Epidemiology of Plague and Potential for Bioweapon Use

1. بسم الله الرحمن الرحيم BIODEFENCE Epidemiology of Plague Shahid Beheshti University of medical sciences, 2005 By: Hatami H. MD. MPH

2. الف ـ مقدمه و معرفي بيماري ب ـ اپيدميولوژي توصيفي و وقوع(OCCURRENCE) • 1- تعريف و اهميت بهداشتي • 2 – عامل يا عوامل اتيولوژيك ج ـ پيشگيري و كنترل

3. 1- Definition • A special zoonosis involving rodents and their fleas • Transmits to various animals and to human

4. Importance • One of three WHO quarantinable diseases • Estimated 200 million deaths recorded • Three prior pandemics • Justinian 541 AD • Black Death 1346 • China 1855

5. Importance • Naturally occurring human outbreaks parallel and follow epizootics • BT event may also spawn sylvatic plague • Following disasters • Disruption of rat habitats • Transport of disease • through rat relocation

6. Bioweapon Potential • One of top 6 agents identified by CDC (category A) • Known attempted uses • In kaffa • Japanese (Unit 731) WWII infected fleas released over China • Weapons programs • U.S. terminated 1970 • Russia unknown

7. Bioweapon Potential • Estimated Effect • Aerosol release 50kg Y. pestis over city of 5 million people • 150,000 infected • 36,000 die

8. Bioweapon Potential • Delivery Mechanism • Aerosol • Bioweapons programs developed techniques to aerosolize plague directly • Pneumonic form would be expected • Proven infectivity of primates

9. Factors suggesting BT aerosol • Several cases of primary pneumonic (no or few bubonic) • Peak in number of previously healthy persons with cough, fever, death • Many with GI symptoms • Occurs in non-endemic area

10. Factors suggesting BT aerosol • Epidemic of severe/fatal pneumonia (hemoptysis) • Symptoms 1-6 days after exposure • Occurs in persons without risk factors

11. 2- Etiologic agent • Taxonomy • Family Enterobacteriaceae • 11 Yersinia species – 3 human pathogens • Y. pestis • Y. pseudotuberculosis • Y. enterocolitica

12. Microbiology • Staining • Gram negativecoccobacillus • Giemsa, Wright, Wayson stains – bipolar staining

13. Environmental Survival • Requires host • Does not survive in environment well • Can live weeks in water, moist soil • Lives months/years at just above freezing temperature • Lives only 15 minutes in 55 C • Lives in dry sputum, corpses, flea feces • Inactivated by sunlight in a few hours

14. Pathogenesis • Highly virulent and invasive • Four routes human disease: • Flea-bite (most common) • Handling infected animals- skin contact, scratch, bite • Inhalation – from humans or animals • Ingesting infected meat

15. Pathogenesis • Intracellular organism • Survives in monocytes/macrophages • Inhalation (pneumonic form) • Deposition into alveoli • Classic lobular pneumonia • Resulting manifestation • liquefaction necrosis, residual scarring

16. ب ـ اپيدميولوژي توصيفي و وقوع طاعون 1 – دوره نهفتگي(Incubation period) 2 – سير طبيعي(Natural course) 3 – انتشار جغرافيائي(Geographical distribution) 4 – روند زماني(Timeline trend) 5 – تاثير سن، جنس، شغل و موقعيت اجتماعي 6 – تاثير عوامل مساعد كننده(Predisposing factors) 7 – حساسيت و مقاومت(Susceptibility & Resistance) 8 – ميزان حمله هاي ثانويه(Secondary attack rate) 9 – نحوه انتقال و دوره قابليت سرايت (Mode of transmission & period of communicability)

17. 1 ـ دوره نهفتگي • Incubation Period • 1-7 days • Longer in immunized individuals • For primary pneumonia, 1-4 days • Ref. : Control of communicable diseases

18. 2 ـ سير طبيعي Clinical Features • Three types of Disease • Bubonic • Septicemic • Pneumonic

19. Clinical Features • Bubonic • Classic • Predominates )84%( • Usually from bite of infectious flea • Contact ingestion of infected animals

20. Clinical Features • Buboes • Enlarged tender lymph nodes • Usually unilateral • Usually inguinal/femoral in adults • Cervical/submaxillary more common in age < 10 Image: Armstrong & Cohen

21. Clinical Features • Bubonic • Mortality • 40-60% untreated, <5% treated • Overall case fatality 14% in U.S. • Usually from delayed Dx and Rx • Complications • Often develop bacteremia • Some develop: • Septicemia (secondary septicemic plague) • Pneumonic (secondary pneumonic plague) • meningitis

22. Clinical Features • Septicemic • Historically 12% • Secondary • if complication of bubonic • Primary • if no buboes detected

23. Clinical Features • Septicemic • Similar to other gram-negative sepsis • Mortality • Overall 50% • > 90% untreated • Usually from late diagnosis and Rx

24. Clinical Features • Pnuemonic • Approx. 2% all plague are primary pneumonic • Secondary • if preceding bubonic (most cases) or septicemic

25. Clinical Features • Pneumonic • Primary if result of droplet inhalation • From other pneumonic plague patients or infected animals • From expected if aerosolized as a bioweapon • Extremely infectious via droplets and purulent sputum

26. Clinical Features • Pneumonic • Mortality • Nearly 100% untreated or if delayed > 24 hrs after symptom onset • High despite treatment • Overall case fatality 57% in U.S.

28. Clinical Features • In BT event pneumonic form most likely • Pneumonic • incubation 1-6 days for primary • Initial–acute flu-like , myalgia, malaise • Often prominent GI , abd pain • Severe pneumonia • Within 24hr of onset • Cough, hemoptysis • Progresses to cyanosis, stridor • Death usually occurs 2-4 days after exposure

29. Clinical Features • Immunity • Several days after infection • <5% never • Transient, not life-long immunity after surviving • May not protect against a large inoculum • Antibody levels normalize in months-years

30. 2 ـ سير طبيعي (مرور) • ميزان موارد بدون علامت (ساب كلينيكال) • ميزان موارد حاد • ميزان موارد مزمن • ميزان موارد بهبودي خودبخودي • سير بعدي بيماري با درمان و بدون درمان • ميزان مرتاليتي و مربيديتي

31. 3 ـ انتشار جغرافيائي

32. Geographic distribution • Globally • Approximately 1500 cases/year since 1965 • 25 countries reported cases • > 50% Eastern, S. Africa, • U.S. • 390 cases/year reported 1947-96 • Southwest region of U.S. endemic

36. 4 ـ روند زماني • پاندمي ها ؟(Pandemics) • اپيدمي ها ؟(Epidemics) • طغيان ها ؟ (Outbreaks) • تناوب زماني ؟ (Duration) • الگوي فصلي ؟(Seasonality)

37. 5 ـ تاثير سن، جنس ، شغل و موقعيت اجتماعي • تاثير سن بر ميزان بروز و شيوع ، موارد با علامت و بدون علامت و شديد و خفيف و احتمال مزمن شدن و ميزان مرگ و مير • تاثير جنس بر عوامل مذكور • شغل و موقعيت اجتماعي ؟

38. 6 ـ تاثير عوامل مساعد كننده • عوامل فرهنگي و عقيدتي • زمينه هائي نظير ضعف ايمني ، ابتلاء به بيماريهاي سركوبگر ايمني ، مصرف داروهاي مضعف سيستم ايمني • استرس هاي مختلف • فقر و بي خانماني

39. Risk factors • Close contact with case • Contact with infected animal • Living or recent travel in endemic area • Residing in crowded conditions • Cool, wet weather • Exposure to a known intentional release

40. 7 ـ حساسيت و مقاومت در مقابل بيماري • مقاومت طبيعي • مصونيت اكتسابي بعد از ابتلاء • مصونيت اكتسابي بعد از واكسيناسيون

41. 8 ـ ميزان حملات ثانويه • Pneumonic plague may be highly communicable under appropriate climatic conditions

42. 9 ـ منابع و مخازن ، نحوه انتقال بيماري و دوره قابليت سرايتطاعون

43. Transmission • Mostly endemic sylvatic plague with sporadic cases • Person to person spread • Higher risk in: • Overcrowding, • Indoor contacts, • Cold/wet weather • Fleas may remain infective for months

44. Transmission Bioterrorism

45. Period of communicability • Duration of isolation • 2 days after initiating antibiotics and clinically improved • After sputum cultures negative

46. Reservoir • Wild rodents • Rabies & hares • Wild carnivores • Domestic cats

47. ج ـ پيشگيري و كنترل طاعون • Primary Prevention: • Prevention of disease in “well” individuals • Secondary Prevention: • Identification and intervention in early stages of disease • Tertiary Prevention: • Prevention of further deterioration, reduction in complications

48. 1 ـ پيشگيري سطح اوّل 1 ـ ارتقاء آگاهي‌هاي بهداشتي مردم 2 ـ قطع زنجيره انتقال (منبع، مخزن، وسايل انتقال . . . 3 ـ پروفيلاكسي با ايمنسازي (فعال، انفعالي) و كموپروفيلاكسي

49. Prevention • Vaccination • - Bubonic only • Killed virulent strain • No longer commercially available • Series • 3 primary (0 , 3 mo and 6 mo later) • boosters at 6 mo intervals

50. Prevention • Vaccination • Indications • Lab workers • Military personnel stationed in endemic areas • Efficacy • Based on WWII (0 cases) and Vietnam (3 cases) troops • Protects vs. bubonic only, not pneumonic