Continuing Education Column pissn 1975-8456 / eissn 2093-5951 http://dx.doi.org/10.5124/jkma.2016.59.6.452 여행자에서열대성질환의감별진단 염준섭 성균관대학교의과대학강북삼성병원감염내과 Differential diagnosis of tropical diseases in travelers Joon Sup Yeom, MD Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea Travel-related health problems such as febrile illness have been reported in many travelers going to developing countries. With the emergence of new infectious diseases occurring in many parts of the world and their spread worldwide, early diagnosis of emerging infectious diseases or tropical diseases has become a very important part of controlling these diseases. In doing so, the itinerary of the ill returning traveler is crucial to formulating a differential diagnosis because exposure to pathogens differs depending on the area of travel. With up-to-date information on infectious diseases occurring worldwide, a differential diagnosis can be made by adding information on duration of travel, incubation period, underlying medical illness, history of prophylactic vaccines received, and knowledge of the patient s exposures during travel including insect bites, contaminated food or water, or freshwater swimming. Some travelers may have specific symptoms and signs such as fever, rash, or hemorrhagic manifestations. For example, eosinophilia suggests a possible helminth infection. In this article, the general approach to returnning travelers with suspected tropical disease will be described. Key words: Travel; Travel medicine; Malaria; Dengue 서론 해외여행후건강의이상을경험하게되는경우는매우 흔하다. 선진국국민들이저개발국가또는개발도상국가여행후적게는 22% 에서 64% 가건강의이상을경험하게되고 8% 는의료기관을방문해야할정도의질환을앓게된다 [1]. 이때여행자들이앓게되는질환은본인이가지고 Received: April 10, 2016 Accepted: April 24, 2016 Corresponding author: Joon Sup Yeom E-mail: jsyeom@skku.edu Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 있는기저질환의악화부터감염질환, 외상등매우다양하다. 하지만2003년의중증급성호흡기증후군 (severe acute respiratory syndrome), 2009년신종인플루엔자의범유행, 2014년서아프리카의에볼라유행과확산, 2015년중동호흡기증후군 (Middle East respiratory syndrome, MERS) 의국내유입, 최근브라질에서의지카바이러스감염유행으로열대성감염질환에대한관심과관리의중요성이증가하고있다. 해외여행이자율화된 1989년이후해외로떠나는우리국민들의수는지속적으로증가하였고, 이에따라해외유입감염병도꾸준히증가하여왔다 [2]. 특히여행객들의행선지가점차다양해지면서유입되는질병의양상도달라져서과거에는유입되지않았던열대성질환들도점차증가하는추세이다. 2003년에유비저환자가첫보고된이후지속적으로유비저환자의보고가있었고 452 대한의사협회지
Yeom JS Tropital diseases in travelers Table 1. Differential diagnosis of infectious diseases by region Geographic area Caribbean Central America South America South-central Asia Southeast Asia Sub-Saharan Africa More common tropical disease causing fever Dengue fever, chikungunya, malaria Dengue fever, chikungunya, malaria (primarily Plasmodium vivax) Dengue fever, malaria (primarily vivax) Dengue fever, enteric fever, malaria (primarily nonfalciparum) Dengue fever, malaria (primarily non-falciparum) Malaria (primarily Plamodium falciparum), tickborne rickettsiae, acute schistosomiasis, filariasis Other infections causing outbreaks or clusters in travelers chikungunya virus infection, acute histoplasmosis, leptospirosis leptospirosis, histoplasmosis, coccidioidomycosis chikungunya virus infection, bartonellosis, leptospirosis Chikungunya virus infection, Middle East respiratory syndrome Chikungunya virus infection, leptospirosis, Japanese encephalitis African trypanosomiasis [3], 2012년에는국내최초로해외유입웨스트나일열환자가보고되었고 [4], 2013년에는치쿤구니야열 [5], 2015년에는 MERS 그리고 2016년에는지카바이러스감염발생보고가있었다. 또한해외유입말라리아는매년 50여건이보고되고있고, 뎅기열은지속적으로증가하여 2015년에는 259명이신고되었고올해에는더많은환자가발생할것으로예상되고있다 [2,6]. 이처럼우리국민들에서다양한해외유입열대성질환이증가하면서해외여행후발생한질환의감별진단을위해서는전세계적으로유행하고있는감염질환의발생현황에대해서알아야하고이에다른해당질환의임상적특징을알고있어야한다. 본글에서는열대성질환중심으로해외여행자에서여행후발생하는발열질환의감별진단을위한접근법에대해서소개하고자한다. 는질환을좁혀나갈수있다. 가장중요한것은여행일정으로, 구체적인체류지역과체류기간을확인해야한다. 일반적으로감염질환의발생정도가한국가내에서도지역에따라차이가있을수있으며, 질병의특성에따라도시와시골지역의발생빈도가큰차이를보이는경우가많기때문이다. 대표적인모기매개감염질환인말라리아는발생률이대단히높은아프리카의일부지역을제외하면대부분시골에서발생하는질병인반면최근큰문제가되고있는뎅기열은시골은물론도시에서도발생하는질환이다. 중증급성호흡기증후군, MERS, 조류인플루엔자와같은질환은야생동물과의접촉이있어야하므로기본적으로시골에서감염될수있겠지만사람간전파가가능하므로도시에서도감염될수있음을고려해야한다. 또한항공기환승을위해잠시체류하는공항혹은그주변지역에서도사람간전파등을통해감염질환에노출될수있다. 환자와관련된의학적정보로는심장병, 당뇨병등의기저질환유무, 여행전접종받은백신의종류와접종시기등을파악해야한다. 백신접종으로예방가능한감염질환들이있고특히다양한열대성질환이유행하는지역여행자들은장티푸스, A형간염, 인플루엔자백신은물론지역에따라서는황열, 공수병백신을접종하고떠나는경우들이일반여행자들보다높다. 그외에도여행기간동안이용한숙박장소 ( 호텔, 민박등 ), 섭취한음식이나식수의위생상태, 호수나강물에서수영, 래프팅등의수상활동, 야생동물과의접촉이나교상, 사용한곤충기피방법, 현지에서의성생활등다양한감염의경로가될수있는행위나상황에대해서파악해야한다. 여행지역에따른감염질환의감별 여행후열대성질환의심환자의평가 다양한질환이다양한지역에서발생하고있으므로여행과관련된자세한정보를알아야하고이를토대로의심되 여행자들에서발생할수있는감염질환은다양하다. 그러나지역별로유행하는질환이조금씩달라서여행지역에따라서가능성이높은질환들을구분해볼수있다 (Table 1). 미국을중심으로전세계적으로분포되어있는여행자클리닉에서여행자들의질병데이터를수집하는연구네트워크 여행자의열대성질환 453
Table 2. Differential diagnosis of infectious diseases by incubation period Disease Incubation <14 days Zika Chikungunya Dengue Encephalitis, arboviral Enteric fever Acute human immunodeficiency virus Influenza Legionellosis Leptospirosis Malaria, Plasmodium falciparum Malaria, P. vivax Spotted-fever rickettsiae Incubation 14 days to 6 weeks Enteric fever, leptospirosis, malaria Amebic liver abscess Hepatitis A Hepatitis E Acute schistosomiasis (Katayama syndrome) Incubation >6 weeks Amebic liver abscess, hepatitis B, hepatitis E, vivax malaria Leishmaniasis, visceral Tuberculosis Usual incubation period (range) 2-7days (2-14 days) 2-4 days (1-14 days) 4-8 days (3-14 days) 3-14 days (1-20 days) 7-18 days (3-60 days) 10-28 days (10 days to 6 weeks) 1-3 days 5-6 days (2-10 days) 7-12 days (2-26 days) 6-30 days (weeks to years) 8-30 days (often >1 month) Few days to 2-3 weeks See above incubation periods for relevant diseases Weeks to months 28-30 days (15-50 days) 26-42 days (2-9 weeks) 4-8 weeks See above incubation periods for relevant diseases 2-10 months (10 days to years) Primary, weeks; reactivation, years 유럽의 Eurosurveillance (eurosurveillance.org) 와같은정부기관홈페이지는물론이고 World Health Organization (who.int), Healthmap (healthmap.org), 글로벌감염병센터 (gcid.or.kr), CIDRAP (Center for Infectious Disease Research and Policy, cidrap.umn.edu) 등다양한기관홈페이지를통해서도문제가되고있는감염질환에대한발생현황과기타정보들을얻을수있다. 잠복기에따른질환의감별 환자가여행을다녀온후증상이나타나는시기는감염병의감별진단에대단히중요하다. 잠복기를통해서감별해야할질환들은대단히많으나대표적인질환들을요약하면 Table 2와같다. 정확한감염시기를알수없는경우가많아귀국후발열등의증상으로의료기관을방문하게되는시점까지의기간을기준으로보면, 뎅기열환자의 66% 는귀국후첫 1주이내에병원을찾게되며, 열대열말라리아환자의 65% 는귀국후 2주이내에병원을찾았다 [9]. 그러나삼일열 말라리아환자는 27% 만이귀국후 2 주내에병원을찾게되 인 Geosentinel의자료에따르면말라리아는아프리카를중심으로동남아시아와남아메리카방문자의감염질환의주요원인이었고, 뎅기열은동남아시아지역중심으로카리브해지역, 중앙 남아메리카지역방문자에서발열의주요원인이었다 [7,8]. 설사질환특히장티푸스는인도를중심으로파키스탄, 방글라데시등중남아시아국가여행자들에서특히많이발생하였고기생충감염에의한설사는전지역 는데그이유는온대지역과아열대지역에서광범위하게발생하는삼일열말라리아의경우길게는약 1년정도의긴잠복기를보내고발병하는경우가있기때문이다. 삼일열말라리아로진단되는여행자의 54%, A형간염으로진단되는여행자 34% 는귀국 6주이후에발병하였다고보고되므로귀국후 6주이상지난여행자에서도여행과관련된감염병이발생할수있음을고려해야한다 [9]. 의저개발 개발도상국여행자에서고르게발생하였다. 그 러나이러한질병에노출될위험도는한국가내에서도일정하지않고계절, 유행의정도등시간에따라실시간으로변화하므로해당지역의감염병발생현황에대해서최신정보를확보하고있어야한다. 최근에는인터넷, 휴대폰어플리케이션등을통해전세계적으로발생하고있는감염병의지역별발생정보를확인할수있다. 우리나라의질병관리본부해외여행질병정보센터 (travelinfo.cdc.go.kr), 미국 Centers for Disease Control and Prevention (cdc.gov ), 출혈이동반될수있는열대성질환 열대성질환중에는점상출혈부터보다중증의출혈까지다양한출혈소견이동반되는경우가많다. 특히바이러스성질환중에서많이볼수있는데뎅기열, 치쿤구니야열, 지카열, 황열, 라싸열, 에볼라출혈열등이대표적이다. 우리나라여행자들에서도빈번한뎅기열의경우피부의점상출혈이나 454 대한의사협회지
Yeom JS Tropital diseases in travelers 결막출혈이자주나타나고이러한소견은치쿤구니야열이나지카열에서도동일하며이들질환들은발생지역이유사하여임상소견만으로감별을어렵게한다. 뎅기열의경우에는다른혈청형에의한반복감염이뎅기출혈열의위험인자로알려져있으므로중증출혈의소견이동반된경우에는과거뎅기열감염력이있는지확인해야한다. 황열은최근앙골라를중심으로아프리카일부지역에서유행하고있으나대부분백신접종후에위험지역을방문하고있어우리나라여행자들에서발생할가능성은희박하다. 라싸열이나에볼라출혈열은아프리카의일부지역에서산발적으로유행하므로현지상황에따라여행자들의감염가능성을고려하여감별진단에포함시켜야한다. 호산구증이있는경우 호산구증의원인은알러지, 종양, 약물등다양하지만여행자에서는특히기생충감염을의심해야한다. 실제로여행자에서발생한호산구증의 30-60% 가연충 (helminth) 감염에의한것이다 [10,11]. 주혈흡충증, 분선충증, 사상충증이가장흔하며이들에서모두호산구증이나타날수있지만모든환자에서나타나는것은아니라는점에유의해야한다. 기생충감염의정도에따라호산구증의정도에차이가있는데, 3,000/mm 3 이상심한호산구증은회충증, 구충증, 분선충증, 선모충증, 사상충증, 간흡충증, 폐흡충증, 간질증, 주혈흡충증등에서나타날수있다 [12]. 기생충감별에도움이되는이학적소견으로피부증상 ( 회선사상충증, 피부이행증 ), 객혈 ( 폐흡충증 ), 복부압통 ( 유극악구충증, 고래회충증, 간흡충 ), 림프부종 ( 사상충 ) 등이있다 [13,14]. 결론 신종감염병의전세계적인유행과지속적인여행자의증가, 기후변화등으로해외유입감염병특히열대성질환에대한관심과중요성이증가하고있다. 이러한열대성질환이여행 자를통해서유입될경우 2014년일본의뎅기열유행, 2015 년우리나라의 MERS 유행, 2016년진행중인브라질의지카열유행과같이사회적으로큰문제가될수있어조기에정확한진단을내리고확산방지를위한적절한대응이필요하다. 조기진단을위해서는세계여러곳에서유행하는감염병에대한최신정보를가지고있어야하고, 환자가방문했던지역, 증상과이학적소견등을통해서감염가능성이있는질환들을생각하고진단에필요한검사를의뢰해야한다. 찾아보기말 : 여행 ; 여행의학 ; 말라리아 ; 뎅기열 ORCID Joon Sup Yeom, http://orcid.org/0000-0001-8940-7170 REFERENCES 1. Fairley JK. General approach to the returned traveler. In: Centers for Disease Control and Prevention. CDC health information for international travel 2016. New York: Oxford University Press; 2016. p. 496-500. 2. Cho SH, Cho EH. The reported cases of imported infectious disease from 2001 to 2014. Public Health Wkly Rep 2015;8: 1128-1138. 3. Kwon KY, Yoon SK. Characteristic of melioidosis and current status of infection in Korea. Public Health Wkly Rep 2012;5:10-12. 4. Park JH, Kwon DH, Yoon SK, Choi WY. The first imported case of West Nile virus disease in Korea. Public Health Wkly Rep 2012;5:823-824. 5. Park JH, Kwon DH, Yoon SK, Lee JK, Park JM. Two imported cases of chikungunya infection in South Korea, 2013. Public Health Wkly Rep 2014;7:167-168. 6. Korea Centers for Disease Control and Prevention. Notice about infection caution according to increasing declarations of Dengue fever [Internet]. Cheongju: Korea Centers for Disease Control and Prevention; 2016 [cited 2016 May 20]. Available from: http://www. cdc.go.kr/cdc/intro/cdckrintro0201.jsp?menuids=home001- MNU1154-MNU0005-MNU0011&cid=67242. 7. Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, Keystone JS, Pandey P, Cetron MS; GeoSentinel Surveillance Network. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354:119-130. 8. Leder K, Torresi J, Brownstein JS, Wilson ME, Keystone JS, 여행자의열대성질환 455
Barnett E, Schwartz E, Schlagenhauf P, Wilder-Smith A, Castelli F, von Sonnenburg F, Freedman DO, Cheng AC; GeoSentinel Surveillance Network. Travel-associated illness trends and clusters, 2000-2010. Emerg Infect Dis 2013;19:1049-1073. 9. Wilson ME, Weld LH, Boggild A, Keystone JS, Kain KC, von Sonnenburg F, Schwartz E; GeoSentinel Surveillance Network. Fever in returned travelers: results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007;44:1560-1568. 10. Moore TA, Nutnam TB. Eosinophilia in the returning travelers. Infect Dis Clin North Am 1998:12:503-521. 11. Van den Ende J, van Gompel A, van den Enden E. Hypereosinophilia after a stay in tropical countries. Trop Geogr Med 1994;46:191. 12. Harries AD, Myers B, Bhattacharrya D. Eosinophilia in Caucasians returning from the tropics. Trans R Soc Trop Med Hyg 1986;80:327-328. 13. Klion AD. Eosinophilia. In: Keystone JS, Freedman DO, Kozarsky PE, Connor BA, Nothdurft HD, editors. Travel medicine. 3rd ed. Philadelphia: Elsevier; 2013. p. 501-509. 14. Chin BS. Travel medicine. In: Korean Society for Infectious Diseases. Infectious diseases. Paju: Koonja; 2014. p.1377-1387. Peer Reviewers Commentary 여행관련질환을대하는데있어어려운점은무엇보다도생소하다는점이다. 여행자설사같이비교적흔한질병도있지만웨스트나일열, 뎅기열등은국내에서발생하지않는질환이므로의료진의경험이나지식이제한적일수밖에없다. 또한해외유입감염병은그질병이발생하는지역이나계절등유행양상이변하는경우가많기때문에최신정보가신속하고정확한진단에있어중요하다. 본논문에서는여행지역과잠복기에따라서감별해야할질환들을체계적으로정리하고있으며무엇보다도지카바이러스감염, 치쿤구니야열등최근문제가되고있는질병등도포함하고있어서현장의의료진에게실질적인도움을줄수있을것으로생각된다. 또한여행관련질환에접근하기위해서는무엇보다도여행력을확인하는것이그출발이될수있다. 특징적인증상을보이는여행관련질환도있지만발열, 발진등비특이적인경우도많으므로환자문진과정에서여행력을확인하는것을진료의기본적인과정으로하는게필요하겠다. [ 정리 : 편집위원회 ] 456 대한의사협회지