Anthrax Zoonotic disease caused by Bacillus anthracis

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Presentation transcript:

Anthrax Zoonotic disease caused by Bacillus anthracis Described in biblical times First animal vaccine developed by Louis Pasteur in 1881 Used for bioterrorism in 2001

باسیل گرم مثبت یافت شده در خاک در محیط کشت وبافت زنده :زنجیرهای طویل boxcarیا شبیه سیگار اشکال وژتاتیو درخاک:اسپور تخریب اسپور:جوشاندن بمدت 10-20دقیقه تماس بامواد اکسیدان مثل پرمنگنات پتاسیم و پراکسیدهیدروژن و فرمالدییدوفنل و هیپوکلریت سدیم اتوکلاو 15دقیقه

راه انتقال به انسان :تماس با فراورده دامی یا دام گوارشی:خوردن گوشت آلوده ترشحات دام ولاشه آن برای انسان الوده است عامل بیماریزایی:توکسین ایجاد شده بعد از تبدیل اسپور به فرم وژتاتیو پروتئینهای توکسین سیاه زخم:آنتی ژن محافظتی-عامل ادم-فاکتور نابودکننده

Bacillus anthracis Dry weather induces sporulation and Spores may remain viable in soil for years Toxins responsible for tissue damage and edema

Anthrax Epidemiology Reservoir Infected animals, soil Transmission Direct contact (cutaneous) Ingestion (gastrointestinal) Inhalation Communicability Not communicable (inhalation) very rare (cutaneous)

Anthrax Epidemiology Persons at Risk Agricultural exposure to animals (rare) Laboratorians exposed to B. anthracis spores (rare) Processors of wool, hair, hides, bones or other animal products (extremely rare) Biological terrorism زراعتی-پوست

Anthrax—United States, 1951-2002 Animal vaccine Human vaccine Bioterrorism

Anthrax: Pathophysiology NEJM, 1999

Anthrax Toxins Protective Antigen Lethal Factor Edema Factor Edema Toxin Lethal Toxin Tissue damage, shock Edema

Anthrax: Clinical Features Inhalational: “Woolsorter’s disease” high mortality Gastrointestinal: meat ingestion mortality 100% Cutaneous(most common in natural Exposure situation) low mortality

Cutaneous Anthrax Pathogenesis Spores enters through broken skin or mucous membranes Germinate in macrophages, replicate in lymph nodes and intracellular space Bacteria produce antiphagocytic capsule Production of toxins cause tissue destruction and edema

Cutaneous Anthrax Incubation period 1-12 days Head &neck&upper limb Pruritic Papule(usually painless), then vesicle, then necrotic ulcer (eschar) with black center Painful LAN may last for weeks Case-fatality: without antibiotics – 5%-20% with antibiotics – <1%

اسکار طی 1-2 هفته کنده میشودو بهبودی کامل ممکنه 6هفته طول کشد. مرگ:باکترمی –مننژیت-فشار به راه هوایی در اثر ادم اکثر موارد سیاه زخم جلدی تب و علایم سیستمی ندارند

Cutaneous: “malignant pustule” Textbook of Military Medicine

Anthrax: Clinical Features Pediatric case: systemic illness seen transient DIC renal dysfunction unique susceptibility? NEJM, 2001

Diagnosis: Cutaneous Anthrax سواپ اگزودای زخم و تهیه اسمیر ورنگ آمیزی گرم یا فلورسنس مستقیم پانچ بیوپسی کشت خون تست الیزا PCR

Inhalational Anthrax Pathogenesis استنشاق اسپور-آلوئول-فاگوسیته شدن توسط ماکروفاژ-غددلنفاوی ناحیه-فرم وژتاتیو-ایجاد توکسین پهن شدن مدیاستن و پلورال افیوژن مرگ:تقریبا 100% سیاه زخم تنفسی واگیردار نیست و نیاز به ایزوله شدن ندارد

Inhalation Anthrax Incubation period: 1-7 days (range up to 43 days) Prodrome of cough, myalgia, fatigue, and fever Rapid deterioration with fever, dyspnea, cyanosis and shock, often with radiographic evidence of mediastinal widening Case-fatality: without antibiotic treatment : 85%- 97% with antibiotic treatment : 75% (45% in 2001)

Anthrax Pathogenesis Inhaled spores may reside in alveoli without germination for weeks Antibiotics effective against vegetative form but not spores Disease may develop after antibiotics discontinued

Inhalational Anthrax Textbook of Military Medicine

Diagnosis: Inhalational Anthrax CXR +/- chest CT Gram stain and blood cultures are positive for the bacillus (not spores) late in the illness Textbook of Military Med

Gastrointestinal Anthrax Incubation period 1-7 days Pharyngeal involvement includes oropharyngeal ulcerations with cervical adenopathy and fever Intestinal involvement includes abdominal pain, fever, bloody vomiting or diarrhea

GI Anthrax فرم دهانی حلقی:نادرتر از روده ای-تب و تورم دردناک گردن-دیسفاژی و خشونت صدا-ضایعات لوزه و کام سخت و خلف حلق(زخمی و نکروز و پچ سفیدو غشای کاذب) فرم روده ای :تب و بیحالی و سنکوپ –درد و اتساع شکم-توده با حاشیه نامشخص در دور ناف یا RUQ-آسیت واسهال خونی-شوک کمتر از 5%موارد سیاه زخم در اثر گوشت نیم پز

بعداز هر سه فرم سیاه زخم: مننژیت کشندگی :95% خونریزی و مایع نخاعی خونی

درمان پنی سیلین –داکسی سیکلین –سیپروفلوکساسین- کلیندا مایسین-ریفامپین-آموکسی سیلین (بچه ها) آنتی بیتیک روی اسپور موثر نیست بیوتروریسم:سیپرو یا داکسی بمدت 60 روز درمان وریدی با دو یا چند آنتی بیو تیک:درگیری سیستمی –ضایعات سر و گردن یا ادم وسیع یا سن کمتر 2 سال بمدت 60 روز اریترو –سفالوسپورین و کوتری موثر نمیباشد کورتن:در گیری مغزی vancomycin, ampicillin, chloramphenicol, imipenem, clarithromycin

Anthrax Bioterrorism Attacks–United States, 2001 22 cases (11 inhalation, 11 cutaneous) in 4 states B. anthracis sent through U.S. mail Most exposures occurred in mail sorting facilities and sites where mail was opened

Safe Mail Handling Do not open suspicious mail inappropriate or unusual labeling strange or no return address postmark different from return address excessive packaging material Keep mail away from face No not blow or sniff mail or mail contents Wash hands after handling Avoid vigorous handling (tearing, shredding) Discard envelopes مظنون-ناشناس-مهر باطله-بوکشیدن-دور انداختن

Anthrax Vaccines 1881 Pasteur develops first live attenuated veterinary vaccine for livestock 1939 Improved live veterinary vaccine 1954 First cell-free human vaccine 1970 Improved cell-free vaccine licensed

Anthrax Vaccine Efficacy 95% seroconversion following 3 doses Duration of immunity unknown

Anthrax Vaccine Pre-exposure Vaccination Persons working with production quantities or concentrations of B. anthracis cultures Persons engaged in activities with a high potential for production of aerosols containing B. anthracis Persons with increased risk of exposure to intentional release of B. anthracis (e.g., certain military personnel)

Anthrax Vaccine Postexposure Vaccination No efficacy data for postexposure vaccination of humans Postexposure vaccination alone not effective in animals Combination of vaccine and antibiotics appears effective in animal model

Anthrax Vaccine Adverse Reactions Local reactions minor 20%-50% severe 1% Systemic symptoms 5%-35% Severe reactions rare

آنتی بیوتیک مانع تشکیل اسکار نمیشود دبریدمان زخم نباید انجام شود پیشگیری دارویی:داکسی 100 bd یا سیپرو 500bd بمدت 60 روز(در صورت حساس به پنی سیلین:آموکسی500 tds)

واکسیناسیون: علفخواران اهلی:زنده ضعیف شده حاوی اسپور انسان:واکسن غیرزنده با ترکیب آنتی ژن محافظتی:نوبت 0-2-4 هفته و بعد 6-12-18 ماه زیرجلدی و سپس یادآور سالیانه لاشه دامها دفن شده و یا سوزانده شوند.(اسپورسازی در حضور اکسیژن است)

Anthrax Postexposure Antibiotic Prophylaxis Discontinue antibiotics after third dose of vaccine

Recommended Postexposure Prophylaxis to Prevent Inhalational Anthrax Initial Therapy Duration Adults Ciprofloxacin 60 days (including pregnant 500 mg PO BID women and OR immunocompromised) Doxycycline 100 mg PO BID Children Ciprofloxacin 60 days 10-15 mg/kg PO Q 12 hrs* OR Doxycycline: >8 yrs and >45 kg: 100 mg PO BID >8 yrs and <45 kg: 2.2 mg/kg PO BID <8 yrs: 2.2 mg/kg PO BID *Ciprofloxacin dose should not exceed 1 gram per day in children.