E coli O4 談食品安全與溶血性尿毒 Dr. Wong Wing Wai Infectious Diseases, Depart., of Medicine Taipei Veterans General Hospital 人類飲食習慣的改變 圖片摘自 http://www.wretch.cc/blog/xyxyx/26249
我國法定傳染病分類 類別第一類第二類第三類第四類第五類 傳染病名稱 天花 鼠疫 狂犬病 炭疽病 H5N 流感 SARS 白喉 麻疹 德國麻疹 流行性腦脊髓膜炎 多重抗藥性結核病 登革熱 瘧疾 屈公病 西尼羅熱 霍亂 傷寒 副傷寒 小兒麻痺症 桿菌性痢疾 腸道出血性大腸桿菌感染症 阿米巴性痢疾 急性病毒性 A 型肝炎 漢他病毒症候群 流行性斑疹傷寒 百日咳 破傷風 日本腦炎 結核病 ( 除多重抗藥性結核病外 ) 癩病 先天性德國麻疹症候群 急性病毒性肝炎 ( 除 A 型外 ) 腮腺炎 退伍軍人病 侵襲性 b 型嗜血桿菌感染症 梅毒 淋病 新生兒破傷風 腸病毒感染併發重症 疱疹 B 病毒感染症 鉤端螺旋體病 類鼻疽 Q 熱 地方性斑疹傷寒 萊姆病 兔熱病 恙蟲病 貓抓病 弓形蟲感染症 庫賈氏病 肉毒桿菌中毒 水痘 侵襲性肺炎鏈菌感染症 流感併發重症 NDM- 腸道菌感染症 裂谷熱 馬堡病毒出血熱 拉薩熱 伊波拉病毒出血熱 黃熱病 依傳播途徑區分 經動物與昆蟲感染 狂犬病 弓形蟲感染症 日本腦炎 西尼羅熱 裂谷熱 鼠疫 拉薩熱 鉤端螺旋體病 萊姆病 恙蟲病 炭疽病 伊波拉病毒出血熱 馬堡出血熱 漢他病毒症候群 疱疹 B 病毒感染症 兔熱病 Q 熱 地方性斑疹傷寒 流行性斑疹傷寒 貓抓病 鼠咬熱 經空氣或飛沫傳染 經飲食傳染 經血液或皮膚傳染 禽流感 Q 熱 漢他病毒症候群 炭疽病 鉤端螺旋體病 類鼻疽 鸚鵡熱 布氏桿菌症 阿米巴痢疾 腸道出血性大腸感菌感染症 新型庫賈氏病 肉毒桿菌中毒 布氏桿菌症 沙門氏菌 蛔蟲 肝吸蟲 廣東住血線蟲 胞蟲症 旋毛蟲 伊波拉病毒出血熱 馬堡出血熱 鉤端螺旋體病 類鼻疽 其他 庫賈氏病 藍色字體標示處 : 非法定傳染病, 但疾管局提供相關檢驗及部分罕見用藥 2
98~2 年食品中毒案件病因物質案件數統計 Taiwan FDA 2 年網購三明治沙門氏菌污染事件 3
網購三明治沙門氏菌污染事件之規模 分局別 追蹤件數 食用人數 生病人數 侵襲率 第一分局 3 586 36 52% 第二分局 6 3 22 73% 第三分局 % 第四分局 6 266 224 84% 第五分局 5 29 2 7% 第六分局 % 總計 48 9 554 6% 食用真空包裝豆乾導致肉毒桿菌中毒事件 4
27 年至 2 年 月肉毒桿菌中毒本土病例趨勢圖 名病例中有 例曾食用黃豆類製品 ;9 例曾食用真空包裝黃豆類製品 5
2 年肉毒桿菌中毒事件 CDC 及 TFDA 利用新聞稿 媒體及教育訓練等, 針對民眾與醫護人員進行分眾宣導 大溪正 真空豆干 2 名病例 大溪正 真空豆干 TFDA 召開 真空包裝黃豆即食食品安全管理業者說明會 TFDA 制定 真空包裝即食食品良好衛生規範 及 真空包裝即食食品標示相關規定 大溪正 真空豆干 3 名病例 大溪仁 真空豆干 大溪大 真空豆干 引起集體食物中毒的大腸桿菌 O 2 / 8 月號牛頓 2 年 4 月下旬發生在日本烤肉連鎖店的集體食物中毒的主要禍首就是大腸桿菌 O 至 5 月 3 日止, 仍未能確認被 O 汙染的食物是否就是生牛肉 O 會產生一種稱為 verotoxin 的毒性蛋白質, 引起出血性腹瀉 再者, 當 verotoxin 隨著血液流到全身, 也可能會引發重症造成死亡 雖然也曾經發生過數起 O 引起食物中毒的事件, 但卻以這次造成重症比率最高 2 年 4 月下旬, 在日本富山縣 福井縣和神奈川縣的同一烤肉連鎖店相繼發生用餐者食物中毒的情形 根據日本厚生勞働省 ( 相當於衛生署 ) 於 5 月 日下午 4 時所公布的資料表示, 具有食物中毒症狀的人有 8 位, 其中重症者達 24 人, 死亡人數 4 人 ( 數字為三縣之合計 ) 日本 NIID 流行病學分析, 與生牛肉料理具有高度關聯性 6
Escherichia coli Known as commensal of the large intestine since first described in 885 Enterobacteriaceae, the enteric bacteria, are facultatively anaerobic Gram-negative rods genera within the family are human intestinal pathogens (e.g. Salmonella, Shigella, Yersinia). several others are normal colonists (e.g. Escherichia, Enterobacter, Klebsiella) The entire DNA base sequence genome has been known since 997 Escherichia coli E. coli inhabitant of the human intestinal tract Only a very small proportion of the total bacterial content. The anaerobic Bacteroides species in the bowel outnumber E. coli by at least 2: Can grow in the presence or absence of O 2 Adapt to its intestinal (anaerobic) and its extraintestinal (aerobic or anaerobic) habitats Indicator of fecal pollution and water contamination 7
Pathogenesis Over 7 serotypes based on O, H, and K antigens the serotype O57:H7 causing hemolytic uremic syndrome (HUS) an outbreak in the United States of America. EHEC in 982 second to Salmonella as a cause of bacterial diarrhea in NW Pacific Diarrheagenic strains pathogenic E. coli are classified based on their unique virulence factors Enterovirulent E coli, EEC 5 virotypes cause diarrheal diseases: enterotoxigenic E. coli (ETEC) enteroinvasive E. coli (EIEC) enteropathogenic E. coli (EPEC) enterohemorrhagic E. coli (EHEC) enteroaggregative E. coli (EAEC) Each class falls within a serological subgroup and manifests distinct features in pathogenesis. 8
Virulence determinants and characteristics Kenneth Todar, PhD Online Textbook of Bacteriology ETEC fimbrial adhesins e.g. CFA I, CFAII, K88, K99 non invasive produce LT and/or ST toxin watery diarrhea in infants and travelers no inflammation, no fever Virulence determinants and characteristics Kenneth Todar, PhD Online Textbook of Bacteriology EIEC nonfimbrial adhesins, possibly outer membrane protein invasive (penetrate and multiply within epithelial cells) does not produce shiga toxin dysentery-like diarrhea (mucous, blood), severe inflammation, fever 9
EPEC Virulence determinants and characteristics Kenneth Todar, PhD Online Textbook of Bacteriology non fimbrial adhesin EPEC adherence factor (EAF) enables localized adherence of bacteria to intestinal cells moderately invasive (not as invasive as Shigella or EIEC) does not produce LT or ST; some reports of shiga-like toxin usually infantile diarrhea; watery diarrhea with blood some inflammation, no fever symptoms probably result mainly from invasion rather than toxigenesis EAEC Virulence determinants and characteristics Kenneth Todar, PhD Online Textbook of Bacteriology adhesins not characterized non invasive produce ST-like toxin (EAST) and a hemolysin persistent diarrhea in young children without inflammation or fever
Virulence determinants and characteristics Kenneth Todar, PhD Online Textbook of Bacteriology EHEC adhesins not characterized, probably fimbriae moderately invasive does not produce LT or ST but does produce shiga toxin pediatric diarrhea, copious bloody discharge (hemorrhagic colitis) intense inflammatory response may be complicated by hemolytic uremia Reservoir of EEC Mainly cattle, occasionally pork and chicken meat mutton samples have been examined to have E. coli O57:H7 Human being may also be reservoir and caused the transmission among people.
Mode of Transmission Intake of contaminated food, most frequently, the improperly prepared beef ( specially mince) and raw milk Through contaminated water supply Food processing by patient contaminated with EEC Clinical Symptom 2~8 days, normally 3~4 days Afebrile, mild diarrhea, acute to dull abd. pain, Initial watery diarrhea, then significant bloody (hemorrhagic) colitis 6-7%, some report as high as 5%, will complicate hemolytic uremic syndrome or brain disease in about 2 weeks renal failure and hemolytic anemia fever and neurologic symptoms, constitutes TTP can have a mortality rate in the elderly as high as 5% 2
Microbiologic Diagnosis Isolation of E. coli of serotype O57:H7 or other verotoxin-producing E. coli from diarrheal stools Can t grow at 44~45 C sorbitol-macconkey (SMAC) agar tested for the presence of verotoxin DNA probes to detect genes encoding for the production of verotoxins (VT and VT2) Treatment Supportive No evidence that antibiotics improve outcome Some antibiotics may precipitate kidney complications Antidiarrheal agents, such as loperamide should also be avoided Hemolytic uremic syndrome is life-threatening required blood transfusions and kidney dialysis 3
Preventive measure Identify and isolation Meat can become contaminated during slaughter, and organisms can be thoroughly mixed into beef when it is ground Unpasteurized milk and sewagecontaminated water Young children typically shed the organism in their feces for a week or two after their illness resolves Sometimes carry the organism without symptoms 2 Germany E. coli O4:H4 outbreak 4
2 Germany outbreak Serious outbreak of food borne illness focused in northern Germany in May through June 2 Characteristic bloody diarrhea, abd. cramp, nausea and with a high frequency of hemolytic-uremic syndrome (HUS) Low febrile Adults with HUS Acute onset, 7- days, some prolong to 2 days All affected people had been in Germany or France 2 Germany outbreak The agriculture authority incorrectly linked EHEC to cucumbers imported from Spain An organic farm in Bienenbüttel, Lower Saxony, which produces a variety of sprouted foods, as the likely source of the E. coli outbreak 5
A deadly E. coli contamination were found on sprouts at a farm in Lower Saxony, German It's the sprouts", the president of the Robert Koch Institute (RKI), Reinhard Burger, said 2 Germany outbreak Originally thought to have been caused by an enterohemorrhagic (EHEC) strain of E. coli later shown to have been caused by an enteroaggregative E. coli (EAEC) strain Acquired the genes produce Shiga toxins 6
2 Germany outbreak 說明沒有病例疑似病例確定病例死亡病例 標示顏色俄羅斯葡萄牙 芬蘭 美國 加拿大丹麥 法國德國 瑞典 EHEC Outbreak Number of cases reported as for 2 July 2 Deaths 2 HUS case 3 Non HUS case Austria Canada Czech Republic Denmark France Germany Greece Luxembourg Netherlands Norway Poland Spain 48 7 857 4 2 4 5 378 7 Sweden Switzerland United Kingdom United States Total 5 8 5 3 4 98 2 35 4 2 3,67 3 7
2 Germany outbreak Origins of the E. coli Strain Causing an Outbreak of Hemolytic Uremic Syndrome in Germany An unusual serotype of Shiga-toxin producing E coli (O4:H4) began in Germany in May 2. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin producing E. coli have been reported. The outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance. David A Rasko, et al. N Engl J Med 2; 365:79-77August 25, 2 Holger Rohde, et al. N Engl J Med 2; 365:78-724August 25, 2 2 Germany outbreak 367 without the hemolytic uremic syndrome (6 deaths) and 98 with the hemolytic uremic syndrome (34 deaths), indicating that this strain is notably more virulent than most of the Shiga-toxin producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested strains should be classified within the enteroaggregative pathotype of E. coli. The enteroaggregative E. coli O4:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. The genome of the German outbreak strain can be distinguished from those of other O4:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of antibiotic-resistance factors. 8
Enteroaggregative E. coli O4:H4 Shiga-like toxin-producing E. coli Heat stable at 7 C to 5 C, deactivated over 7 C Destroy gut endothelium cause hemorrhage and bloody stool Circulating toxin combined with endothelial cell membrane of glomerulus, inhibit ADAMTS3 enzyme that induced intravascular coagulopathy and HUS Enteroaggregative E. coli O4:H4 Most diarrheagenic pathogenic E. coli are EHEC EAEC with Shiga-like toxin, SLT O57:H7 cause outbreaks in beef O4:H2 in Montana, USA in 994 24 a Korean female with HUS had isolated O4:H4 Taiwan first report EHEC hemorrhagic diarrhea from a 6 year old American-born boy in 2 9
Diagnosis and Detection of EHEC/EAEC A EU/International standard for the detection of E. coli O57 Food, diary Water Specimen Molecular typing At least 2 methods-german, France Phenotyping, serotyping, antibiotic resistant pattern OMP patterns, LPS patterns, multilocus enzyme electrophresis Genotyping: plasmid analysis, RFLP, ribotyping, PFGE, PCR, RAPD Treatment of EHEC diarrhea and complication Mainly supportive Controversial of antibiotics usage Isolations Source identify Food/diary processing 2
Eat health and Thanks for your attention 2