virus), 2013-236 -
오덕자외 : 신종감염병과혈액제제안전 Table 1. Prioritization of emerging infectious disease agents classified by American Association of Blood Banks Category Definition Agents Red Orange Yellow White Agents with low to high scientific/epidemiologic evidence of risk regarding blood safety with the potential for severe clinical outcomes. Agents with scientific/epidemiologic evidence of risk regarding blood safety that might support their elevation to a higher priority at some time in the future Agents with absent to low scientific/epidemiologic evidence of risk regarding blood safety for which there is public and/or regulatory concern Agents evaluated but for which no higher prioritization appears warranted at this time Variant Creutzfeldt-Jakob disease prion (vcjd prion), Dengue virus (DENV), Babesia species Chikungunya virus, St. Louise Encephalitis Virus (SLEV), Leishmania Species, Plasmodium species, Tripanosoma cruzi (T.cruzi) Chronic Wasting Disease Prion (CWD prion), Human Herpesvirus-8 (HHV-8), HIV variants, Human parvovirus B19 (B19V), Influenzy A subtype H5N1, Simian Foamy Virus (SFV), Borrelia burgdorferi, Hepatitis A Virus (HAV) Classical CJD, Borna disease virus (BDV), Colorado tick fever virus (CTFV), Crimean-Congo hemorrhagic fever virus (CCHFV), Eastern equine encephalitis virus (EEEV), Ebola virus, Enteroviruses, Epstein-Barr virus (EBV), GB/Hepatitis G virus (HGV), Hantavirus, HBV variant, Hepatitis E Virus (HEV), Herpesvieus other than CMV, EBV, and HHV-8, HTLV variant, Influenza A and B other than H5N1, Japanese encephalitis virus (JEV), La Crosse virus, Lassa virus, lymphocytic choriomeningitis virus (LCMV), Marbug virus (MARV), monkeypox virus (MPV), Mumps virus, Papillomavirus, Polyomavirus, Porcine endogenous retrovirus (PERV), Porcine parvovirus (PPV), Rhabdovirus, SARS- Corona virus (SARS-CoV), Tick-borne encephalitis virus complex (TBEV), Torque teno virus (TTV), Vaccinia virus, Variola virus, Western equine encephalitis virus (WEEV), Anaplasma phagocytophilum, Coxiella burnetii, Ehrlichia chaffeensis, Orientia tsutsugamushi, Rickettsia prowazekii, Rickettsia rickettsii, Bacillus anthracis, Bartonella henselae, Borrelia species, Brucella species, Chlamidia pneumomiae, Francisella tularensis, Listeria monocytogenes, Yersinia enterocolitica, Yersinia pestis, Filariae, Toxoplasma gondii, Trypanosoma brucei 년에 Human Parvovirus 4와, MERS-CoV를추가로지정하여 Fact Sheet에기재하였다. 16) 수혈감염가능성이있는다양한 EID 중에서전 세계적으로혈액제제의안전과관련하여비교적크게관심을받았던주요질환과이와관련된혈액안전대책을다음과같이정리하였다 (Table 2). - 237 -
Korean J Blood Transfus Vol. 26, No. 3, 235-248, Dec. 2015 Table 2. Summary of the current situation of strategy for blood safety related with transfusion-transmissible emerging infectious disease agents in other countries Agents/Countries vcjd prion United Kingdom Japan West Nile Virus Japan Plasmodium species Japan Denmark, United Kingdom, Finland and New Zealand SARS-CoV WHO Influenza A subtype Japan MERS-CoV Tripanosoma cruzi Strategy for blood safety Import of blood product from BSE-free area Introduction of universal leukoreduction Deferral for the donors who have been resided in United Kingdom for 3 months or more from 1980 through 1996, in the rest of Europe for 5 years or more since 1980 Deferral for the donors who have been resided in United Kingdom for 1 months or more from 1980 through 1996, for 6 months or more from 1997 to 2004, in Ireland, Italy, Netherland, Saudi Arabia, Spain, Germany, France, Belgium, and Portugal for 6 months from 1980 through 2004, in Austria, Greece, Sweden, Denmark, Finland and Luxemburg for 5 years from 1980 through 2004, in Switzerland for 6 months or more since 1980, in the rest of Europe for 5 years or more since 1980 Introduction of nucleic acid amplification test Prohibition of blood collection for 4 weeks from the donors who returned from abroad Stockpile of reagent for nucleic acid amplification test for about 95,000 donors Deferral for 1 year for travel to endemic areas, 3 years for those who have lived for or more years in endemic areas or previously had malaria and are now asymptomatic Deferral for 1 year for travel to endemic areas, 3 years for those who have lived for 1 or more years in endemic areas Antibody test for those who lived for 5 or more years in endemic area, or developed febrile illness within 6 months after a stay in endemic area, or have history of malaria within 3 years. Deferral for 3 weeks after the last day of contact, for 1 month after full recovery and cessation of therapy for the suspected case, 3 months after full recovery and cessation of therapy for the probable case Deferral for 14 days after the last day of contact, 28 days after full recovery and cessation of therapy for the suspected or probable case Deferral until at least after free of fever without use of medication Deferral for 7 days for suspected case Deferral for 14 days from last expoor arrival in the US following travel/residence exposure, or 28 days after complete symptom resolution and the cessation of a treatment. Permanent deferral for the history of Chagas disease Antibody screening for suspected case - 238 -
오덕자외 : 신종감염병과혈액제제안전 Table 2. Continued Agents/Countries Canada and Spain Japan Babesia species Japan Strategy for blood safety Antibody screening for suspected case Deferral for the donors who have been resided in Latin America for 4 weeks or more Donor screening for the endemic area Deferral for the history of Babesia Abbreviations: vcjd, variant Creutzfeldt-Jakob Disease; BSE, Bovine Spongiform Encephalopathy; SARS-CoV, Severe Acute Respiratory Syndrome Coronavirus; WHO, World Health Organization; MERS-Cov, Middle East Respiratory Syndrome Coronavirus. 1) 변종크로이츠펠트야콥병 (variant Creutzfeldt- Jakob Diseas prion, vcjd prion) vcjd는변종프리온단백에의해유발되는질환으로 1994년영국에서처음보고되었다. 2008년 10월까지전세계적으로 206명의감염이보고되어이중 203명이사망하였고대부분영국인이거나영국에서육류를섭취한자들이었다. 4) vcjd 의수혈과관련된위험성에대해서는여러사례가보고되고있다. 2004년 15명의 vcjd 환자로부터헌혈된혈액을수혈받은 48명의수혈자중한명이수혈후 6년 6개월뒤 vcjd로진단되었고, 1996년에는 24세의남성이헌혈후 3년뒤 vcjd 로사망하였는데이헌혈자의혈액을수혈받은수혈자가 6년 6개월뒤 vcjd 관련증상을보였고, 13개월뒤사망한사례, 또한헌혈후 18개월뒤 vcjd로진단된환자가헌혈하였던혈액을수혈받은환자로부터프리온단백이검출된사례등이보고되고있다. 17) 혈장분획제제에의한수혈전파가능성의확인사례는아직나타난바없으며, 수혈전파가능성을보였던사례는모두백혈구가제거되지않은혈액제제를수혈받은경우이다. 현재 vcjd에대한헌혈혈액에대한선별검사가가능하지않아문진으로 vcjd 발생지거주및여행경력에대한확인이가능할뿐이다. 영국은 1994년 vcjd가처음보고되고 1997년이후부터 vcjd가발병한헌혈자로부터헌혈된혈액제제를회수하고, 소에서 BSE가발생하지않은지역으로부터혈장제제를수입하고, 모든혈액제제에서백혈구를제거하는대책 (universal leukoreduction) 을취하였다. 18) vcjd 관련한혈액제제의안전을위하여미국 FDA에서는 1980 1996년동안영국에서합산 3개월이상체류한자, 1980년이후프랑스에서합산 5년이상체류한자에대하여영구적으로헌혈을보류하고있으며, 군인및군무원의경우독일, 영국, 벨기에, 네덜란드에서 1980 1990년동안 6년이상체류하거나, 그밖의유럽지역에서 1980 1996년동안 6년이상체류한경우영구적으로헌혈을보류하고있다. 4) 일본은영국에서 1980 1996년동안합산 1개월이상, 1997 2004년동안합산 6개월이상, 1980 2004년동안아일랜드, 이탈리아, 네덜란드, 사우디아라비아, 스페인, 독일, 프랑스, 벨기에, 포루투갈에서합산 6개월이상, 오스트리아, 그리스, 스웨덴, 덴마크, 핀란드, 룩셈부르크에서합산 5년이상, 스위스에서 1980년이후현재까지합산 6개월이상, 기타유럽국가에서 1980년이후현재까지합산 5년이상체류한경우, 헌혈을영구적으로보류하여더강화된기준 - 239 -
Korean J Blood Transfus Vol. 26, No. 3, 235-248, Dec. 2015 을적용하고있다. 11) 2) 웨스트나일바이러스 (West Nile Virus, WNV) WNV 는일본뇌염군에속하는 flavivirus 로 1937 년우간다에서처음규명된바이러스다. 이는야생조류와모기를 vector로감염사이클이유지되며, 사람, 개, 말등이최종숙주이며, 수혈이나장기이식에의한감염등을제외하면, 일반적으로사람간의감염은일어나지않는다. 미국, 유럽, 서아시아에서웨스트나일열, 뇌염의유행이있었으며, 미국의경우 1999년부터유행하여 2002년에는무증상바이러스혈증헌혈자의혈액으로수혈에의한 WNV 감염이확인되었다. 19) 미국은수혈에의한 WNV 감염을막기위하여 2003년 WNV 핵산증폭검사 (nucleic acid amplification test, NAT) 시약을개발하여우선 IND (investigational new drug) 로선별검사를실시하였고, 2005년에 FDA로부터승인받았다. FDA는선별검사를선택적선별검사의원칙하에지역별로조정하며, WNV의활동성이높은시기에는개별 NAT로, 활동성이주춤하면 minipool NAT (6 pool 또는 16 pool) 로전환하도록권고하고있다. 5) 일본은 EID 관련혈액안전대책으로 2003년 수입감염병대책관련문진강화 (2003년 2월 21일医藥發제0221008호후생노동성의약국장통지 ) 지침에의해, 외국에서입국후 3주이내의헌혈을금지시켰는데 2004년 8월부터는입국후헌혈금지기간을 4주로연장하였다. 일본내 WNV감염사례는없지만, 발생시사람, 모기, 말또는동물등감염매체별로접촉여부에대한헌혈제한범위와 WNV의핵산증폭검사실시가이드라인을제시하고있다. 일본에있는모기, 말및야생동물에서 WNV가확인된경우에는헌혈제한의범위가확인지역반경십수km 이내및접경지구거주자로확대하고, 감염확인후 11월경까지해당지역의광역행정구역단위에서 NAT를실 시하도록하고있다. 이를위해 WNV-NAT 시약을 5,000회검사분량 (20 pool 검사의경우약 95,000검체 ) 을비축하고있다. 12) 3) 말라리아 (Plasmodium spp) 말라리아는 Plasmodium 속원충이적혈구와간 세포내에기생함으로써발병하는급성열성감염증이다. 이는얼룩날개모기 (Anopheline) 속에속하는암컷모기가흡혈과정에서원충, 즉포자소체 (sporozoite) 를인체내로주입함으로써주로전파된다. 수혈에의한말라리아는주로적혈구제제에의하여발생되지만간혹혈소판제제에의한감염도보고되고있으나, 이는혈소판제제에포함된소량의적혈구제제에의한것으로알려져있다. 유행지역에서의수혈에의한말라리아감염은빈번하게일어나지만미국의경우 1998년 2007년동안 3건만이수혈에의한감염으로보고되어있다. 20) 미국 FDA에서는말라리아에대한수혈감염예방대책으로유행지역여행자에대하여 1년간, 유행지역에서 5년이상거주한경우와과거말라리아병력이있는경우 3년간헌혈을보류하도록권고하고있으며, 6) 일본은말라리아유행지역방문자의경우 1년간, 유행지역에 1년이상체류한경우 3년간헌혈을보류하고있다. 21) 덴마크, 영국, 핀란드, 뉴질랜드는유행지역방문자에대한헌혈보류조치외에도유행지역에서 5년이상거주자, 최근 6개월이내에유행지역방문자중발열을보인경력이있는자, 과거말라리아병력자중 3년이지나지않은헌혈자에대해서는선택적으로항체검사를실시하고있다. 22) 최근에는 P.knowlesi라는새로운종의말라리아가사람에감염됨이확인되었는데수혈감염등의문제에대해서는가능성은충분이있지만이를뒷받침할자료나연구는매우드문것으로알려져있다. - 240 -
오덕자외 : 신종감염병과혈액제제안전 4) SARS 코로나바이러스 (SRAS Corona virus, SARS-CoV) SARS-CoV는중증급성호흡기증후군을유발한새로운유형의코로나바이러스인데, 동남아시아의사향고양이 (Paguma larvata), 흰족제비 (Meliorate moschata) 에서인간으로감염되었다. 2002년 11월 광동에서첫사례가발생, 2003년 6월부터 7월에걸쳐중국, 홍콩, 베트남, 싱가폴등의동남아시아국가에서주로발생하였고, 북미에서는토론토에서주로발생하였고, 미국에서는 2003년말부터 2004년초까지만일부보고되고있다. WHO는 SARS 전파가보고된지역에서증상을보인자에대하여, 완치또는치료중단이후 SARS 의심및가능여부에따라 1개월또는 3개월동안의헌혈보류기간을권고하고있다. 또증상이없다하더라도 SARS 관련자와밀접한접촉이있거나, 전파가보고된지역을방문하였을경우에는 3주동안헌혈을보류하도록권고하고있다. 2) 반면미 FDA에서는 SARS로진단되거나의심되는경우완치후 28일동안, 증상이없다하더라도 SARS 관련자와접촉이있는경우 14일동안헌혈보류를권고하여, WHO의기준보다완화된조건을보이고있다. 7) 5) 신종인플루엔자 (Influenza A subtype) 신종인플루엔자바이러스 (pandemic influenza H1N1 2009) 는 Orthomyxoviridae에속하는 influenza A virus의 subtype으로 2009년 4월이후전세계적으로유행하고있는데, 이는유전자재조합으로항원대변이가일어나새로운인플루엔자바이러스가만들어진것이다. 대표적으로 1918년 스페인독감 이라고하는 H1N1 바이러스는조류로부터사람과돼지에전파되어대유행을일으켜전세계 5억명이감염되어, 약 1억명이사망한사례가있다. 또한 H1N1 A형이변이를일으켜사람에게감염을일으켰던 2009년신종인플루엔자 A (H1N1) 의세계적인유행이있었고 조류독감 이라고부르는변형 H5N1, 2013년중국에서의변형 H7N9 등다양한신종인플루엔자의유행사례가보고되고있다. 인플루엔자바이러스의수혈에의한감염사례는보고되고있지는않지만, 발병전바이러스혈증의경과로보아수혈로인한감염의가능성을완전히배제할수는없으며 3) 2009년 11월에미 FDA로부터 H1N1과관련하여가이드라인이나오긴했었으나, 2010년 6월 23일미보건당국의 H1N1에대한긴급상황의종료로더이상권고사항이시행되지는않고있다. 당시가이드라인은 H1N1 감염이확인된자및의심이되는자는해열제를사용하지않고열이내려가거나, 무증상으로된후최소 24시간이경과할때까지헌혈을금지하도록권고하고있었다. 3) 일본은신종인플루엔자의심의경우또는 7일이내감염자와의밀접한접촉이있는경우증상이없어도채혈을금지하도록하였고, 헌혈후 7일이내신종인플루엔자의심또는판명시혈액원에연락하여해당헌혈혈액출고금지와출고된혈액의즉시회수를권고하고있다. 23) 6) MERS-CoV MERS-Cov는중동지역에서집중적으로발생한 beta-coronavirus이다. 이바이러스가유발하는중동호흡기증후군 (MERS) 은 SARS와유사한고열, 기침, 호흡곤란등심한호흡기증상을일으키며, 명확한감염원과감염경로는확인되지않았다. 낙타와의접촉으로인한감염의가능성이높으며사람간에는확진자또는의심환자와동일한장소에머문사람에의한전파가가능하다고보고되고있다. MERS의경우 SARS와유사한코로나바이러스가병원체로, 대부분의국가에서는 SARS 유행당시의대책을적용하도록권고하고있다. 24) - 241 -
Korean J Blood Transfus Vol. 26, No. 3, 235-248, Dec. 2015 7) 크루스파동편모충 (Tripanosoma cruzi, T.cruzi) 원충 T.cruzi은기생충의일종인데, 이는열대질병인샤가스병등을유발한다. 인수공통감염증으로멕시코를포함한중남미국가가유행지역이다. T.cruzi는매개곤충 heamatophagous insect (triatominae subfamily) 의분변에존재하며, 분변내의원충이사람에게감염한다. 미 FDA에서는샤가스병의병력이있는자는영구적으로헌혈을제한하도록권고하고있다. 또한미국, 캐나다및스페인등의유럽은선택적인 T.cruzi 항체선별검사를실시하고있고유행지역인중남미국가들에서는대부분 T.cruzi 항체선별검사를실시하고있다. 9) 일본은최근취업목적으로유입되는남미 ( 주로브라질 ) 이주자들이증가하고, 이들중 T. cruzi 항체양성자가확인되고있다. 현재수혈로인한샤가스병감염사례는없으나, 무증상 T. cruzi 항체양성자가있어, 수혈감염위험성이존재한다고보고있다. 그래서헌혈문진표에 샤가스병병력이있는경우는채혈하지않는다 라고명시되어있고, 본인혹은모친이중남미국가에서태어났거나자란경우에는채혈을금지하고있다. 태어나지는않았더라도중남미국가에서합산 4주이상체류한경우에도채혈을금지하고있다. 13) 8) 뎅기바이러스 (Dengue virus, DENV) DENV는 Flaviviridae에속하는 RNA virus로모기가매개가되어감염을일으키며뎅기열을유발한다. 전세계적으로아주중요한모기매개바이러스성질병이며, DENV-1, -2, -3, -4의 4종류의혈청학적및유전학적으로구분된바이러스에의해유발된다. 과거 50년동안뎅기열의발생은전세계적으로 30배증가하였으며, 아시아와아메리카의열대및아열대지역에서높은유행을보이고, 아프리카에도존재하지만, 유행의정도는불확실하다. 푸에르코리코, 버진아일랜드와대부분 의미국령태평양군도에서유행하며, 매년고온건조한시기에발생이증가한다. 연간유행의강도는순환의형태를보인다. 미국전역에걸쳐발생하며, 아시아및아메리카대륙여행자에서의가장주요한발열원인으로꼽히고있다. 이질환에대한미국의혈액안전대책은유행지역에서의채혈을보류하는방법이나, 발생이더확대될경우에는채혈금지지역범위가넓어져혈액공급에도영향을줄수있다고보고다양한대안이필요하다고지적되고있다. 25) 일본의경우 2014년요요기공원을중심으로자체발생뎅기열이발견되었으며, 이로인하여일본적십자사에서는 2014년 8월 26일부터발생지역방문자에대하여 4주간헌혈을보류하도록하였으며, 헌혈후 14일이내에발열등의증상이있는경우혈액원으로연락을취하도록하였다. 그러나동년 10월 31일이후부터자국내감염이확인되지않아 11월 4일부터는이러한조치를해제하였다. 26) 9) 바베스열원충 (Babesia species) Babesia species는적혈구에기생하는원충인데, 이는바베시아병을유발한다. 이는말라리아와아주비슷하며, 원충이적혈구에기생하여발열과용혈성빈혈을주요증상으로보인다. 미국의 2008년부터 2012년까지의 5년간수혈감염사망예인 21예중 8예가 Babesia species에의한것이었다. 미국에서는특히북동부지역을중심으로과거수년간바베시아증발병의사례가증가하고있으며, 연중발생하기때문에미 FDA에서는 5개주의유행지역에대하여헌혈자에대한선별검사를실시하도록권고하였다. 10) 일본에서도 1999년에수혈감염사례가있었고그이후문진을통해 바베시아증의병력이있는경우채혈하지않는다 는항목으로채혈을금지시키고있다. - 242 -
오덕자외 : 신종감염병과혈액제제안전 3. 수혈감염가능 EID 의국내현황및혈액안전대책 질병관리본부감염병웹통계사이트에따르면, 국제적으로이슈화된 EID 병원체중국내에서지속적인발생을보이고있는것은말라리아와 DENV뿐이며, 2012년도해외유입에의한 1건의 WNV 감염사례가있었다. 1) 국내에서의주요 EID의안전대책현황을보면다음과같다 (Table 3). 1) 말라리아 말라리아의경우계절적인유행을보여 7 월과 8월에높은유병률을보이고있으며, 주로인천광역시, 강원도및경기도의북부지역에서높은유병률을나타내고있지만, 2001년도이후국내에서의말라리아발생은점차감소하는양상을 보이고있다 (Fig. 1). 국내에서수혈에의한말라리아감염은 1997년 3건, 1998년 4건, 2000년 3건이보고되고있다. 27) 안전대책으로는헌혈자로부터유행지역여행경력과국내거주지역에따른채혈금지여부를선별하고있으며서울, 경기, 인천지역의혈액원에서헌혈되는혈액에대하여항체선별검사를선택적으로실시하고있다. 2) 뎅기바이러스 2001년도이후국내에서의 DENV 감염에의한뎅기열의발생은점차적으로증가하는양상을보이고있으며 (Fig. 2), 대부분국외유입의사례였으나 2013년과 2014년의각각 1건은국내에서의발생이었다. 1) 혈액안전과관련된대책으로는모든헌혈지원자에대한해외여행이후 1개월간헌혈을금지하는것이유일한대책이다. Table 3. Summary of the current situation of strategy for blood safety related with transfusion-transmissible emerging infectious disease agents in Korea Agents vcjd prion Plasmodium species SARS-CoV Influenza A subtype Avian influenza MERS-CoV Dengue virus, West Nile Virus, Tripanosoma cruzi, Babesia species Strategy for blood safety Deferral for the donors who have been resided in United Kingdom for 1 months or more from 1980 through 1996, for 6 months or more since 1997, in the rest of Europe for 5 years or more since 1980 Deferral for the donors who have visited endemic area Antibody screening for the donors in northern province Deferral for 3 weeks after the last day of contact, for 1 month after full recovery and cessation of therapy for the suspected case, 3 months after full recovery and cessation of therapy for the probable case Deferral for 2 weeks after full recovery and cessation of therapy for the suspected case, Deferral for 1 month for the donor in endemic area during the endemic period Deferral for 14 days for the donors who reside in the occurrence, 28 days after full recovery and cessation of therapy for the suspected or probable case Deferral for 1 month for the donor from abroad Abbreviations: vcjd, variant Creutzfeldt-Jakob Disease; SARS-CoV, Severe Acute Respiratory Syndrome Coronavirus; MERS-Cov, Middle East Respiratory Syndrome Coronavirus. - 243 -
Korean J Blood Transfus Vol. 26, No. 3, 235-248, Dec. 2015 Fig. 1. Trend of occurrence of malaria infection in Korea (2001 2014). Most of the occurrences (about approximately 96.4%) are domestic cases. Fig. 2. Trend of occurrence of Dengue fever in Korea (2001 2014). Excluding 2 cases, all of the occurrences are imported cases. 3) 변종크로이츠펠트야콥병국내에서의 vcjd 발생보고는없으며, vcjd 관련혈액제제안전대책으로모든헌혈지원자들에대한문진을통하여영국에서 1980년부터 1996년동안합산 1개월이상, 1997년부터현재까지합산 6개월이상, 기타유럽국가에서 1980년부터현재까지합산 5년이상체류한경우, 그리고 1980년이후영국, 프랑스에서수혈을받은경우헌혈을영구적으로보류하고있다. 4) SARS 코로나바이러스 2002년 11월최초발생이후국내에서는 3명의 SARS 추정환자가발생하였으나, SARS로확인된사례는없었다. 그러나수혈전파의가능성을고려하여혈액안전대책으로 2003년질병관리본부권고에따라헌혈지원자가최근 SARS 감염위험지역여행또는거주경력이있으면서무증상인경우입국후 3주동안, SARS 추정환자의경우치료종료및완치후 3개월동안, SARS 의심환자 ( 의심후 SARS가배제된경우포함 ) 의경우에는치료종료및완치후 1개월동안헌혈을보류 하도록하고있다. 28) 5) 조류인플루엔자국내에서조류인플루엔자의유행은 2003년, 2006년, 2008년, 2011년, 2014년 5차례에걸쳐발생하였다. 조류인플루엔자는혈액으로감염될가능성이매우낮지만, 수혈자의안전을위해조류인플루엔자의유행당시대한적십자사혈액관리본부에서는조류인플루엔자발생지역의반경 3 km 이내지역의단체채혈을금지하도록하였고, 채혈장소에 조류인플루엔자위험지역과채혈금지대상자 에대한안내문을게시또는비치하여해당자는헌혈을할수없음을안내하도록하고, 채혈금지대상자의헌혈사례가확인된경우는혈액제제를즉시회수및폐기하도록하였다. 또한조류인플루엔자예방약을복용한경우투약종료후 1개월까지, 해당지역이위험지역에서해제되거나위험지역을벗어난후 1개월까지헌혈을보류하도록하였다. 6) 신종인플루엔자국내의경우 2009년유행당시 1일최대약 9천 - 244 -
오덕자외 : 신종감염병과혈액제제안전 명이감염된것으로나타나있으며, 혈액안전대책으로대한적십자사자체지침에의하여단체에서환자 ( 유사증상자포함 ) 가 2명이상발생한경우는환자치료가완치된후 2주동안그단체의채혈을금지토록조치하였고, 헌혈지원자의체온을측정하고, 발열이나호흡기증상등신종인플루엔자유사증상이있는자들의헌혈장소접근을차단하였다. 29) 또한헌혈장소에손세정제를비치하고, 헌혈후신종인플루엔자확진판정을받은경우및신종인플루엔자관련유사증상이발현한경우해당혈액은즉시폐기, 출고시회수조치하였다. 7) MERS 혈액안전을위하여 MERS 전파보고지역거주자의경우증상이없더라도 14일간헌혈을보류하도록하고, 증상을보이거나의심되는경우완치후 28일동안헌혈을보류할것을권고하였다. 8) 기타 WNV, T.cruzi, Babesia의경우, 2012년해외유입에의한 1건의 WNV 감염을제외하고는명확하게드러난국내의감염사례가없으며, 현재이들에대한혈액안전관련대책으로는모든헌혈지원자에대한해외여행이후 1개월간헌혈을금지하는것이유일한대책이다. 결론 혈액을매개로전파되는 EID의병원체는수혈감염을일으킬수있으므로, EID에대한혈액제제의안전대책을사전에강구해두어야하며, 이를위해혈액원에종사하는관계자뿐아니라, 정부기관, 의료기관및학술기관의다각적협조체계구축이필요하겠다. 요약 최근국내에서유행하였던중동호흡기증후군으로신종감염병에대한경각심이다시커지고, 이는혈액에대한안전성강화정책에도영향을미치게되었다. 미국에서의 West Nile Virus 감염, 일본에서의 E형간염등특정국가에서제한적으로유행하는경우도있으나, 국가간교통수단의발달과교류가활발한현재상황에서는특정감염병의발생은그나라에국한되지않고전세계적으로영향을끼칠수있게되었다. 혈액을매개로하는신종감염병의발생은수혈안전성에대한우려를증폭시키고, 헌혈자에대한선별검사를실시하지못하는경우에대체할수있는혈액제제의안전성확보방안이고려되어야한다. 본연구자들은그동안국내외적으로유행하고이슈화되었던수혈매개가능신종감염병에대하여자료를통한특성을살펴보고혈액제제의안전을위하여취해진국외및국내대안을정리해보았다. References 1. Korean Center for Disease Control and Prevention. Infectious disease statistics system. Disease web statistics system. http://is.cdc. go.kr/dstat/index.jsp [Online] (last visited on 12 October 2015). 2. World Health Organization. WHO recommendations on SARS and blood safety. Emergencies preparedness, response. http://www. who.int/csr/sars/guidelines/bloodsafety/en/ [Online] (last visited on 8 October 2015). 3. World Health Organization. Influenza update. Influenza. http://www.who.int/influenza/ surveillance_monitoring/updates/latest_upda te_gip_surveillance/en/ [Online] (last visited - 245 -
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