Open Access Volume: 39, Article ID: e2017014, 5 pages https://doi.org/10.4178/epih.e2017014 EPIDEMIOLOGIC INVESTIGATION 식중독원인으로서의칠성쿠도아충과감별진단 이성욱제주도청보건위생과 Analysis of Kudoa septempunctata as a cause of foodborne illness and its associated differential diagnosis Sung Uk Lee Jeju Special Self-Governing Provincial Office, Jeju, Korea 최근광어섭취후발생한식중독의한원인으로쿠도아충이지목되고있다. 하지만쿠도아충에의한식중독은인체감염에대한근거가 부족하고, 황색포도알균이나바실루스세레우스식중독과감별이어려워진단에있어주의를요한다. KOREAN SUMMARY Objectives: Recently kudoa septempuctata in s is suggested as a cause of food poisoning, however whether kudoa septempuctata can affect human gastrointestinal systems is controversial and its pathogenecity remains unclear. In view of the field epidemiology, food poisonings caused by kudoa septempuctata should be distinguished from those caused by staphylococcus aureus and bacillus cereus. Methods: The statistics of food poisoning investigations published by Korea Centers for Disease Control and Prevention in 2013-2015 were reviewed. The characteristics of kudoa septempuctata food poisoning reported by Korea Centers for Disease Control and Prevention were reviewed. Information regarding clinical symptoms or epidemiology was extracted. Results: Total eleven kudoa septempuctata food poisoning cases were analyzed. Food poisonings caused by kudoa septempuctata, staphylococcus aureus and bacillus cereus have clinical and epidemiological similarities. Forty five percent of food poisoning outbreaks occurred in Korea was concluded as unknown. The food poisoning caused by staphylococcus aureus and bacillus cereus accounted for 4.5% (50/1,092) of all food poisoning outbreaks in Korea between 2013 and 2015. Conclusions: This study suggests the possibilities of misdiagnosis in the investigations of food poisoning by staphylococcus aureus and bacillus cereus with kudoa septempuctata. KEY WORDS: Food parasitology, Myxozoa, Kudoa septempunctata, Staphylococcus aureus, Bacillus cereus, Korea Correspondence: Sung Uk Lee Jeju Special Self-Governing Provincial Office, 6 Munyeon-ro, Jeju 63122, Korea E-mail: sulee86rad@gmail.com Received: Mar 23, 2017 / Accepted: Mar 31, 2017 / Published: Mar 31, 2017 This article is available from: http://e-epih.org/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 2017, Korean Society of Epidemiology 서론한국질병관리본부에서발간한 2015년감염병역학조사연보에서는칠성쿠도아충에의한식중독의사례조사및특성을보고하고, 칠성쿠도아충으로인한식중독예방을위한범국가적정책의필요성에대하여제안하였다 [1]. 쿠도아속점액포자충은전세계적으로수많은종류가보고되어오고인체에대한병원성이없는것으로생각되어왔지만 [2], 쿠도아속중최초로광어에서발견되는칠성쿠도아충의인체에대한병원성이최근제기되었다. 칠성쿠도아충은 2012년 12월일본보건후생성에의해식중독 www.e-epih.org 1
Epidemiol Health 2017;39:e2017014 원인병원체로지목되었고, 연령이 4-5일인 ddy mice를이용한동물실험을근거로병인성이주장되었다 [3,4]. 하지만타연구자에의한 mice를이용한동일한실험에서정반대의결과가보고되었고 [5], 인체에대한임상연구는보고된적이없어, 최근 Chung et al. [6] 은칠성쿠도아충과식중독간의역학적인과성의과학적타당성이떨어짐을주장하였다. 한편식중독역학조사의관점에서칠성쿠도아충에의한것으로추정되는식중독사례들은짧은잠복기와경미한소화기계증상을특징으로하는데 [4], 이는독소형식중독 ( 황색포도알균증또는바실루스세레우스 ) 의식중독의역학적특성및임상적증상과유사하다. 칠성쿠도아충을식중독의새로운병원체로지정하기위해선위두식중독병원체와감별하는것이중요하다. 이에저자는먼저쿠도아충식중독의개별사례를살펴보고, 쿠도아충식중독과황색포도알균과바실루스세레우스로인한식중독을비교해보겠다. 마지막으로최근 3년간의식중독원인병원체규명현황을살펴보겠다. 연구방법칠성쿠도아충식중독사례의정확한특성을파악하기위해 2015년도감염병역학조사연보에수록된칠성쿠도아충의식중독사례보고및부록이검토되었다 [1]. 사례보고에기술된칠성쿠도아충의특성과 Pathogens and Toxins in Food [10] 에기술된황색포도알균 (Chapter 8) 과바실루스세레우스 (Chapter 1) 식중독특성을비교하였다. 또한부록에포함된쿠도아충식중독개별사례분석을통해칠성쿠도아충식중독의역학조사현황및특성에대하여파악하였다. 한국의식중독사례규명현황분석을위해한국질병관리본부에서발간한 2013-2015년감염병역학조사연보에포함된연도별수인성및식품매개질환발생현황이검토되었다 [7-9]. 식중독원인불명률과황색포도알균과바실루스세레우스식중독의규명률이각각파악되었다. 연구결과 1. 칠성쿠도아충, 황색포도알균과바실루스세레우스식중독특성비교황색포도알균은열저항성이있는장독소를생성하고바실루스세레우스는열저항성이있는포자가식중독을일으키는것으로알려져있다 (Table 1)[10]. 이두병원체는음식제공전재가열하게되면원인병원체는열에의해사라지지만식중독을일으키는독소와포자는여전히음식에남아있는다. 칠성쿠도아충은인체장세포를이용한실험에서포자원형질이장세포를침범하여식중독을일으키는것으로추정하였다. 황색포도알균과바실루스세레우스는가장흔한식중독원인들이지만전세계적으로식중독증상의가벼움으로인한미신고와역학조사시실험실적병원체검출의어려움등으로인하여통상적으로전체발생률이실제발생률에비해매우저평가되는식중독원인들로알려져있다 [11, 12]. 아직칠성쿠도아충이전체식중독에서차지하는비중은제대로파악되지않았다. 황색포도알균과바실루스세레우스는상온 (20-37 C) 에서가장활성화되고, 겨울보다는기온이따뜻해질수록발생률이증가한다. 칠성쿠도아충은연중비슷한수준 (5-15 명 / 월 ) 으로식중독을일으키나 5월에특히증가하고 6, 7월은전혀보고되지않았다. 질병관리본부에서는이를수온의변화에따른영향으로추측하였지만 [1], Song et al. [2] 에따르면광어에서칠성쿠도아충이 6, 7월에검출률이떨어지는것은아니고 1월부 Table 1. Comparison of clinical and epidemiological characteristics between K. septumpunctata, S. aureus, and B. cereus food poisonings K. septumpunctata S. aureus 1 B. cereus 1 Pathogenesis Invasion of intestinal epithelium by Heat-resistant enterotoxin Heat-resistant spore sporoplasm (in vitro) Proportion of food borne illness Not assessed 1-5%, usually underestimated 1-30%, usually underestimated Seasonal variation Peak in May, but reduces in summer season May be more in warm-hot season than cold, rapid growth at room air May be more in warm-hot season than cold, rapid growth at room temperature Main clinical symptoms Diarrhea, vomiting, abdominal pain Diarrhea, vomiting, abdominal pain Diarrhea, vomiting, abdominal pain Incubation periods (hr) Average 2 (1-15) 0.5-8.0 Vomiting: 1-6 Diarrhea: 6-24 Duration and severity of illness Usually resolved within 24 hr, Usually resolved within 24 hr, Usually resolved within 24 hr, Life cycle Unknown Human skin, nasal passage, hair Soil Common source of infection Intake of raw Meat, poultry, egg and dairy product, salads Rice, meat, soup 1 Characteristics of S. aureus and B. cereus referred from Juneja et al. Pathogens and toxins in foods: challenges and interventions. Washington, DC: ASM Press; 2010 [10]. 2 www.e-epih.org
식중독원인으로서의칠성쿠도아충과감별진단 이성욱 Table 2. Summary of cases of food poisoning caused by K. septempunctata Case I II III IV V VI VII VIII IX X XI Population size (n) 8 13 4 4 27 12 11 18 10 9 38 No. of patients 7 13 3 4 13 8 9 12 9 6 8 Mix of sauced sashimi and vegetables and sushi Buffet including sushi and sushi, beef tartare with various fish and shellfish and shellfish Causative food and sushi, soup Symptoms D>V V>D D>V D>V V>D V>D D>V V>D D>V V>D D>V Incubation period, 5.8 4.0 3.5 4.5 6.0 3.8 10.0 4.1 3.6 5.0 2.0 average (hr) Laboratory test Food (-) Kudoa (-) (-) (-) Kudoa (-) (-) Kudoa Kudoa (-) Environment (-) (-) (-) (-) Problem in (-) (-) (-) (-) (-) (-) sanitation Food preparer (-) (-) (-) (-) (-) (-) (-) (-) (-) (-) (-) Kudoa (1) Kudoa (2) Kudoa (3) (-) Kudoa (6) Kudoa (2), but Kudoa in healthy (1) Kudoa (6) Kudoa (8) Kudoa (1) Kudoa (2) Kudoa (1) B. cereus (1) Patient (no. of positive) V, vomiting; D, diarrhea. 터 12월까지연중검출되는것으로보고하였다. 그러므로해당식중독의연중발생률변동에대하여장마철이나한여름에는광어회섭취를기피하게되는판매량변동과관련성또한고려해보아야한다. 임상적증상은세병원체모두설사나구토를주소로 6시간이내의잠복기를가지고, 24시간이내에증상소실되는동일한특징을보였다. 황색포도알균은인간의피부나코점막에상재하고, 바실루스세레우스는토양이나자연계에널리분포하는것으로알려져있다. 쿠도아충의자연사는잘알려져있지않지만, 지금까지밝혀진바로는광어에서기생하는것으로알려져있다 [13]. 주된감염경로는황색포도알균은육류및유제품등매우다양한경로로발생가능하며, 바실루스세레우스는밥이나육류등을통해발생가능하다. 칠성쿠도아충은현재광어섭취후에만발생하는것으로되어있다. 2. 칠성쿠도아충식중독사례고찰 2015년발생한쿠도아충식중독개별사례 11례에대하여요약해보았다 (Table 2). 전체 11예중광어회만섭취한경우는 2예였고, 나머지 9예는우럭, 조개류등이섞여있는모듬회또는초밥류내에광어가포함되어있었다. 11예중설사가구토보다우세하였던경우는 6예, 구토가우세하였던경우는 5예였다. 평균잠복기는 2-10시간이었다. 실험실적결과에서 10예는환례검체에서쿠도아충이검출되었고, 1예 ( 사례 9) 는환례에서는쿠도아충이검출되지않고보존식에서검출되었다. 사례 5에서는환례검체에서쿠도아충과함께바실루스세레우스가함께검출되었고, 위생상문제점이발견되었다. 사례 11에서는환례 2명의검체에서쿠도아충이검출되었지만, 증상이없던대조군 1예에서도쿠도아충이검출되었다. 3. 식중독원인균규명현황최근 3년 (2013-2015년도) 의수인성및식품매개질환의원인파악현황을살펴보았다 (Table 3). 원인병원체불명이 36-51%, 식중독유발감염원 ( 음식또는식수 ) 불명이 75-81% 비율 (2015년도미보고 ) 로보고되었다. 밝혀진원인균중겨울철의대표적인소화기계감염증인노로바이러스 (16-19%) 가가장높게보고되었다. 뒤이어병원성대장균 (6-10%), 클로스트리듐퍼프린겐스 (3-11%), 살모넬라 (2-7%) 가식중독원인체로규명되었다. 황색포도알균증은 3년간총 26건으로전체의 2.4% (26/1,092) 를차지하였고, 바실루스세레우스는전체의 2.2% (24/1,092) 를차지하였다. 2015년을기준으로쿠도아충식중독사례가총 11예이므로전체 2015년식중독사례들중 2.6% 이고 5번째로흔하게관찰되는식중독원인이된다. www.e-epih.org 3
Epidemiol Health 2017;39:e2017014 Table 3. Annual trends in cause of food poisoning 1 Rank 2015 2014 2013 Total 422 Total 409 Total 261 Unknown 215 (51) Unknown 186 (45) Unknown 94 (36) 1 Norovirus 79 (19) Norovirus 48 (12) Norovirus 42 (16) 2 E. coli 26 (6) E. coli 41 (10) C. perfringens 30 (11) 3 Campylobacter 22 (5) C. perfringens 29 (7) E. coli 19 (7) 4 C. perfringens 14 (3) Salmonellosis 28 (7) Salmonellosis 12 (5) 5 Salmonellosis 10 (2) Campylobacter 23 (6) Shigella spp. 8 (3) 6 S. aureus 8 (2) S. aureus 13 (3) B. cereus 8 (3) 7 B. cereus 6 (1) B. cereus 10 (2) V. parahaemolyticus 8 (3) 8 V. parahaemolyticus 3 (1) V. parahaemolyticus 6 (1) S. aureus 5 (2) Values are presented as number (%). 1 Data from Korea Centers for Disease Control and Prevention. Epidemiological investigation of infectious diseases in Korea, annual report from 2013 to 2015 [7-9]. 고찰칠성쿠도아충은광어취식후발생하는식중독의강력한원인으로최근제시되었고식중독역학조사에서광어가식단에포함되어있을시쿠도아원충검사가권장되고있다. Song et al. [2] 은양식육성어의 4.9% 에서칠성쿠도아충이검출됨을보고하였고, 광어회가국민적기호식품임을감안하면상당한양의칠성쿠도아충이포함된광어가소비됨을추측해볼수있다. 칠성쿠도아충식중독의특징은조리자의주의여부와상관없이양식육성어공급시에이미쿠도아충감염여부가결정되어있는것이므로, 양식장단계에서쿠도아충감염을막는것이유일한예방책일것이다. 또한현재까지칠성쿠도아충은광어에서만발견되는것으로되어있어, 타식중독역학조사와다른점은환례검체에서쿠도아충 DNA가검출되고 1일이내광어취식력이있다면다른보존식이나환경검체검사결과에관계없이쿠도아충으로인한식중독으로결론내려질수있다는것이다. 하지만위와같은결론을내리기에는광어쿠도아충이식중독의원인으로서의병원성여부가명확하지않아성급하다고생각된다. 인체에서의병원성여부를증명하기어려운상황에서동물실험결과가상충됨은이미 Chung et al. [6] 에의해논의된바있다. 식중독환례의검체에서쿠도아충이발견되었기때문에식중독병원체로추정하기에는, 소화기계증상을일으키지않았던 mice에서도쿠도아충 DNA가여전히검출됨을증명한 Ahn et al. [14] 의결과가상충하게된다. 이를근거로한다면쿠도아충이포함된광어를섭취한경우식중독발생여부와관계없이대변에서쿠도아충의 DNA가검출될수있음을가정해볼수있다. 결과 1 에서살펴보았던총 11예중에서도사례 11에서증상이없었던대조군의검체에서쿠도아충이발견되었음이보고되었다. 그러므로식중독환례검체에서의쿠도아충 DNA가검출여부만으로식중독발생의기여도를판정하기에는한계가있다. 그렇다면쿠도아충이포함된광어를취식하고왜식중독이발생하는것인가? 저자는황색포도알균이나바실루스세레우스에의한식중독이쿠도아충에의한식중독으로오인혹은동시에혼재할가능성을제시해본다. 결과 2에서살펴보았듯이쿠도아충식중독과위두병원체에의한식중독은광어회섭취력만제외하면역학적및임상적특징이매우유사해구분하기에어려움이따른다. 또한결과 3에서보았듯이황색포도알균이나바실루스세레우스는가장흔한식중독원인임에도불구하고, 각각최근 3년간전체식중독의 2% 정도만차지하는것으로되어있다. 2015년을기준으로하면오히려쿠도아충에의한식중독보다숫자가작은수준이다. 전체식중독의절반에서원인병원체를밝혀내지못한것을생각해보면, 황색포도알균이나바실루스세레우스식중독이제대로증명되지못한사례의비율또한높을것이며, 보고된발생률보다실제발생률은훨씬높을것으로생각된다. 불명으로처리된황색포도알균이나바실루스세레우스식중독이쿠도아충식중독으로오인될가능성또한존재하는것이다. 결과 1의사례 5에서는환례검체에서쿠도아충이 1예검출되었지만동시에바실루스세레우스가 1예검출된것으로보고되었다. 쿠도아충의병원성이불명확하다고생각한다면사례 5는바실루스세레우스에의한식중독으로결론내릴수도있을것이다. 이와같은고민의주원인은황색포도알균이나바실루스세레우스식중독의원인체규명이다른식중독원인보다어렵다는데기인한다. 황색포도알균이나바실루스세레우스식중독을증명하는데있어역학적연관성이있는음식에서균증식혹은장독소를증명하고, 독소형식중독에합당한임상증상 ( 짧은잠복기, 가벼운소화기계증상 ) 을보인다면충분히역학적추정이가능할것이다. 하지만일반적으로발생하는식중독에서임상양상으로독소형식중독이의심되더라도, 보존식이있는사례가매우드물고, 환례의대변배양을할수있는경우도극히제한되어서실험적인근거로증명되는경우는매우소수이고대부분이원인불명 4 www.e-epih.org
식중독원인으로서의칠성쿠도아충과감별진단 이성욱 으로분류되게된다 [10]. 또한독소형식중독의원인음식이재조 리되어제공된경우, 원인병원균은사라지고열저항성이있는장 독소나포자만남아식중독을일으키기때문에실험실적으로증 명하기매우어렵다. 식중독역학조사에있어원인을규명한다는것은원인제공업 체에대한행정적처분이따르고, 미래의보건정책에도영향을 줄수있기에매우신중하여야하겠다. 칠성쿠도아충이식중독을 일으켰다는주장이설득력을얻기위해선황색포도알균이나바 실루스세레우스식중독과같은형태의규명률을높이기위한꾸 준한노력과칠성쿠도아충의병인성에대한연구가계속해서보 강되어야하겠다. 참고문헌 1. Korea Centers for Disease Control and Prevention. Case reports of Kudoa food poisoning in 2015; 2016 [cited 2016 Dec 11]. Available from: http://cdc.go.kr/cdc/notice/cdckrtogether0302.jsp?menuids=home 001-MNU1154-MNU0005-MNU0088&cid=71877 (Korean). 2. Song JY, Choi JH, Choi HS, Jung SH, Park MA. Monitoring of Kudoa septempunctata in cultured and wild fish in Jeju Island during 2012. J Fish Pathol 2013;26:129-137 (Korean). 3. Kawai T, Sekizuka T, Yahata Y, Kuroda M, Kumeda Y, Iijima Y, et al. Identification of Kudoa septempunctata as the causative agent of novel food poisoning outbreaks in Japan by consumption of Paralichthys olivaceus in raw fish. Clin Infect Dis 2012;54:1046-1052. 4. Yoshiko Sugita-Konishi Y, Sato H, Ohnishi T. Novel foodborne disease associated with consumption of raw fish, (Paralichthys olivaceus). Food Saf 2014;2:141-150. 5. Jang Y, Ahn M, Bang H, Kang B. Effects of Kudoa septempunctata genotype ST3 isolate from Korea on ddy suckling mice. Parasite 2016;23:18. 6. Chung YB, Bae JM. Is there evidence that Kudoa septempunctata can cause an outbreak of acute food poisoning? Epidemiol Health 2017;39: e2017004. 7. Korea Centers for Disease Control and Prevention. Epidemiological investigation of infectious diseases in Korea, annual report 2013; 2014 [cited 2014 Apr 21]. Available from: http://www.cdc.go.kr/cdc/contents/ CdcKrContentLink.jsp?fid=43&cid=26002&ctype=1 (Korean). 8. Korea Centers for Disease Control and Prevention. Epidemiological investigation of infectious diseases in Korea, annual report 2014; 2016 [cited 2016 Apr 14]. Available from: http://www.cdc.go.kr/cdc/contents/ CdcKrContentLink.jsp?fid=43&cid=67789&ctype=1 (Korean). 9. Korea Centers for Disease Control and Prevention. Epidemiological investigation of infectious diseases in Korea, annual report 2015; 2016 [cited 2016 Nov 16]. Available from: http://www.cdc.go.kr/cdc/contents/ CdcKrContentLink.jsp?fid=51&cid=71877&ctype=1 (Korean). 10. Juneja VK, Sofos JN. Pathogens and toxins in foods: challenges and interventions. Washington, DC: ASM Press; 2010, p. 1-130. 11. Hennekinne JA, De Buyser ML, Dragacci S. Staphylococcus aureus and its food poisoning toxins: characterization and outbreak investigation. FEMS Microbiol Rev 2012;36:815-836. 12. Granum PE, Lund T. Bacillus cereus and its food poisoning toxins. FEMS Microbiol Lett 1997;157:223-228. 13. Kasai A, Li YC, Mafie E, Sato H. New host records of monacanthid fish for three Kudoa spp. (K. septempunctata, K. thyrsites, and K. shiomitsui) prevalent in the (Paralichthys olivaceus), with the description of K. parathyrsites n. sp. from a black scraper (Thamnaconus modestus). Parasitol Res 2016;115:2741-2755. 14. Ahn M, Woo H, Kang B, Jang Y, Shin T. Effect of oral administration of Kudoa septempunctata genotype ST3 in adult BALB/c mice. Parasite 2015;22:35. www.e-epih.org 5