炭疽 The photo above shows, from left to right, gram stains of Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia).

Presentation on theme: "炭疽 The photo above shows, from left to right, gram stains of Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia)."— Presentation transcript:

1 炭疽 The photo above shows, from left to right, gram stains of Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia). The source for the first two photos is the CDC, and for the gram stain of F. tularensis, the Armed Forces Institute of Pathology.

2 概述 流行于食草动物中的疾病 芽孢，长期保存 自然状态下，人类因接触染疫动物及其制品感染。
法定报告每年-1000例，近两年 例左右 美国最后一个自然感染病例发生在1976年 可作为生物武器 2001年美国遭受信件炭疽袭击 Source of slide: Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Overview (Slide 5) The causative agent of anthrax is Bacillus anthracis, a gram positive, spore-forming bacteria. Anthrax is primarily a disease of herbivores (e.g., sheep, cows), which acquire infection via exposure to B. anthracis spores in soil. Humans acquire infection through contact with infected animals or contaminated animal products; hence hunters and textile workers (‘woolsorter’s disease”) have historically been high-risk groups. The last U.S. case of inhalational anthrax, prior to the 2001 outbreak, occurred in a home craftsman and was acquired from imported animal-origin yarn (Suffin et al., Hum Pathol 1978 Sep;9(5):594-7). Animal vaccination programs have dramatically decreased the number of animal deaths due to anthrax. Industrial hygiene practices and restrictions on imported animal products helped to decrease the incidence of anthrax among humans in the United States. Cutaneous anthrax is the most common natural form of the disease (gastrointestinal anthrax is very rare), but inhalational anthrax is the most likely presentation in a BT attack.

3 病原体 粗大杆菌，竹节样排列 炭疽芽胞可在土壤、污水和皮毛上多年不死，在干燥状态下可存活几十年 华北地区日本军马事件，40年后感染村民
1997年，英博物馆发现1918德国

4 芽胞 华北地区日军军马 英国警察博物馆 抗日战争时期，有一批军马患了炭疽，被封闭在一间窑洞里面 80年代，扬尘感染
1997年发现1918年的炭疽杆菌芽胞，仍有致病力

5 传染病学 传染源 患病的动物、污染的环境和制品 患病的人（国内外存在分歧） 传播途径 皮肤接触 呼吸道 消化道 人群易感性 普遍易感

6 流行态势 国内 美国 全国每年发病数波动在400—1000 人,主要集中在贵州、新疆、甘肃、四川、广西、云南等西部地区。
目前我国尚未建立规范的炭疽监测体系，缺乏炭疽病原、自然界分布及发病影响因素等方面的系统资料 美国 20世纪早期，每年病例数~130例 1976年报告最后一例炭疽自然感染病例 2001年，恐怖袭击17人患病，5人死亡

7 发病机制 损伤微血管 内皮细胞 释放 组织凝血活酶 DIC 外毒素 微循环障碍 感染性休克 出血 坏死 水肿

8 临床分型 WS-238

9 皮肤炭疽 自然感染约95%的病例为皮肤炭疽 感染途径: 皮肤破损 潜伏期：小时- 14天（USA:12 days）？
丘疹Papule  水泡vesicle  溃疡ulcer/无痛 焦痂 病变部位和临近淋巴结周边典型非凹陷性水肿 伴有发热、头痛和不适 病死率：不治疗 20%; 正确治疗几乎没有死亡 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Original source of photo: Arnold Kaufmann, Ph.D., National Center for Infectious Disease, Centers for Disease and Control and Prevention Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Papule=a small, circumscribed solid elevation on the skin Vesicle=A small, circumscribed elevation on the skin containing fluid (I.e., blister) Eschar= A thick, coagulated crust or slough Edema=an accumulation of an excessive amount of watery fluid in cells or tissues Cutaneous anthrax (Slides 13-14) Cutaneous anthrax is the most common naturally occurring form of anthrax, and may occur in a BT attack (as was seen in the 2001 “anthrax letter” cases). The clinical presentation is summarized in slide 13. The photo on the right shows an anthrax eschar (necrotic ulcer).

10 皮肤炭疽 临床进程 Day 5 Day 10-12 Day 7 Day 15 CDC
皮肤炭疽 临床进程 Day 5 Day 10-12 Source: Centers for Disease Control and Prevention Slide 14 shows four stages of a cutaneous anthrax lesion. On day seven, there is a depressed black eschar with minimal erythema and swelling. By day 10-12, the eschar is drying, and the edema and erythema have disappeared. The photo in the right lower corner of the slide shows another anthrax lesion on day 15; there is an area of hard necrosis that is beginning to separate from the surrounding tissue. Day 7 Day 15 CDC

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18 皮肤炭疽和恙虫病的区别 焦痂或溃疡 恙虫病东方体 治疗：四环素类 北京发病情况 恙螨

19 肺炭疽 感染剂量 约 8-50,000 个芽孢 可造成感染 具体剂量尚无定论 >5颗粒容易沉降，吸附在物体表面，不容易造成感染
生物恐怖袭击中所需菌量较少 和宿主体制和细菌特征有关 具体剂量尚无定论 >5颗粒容易沉降，吸附在物体表面，不容易造成感染 1-5颗粒，悬浮，沉积在肺泡，一般无环境残留 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Inhalational Anthrax: Acquisition of Infection (Slides 6-7) The infectious dose of anthrax for humans is not precisely known. The anthrax outbreak of 2001 and historical data suggest that the infectious dose may vary, with increasing patient age and underlying medical conditions corresponding to increased susceptibility to infection. In addition, infection rates would also be expected to vary according to the preparation method and the ability of a particular preparation of anthrax spores to remain aerosolized in respirable particles. Because anthrax prepared for use as a weapon may employ particularly virulent organisms, the infectious dose may be lower than in naturally occurring infection.

20 肺炭疽 临床特征 潜伏期: 1- 43 天甚至更长; 与接触剂量和宿主体制有关 一般2-5天出现初始症状 后期症状
国内一般界定在14天 一般2-5天出现初始症状 非特异性:发热、干咳、肌肉疼痛、精神差 、疲劳、多汗 胃肠道症状 后期症状 出血性中隔炎 , 呼吸困难 脑膜炎 休克、死亡 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Dyspnea=difficulty breathing Hemorrhagic mediastinitis=bloody fluid in the chest cavity Clinical features (Slides 11-12) The next two slides summarize the clinical features of inhalational anthrax. The incubation period ranges from 1-43 days and may be relatively short if the inhaled dose is very high, or greater than a month under some circumstances, such as low inoculum or premature discontinuation of treatment. Typically, symptoms appear two to five days after exposure. The first stage of illness consists of nonspecific flu-like symptoms and lasts hours to a few days. The second stage comes on abruptly and progresses quickly. Historically, cases were nearly always fatal. Outcome in the 2001 anthrax outbreak was better than previously observed, with a 45% case fatality rate (5 deaths/11 cases) (slide 16). Several possible reasons exist for the improved survival rate observed, including differences in host resistance (most cases were middle-aged and relatively healthy), early recognition and initiation of treatment, the use of a combination of antibiotics effective against anthrax, and better supportive care.

21 肺炭疽 传播和病死率 不存在人传人？ 中晚期即使积极抗生素治疗病死率仍可能是100% 早期治疗可降低病死率
2001年恐怖袭击中，早期积极治疗，11例中有6例存活。 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Outcome in the 2001 anthrax outbreak was better than previously observed with a 45% case fatality rate (5 deaths/11 cases)(slide 17). Several possible reasons exist for the improved survival rate observed, including differences in host resistance (most cases were middle-aged and relatively healthy), early recognition and initiation of treatment, the use of a combination of antibiotics effective against anthrax, and better supportive care.

22 细菌感染造成的疾病 进展快，病死率高 早期应用抗生素效果好 中晚期一般较差 近几年关注疾病 鼠疫 人感染猪链球菌病 炭疽

23 炭疽治疗 国内现有治疗方案 《炭疽诊断标准及处理原则》（GB17015-1997）（已经废止） 青霉素G为首选抗生素
氯霉素或大环内酯类抗生素 抗休克与DIC治疗

24 美国CDC治疗方案 环丙沙星、多西环素首选 环丙沙星用于儿童和孕妇的争论

25 炭疽治疗 抗生素对生长状态的炭疽杆菌有效 阻止疾病发生和进展 对芽孢形态无效 维持有效浓度的抗生素应对炭疽杆菌
芽孢被清除或被免疫系统控制 (duration unclear) Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Anthrax Treatment and Post-exposure Prophylaxis (Slides 18-22) Key Points Antibiotic treatment and prophylaxis for anthrax should be continued for at least 60 days to prevent the development of disease from germinating spores. Inhalational anthrax is not transmitted person to person, and thus, only standard precautions are necessary. Dressings used to cover cutaneous lesions should be treated as biohazard waste.

26 炭疽 预防和治疗 病例治疗 生物恐怖暴露者的预防性治疗 抗生素治疗60天 皮肤炭疽可仅治疗7-10 天 抗生素治疗60-100天
可抗生素联合疫苗使用 Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281: Inglesby TV, O’Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287: Isolation of inhalational anthrax cases is not necessary, due to the lack of person-person transmission. There is a theoretical possibility of transmission of infection from cutaneous anthrax lesions; therefore covering the area with a dressing that is then disposed of as biohazard waste is recommended. A shorter course of antibiotic therapy (7-10 days) can be given in cases of naturally occurring cutaneous anthrax without potential aerosol exposure. In the context of bioterrorism, however, an unrecognized aerosol exposure is possible, and thus. treatment is recommended for the entire 60 days. Intravenous antibiotics are indicated for more extensive disease, head and neck lesions, and signs and symptoms of systemic illness. Post-exposure prophylaxis (PEP) is outlined in slides Antibiotic prophylaxis should be continued for at least 60 days. Animal studies have demonstrated viable spores in mediastinal lymph nodes as far out as 100 days post-exposure. The limited data available to assess the magnitude of risk beyond 60 days led CDC to offer an additional 40 days of PEP to those exposed during the 2001 anthrax outbreak.

27 暴露后预防为什么要大于60天 接种咨询委员会推荐：如果有疫苗可用，可在3剂疫苗后停用抗生素
动物实验：猴子纵隔淋巴结在暴露后100天仍可发现芽孢 接种咨询委员会推荐：如果有疫苗可用，可在3剂疫苗后停用抗生素 Source: CDC Responds: Update on Options for Preventive Treatment for Persons at Risk for Inhalational Anthrax, Dec 21, 2001 The use of anthrax vaccine in the United States. MMWR 49(RR-15), December 15,2000. The CDC program for use of the anthrax vaccine as additional prophylaxis in individuals exposed during the 2001 outbreak is outlined in slides Both of the additional options are considered investigational.

28 美国CDC :暴露后预防 早期推荐：60天抗生素治疗+医学观察 后修订为： 再增加40天抗生素治疗+医学观察 或
再增加40天抗生素治疗+医学观察+4周3剂疫苗 Source: Lingappa, J. CDC Responds: Update on Options for Preventive Treatment for Persons at Risk for Inhalational Anthrax, Dec 21, 2001 The CDC program for use of the anthrax vaccine as additional prophylaxis in individuals exposed during the 2001 outbreak is outlined in slides Both of the additional options are considered investigational. *Total=100 days

29 炭疽疫苗 美国用疫苗为减毒活疫苗 人体实验证实皮肤划痕具有保护作用 动物实验证实吸入也具有保护作用
免疫步骤0、2、4周和6, 12, 18月; 每年加强 3 剂 (0, 2, 4周) 联合抗生素对暴露后预防有作用 3剂后保护率达83% 5剂后100% 供应有限 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) CDC. The use of anthrax vaccine in the United States. MMWR 2000;49(RR-15):1-20. Anthrax Vaccine (Slides 23-24) An anthrax vaccine is available through CDC under investigational new drug protocol (although in limited supply) for use in post-exposure prophylaxis of persons exposed to anthrax in the setting of a biological attack. The vaccine is routinely recommended for persons processing B. anthracis cultures, or other workers engaged in activities with high potential for B. anthracis aerosol production. The human vaccine is created from a cell-free filtrate of B. anthracis culture, and is different from the live-virus animal vaccine, not considered sufficiently safe for humans. Primary vaccination consists of three subcutaneous injections at 0, 2, and 4 weeks, and three booster vaccinations at 6, 12, and 18 months. To maintain immunity, the manufacturer recommends an annual booster injection.

30 疫苗副反应 安全性和其他疫苗基本一致 超过30%在72小时内接种部位有轻微不适 <2% 有严重的局部反应，1-2天内接种侧肢体活动受限
红、肿、痒 <2% 有严重的局部反应，1-2天内接种侧肢体活动受限 全身反应少见 Duchin JS, Communicable Disease Control, Epidemiology & Immunization Section, Public Health - Seattle & King County. Bioterrorism: Recognition and Clinical Management of Anthrax and Smallpox (presentation) CDC. The use of anthrax vaccine in the United States. MMWR 2000;49(RR-15):1-20. Side effects of the vaccine are usually mild and self-limited. The anthrax vaccine was suggested as a possible cause of illness in Persian Gulf War veterans, but a CDC evaluation did not find a specific association between anthrax vaccination and self-reported illness. An Institute of Medicine Report (Gulf War and Health: Volume 1. Depleted Uranium, Pyridostigmine Bromide, Sarin, and Vaccines, 2000) concluded that there is “inadequate/insufficient evidence to determine whether an association does or does not exist between anthrax vaccination and long-term adverse health effects.”

31 自然状态下预防措施 严格管理传染源 切断传播途径 保护易感者 病畜：严谨宰杀，焚烧或深埋2米以下 环境 人
环氧乙烷、二氧化氯薰蒸、含氯消毒剂 人 切断传播途径 保护易感者

32 美国2011年炭疽生物恐怖 2011年9月份 邮寄信件 武器级别 气溶物理 调查过程漫长 艾文斯 污染环境清除困难

33 流行病学 CT NYC Senate letters* letters* Inhalation Case NYC FL NJ* DC
5 4 3 Cases 2 BT-related Anthrax (Slides 15-17) Key Points Symptoms, signs, and epidemiologic clues can help determine the likelihood of anthrax in a patient with flu-like illness. The differential diagnosis for inhalational anthrax includes influenza, other community-acquired respiratory tract illnesses, and pneumonia. Slide 15 shows the epidemiological curve (graph of cases by date of onset and location) for the 2001 bioterrorism-associated anthrax cases. The y-axis indicates the number of cases (cutaneous and inhalational); the x-axis, the date of illness onset for each case (September 17-November 14); the colored blocks denote the location of the cases (New York City, District of Columbia, New Jersey, Florida, Connecticut); and the white arrows denote inhalational anthrax cases. The curve illustrates several epidemiological clues of a BT incident: *      Claims* by a terrorist or aggressor of a release of anthrax (The letters contained a threat of anthrax exposure.) *      Illness in persons with a common ventilation system or other exposure (All but two of the cases were postal workers, mail handlers, or sorters or individuals who processed, handled, or received letters containing B. anthracis spores.) *      Cluster of cases with a similar or unusual syndrome *      Severe disease * Atypical route of transmission (inhalational vs. cutaneous) 1 9/17 9/21 9/25 9/29 10/3 10/7 10/11 10/15 10/19 10/23 10/27 11/14 Date of Onset *Postmarked date of known contaminated letters. *10/19 susp cutaneous case later removed Modified from: MMWR Nov 2, 2001; 50(43)

34 发病死亡情况 MMWR Weekly 50(48);1077-9
Update: Investigation of Bioterrorism-Related Anthrax --- Connecticut, MMWR Weekly, Dec 7, 2001: 50(48); Outcome in the 2001 anthrax outbreak was better than previously observed, with a 45% case fatality rate (5 deaths/11 cases)(slide 17). Several possible reasons exist for the improved survival rate observed, including differences in host resistance (most cases were middle-aged and relatively healthy), early recognition and initiation of treatment, the use of a combination of antibiotics effective against anthrax, and better supportive care MMWR Weekly 50(48);1077-9

35 炭疽生物恐怖袭击 生物恐怖袭击最有可能是肺炭疽，皮肤 炭疽也有可能 早期诊断：不容易从类流感病例中筛查 出肺炭疽病例 抗生素预防、疫苗
肺炭疽不存在人传人？

36 谢谢您们的耐心 窦相峰 传染病地方病控制所 北京市疾病预防控制中心