Korean J Fam Pract. 2012;2:127-133 말라리아와뎅기열의예방과치료 Symposium 김선아 * 건국대학교병원과 Treatment and Prevention of Malaria and Dengue Fever Seonah Kim* Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea Though tropical febrile diseases are not endemic in Korea, their incidence is steadily increasing, as the number of travelers to subtropical areas grows. Malaria and dengue fever are the most common tropical febrile diseases and are transmitted by the bite of an infective female mosquito in large areas in tropical and subtropical countries. Malaria is prevented by mosquito avoidance measures and chemoprophylaxis, while dengue fever can be prevented only by mosquito avoidance measures. Malaria is treated by anti-malaria drugs. There are no specific therapeutic agents for dengue virus infection, however resting and fluid treatment is needed. It is necessary to learn about diseases related to overseas travel and advise overseas travelers in Korea on methods for disease prevention. Keywords: Travel; Malaria; Dengue; Dengue Hemorrhagic Fever 서론 최근해외여행의증가에따라다른나라에서풍토병으로만연해있던질환들의국내유입이증가하고있다. 이는이동수단의발달에의해빠른시간에세계각국을이동할수있게되면서나타나는현상으로, 우리나라뿐아니라모든국가들의문제이며, 이에대해세계각국에서는해외에서유입되는질환에대한체계적인감시체계를구축하기위해노력하고있다. 관광지식정보시스템에서의통계에따르면우리나라에서는 2011년도에우리나라에서해외여행을한사람수가 1,200만명이넘었고, 2005년통계에서, 열대지방인아시아나아프리카로여행을한사람이전체출국자중아시아지역이 68.5%, 아프리카지역이 0.9% 로높은비율을차지하는것으로나타났다. 1,2) 그결과열대지방에서발생하게되는말라리아와뎅기열이법정감염병국외유입환자의 30% 를차지하고있다. 3) 최근각항공사별로아시아지역및아프리카지역으로의직항편을늘리고있는추세로우리나라의아시아, 아프리카여행객들도이에비례하여더욱증가할것으로생각된다. 따라서아시아및아프리카지역에서호발하는열대성질환인말라리아와뎅기열의국내유입도증가할수있으며, 일차의료진들은이에대한지식을기본으로적극적인예방과치료로의접근이필요하다. 본글에서는아시아나아프리카여행을통해걸릴수있는대표적인열대발열성질환인말라리아와뎅기열에대한진단, 치료및예방에대해살펴보고자한다. Received: May 9, 2012, Accepted: June 7, 2012 *Corresponding Author: Seonah Kim Tel: 02-2030-7628, Fax: 02-2030-5339 E-mail: pango301@naver.com Korean Journal of Family Practice Copyright 2012 by The Korean Academy of Family Medicine 말라리아 말라리아는열대, 아열대, 및일부온대기후지역에서광범위하게발생하는원충질환으로, 세계인구의약 40% 가말라리아유행지역에살고있으며, 매년약 3-5억의말라리아환자가발생하여그중 100만명이상이사망하고있는급 Vol. 2, No. 2 Jun 2012 127
Seonah Kim: Treatment and Prevention of Malaria and Dengue Fever 성열성감염증이다. 3,4) 우리나라에서는 1980년대이후사라졌다고생각된삼일열말라리아가 1995년휴전선인근지역에발생한후연간 1,000여명이상의환자가꾸준히휴전선인근지역에서발생하고있다. 1994-2008년까지해외유입말라리아의지역별발생은해외유입말라리아감염증환자총 621명중아시아 291명 (46.9%), 아프리카 268명 (43.1%) 등으로아시아와아프리카를방문하여감염된사람이 90.0% 로대부분을차지하였다. 3) 또한해외유입말라리아감염증의경우 2002-2008년간분석에따르면 Palsomdium falciparum 병원체가 41.5% 로높은비율을차지하여열대열말라리아의감염이높은것을알수있었다. 1. 병원체말라리아는얼룩날개모기속 (anopheline) 에속하는암컷모기를매개로 Plasmodium속원충이사람의혈액내로유입되어적혈구에기생하여생기는열병이다. 약 170종의 Plasmodium이존재하나사람을주숙주로하는말라리아의병원체는열대열원충 (P. falciparum), 삼일열원충 (P. vivax ), 사일열원충 (P. malariae), 난형열원충 (P. ovale) 등 4종이다. 전세계적으로는삼일열원충과열대열원충이 95% 이상차지하며, 국내감염사례의말라리아는삼일열원충감염에의한다. 열대열원충은아프리카에서우세하며, 가장심각한증상을유발하여, 말라리아로사망하는대부분의경우의원인균이다. 삼일열원충은아시아의열대지방에서발견되며, 증상은덜중하지만간에서잠복하며 3년까지도존재하여, 길게는감염후 3년경과하여발병하기도한다. 사일열원충은주로아프리카에서발견되며전형적인말라리아감염증의증상으로보이며, 수년이상증상없이혈액내에머물기도하여, 감염중인사람을문모기를통하여전염되거나수혈을통해다른사람에게전염되기도한다. 난형열원충은서부아프리카에서발견되며드물게재발하기도한다. 2,3) 2. 임상특징잠복기는병원균에따라차이가있으며, 열대열원충및사일열원충의경우는 10-30일정도로잠복기가비교적짧은편이나, 삼일열원충과난혈열원충의경우 14일-12개월까지다양하게나타날수있고, 온대지방과국내에서유행하는삼일열말라리아의경우 6-12개월의긴잠복기를보이는편이다. 3) 말라리아는열과독감과같은증상을특징으로, 발열, 오한, 두통, 몸살, 전신통증등이간격을두고나타난다. 오한, 발열, 발한후해열이반복적으로나타나며, 병원균이적혈구를파괴하며증상을유발하기때문에빈혈과황달이동반된다. 심한경우, 경기, 정신혼탁, 신기능저하, 급성호흡기증후군 (acute respiratory distress syndrome), 혼수상태, 사망까지나타나기도한다. 주로, 열대열원충감염인경우증상이심하며, 신속한치료가예후에결정적인영향을미치므로열대열원충감염이진단되면즉시치료를시작해야한다. 열대열원충의경우적절한치료가이루어지지않을경우사망률은 10% 이상이며, 치료를해도사망률이 0.4-4% 에달한다. 3,4) 3. 진단말라리아와관련된증상을보이는환자에게는경기도북부, 강원도, 인천광역시의위험지역에거주하거나방문한병력이있는지, 해외말라리아유행지역으로의여행여부에대해방문기간을명확히청취하여말라리아의잠복기를고려하여야한다. 확진을위해혈액도말검사를시행하며, 도말검사의진단율을높이기위해서는후층도말과박층도말을동시에실시하여야한다. 다양한검사키트가보조적으로사용될수있으며, 비교적말라리아발생이높고, 혈액도말검사가용이하지않은지역에서는보조적으로사용할수있다. 결과는 2-15분내감염여부를확인할수있다는장점이있으나, 감염종을구분할수는없으므로, 확진을위해혈액도말검사가추후다시이용되어야한다. 혈액도말검사와함께 polymerase chain reaction 검사가또한이용가능하며, 이경우혈액도말검사보다민감도가높아진단적목적보다는혈액도말검사의보조적역할이나, 말라리아의종을확인하는검사로이용하는것이적절하다. 3-5) 일반혈액검사상적혈구파괴로인한헤모글로빈감소와혈소판감소가관찰되며, 백혈구수치는보통정상범위에있다. Aspartate aminotransferase/alanine aminotransferase, bilirubin 의상승소견을보일수있다. 3-5) 4. 치료말라리아치료를위해서는우선, 열대열말라리아의가능성, 합병증유무, 감염된지역의약제내성상황, 환자의나이및기저질환, 증상의위중, 약제부작용등을고려하여치료방침을세우게된다. 대부분의환자는경구약제로치료가능하나, 열대열말라리아가의심되거나, 상태가위중한경우에는주사제로치료하여야한다. 3) 국내에서사용가능한약제로는 atovaquone-proguanil, doxycycline, tetracycline, clindamycin, mefloquine, chloroquine phosphate, hydroxychloroquine sulfate, primaquine phosphate 등이있다. Table 1에서는감염지역및상태에따른치료를보여주 128 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract
김선아 : 말라리아와뎅기열의예방과치료 Table 1. Treatment of malaria*. Plasmodium species Region Drug Uncomplicated malaria/ P. falciparum or species not identified Uncomplicated malaria/ P. falciparum or species not identified Uncomplicated malaria/ P. malariae or P. knowlesi Uncomplicated malaria/p. vivax or P. ovale Chloroquine-resistant or unknown resistance Chloroquine-sensitive All regions All regions Atovaquone-proguanil or artemether-lumefantrine or quinine sulfate plus one the following: doxycycline, tetracycline, or clindamycin or mefloquine (not recommended in person from Southeast Asia due to drug resistance) Chloroquine phosphate or hydroxychloroquine Chloroquine phosphate or hydroxychloroquine Chloroquine phosphate plus primaquine phosphate or hydroxychloroquine plus primaquine phosphate Uncomplicated malaria/p. vivax Chloroquine-resistant Quinine sulfate plus either doxycycline or tetracycline plus primaquine phosphate Atovaquone-proguanil plus primaquine phosphate Mefloquine plus primaquine phosphate Uncomplicated malaria: alternatives for pregnant women Chloroquine-sensitive Chloroquine-resistant Chloroquine phosphate hydroxychloroquine Quinine sulfate plus clindamycin or mefloquine Severe malaria All regions Quinidine gluconate plus one of the following: doxycycline, tetracycline, or clindamycin *If a person develops malaria despite taking chemoprophylaxis, that particular medicine should not be used as a part of their treatment regimen. Use one of the other options instead. 며, Table 2에서각약물의복용량을제시하였다. 4) 인터넷해외여행질병정보센터 (http://travelinfo.cdc.go.kr) 에서말라리아유행지역여부, 말라리아예방약제내성여부및기타여행건강에대한정보를얻을수있다. 5. 여행객을위한예방말라리아의예방을위해서는모기에물리지않게하는개인적인보호법과항말라리아제를투여하는예방적화학요법이있다. 개인보호를위해말라리아발생지역에서는가능하면모기가무는저녁부터새벽까지는외출을하지말아야하며, 외출이부득이한경우는긴소매의상의와긴바지를입으며, 가급적밝은옷을입어어두운곳을좋아하는말라리아를피해야한다. 노출된피부에는해충기피제 (N-diethylm-toluamide [DEET] 함유 ) 를도포하도록하고, 곤충기피제 (permethrin 성분 ) 처리가된방충망이나모기장을사용하여모기에의노출을최소화하여야한다. 항말라리아약제로예방요법을한다고해서말라리아에전혀감염되지않는것은아니므로모기에게덜물리기위한개인보호는필수적이다. Table 3에서말라리아예방을위한항말라리아제를소개하고있다. 3,4) 항말라리아약제는약제에따라복용법이다르지만보통출발 1-2주전부터복용을시작하게되며, 예기치않은부작용이발생할때는필요에따라약제를변경하여야한다. 3,4,6) 일년이상말라리아발생지역에거주할경우는매일또는 1주간격으로말라리아예방약을먹는것은부작용발현이높아권장되지않는다. 뎅기열 뎅기열은모기에의해뎅기바이러스가인체로감염되면서발병하는급성열성질환으로, 열대지방, 아열대지방인아시아, 남태평양지역, 아프리카, 아메리카대륙에서호발하는질병이다. 7) 뎅기열은국내에서는 2000년이후법정전염병 4 군으로지정된이후, 유행지역을다녀온이후발병하는경우가 2001년 6명에서 2010년 125명으로증가추세를보이고있으며, 2011년보고된법정감염병의국외유입환자현황을보면뎅기열이가장흔한유입질환이되었다. 7,8) 1988년해외여 Vol. 2, No. 2 Jun 2012 129
Seonah Kim: Treatment and Prevention of Malaria and Dengue Fever Table 2. Recommended drug dose for treatment of malaria. Drug Adult dose Pediatric dose (pediatric dose should never exceed adult dose.) 250 mg atovaquone/100 mg proguanil 4 adult tabs po qd 3 d Peds tab=62.5 mg atovaquone/25 mg proguanil 5-8 kg: 2 peds tabs po qd 3 d 9-10 kg: 3 peds tabs po qd 3 d 11-20 kg: 1 adult tab po qd 3 d 21-30 kg: 2 adult tabs po qd 3 d 31-40 kg: 3 adult tabs po qd 3 d >40 kg: 4 adult tabs po qd 3 d Atovaquoneproguanil (Malarone) Artemetherlumefantrine (Coartem) 1 Tablet=20 mg artemether and 120 mg lumefantrine A 3-day treatment schedule with a total of 6 oral doses is recommended for both adult and pediatric patients based on weight. The patient should receive the initial dose, followed by the second dose 8 hours later, then 1 dose po bid for the following 2 days. 5-15 kg: 1 tablet per dose 15-25 kg: 2 tablets per dose 25-35 kg: 3 tablets per dose 35 kg: 4 tablets per dose Quinine sulfate 542 mg base (=650 mg salt) 4 po tid 3 or 7 d 8.3 mg base/kg (=10 mg salt/kg) po tid 3 or 7 d Doxycycline 100 mg po bid 7 d 2.2 mg/kg po every 12 h 7 d If patient not able to take oral medication, give 100 mg IV every 12 hours and then switch to oral doxycycline (as above) as soon as patient can take oral medication. For IV use, avoid rapid administration. Tetracycline 250 mg po qid 7 d 25 mg/kg/d po divided qid 7 d Clindamycin 20 mg base/kg/d po divided tid 7 d 20 mg base/kg/d po divided tid 7 d If patient not able to take oral medication, give 10 mg base/kg loading dose IV followed by 5 mg base/kg IV every 8 hours. Treatment course: 7 d Mefloquine (Lariam and generics) Chloroquine phosphate (Aralen and generics) Hydroxychloroquine (plaquenil and generics) 684 mg base (=750 mg salt) po as initial dose, followed by 456 mg base (=500 mg salt) po given 6-12 h after initial dose Total dose: 1,250 mg salt 600 mg base (=1,000 mg salt) po immediately, followed by 300 mg base (=500 mg salt) po at 6, 24, and 48 h Total dose: 1,500 mg base (=2,500 mg salt) 620 mg base (=800 mg salt) po immediately, followed by 310 mg base (=400 mg salt) po at 6, 24, and 48 h Total dose: 1,550 mg base (=2,000 mg salt) 13.7 mg base/kg (=15 mg salt/kg) po as initial dose, followed by 9.1 mg base/kg (=10 mg salt/kg) po given 6-12 h after initial dose Total dose: 25 mg salt/kg 10 mg base/kg po immediately, followed by 5 mg base/kg, po at 6, 24, and 48 h Total dose: 25 mg base/kg 10 mg base/kg po immediately, followed by 5 mg base/kg po at 6, 24, and 48 h Total dose: 25 mg base/kg Primaquine phosphate Quinidine gluconate 30 mg base po qd 14 d 0.5 mg base/kg po qd 14 d 6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 h, then 0.0125 mg base/kg/min (=0.02 mg salt/kg/min) continuous infusion for at least 24 h An alternative regimen is 15 mg base/kg (=24 mg salt/kg) loading dose IV infused over 4 hours, followed by 7.5 mg base/kg (=12 mg salt/kg) infused over 4 hours every 8 hours, starting 8 hours after the loading dose (see package insert). po qd: peroral quaque die, Peds: pediatric, tid: ter in die, bid: bis in die, IV: intravenous, qid: quater in die. 130 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract
김선아 : 말라리아와뎅기열의예방과치료 Table 3. Chemical prophylaxis of malaria. Drug Usage Adult dose Pediatric dose Comment Contraindication Prophylaxis in areas with chloroquine-sensitive malaria Chloroquine In areas with chloroquinesensitive malaria 300 mg base (500 mg salt) orally, once/wk 5 mg/kg base (8.3 mg/kg salt) orally Begin 1-2 weeks before travel to Psoriasis Take weekly and for 4 weeks after leaving such areas. Prophylaxis in areas with chloroquine-resistance malaria In all areas Adult tablets contain 250 mg atovaquone+100 mg proguanil hydrochloride. 1 Adult tablet orally, daily (Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride.) 5-8 kg: 1/2 pediatric tablet daily >8-10 kg: 3/4 pediatric tablet daily >10-20 kg: 1 pediatric tablet daily >20-30 kg: 2 pediatric tablets daily >30-40 kg: 3 pediatric tablets daily >40 kg: 1 adult tablet daily Begin 1-2 days before travel to Take daily and for 7 days after leaving such areas. Pregnant Breast feeding a child that weigh <5 kg Severe renal impairment Doxycycline In all areas 100 mg orally, daily 8 y: 2.2 mg/kg Max dose of 100 mg/d Begin 1-2 days before travel to Take daily and for 4 weeks after leaving such areas. Pregnant women Children aged <8 y Atovaquoneproguanil Mefloquine In areas with mefloquinesensitive malaria 228 mg base (250 mg salt) orally, once/wk 9 kg: 4.6 mg/kg base (5 mg/kg salt) orally, once/wk >9-19 kg: 1/4 tablet once/wk >19-30 kg: 1/2 tablet once/wk >30-45 kg: 3/4 tablet once/wk >45 kg: 1 tablet once/wk Begin 2 weeks before travel to Take weekly and for 4 weeks after leaving such areas. Psychiatric conditions Seizure disorder Cardiac conduction abnormalities Primaquine For short-duration travel to areas with principally P. vivax 30 mg base (52.6 mg salt) orally, daily 0.5 mg/kg base (0.8 mg/kg salt) Max dose orally, daily Begin 1-2 days before travel to Take daily and for 7 days after leaving such areas. Glucose-6-phosphate dehydrogenase deficiency Pregnant women Used for presumptive antirelapse therapy (terminal prophylaxis) 30 mg base (52.6 mg salt) orally, daily for 14 d after departure from the malarious area 0.5 mg/kg base (0.8 mg/kg salt) Max dose orally, daily for 14 d after departure from the malarious area Indicated for people who have had prolonged exposure to P. vivax, P. ovale, or both. Vol. 2, No. 2 Jun 2012 131
Seonah Kim: Treatment and Prevention of Malaria and Dengue Fever 행자유화로뎅기열발생지역으로의해외여행이증가하게되면서국내유입환자현황에서보면뎅기열의 98% 이상이아시아지역에서의감염으로나타나고있으며, 나머지는아프리카지역에서의감염으로나타났다. 9) 그러므로아시아지역여행이후발생한급성열성질환의경우뎅기열의가능성을염두하여진료에임하는것이필요하겠다. 1. 병원체 Flaviviridae종 flavivirus과의뎅기바이러스를가진모기가사람을무는과정에서감염되어뎅기열과뎅기출혈열이발생하게된다. 열대, 아열대지방에서열대숲모기 (Aedes aegypti) 에물려감염되게되며, 이모기는사람거주지역에적응이잘된모기로, 사람인접지역에서도산란을하고흡혈을하게되어도시지역에서도전파가잘이뤄지게되며, 낮동안에바이러스에감염된사람을문이후, 다른숙주를물어바이러스를감염시키게된다. 뎅기바이러스에는 DEN-1, DEN-2, DEN-3, DEN-4형네개의혈청형이있으며, 7,10) 각혈청에대한항체는그혈청형에대한영구면역을제공하지만, 10,11) 다른혈청형감염을완전히막지못하며, 오히려이러한면역에의해다른혈청형감염의증상을더욱악화시키며, 중증의증상을나타내게되는뎅기출혈열의경우이전감염의면역이있는경우더잘생긴다. 7,12) 2. 임상특징뎅기열은급성열성질환으로, 증상발생 2주내에열대, 아열대지역을여행한적이있는경우고려해보아야한다. 잠복기는보통 4-7일정도이며, World Health Organization 13) 에서는두통, 안와주위통증, 근육통, 관절통, 발적, 출혈소견또는백혈구감소증중 2가지이상의증상을있는경우로정의하고있으며, 피부홍조, 오심, 구토등의증상도나타날수있다. 뎅기열환자중 1% 정도는열이시작하고약 3-8일후열이호전되면서뎅기출혈열로진행하게된다. 뎅기출혈열의경우는혈과투과성증가와혈장유출이나타나게되고, 압박띠검사 (tourniquet test) 결과양성이거나출혈소견, 혈소판감소증 ( 100,000 cells/mm 3 ), 혈장유출에따른혈액농축소견 ( 수액치료후 hematocrit 20% 이상감소 ), 흉수, 복수, 저단백혈증등의소견을보이게된다. 뎅기쇼크증후군은뎅기출혈열소견과함께, 저혈압, 맥압이 20 mm Hg 이하로좁아지고심한복통이발생하게되는데, 사망률이높아쇼크발생을막는것이가장중요한치료이다. 7,11,14) 3. 진단 2000년부터질병관리본부에서뎅기열에대한검사가가능하게되었다. 확진검사는질병관리본부에의뢰하면가능하며, immunoglobulin M이양성이거나, 급성기에비해회복기항체가가 4배이상증가하거나음성에서양성으로전환되게되면진단이가능하다. 7,11,14) 또한바이러스배양및중합효소연쇄반응검사도가능하다. 뎅기열발생지역은말라리아, 장티푸스, A형간염, 장티푸스, 렙토스피라등비슷한증상을나타내는열성질환및발진성질환이많으므로, 뎅기열이의심될때는이러한질환들에대한검사도함께하여배제하는것이필요하겠다. 4. 치료뎅기열에대한특이적인예방백신이나치료제는없다. 현재로는보조요법으로치료하며, 발열기에는안정및수분섭취를권하여탈수를예방하며, 해열을위해서는아세타미노펜을사용하도록한다. 아스피린, 아스피린함유약제, nonsteroidal anti-inflammatory drugs는약제의항응고효과로인하여출혈성경향을악화시킬수있으므로사용을피하도록한다. 환자에게열이떨어지면서발생될수있는뎅기출혈열및뎅기쇼크증후군과관련된증상을알려주고, 유사증상이발생할경우바로병원을방문할수있도록한다. 증상이심하거나, 뎅기출혈열또는뎅기쇼크증후군이발생한환자의경우입원하여집중관찰을해야한다. 7,11,14) 5. 여행객을위한예방뎅기열에대한예방접종및화학적예방은없다. 뎅기열에대한예방을위해서는개인보호가필요한데뎅기열의매개모기인열대숲모기는낮동안에감염을일으키며, 도시에서도감염이일어날수있으므로, 해충기피제 (DEET 함유 ) 를사용하고, 곤충기피제 (permethrin 성분 ) 처리가된방충망이나모기장을사용하며, 살충제를사용하여주위의매개모기를줄이는노력이필요하겠다. 7,11,13,14) 결론 해외여행을통하여발생할수있는열성질환중말라리아와뎅기열에대하여알아보았다. 의료진은해외여행과관련된질환에관하여숙지하고해외여행예정인환자들에게개인보호및질병예방을위한방법을적극적으로안내하여감염을최소화하도록노력하여야할것이며, 열성질환의환자 132 Vol. 2, No. 2 Jun 2012 Korean J Fam Pract
김선아 : 말라리아와뎅기열의예방과치료 를접한경우해외여행력등을자세히청취하여해외여행를통한감염질환의경우, 발병초기부터적극적인진단및치료를임할수있도록하여야겠다. 요약 해외여행이증가함에따라한국에서열대성열성질환들의발생이증가하고있다. 말라리아와뎅기열은가장흔한열대성열성질환이며, 열대, 아열대지역에서감염되어있는암컷모기에의해전염되게된다. 말라리아는모기를피하는개인보호와항말라리아제의예방적투여로예방할수있으나, 뎅기열은단지모기를피하는방법으로예방할수있다. 말라리아는항말라리아제로치료를하며, 뎅기열은치료제가없으며, 고열발생시탈수를피하고안정하는것이필요하다. 가정의는해외여행과관련된질환에대해숙지하고, 해외여행객에서질병의예방등에대한교육을실시하며, 열성질환의환자를접한경우, 여행력등을자세히청취하여해외여행관련질병에관하여적극적으로대처할수있어야하겠다. 중심단어 : 해외여행 ; 말라리아 ; 뎅기열 ; 뎅기출혈열 REFERENCES 1. Tourgo: statistics of tourist [Internet]. Seoul: Tourism Knowledge & Information System; c1995-2011 [cited 2012 Jun 13]. Available from: http://stat.tour.go.kr/ptour1/index.do. 2. Ahn MH. Traveling and imported parasitic diseases. J Korean Med Assoc 2007;50:993-1004. 3. Korea Centers for Disease Control and Prevention. Malaria [Internet]. Cheongwon: Korea Centers for Disease Control and Prevention [cited 2012 Jun 13]. Available from: http://www. cdc.go.kr/. 4. Centers for disease Control and Prevention. Diseases related to travel: malaria [Internet]. Atlanta: Centers for disease Control and Prevention [cited 2012 Jun 13]. Available from: http:// wwwnc.cdc.gov/travel/page/diseases.htm#malaria. 5. Yeom JS. Diagnosis and treatment of vivax malaria. Korean J Med 2009;77:52-4. 6. World Health Organization. Malaria [Internet]. Geneva: World Health Organization [cited 2012 Jun 13]. Available from: http:// www.who.int/topics/malaria/en/. 7. Korea Centers for Disease Control and Prevention. Dengue [Internet]. Cheongwon: Korea Centers for Disease Control and Prevention [cited 2012 Jun 13]. Available from: http://www. cdc.go.kr/. 8. Choi HH, Park JA, Kim JS, Hur YJ, Song MS, Hwang TG, et al. A case of an imported dengue hemorrhagic fever with spontaneous bleeding: case report and review of the literature. Korean J Pediatr Infect Dis 2011;18:207-11. 9. Korea Centers for Disease Control and Prevention. Disease web statistics system: dengue [Internet]. Cheongwon: Korea Centers for Disease Control and Prevention [cited 2012 Jun 14]. Available from: http://www.cdc.go.kr/kcdchome/jsp/ observation/stat/rgt/statrgt0003list.jsp. 10. Park HS, Kim KK, Yoon J, Lee KR, Suh HS. Two cases of dengue fever in family medicine. J Korean Acad Fam Med 2008;29:48-51. 11. Chung MH. Dengue fever. Korean J Med 2009;77:165-70. 12. Lopez Antunano FJ, Mota J. Development of immunizing agents against dengue. Rev Panam Salud Publica 2000;7:285-92. 13. World Health Organization. Dengue [Internet]. Geneva: World Health Organization [cited 2012 Jun 14]. Available from: http:// www.who.int/tdr/research/ntd/dengue/en/. 14. Centers for Disease Control and Prevention. Diseases related to travel: dengue fever [Internet]. Atlanta: Centers for Disease Control and Prevention [cited 2012 Jun 14]. Available from: http://wwwnc.cdc.gov/travel/page/diseases.htm#dengue. Vol. 2, No. 2 Jun 2012 133