소아에 발생한 삼일열 말라리아의 임상적 특성

이은진,이종국,조종래,Lee, Eun Jin,Lee, Chong Guk,Cho, Chong Rae 대한소아감염학회 2003 Pediatric Infection and Vaccine Vol.10 No.2

목 적 : 말라리아는 국내에서 1970년대 말에 소멸된 것으로 알려져 있었으나, 1993년 비무장지대에 근무하던 군인에서 첫 환자가 발생한 이후, 지속적으로 증가되어 2000년에는 4,142명, 2001년에는 2,556명, 2002년에는 1,797명의 말라리아 환자가 보고되었다. 1999년부터는 민간인의 비율이 점차 증가되고 있고, 토착형 말라리아 환자가 늘어남에 따라 국내에 존재하는 매개숙주(중국 얼룩날개 모기)에 의해 주민간에 전파될 가능성도 높아진다. 저자들은 말초혈액 도말 검사 및 말라리아 항체 검사에서 말라리아로 확진된 소아 환자 13명을 조사하여 역학적 분석 및 임상적 특성을 알아보고자 하였다. 방 법 : 2000년 1월부터 2003년 8월까지 일산백병원에 내원한 소아 환자 중 말초혈액 도말 검사 및 말라리아 항체 검사로 확진된 15세 이하의 소아 환자 13명에 대하여 의무기록을 후향적으로 조사하였다. 결 과 : 13례 모두 토착형 말라리아 감염이었고, 원인 원충은 삼일열 말라리아(Plasmodium vivax)였다. 13례 중 남아와 여아의 비율은 9 : 4이었고, 발병 당시 평균 연령은 $9.5{\pm}3.6$세였다. 지역별로는 13례 중 9례가 일산 시내였으며, 11례의 발병 시기가 6~8월로 여름에 주로 발생했다. 13례 중 2례만이 3일 주기의 발작적인 발열을 보였고 나머지 11례는 지속적인 발열 및 불규칙한 발열 양상을 보였다. 혈소판 감소증은 가장 두드러진 소견으로 13례 중 12례에서 동반되었으며, 3례에서는 범혈구 감소증을 보였다. 신생아를 제외한 12례에서 hydroxychloroquine과 primaquine을 투약했고, 이후 시행한 혈액 도말 검사상 더 이상의 원충은 발견되지 않았고 혈액학적 이상 소견 역시 호전되었다. 결 론 : 저자들이 경험한 소아 말라리아 환아는 모두 Plasmodium vivax에 의해 발병되고 일부 환아는 유행외 지역에서 발병된 것으로 보아 이 원충에 의한 토착화의 확산을 추정할 수 있었다. 또한 전형적 삼일열 말라리아의 발열 양상이 없다하여도 혈소판 감소증 소견이 동반된 발열 환아에서 이 질환을 의심하여야 하며 말라리아 항체 검사가 선별 검사로 유용한 것으로 추정된다. Purpose : Malaria is known to have been eradicated for a few decades through persistent national health program in South Korea. However, malaria caused by Plasmodium vivax has started to reappear incidiously among military personnel near to DMZ since 1993. After then, the number of malarial cases have been increased abruptly year by year. We analyzed the children of indigenous malaria who were diagnosed by peripheral blood smear and malarial antibody test with regards to epidemiologic and clinical manifestations. Methods : The study 13 cases below 15 years of age, who were confirmed as vivax malaria during from January 2000 to August 2003. We retrospectively analyzed epidemiologic data, clinical manifestations, laboratory findings and therapeutic responses. Results : All of 13 cases were indigenous and tested positive for Plasmodium vivax. Of 13 patients, 9 were male and 4 were female. Mean age of onset was $9.5{\pm}3.6$ years old. Ilsan(n=9) was the most prevalent area, the most patients(n=11) were presented in summer (from June to August). A characteristic feature of periodic 3 day fever in patients with P.vivax infection was reported in only 2 among 13 cases. Thrombocytopenia was most prominent findings, which was accompanied by 12 of 13 patients and pancytopenia was appeared in 3 patients on this study. The therapeutic responses of hydroxycholoquine were very good in all cases, and abnormal laboratory findings were recovered and no relapse during follow-up period. Conclusion : Vivax malaria is indigenous in Korea near to DMZ, but recently endemic area seemed to be extended southward. Plasmodium vivax is the cause of indigenous malaria of children. As for children with high fever accompanying thrombocytopenia in endemic area of Korea, malaria must be included in differential diagnosis whether the type of fewer is periodic 3 day fever or not. Malaria antibody test is helpful as a screening test for malaria.

Development of Monoclonal Antibodies for Diagnosis of Plasmodium vivax

Nguyen Thi Phuong Linh,박현,이진영,Dong-Xu Liu,서가은,손혜진,한진희,한은택,신호준,여선주 대한기생충학ㆍ열대의학회 2017 The Korean Journal of Parasitology Vol.55 No.6

Plasmodium lactate dehydrogenase (pLDH) is a strong target antigen for the determination of infection with Plasmodium species specifically. However, a more effective antibody is needed because of the low sensitivity of the current antibody in many immunological diagnostic assays. In this study, recombinant Plasmodium vivax LDH (PvLDH) was experimentally constructed and expressed as a native antigen to develop an effective P. vivax-specific monoclonal antibody (mAb). Two mAbs (2CF5 and 1G10) were tested using ELISA and immunofluorescence assays (IFA), as both demonstrated reactivity against pLDH antigen. Of the 2 antibodies, 2CF5 was not able to detect P. falciparum, suggesting that it might possess P. vivax-specificity. The detection limit for a pair of 2 mAbs-linked sandwich ELISA was 31.3 ng/ml of the recombinant antigen. The P. vivax-specific performance of mAbs-linked ELISA was confirmed by in vitro-cultured P. falciparum and P. vivax-infected patient blood samples. In conclusion, the 2 new antibodies possessed the potential to detect P. vivax and will be useful in immunoassay.

삼일엽 원충(Plasmodium vivax)감염에 의한 부정맥 및 심막 삼출액 발생 1예

유제성,이진희,정성필,구홍두,박인철 대한감염학회 2006 감염과 화학요법 Vol.38 No.6

말라리아에 감염되었을 경우, 고열 외에 뇌형 말라리아, 급성신부전, 급성 폐부종, 저혈당, 세균성 감염 등의 합병증을 유발하는 것으로 알려져 있다. 드물지만, 외국에서는 열대열 원충에 의해 부정맥이나 심막 삼출액 등과 같은 심장 질환이 발생한 보고도 있다. 하지만 본 예와 같이 삼일열 원충에 의해서도 서맥, 2도, 3도 방실결절 차단의 부정맥과 심막 삼출액 발생할 수도 있다. 말라리아가 빈발하는 지역에서 이런 증상의 환자를 발견하는 경우, 반드시 말라리아 감염을 의심하고, 적절한 진단 및 치료가 이루어지도록 해야 할 것이다. 저자들은 삼일열 원충에 의해 부정맥 및 심막 삼출액이 발생한 환자 1예를 경험하였기에 보고하였다. Plasmodium vivax is a typically seen infectious disease in Korea. The incidence of Plasmodium vivax malaria has been increasing in recent year despite of worldwide attempts at control. Fever, anemia, thrombocytopenia, and splenomegaly are the most common manifestations seen in Korean patient with P. vivax. Cardiac involvement is thought to be a very rare complication of malaria infection. Cardiac complication seems to be limited to acute infection with Plasmodium falcifarum. However we have experienced cardiac complication such as pericardial effusion, and complete AV block by Plasmodium vivax. Physicians should consider cardiac involvement in patient who present hypotension, fever and arrhythmia in malaria endemic area.

인도네시아에서 유입된 클로로퀸 내성 삼일열 말라리아 1예

김은실,나병국,박윤규,정문현,이진수,천승민,이제,신정훈,김은영,배현주 대한감염학회 2008 Infection and Chemotherapy Vol.40 No.1

Resistance of falciparum malaria to antimalarial agents is prevalent in many areas, whereas chloroquine-resistant vivax malaria has been reported mainly around New Guinea since 1989. Concomitant with the spread of chloroquine-resistant P. vivax and increase in number of international travelers, imported cases of chloroquine-resistant vivax malaria in travelers returning from these areas has been reported. We experienced a case of chloroquine resistance P. vivax infection imported from Mangole Island, Indonesia. Its origin is confirmed not to be indigenous by the gene encoding analysis for the polymorphic region of apical membrane antigen-1 in P. vivax. Gene sequencing of the P. vivax mdr1 gene revealed only one substitution located at the codon 1076 (F1076L). The case was managed with oral quinidine with successful outcomes. 열대열 말라리아에서 항말라리아에 대한 내성은 세계적인 현상이지만, 삼일열 말라리아에서 클로로퀸 내성은 1989년부터 뉴기니 주변 지역에서 주로 발생하고 있다. 이들 지역으로 여행하는 여행객이 증가하면서 클로로퀸 내성 삼일열 말라이아 예들 보고가 늘고 있다. 저자들은 인도네시아의 망골 섬 여행 후 발생한 클로로퀸 내성 삼일열 말라리아를 경험했으며, P. vivax의 apical membrane antigen-1을 코딩하는 polymorphic region 분석에서 환자의 삼일열 말라리아 원충은 국내 발생주와는 다른 것을 증명했고, P. vivax mdr1 gene의 염기서열 분석에서 1076 코돈이 L에서 F로 변한 것을 확인하였다. 경구 퀴니딘으로 치료하여 증상과 원충혈증이 호전되었다.

급성 신부전, 황달 및 혈소판 감소증이 병발된 일열 말라리아 1예

김현정 ( Hyun Jung Kim ),이서현 ( Seo Hyun Lee ),구태연 ( Tai Yeon Koo ),김경민 ( Kyung Min Kim ),장성수 ( Sung Soo Jang ),이상구 ( Sang Koo Lee ) 대한신장학회 2010 Kidney Research and Clinical Practice Vol.29 No.6

Purpose: Malaria is caused by four species of the genus Plasmodium. Plasmodium vivax malaria is the most common malarial infection in Korea and usually has benign clinical course. However, serious complications such as severe anemia, pulmonary edema, acute renal failure are reported in Plasmodium vivax malaria. We report a case of Plasmodium vivax malaria complicated with acute renal failure, jaundice and thrombocytopenia. A 56-year-old male was transferred to our hospital with acute renal failure, jaundice and thrombocytopenia. 10 days before admission, he had intermittent fever, chill, myalgia, and was treated with some medications under the impression of URI. Laboratory findings showed that hemoglobin was 11.5 g/dL, platelet 44,000/mm3, blood urea nitrogen 73 mg/dL, creatinine 4.0 mg/dL, total bilirubin 5.2 mg/dL, direct bilirubin 4.0 mg/dL. Serologic tests for leptospirosis, rickettsia, EB virus and CMV were negative. Ring form trophozoites were found in red blood cells, suggesting Plasmodium vivax malaria. Following anti-malarial therapy, acute renal failure, jaundice and thrombocytopenia were recovered to normal. From this case, malarial infection should be included as a differential diagnosis in a febrile patient with acute renal failure, jaundice and thrombocytopenia.

A Case of Chloroquine-resistant Plasmodium vivax Malaria Imported from Indonesia

Kim, Eun Sil,Na, Byung Kook,Park, Yun-Kyu,Chung, Moon-Hyun,Lee, Jin-Soo,Cheon, Seung-min,Lee, Je,Shin, Jeong-hun,Kim, Eun-young,Pai, Hyunjoo 대한감염학회 2008 감염과 화학요법 Vol.40 No.1

Resistance of falciparum malaria to antimalarial agents is prevalent in many areas, whereas chloroquine-resistant vivax malaria has been reported mainly around New Guinea since 1989. Concomitant with the spread of chloroquine-resistant P. vivax and increase in number of international travelers, imported cases of chloroquine-resistant vivax malaria in travelers returning from these areas has been reported. We experienced a case of chloroquine resistance P. vivax infection imported from Mangole Island, Indonesia. Its origin is confirmed not to be indigenous by the gene encoding analysis for the polymorphic region of apical membrane antigen-1 in P. vivax. Gene sequencing of the P. vivax mdr1 gene revealed only one substitution located at the codon 1076 (F1076L). The case was managed with oral quinidine with successful outcomes. 열대열 말라리아에서 항말라리아에 대한 내성은 세계적인 현상이지만, 삼일열 말라리아에서 클로로퀸 내성은 1989년부터 뉴기니 주변 지역에서 주로 발생하고 있다. 이들 지역으로 여행하는 여행객이 증가하면서 클로로퀸 내성 삼일열 말라이아 예들 보고가 늘고 있다. 저자들은 인도네시아의 망골 섬 여행 후 발생한 클로로퀸 내성 삼일열 말라리아를 경험했으며, P. vivax의 apical membrane antigen-1을 코딩하는 polymorphic region 분석에서 환자의 삼일열 말라리아 원충은 국내 발생주와는 다른 것을 증명했고, P. vivax mdr1 gene의 염기서열 분석에서 1076 코돈이 L에서 F로 변한 것을 확인하였다. 경구 퀴니딘으로 치료하여 증상과 원충혈증이 호전되었다.

Evaluation of <i>Plasmodium vivax</i> ELISA for the blood screen

Nam, Myung‐,Hyun,Kim, Jang Su,Cho, Chi Hyun,Han, Eun Taek,Lee, Won Ja,Lee, Hee Kyung,An, Seong Soo A.,Lim, Chae Seung,Lee, Kap No Blackwell Publishing Ltd 2010 Tropical medicine & international health Vol.15 No.12

<P><B>Summary</B></P><P> <I>Plasmodium vivax</I> malaria is the indigenous strain in the Republic of Korea (ROK). <I>Plasmodium vivax</I> can be transmitted through the transfusions of various blood components, which became a severe problem with the safety of blood transfusions and blood‐related products in ROK. We evaluated a <I>P.?vivax</I>‐specific enzyme‐linked immunosorbent assay (Genedia Malaria Ab ELISA 2.0, Green Cross, ROK) with blood samples from four groups: 251 samples from <I>P.?vivax</I>‐infected patients, 39 samples from post‐treatment patients upon follow‐up, 200 samples from healthy volunteers and 421 samples from domestic travellers to and from high endemic areas of ROK. The positive cases from the ELISA test were confirmed by both Giemsa microscopic and polymerase chain reaction methods. The clinical sensitivity and specificity of detecting <I>P.?vivax</I> with ELISA test were 94.4% and 99.0%, respectively. Thirteen of 421 domestic travellers (3.0%) to endemic areas tested positive. The results indicate the effectiveness of detecting antibodies against <I>P.?vivax</I> in blood with Genedia Malaria Ab ELISA 2.0 test in a large blood screen setting.</P>

다기관 기능부전을 초래한 치명적인 삼일열 말라리아 증례

박상원,김동우,박주원,이순일,신영학,김의종,오명돈,최강원 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

삼일열 말라리아는 국내에서 재유행하고 있는 감염질환으로, 일반적으로 양성의 임상경과를 거친다. 저자들은 특이한 질병력이 없이 건강하였던 젊은 성인이 국내에서 삼일열 말라리아에 걸린 후 다기관기능부전과 폐출혈으로 사망한 증례를 경험하였다. 환자의 중증 임상경과를 설명할 만한 특이한 인자가 발견되지 않았다. Vivax malaria is a re-emerging infectious disease in Korea with cumulating 19,416 cases as of December 2003 since 1993. Vivax malaria is generally a benign disease with few severe complications. Even in the worldwide literature, there are only small number of case reports on severe complications. We experienced a fatal vivax malaria in a previously healthy young adult with severe multi-organ failure and fatal massive pulmonary hemorrhage. The patient presented with abdominal pain and shock. There were splenic hemorrhage, disseminated intravascular coagulation, oliguric acute renal failure requiring dialysis, and pulmonary hemorrhage leading the patient finally to death. The initial parasitemia was 2,046/μL. Thin smear and PCR revealed only Plasmodium Vivax. There was no explainable cause of death except for the only serological suggestion of Mycoplasma pneumoniae infection without correlating clinical evidence. This is a first case of fatal vivax malaria in Korea since its re-emergence in 1993. Further case monitoring is needed to define whether this is a index case or an isolated one.

<i>Plasmodium vivax</i> Merozoite Surface Protein 1 Paralog as a Mediator of Parasite Adherence to Reticulocytes

Han, Jin-Hee,Cho, Jee-Sun,Cheng, Yang,Muh, Fauzi,Yoo, Won Gi,Russell, Bruce,Nosten, Francois,Na, Sunghun,Ha, Kwon-Soo,Park, Won Sun,Hong, Seok-Ho,Han, Eun-Taek American Society for Microbiology 2018 Infection and immunity Vol.86 No.9

<P>Plasmodium vivax parasites preferentially invade reticulocytes in human beings. P. vivax merozoite surface protein 1 (PvMSP1) and PvMSP1 paralog (PvMSP1P) may have important functions in reticulocyte adherence during invasion. These proteins share similar structures, including the presence of two epidermal growth factor (EGF)-like and glycosylphosphatidylinositol (GPI)-anchored domains at the C terminus. However, there have been no reports concerning the functional activity of PvMSP1P in reticulocyte adherence during P. vivax invasion. In this study, the ability of PvMSP1P-19 to bind to reticulocytes and normocytes was analyzed. The reticulocyte binding activity of PvMSP1P-19 was 4.0-fold higher than its normocyte binding activity. The binding of PvMSP1 P-19 to reticulocytes and normocytes was inhibited in a dose-dependent manner by antibodies from immunized rabbits and by antibodies from vivax parasite-infected patients. Consistently, antibodies against PvMSP1 P inhibited parasite invasion during short-term in vitro cultivation. Similar to the case for PvDBPII binding activity, PvMSP1P-19 binding activity was reduced in chymotrypsin-treated reticulocytes. However, no significant difference between the binding of PvMSP1P-19 to Duffy-positive and Duffy-negative erythrocytes was found. The minimal binding motif of PvMSP1P-19 was characterized using synthetic peptides. The results showed that the residues at amino acid positions 1791 to 1808 may have an important function in mediating merozoite adherence to reticulocytes. The positively charged residues within the EGF-like domain were shown to constitute a key binding motif. This work presents strong evidence supporting the role of PvMSP1P in host target cell selection and invasion of Duffy-independent pathway in P. vivax. Moreover, PvMSP1P-19-specific antibodies may confer protection against P. vivax reinvasion.</P>

1995년 서울지역 거주자에서 발생한 Plasmodium Vivax에 의한 Malaria 1예

김영선,박기령,어은경,최진혁,이정수,정화순 梨花女子大學校 醫科大學 醫科學硏究所 1996 EMJ (Ewha medical journal) Vol.19 No.2

Malaria has a wordwide incidence of more than one thousand to three thousand million clinical cases and results in approximately 200 to 300 million deaths per year. Although Korea was an endemic area of Malaria, it was nearly eradicated from the country. However, indigenous cases of malaria have been reported since 1994. Recently, we experienced a case of Plasmodium vivax infection in a resident of Seoul. A 25-year old young man who had no history of being abroad, blood transfusion nor parenteral use of drug visited our hospital due to fever and chill for 4 days. A peripheral blood smear demonstrated Plasmodium vivax infection. He was treated with hydroxychoroquine and premaquine without relapse.