국내 환자에서 분리된 Orientia tsutsugamushi에서 doxycycline 내성

김은실,김미경,이혜명,길세희,정문현,이진수,강재승 대한감염학회 2008 Infection and Chemotherapy Vol.40 No.5

Background : Doxycycline has been the drug of choice for the treatment of scrub typhus. However, scrub typhus with poor response to doxycycline was first reported in Thailand in 1996. To date, it is not known whether doxycycline resistant scrub typhus is present in Korea. To investigate the doxycycline resistance of scrub typhus in Korea, we performed an experiment to evaluate the degree of growth inhibition of Orientia tsutsugamushi at the minimal inhibitory concentration (MIC) of doxycycline. Materials and Methods : 37 isolates of Orientia tsutsugamushi were collected from Korean patients with scrub typhus during 10 year period (from 1997 to 2007). 34 isolates consisted of Boryong serotype or related serotypes. These strains were stained with FS15, a monoclonal antibody against the linear epitope on the protein located at the outer membrane of O. tsutsugamushi. Three isolates were confirmed as serotype Gilliam, which was stained by anti-Gilliam antibody. The antibody- stainable 35 isolates were incubated in media containing 0.1 and 0.2 µg/mL of doxycycline for 3 days. Then the growth indices of Orientia were measured by flow cytometry. If the growth index was greater than 10%, the isolate was tentatively classified as an isolate resistant to doxycycline and its MIC was measured. Results : Demographic and treatment data were similar to the results of previous reports. Infection was mainly observed in Inchon and the Chungcheongnam province. No patient showed delayed response to antibiotics. Of 35 hospitalized patients, 4 (11.4%) were managed at the intensive care unit, and 1 (2.9%) died of nosocomial pneumonia. All the 2 patients whose isolates were serotype Gilliam Yonchon/Ikeda-like strain were managed at the intensive care unit. Six of the 34 isolates from Korean patients exhibited growth indices greater than 10% at the MIC of doxycycline; however, the MICs of these isolates did not exceed 0.2 µg/mL. One isolate of serotype Gilliam showed an MIC of 0.0125 ug/mL, which seemed to be underestimated due to weak fluorescence of the anti-Gilliam antibody. Conclusions : Although the number of tested isolates is small, insensitivity of scrub typhus to doxycycline is not a major reason for treatment failure in Korea. Serotype Gilliam, especially Yochon/ Ikeda-like strain, may be associated with severe form of scrub typhus. More studies concerning the antibiotic susceptibility for serotype Gilliam are warranted. Background : Doxycycline has been the drug of choice for the treatment of scrub typhus. However, scrub typhus with poor response to doxycycline was first reported in Thailand in 1996. To date, it is not known whether doxycycline resistant scrub typhus is present in Korea. To investigate the doxycycline resistance of scrub typhus in Korea, we performed an experiment to evaluate the degree of growth inhibition of Orientia tsutsugamushi at the minimal inhibitory concentration (MIC) of doxycycline. Materials and Methods : 37 isolates of Orientia tsutsugamushi were collected from Korean patients with scrub typhus during 10 year period (from 1997 to 2007). 34 isolates consisted of Boryong serotype or related serotypes. These strains were stained with FS15, a monoclonal antibody against the linear epitope on the protein located at the outer membrane of O. tsutsugamushi. Three isolates were confirmed as serotype Gilliam, which was stained by anti-Gilliam antibody. The antibody- stainable 35 isolates were incubated in media containing 0.1 and 0.2 µg/mL of doxycycline for 3 days. Then the growth indices of Orientia were measured by flow cytometry. If the growth index was greater than 10%, the isolate was tentatively classified as an isolate resistant to doxycycline and its MIC was measured. Results : Demographic and treatment data were similar to the results of previous reports. Infection was mainly observed in Inchon and the Chungcheongnam province. No patient showed delayed response to antibiotics. Of 35 hospitalized patients, 4 (11.4%) were managed at the intensive care unit, and 1 (2.9%) died of nosocomial pneumonia. All the 2 patients whose isolates were serotype Gilliam Yonchon/Ikeda-like strain were managed at the intensive care unit. Six of the 34 isolates from Korean patients exhibited growth indices greater than 10% at the MIC of doxycycline; however, the MICs of these isolates did not exceed 0.2 µg/mL. One isolate of serotype Gilliam showed an MIC of 0.0125 ug/mL, which seemed to be underestimated due to weak fluorescence of the anti-Gilliam antibody. Conclusions : Although the number of tested isolates is small, insensitivity of scrub typhus to doxycycline is not a major reason for treatment failure in Korea. Serotype Gilliam, especially Yochon/ Ikeda-like strain, may be associated with severe form of scrub typhus. More studies concerning the antibiotic susceptibility for serotype Gilliam are warranted.

Clinical and Laboratory Predictors associated with Complicated Scrub Typhus

김미희,김시현,최정현,위성헌 대한감염학회 2019 Infection and Chemotherapy Vol.51 No.2

Background: Scrub typhus, a mite-borne disease caused by bites of Orientia tsutsugamushiinfected chiggers, is endemic in Asia-Pacific countries. In Korea, it is a seasonal disease prevalent in autumn and one of the important causes of acute undifferentiated febrile illness. The purpose of this study was to identify the risk factors for the prediction of the severe clinical course of scrub typhus and to investigate the differences in the clinical and laboratory findings of hospitalized elderly and non-elderly patients with scrub typhus. Materials and Methods: This study retrospectively reviewed the medical records of patients diagnosed with scrub typhus. Results: A total of 710 patients were enrolled and 43.9% of them were elderly patients. The number of patients with complicated scrub typhus was 168 (23.7%) and the most common complication of severe scrub typhus was hepatic dysfunction (10.7%) followed by pneumonia (7.2%), acute kidney injury (4.9%) and shock (2.4%). Blood urea nitrogen ≥20 mg/dL, adenosine deaminase (ADA) ≥100 IU/L, pulmonary edema or pleural effusion, lactate dehydrogenase ≥500 U/L, alkaline phosphatase ≥400 IU/L, ferritin ≥500 ng/mL and absence of skin rash were independently associated with severe scrub typhus. There was no significant difference in the incidence of complicated scrub typhus between elderly and non-elderly patients. Absence of skin rash, pulmonary edema, pleural effusion, serum creatinine ≥1.5 mg/dL, total bilirubin ≥1.5 mg/dL, ADA ≥100 IU/L and ferritin ≥500 ng/mL were significantly associated with a longer hospitalization (≥10 days). Conclusion: The several independent predictors of complicated scrub typhus were identified in this study. Absence of skin rash, the increased levels of serum ADA and ferritin were identified as the predictors of complicated scrub typhus, which were also associated with a prolonged hospitalization.

쯔쯔가무시증 환자군과 대조군의 인지도와 지식 비교

이관(Kwan Lee),박병찬(Byeong-Chan Park),임현술(Hyun-Sul Lim),권순석(Sun-Seog Kweon),최진수(Jin-Su Choi),김장락(Jang-Rak Kim),김건엽(Keon-Yeop Kim),류소연(So-Yeon Ryu) 한국농촌의학 지역보건학회 2012 농촌의학·지역보건 Vol.37 No.1

이 연구는 지역사회 주민 중 쯔쯔가무시증 환자군과 대조군에 대하여 쯔쯔가무시증 인지도 및 지식 정도를 파악하고, 쯔쯔가무시증 발생과 인지도의 관련성 및 인지도에 영향을 미치는 요인을 파악함으로서 향후 쯔쯔가무시증 방역사업에 활용할 수 있도록 하기위해 수행하였다. 2006년 10월부터 12월까지, 시ㆍ도 단위로 다섯 지역을 선정 후 각 지역별로 2곳 이상의 시ㆍ군을 지정하였다. 환자군은 지난 2주간 동안 확진된 환자 299명으로 하였고, 대조군은 환자가 실제 거주지 이웃 주민중 최근 2년 동안 쯔쯔가무시증의 감염 병력이 없고, 성별, 연령(± 5세)이 일치하며 환자의 집에서 가까운 순으로 2명을 선정하여 598명이었다. 저자들이 전문가의 자문을 통하여 직접 개발한 설문지를 통하여 쯔쯔가무시증에 대한 인지도 및 지식정도를 조사하였다. 쯔쯔가무시증에 대한 인지도는 대조군 79.4%, 환자군 66.6%로 유의한 차이가 있었다(p<0.01). 환자군과 대조군에서 유의한 차이가 있었던 변수, 즉 인지도와 과거 감염력을 이용한 다변량 분석에서 쯔쯔가무시증은 인지도가 없을 경우 그렇지 않은 경우에 비해 1.95배 더 발생하였다. 쯔쯔가무시증에 대한 인지도가 있는 대상자 중 쯔쯔가무시증 인지 경로별 분포는 전체적으로 가족 또는 이웃이 쯔쯔가무시증을 앓은 경우가 54.9%로 가장 많았고, 텔레비전 28.3%, 과거 쯔쯔가무시증을 앓은 경우 5.5% 등의 순이었다. 쯔쯔가무시증에 관한 지식 정도는 전반적으로 대부분의 항목에서 정답률이 70% 미만이었으며, 모든 항목에서 환자군이 대조군보다 유의하게 정답률이 높았다(p<0.01). 다변량 분석 결과 쯔쯔가무시증 인지도에 영향을 미치는 요인은 환자군에서 연령(OR, 0.96; 95% CI, 0.94-0.98)이었고, 대조군에서는 여자(OR, 1.56; 95% CI, 1.03-2.36), 연령(OR, 0.98; 95% CI, 0.96-0.99), 가족력이 있는 경우(OR, 10.18; 95% CI, 1.37-75.99), 교육을 받은 경험이 있는 경우 (OR, 8.47; 95% CI, 1.14-63.00) 등이었다. 쯔쯔가무시증 예방 또는 감소를 위해서는 예방교육을 통해 주민의 인지도를 향상시키고, 이를 통해 예방활동을 수행할 수 있도록 하는 것이 최선의 방법일 것이다. 낮은 인지도 향상과 쯔쯔가무시증 예방을 위해 효과적인 작업 지침 및 교육프로그램이 개발되어야 하며, 예방에 관련된 홍보를 강화하여야 할 것이다. Objectives: To survey the awareness of patient to scrub typhus to provide data for education and communication concerning scrub typhus. Methods: Patients with scrub typhus (case group, n=299) and people without scrub typhus within the previous 2 years (control group, n=598) were matched for age (within 5 years), gender, and occupation (farmer or non-farmer). The participants were recruited from 15 study areas between October and December 2006. Results: The awareness rate of scrub typhus was 75.1%, and was significantly higher than in the case group (79.4% vs. 66.6%, respectively; p<0.01). The major routes of awareness were from ‘past history of scrub typhus in family members or neighbors’ (54.9%), ‘television’ (28.3%), and their past history of scrub typhus (5.5%). The average correct rate of scrub typhus was 48.4%, and the correct response rate of cases was significantly higher than controls (p<0.01). Especially, the correct rate of etiology, incubation period, route of transmission, and acquired immunity was <40%. Through conditional logistic regression test, the factor significantly associated with awareness in case group was age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94-0.98). And the factors associated with awareness in control group were female (OR, 1.56; 95% CI, 1.03-2.36) age (OR, 0.98; 95% CI, 0.96-0.99), family history of scrub typhus (OR, 10.18; 95% CI, 1.37-75.99), history of receiving prevention education (OR, 8.47; 95% CI, 1.14-63.00). Conclusions: The rate of awareness was relatively low in study population. Thus, effective working guidelines and educational program to prevent scrub typhus must be developed, and publicity activities about the prevention of scrub typhus are needed for high-risk groups.

유세포분석법으로 조사한 Orientia tsutusgamushi Boryong주의 항균제 감수성

김은실,김미경,이혜명,정문현,이진수,박재은,강재승 대한감염학회 2008 Infection and Chemotherapy Vol.40 No.4

Background : Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased. In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry. Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on 56-kDa major outer membrane protein of O. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin. Results : Considering the usual serum concentrations of rifampin (MIC=0.025-0.05 µg/mL), azithromycin (MIC=0.05-0.5 µg/mL) and doxycycline (MIC=0.05-0.1 µg/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 µg/mL), clindamycin (MIC=1.0 µg/mL) and chloramphenicol (MIC=1-2 µg/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 µg/mL), ciprofloxacin (MIC=25.6 µg/mL or more) and levofloxacin (MIC=30 µg/mL) exhibited relatively high MICs; and cefotaxime (MIC>50 µg/mL), metronidazole (MIC>30 µg/mL) and linezolid (>30 µg/mL) exhibited high MICs. Conclusions : Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human. Background : Scrub typhus, an infectious disease caused by Orientia tsutsugamushi, is endemic in Korea. With the introduction of tetracycline and chloramphenicol in clinical practice, the mortality due to scrub typhus has markedly decreased. In 1995, scrub typhus poorly responsive to doxycycline was reported in Thailand; the need for safe antibiotics for the treatment of scrub typhus acquired during pregnancy or for children is emerging; also, broader spectrum antibiotics having anti-Orientia activity may be preferred for empirical therapy of enteric fever syndrome and for complicated scrub typhus. The anti-Orientia activities of various antibiotics, including recently licensed antibiotics, were investigated by flow cytometry. Materials and Methods : O. tsutsugamushi strain Boryong was inoculated into the ECV304 cell line. The infected cells were stained with FS15, a monoclonal antibody reacting against a linear epitope on 56-kDa major outer membrane protein of O. tsutsugamushi. Then the antimicrobial susceptibilities were measured by flow cytometry and expressed as a growth index (total mass of Orientia). A concentration at which no further decrease in growth index occurred was defined as the minimal inhibitory concentration (MIC). Microbial susceptibilities to the following antibiotics were measured: quinupristin-dalfopristin (Synercid), levofloxacin, ciprofloxacin, moxifloxacin, metronidazole, linezolid, clindamycin, chloramphenicol, doxycycline, azithromycin, and rifampin. Results : Considering the usual serum concentrations of rifampin (MIC=0.025-0.05 µg/mL), azithromycin (MIC=0.05-0.5 µg/mL) and doxycycline (MIC=0.05-0.1 µg/mL), these antibiotics exhibited very low MICs. Synercid (MIC=0.2-1.0 µg/mL), clindamycin (MIC=1.0 µg/mL) and chloramphenicol (MIC=1-2 µg/mL) exhibited moderately low MICs; moxifloxacin (MIC=8 µg/mL), ciprofloxacin (MIC=25.6 µg/mL or more) and levofloxacin (MIC=30 µg/mL) exhibited relatively high MICs; and cefotaxime (MIC>50 µg/mL), metronidazole (MIC>30 µg/mL) and linezolid (>30 µg/mL) exhibited high MICs. Conclusions : Among the new antibiotics, none was superior to doxycycline, azithromycin or rifampin with respect to anti-Orientia activity. Synercid, clindamycin, and moxifloxacin may show moderate therapeutic efficacies in human.

1989년 한국에서 확인된 급성 출혈성 질환의 혈청 역학적 조사

원중희,백락주,송진원,이호왕 고려대학교 의과대학 1991 고려대 의대 잡지 Vol.28 No.3

Acute hemorrhagic diseases that occurred in Korea have been confirmed as Hemorrhagic fever with renal syndrome (HFRS) and rickettsiosis among suspect hemorrhagic disease patients. In this study, we report the results of serological study of 1.886 sera from suspect HFRS or rickettsiosis patients in Korea, 1989. 1. Of 1,886 sera from acute hemorrhagic disease patient tested in 1989, 344 murine typhus, 352 scrub typhus, 79 spotted fever and 27 leptospirosis were confirmed serologically. 2. It was confirmed that large numbers of murine typhus, scrub typhus and spotted fever patients occurred in Seoul city, Kyunggido and Cheollanamdo. Two murine typhus,two spotted fever and one scrub typhus patients were identified in Chejudo for the first time. 3. Murine typhus, scrub typhus and spotted fever patients occurred mainly in summer or fall and peak was from October to November. Leptospirosis occurred in spring or summer, 4. Of 344 murine typhus, male was 201(59%) and female was 143(41%). In scrub typhus, female were 59% and male were 41%. In leptospirosis, male were predominant, and in spotted fever no sexual difference was found. 5. The majority of age of acute hemorrhagic disease patients in 1989 were above 20 years of age, however small number of children below the age of 10 were also found. 6. In 1985, 14 murine typhus. 6 scrub typhus, 4 spotted fever and one leptospirosis occurred in the Korean Army, and only one scrub typhus occurred in the U.S. Army Above results revealed that a large number of murine typhus, scrub typhus and spotted fever patients occurred In Korea, and murine typhus, scrub typhus and spotted fevor patients were confirmed serologically for the first time in Chejudo.

Epidemiologic characteristics of scrub typhus on Jeju Island

Sung Uk Lee 한국역학회 2017 Epidemiology and Health Vol.39 No.-

OBJECTIVES: Scrub typhus is the most common febrile disease in Korea during the autumn. Jeju Island is the largest island in South Korea and has a distinctive oceanic climate. This study aimed to identify epidemiologic characteristics of scrub typhus on Jeju Island. METHODS: From January 2011 to December 2016, 446 patients were diagnosed with scrub typhus on Jeju Island. The patients’ personal data and the environmental factors that might be related to scrub typhus were investigated and retrospectively analyzed. RESULTS: The median age of the patients was 58-years-old (range, 8 to 91) and 43% of them worked in the agricultural, forestry or livestock industry. Regardless of their job, 87% of the patients had a history of either working outdoors or of other activities before developing scrub typhus. The south and southeast regions of Jeju Island, especially Namwon-eup, showed the highest incidence of scrub typhus. Workers in mandarin orange orchards seemed to be the highest risk group for scrub typhus infection. CONCLUSIONS: Scrub typhus on Jeju Island showed unique characteristics. To efficiently prevent scrub typhus, each year individual regional approaches should be developed based on the epidemiologic characteristics of the disease.

쯔쯔가무시(Tsutusgamushi)병에서 Clarithromycin의 치료 효과

김순,정은미,문경현,여승엽,엄수정,이주형,조성래,마상혁,Kim, Soon,Jung, Eun Mi,Moon, Kyung Hyun,Yoe, Sung Yeob,Eum, Soo Jung,Lee, Joo Hyung,Jo, Sung Rae,Ma, Sang Hyuk 대한소아감염학회 2002 Pediatric Infection and Vaccine Vol.9 No.2

목 적:쯔쯔가무시(Tsutusgamushi)병은 리케치아 (Rickettia) 감염증의 하나로 인체병원체인 R. tsutusgamushi에 감염된 좀 진드기 유충(chigger)에 물렸을 때 감염이 된다. 임상적으로 물린 부위에 가피형성, 발열, 발진을 특징으로 하는 급성 발진성 열 성 질환이다. 치료약제로는 Tetracycline, Doxyctcline, Chloramphenicol 등이 사용되고 있으나 소아에서는 약의 부작용으로 인하여 약의 사용에 있어 많은 제한을 받게 되는 경우가 많다. 최근 산모에서 발생한 쯔쯔가무시병을 macrolide 계통의 항생제인 Azithromycin을 치료한 것을 발표한 바가 있다. 이에 저자들은 소아에서 비교적 사용이 용이한 또 다른 macrolide 계열의 항생제인 Clarithromycin을 사용하여 쯔쯔가무시병에 대한 효과를 알아보고자 하였다. 방 법 2001년11월에 마산파티마병원에 급성 열성 질환으로 내원한 환자 중 임상적으로, 혈청학적으로 쯔쯔가무시병으로 진단을 받은 내과 환자 7명과 소아과 환자 3명을 대상으로 Clarithromycin(Ab- bott Laboratories, NorthChicago, IL, USA) 투여하여 쯔쯔가무시병의 치료효과에 대하여 알아보았다. 쯔쯔가무시병의 임상적 진단은 하루 이상의 발열과 최근 수주 이내에 감염 가능성이 있는 지역인들이나 산 등의 지역에 노출된 병력이 있으며 림프절 종대, 반점 구진상의 피부발진과 특징적인 가피 등 의 특징적인 이학적 소견이 동반된 경우 진단을 위한 검사를 실시하였다. 혈청학적인 기준은O. tsutsugamishi 항원 감작 면양 적혈구(sheep red blood cell)를 이용한 수동응집반응검사(passive hamagglutination assay : PHA)인 GENEDIA Tsutsugamushi PHA IIkit(Green Cross, Korea)를 이용하였는데 O. tsutsugamishi 항체가가 1 : 80 이상이면 양성으로 판정하였고 추적검사는 실시하지 않았다. Clarithromycin의 투여량은 성인의 경우 500 mg을 하루에 2회 경구투여 하였으며 소아의 경우 15 mg/kg으로 하루에2회 경구투여 하였다. 결 과 1) 총 대상 환자는 성인 7명, 소아 3명이었으며 성인의 경우 남자는 3명, 여자는 4명이었고 연령은 28세부터 76세까지이었다. 소아의 경우 남자는 1명, 여자는2명이었고4세부터 7세까지의 연령의 분포를 보였다. 임상증상으로는 전 환자에서 발열과 근 육통, 두통 등이 동반되었고 이학적 검사상 발진과 가피를 발견할 수 있었다. 7례에서 PHA 항체 양성 반응 보였고8례에서 간기능의 이상을 보였고6례 에서는 혈소판 감소가 있었다. 간기능의 이상을 보인 환자8례 중 추적관찰이 가능했던 환자6명에서 간기능 정상이 되었고 혈소판 감소증을 보인 환자 중 추적관찰이 가능했던 5명에서 혈소판의 수가 정상적으로 되었다. 2) Clarithromycin 투약 후 열이 떨어지는데 걸리 는 시간은 평균 1.3일(1 ~ 2일)이었으며 투약기간은 6일에서11일까지 평균7.2일을 사용하였다. 전 환자에서 특별한 합병증 없이 회복이 되었다. 결 론 본 연구에서 쯔쯔가무시병의 환자의 치료에 있어 Clarithromycin 투여가 효과적이었으나 증례 수가 많지 않아 향후 더 많은 연구가 이루어져할 것으로 사료된다. Purpose : Scrub typhus(tsutsugamushi disease) is a febrile disease characterized by fever, rash, eschar, lymphadenopathy. Therapy with tetracycline(doxycycline) or chloramphenicol is currently recommended for the treatment for scrub typhus. But there are limitations in usage a tetracycline(doxycycline) for scrub typhus in the children. Recently, there was a report that azithromycin, a macrolide antibiotic was used for scrub typhus in pregnant woman successfully. So we evaluated the effectiveness of the Clarithromycin, other a macrolide antibiotic, for scrub typhus. Methods : Seven patients with scrub typhus at department of internal medicine and three patients with scrub typhus at department of pediatrics Masan Fatima Hospital were involved for this study. A serologic diagnosis for scrub typhus were performed by use of passive hemagglutination test. Clarithromycin(Abbott Laboratories, North Chicago, IL, USA) was administrated orally in a daily dose of 500 mg for adult patients and 15 mg/kg/bid/day for pediatric patients. Results : There were 7 cases of adult patients, varying from 28 to 76 years of age and 3 cases of pediatirc patients, varying from 4 to 7 years of age with scrub typhus. All of cases had fever, myalgia, headache, rash, eschar. Seven cases had positive passive hemagglutination test and eight cases had abnormal liver function. Mean duration for the removal of fever after medication was 1.3 day(1~2 days) and all cases were recovered without complications. Conclusion : Our results suggest that Clarithromycin therapy may be effective for scrub typhus.

쯔쯔가무시 환자의 단클론성 및 이클론성 감마글로불린병증 빈도 및 유형

조지현,박도심 대한진단검사의학회 2009 Annals of Laboratory Medicine Vol.29 No.2

Background : Korea is an endemic area of scrub typhus and it is a common seasonal febrile illness. Although, various humoral immune responses to scrub typhus have been documented, no association between gammopathy and scrub typhus has ever been reported. We analyzed the incidences and types of monoclonal and biclonal gammopathies in scrub typhus for better coping with those gammopathies in scrub typhus. Methods : Anti-Orientia tsutsugamushi antibody-positive sera identified by indirect immunofluorescence assay were acquired from 40 patients with confirmed scrub typhus. Monoclonal and biclonal gammopathies were screened by protein electrophoresis and were confirmed using immunofixation electrophoresis (IFE). Laboratory findings on admission of the patients with monoclonal or biclonal gammopathy were investigated retrospectively to characterize the gammopathies. Results : Monoclonal or biclonal gammopathies were detected in 30% (12/40) of patients with scrub typhus (IgG-λ, 40%; IgG-κ, 30%; IgM-κ, 10%; IgM-λ, 10%; IgA-κ, 5%; IgA-λ, 5%). Concentrations of clonal immunoglobulin were less than 3 g/dL in all gammopathies, and hypercalcemia was not detected in any of the patients. Conclusions : Our results suggest possible association between gammopathies and scrub typhus. Further studies in larger series will be needed for exact incidence and clinical course of gammopathies in scrub typhus. 배경 : 우리나라는 쯔쯔가무시병의 호발 지역이고, 이 질환은 국내에 흔한 계절성 열성 질환이다. 쯔쯔가무시병에 의한 다양 한 체액성 면역 반응들이 연구된 바 있으나, 이 질환과 감마글로 불린병증의 연관성에 대해서는 보고된 바가 없다. 본 연구에서 는 쯔쯔가무시병증에서 관찰되는 단클론성 및 이클론성 감마글 로불린병증에 대해 보다 적절히 대처하고자 쯔쯔가무시 환자에 서 이들 감마글로불린병증의 빈도와 유형을 조사하였다. 방법 : 쯔쯔가무시병으로 확진된 40명의 환자로부터 간접 면 역 형광법상 항 Orientia tsutsugamushi 항체 양성인 혈청을 얻어 단백 전기영동 검사로 단클론성 및 이클론성 감마글로불 린병증을 선별하였고, 이후 면역고정 전기영동 검사로 확인하였 다. 이들에서 관찰된 감마글로불린병증의 특성을 규명하기 위한 입원시 검사소견은 후향적으로 조사하였다. 결과 : 단클론성 또는 이클론성 감마글로불린병증은 쯔쯔가 무시 환자의 30% (12/40)에서 관찰되었다(IgG-λ, 40%; IgG- κ, 30%; IgM-κ, 10%; IgM-λ, 10%; IgA-κ, 5%; IgA-λ, 5%). 감마글로불린병증 환자들에서 클론성 면역글로불린은 모두 3 g/dL 미만이었고, 고칼슘혈증은 관찰되지 않았다. 결론 : 이러한 결과들은 쯔쯔가무시병과 이들 감마글로불린 병증과의 관련 가능성을 제시한다. 이후 더 많은 쯔쯔가무시 환 자를 대상으로 이들 감마글로불린병증에 대한 정확한 빈도 평가 필요할 것이며, 이들의 임상적 경과에 대해서도 연구가 필요할 것으로 보인다.

Activation of the coagulation cascade in patients with scrub typhus

Lee, H.J.,Park, C.Y.,Park, S.G.,Yoon, N.R.,Kim, D.M.,Chung, C.H. Elsevier Science Pub. Co 2017 Diagnostic microbiology and infectious disease Vol.89 No.1

This retrospective study aimed to evaluate the levels of coagulation factors and presence of disseminated intravascular coagulation (DIC) in patients with scrub typhus. We included patients confirmed to have scrub typhus at the Chosun University Hospital between September 2004 and December 2009. The DIC scores were evaluated in 365 patients and 36 healthy controls. The median concentrations of fibrinogen, d-dimer, and fibrin/fibrinogen degradation products (FDP) were compared between patients and healthy controls (p<0.001 for all tests). Patients with scrub typhus had longer prothrombin time and lower platelet counts than the controls. Major bleeding was observed in 18/365 patients with scrub typhus. Fifty-one (14.0%) patients presented with severe complications of scrub typhus. Overt DIC and thrombocytopenia (<100,000 platelets/mm<SUP>3</SUP>) were observed more frequently in patients with bleeding and severe illness. Furthermore, median platelet counts were low in both groups. Approximately 2.7% (n=10) and 16.4% (n=60) patients with scrub typhus had overt DIC, as defined by the International Society on Thrombosis and Hemostasis DIC score (DIC1) and the DIC-scoring template with a fibrinogen/C-reactive protein-ratio (DIC2), respectively. Three (16.7%) and 10 (55.6%) patients with bleeding had overt DIC, as defined by the DIC1 and DIC2, respectively. Seven (13.7%) and 26 (51%) patients with severe illness had overt DIC, as defined by DIC1 and DIC2, respectively. In conclusion, activation of the coagulation system is an important feature of scrub typhus and is correlated with severe disease, including bleeding. This is the first study to report a relationship between DIC and scrub typhus.

기후 변화 적응을 위한 벡터매개질병의 생태 모델 및 심층 인공 신경망 기반 공간-시간적 발병 모델링 및 예측

김상윤,남기전,허성구,이선정,최지훈,박준규,유창규,Kim, SangYoun,Nam, KiJeon,Heo, SungKu,Lee, SunJung,Choi, JiHun,Park, JunKyu,Yoo, ChangKyoo 한국화학공학회 2020 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.58 No.2

본 연구에서는 발병 횟수가 빠르게 증가하고 있는 벡터매개질병(vector-borne disease) 중 하나인 쯔쯔가무시증의 발병 특성을 공간적 그리고 시간적으로 분석하고 기후변화 시나리오에 따른 미래 발병 특성을 예측하였다. 쯔쯔가무시증의 공간적 분포와 발병률을 예측하기 위하여 환경 그리고 사회 변수의 공간적 특성을 이용하여 maximum entropy(MaxEnt) 생태 모델을 구성하고, 주요 변수의 쯔쯔가무시증 발병에 관한 상관관계를 분석하였다. 공간 특성 중 환경변수인 고도 및 기온이 주요한 변수로 분석되었으며, 이는 쯔쯔가무시증의 매개체인 털진드기의 생육 환경과 주요 관련이 있는 것으로 나타났다. 쯔쯔가무시증의 시간적 발병 횟수는 심층 인공 신경망 모델기반 예측을 하였으며, 특히 쯔쯔가무시증의 주요 특성인 지연 효과를 고려하여 모델을 구성하였다. 심층 인공 신경망을 이용한 예측 결과 여름철의 기온, 강우량, 그리고 습도가 털진드기의 활동에 주된 관련이 있으며 가을철의 쯔쯔가무시증 발병 횟수에 영향을 끼치는 것으로 확인 되었다. 또한, 기존 통계적 예측 모델과 비교하였을 때, 심층 인공 신경망 기반 예측 모델의 예측 정확성이 우수함을 확인하였다. 공간적 그리고 시간적 모델에 기후 변화 시나리오를 이용하여 2040년의 쯔쯔가무시증 발병 특성을 예측한 결과, 최대 발병률이 8% 증가, 발병률이 높은 지역이 9% 확대, 그리고 주된 발병 기간이 2개월 증가하였다. 본 연구 결과를 통해 쯔쯔가무시증의 공간적 및 시간적 발병 특성 분석을 통하여, 공중보건 측면에서 벡터매개 질병 발병 요인 규명을 통해 주민 건강을 위한 질병 관리 및 예측에 기여할 수 있을 것으로 기대한다. This study was carried out to analyze spatial and temporal incidence characteristics of scrub typhus and predict the future incidence of scrub typhus since the incidences of scrub typhus have been rapidly increased among vector-borne diseases. A maximum entropy (MaxEnt) ecological model was implemented to predict spatial distribution and incidence rate of scrub typhus using spatial data sets on environmental and social variables. Additionally, relationships between the incidence of scrub typhus and critical spatial data were analyzed. Elevation and temperature were analyzed as dominant spatial factors which influenced the growth environment of Leptotrombidium scutellare (L. scutellare) which is the primary vector of scrub typhus. A temporal number of diseases by scrub typhus was predicted by a deep neural network (DNN). The model considered the time-lagged effect of scrub typhus. The DNN-based prediction model showed that temperature, precipitation, and humidity in summer had significant influence factors on the activity of L. scutellare and the number of diseases at fall. Moreover, the DNN-based prediction model had superior performance compared to a conventional statistical prediction model. Finally, the spatial and temporal models were used under climate change scenario. The future characteristics of scrub typhus showed that the maximum incidence rate would increase by 8%, areas of the high potential of incidence rate would increase by 9%, and disease occurrence duration would expand by 2 months. The results would contribute to the disease management and prediction for the health of residents in terms of public health.