Plague

PLAGUE

1. PLAGUE Dr.T.V.Rao MD

2. History Y . pestis was discovered in 1894 by Alexandre Yersin, a Swiss/French physician and bacteriologist from the Pasteur Institute, during an epidemic of plague in Hong Kong

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

4. Microbiology Taxonomy Family Enterobacteriaceae 11 Yersinia species – 3 human pathogens Y. pestis Y. pseudotuberculosis Y. enterocolitica Dr.T.V.Rao MD 4

5. Human Y. pestis infection Human Y. pestis infection takes three main forms: pneumonic, septic emic, and bubonic plagues All three forms were responsible for a number of high-mortality epidemics throughout human history, including the Justinianic plague of the sixth century and the Black Death

6. Microbiology Staining Gram negative coccobacillus Giemsa, Wright, Wayson stains – bipolar “safety pin” staining Image courtesy of CDC

7. Historical documentation One of the first mentions of the plague in history was in the year A.D.541. During that time it was called Justinian's plague after the emperor. It took the lives of approximately 200,000 people. That was in about a four month period. For about seven hundred years Justinian's plague went away and reappeared every ten to twenty-four years. Justinian's plague finally ended in the eighth century.

8. Rat Flea Xenopsylla cheopsis When bite blood regurgitate to bite with contaminated feces When rat dies Fleas flee start biting humans Common in North India X cheopsis Common in South India X astia

9. Pathogenesis Environmental Survival Requires host Does not survive in environment well Can live weeks in water, grains, 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

10. 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

11. How the plague spreads

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

13. Clinical Features Three types of Disease Bubonic Septic emic Pneumonic

14. 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

15. Clinical Features Septicemic Historically 12.6% U.S. cases are 1 º Septicemic Secondary if complication of bubonic If clinical sepsis develops Primary if no buboes detected More difficult to diagnose May gain access through breaks in skin May be flea-bite without bubo detectable

16. 17 Bubonic Septicaemic Pneumonic

17. Bubonic Plague Bubon - Groin Incubation 2 – 5 days Lymph nodes enlarge from site of entry from bite of Rat fleas The lymph nodes enlarge suppurate Bacteria can enter blood and produce septicemia Hemorrhages into skin and mucous membranes Fatal in 30 – 90 % if untreated.

18. Septicemic Plague Can lead to Terminal event Meningitis involvement DIC may lead to gangrene of skin, fingers, and Penis

19. Clinical Features Pneumonic Numbers Approx. 2% all plague in U.S. are 1 º pneumonic 12% are secondary pneumonic Usually small % of cases in endemic areas Secondary if preceding bubonic (most cases) or Septicemic Spread hematogenously to lungs Interstitial pattern initially

20. Major manifestations in plague

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

22. Pneumonic Plague Get by droplet Infection, Hemorrhagic pneumonia Cyanosis a major manifestation On examination of sputum shows many bacteria

23. Clinical Features Other complications Meningitis Cutaneous disease Pharyngeal disease Enteric disease Sustained occult fever from abscessed intraabdominal buboes

24. Epidemiology Three forms of plague Bubonic Septicemic Pneumonic Human plague most commonly occurs when plague-infected fleas bite humans Any suspected case in non-endemic areas without risk factors – report immediately

25. Epidemiology Zoonotic Disease Rodents – Rat fleas Spread Bacilli multiply in stomach of flea Block proventrcularis 2 weeks extrinsic incubation Bite if infective, contaminated feces spread the disease

26. Seasonal Spread Cool humid environments help Urban plague Wild Sylva tic plague Microbes survive in Burrows Rats spread 1 Rattus norvegicus (Sewer rat) 2 Rattus rattus Domestic Not possible to eradicate

27. Diagnosis No rapid tests available – treat first Report suspected cases to local health dept. if no risk factor for naturally occurring disease Send out samples if not done in hospital Obtain specimens as indicated: Blood – attempt 4 samples q30 min Bubo aspirate (inject 1-2cc saline and aspirate with 20 Ga needle) Sputum CSF

28. Bacteriological diagnosis is gold standard

29. Diagnosis CXR Inoculate on/in infusion broth, blood agar, McConkey agar Biochemical profiles if automated system has capacity to detect Stains – Gram and Wayson’s or Giemsa DFA testing Acute serum for F1 antibody CDC sample for bacteriophage lysis

30. Treatment Antibiotics General Contained casualties – IV Mass casualties – po equivalent, same as post-exposure prophylaxis Also need intensive supportive care Ventilation Pressors usually not needed Who to treat Suspected cases Index If suspected release – anyone with fever, cough

31. Treatment Special populations Children Same as adults but try avoid TCN if <8yo No chloramphenicol for <2 yo (grey baby syndrome) Pregnant women Try to avoid streptomycin 1 st choice gentamicin, same adult dose 2 nd choice doxy, same adult dose 3 rd choice cipro , same adult dose Breastfeeding women Same recommendations as pregnant Immunosuppressed – no different than competent

32. Treatment Antibiotics for contained casualties (For mass casualties, same as PEP) 1 st choices Streptomycin - FDA-approved 30 mg/kg IM divided q8-12 kids (max 2g/day) 1g IM bid adult bactericidal gentamicin –as effective, more avail, qd dosing 5mg/kg iv qd, w/levels or load 2mg/kg then 1.7mg/kg q8 2.5mg/kg im /iv q8h kids (q12hr for <1wk or premature)

33. Treatment 2 nd choices tetracycline's - as good in vitro, good human data doxycycline single 200mg iv loading dose (some sources) 100mg iv bid or 200 mg iv qd adults& kids >45kg 2.2mg/kg iv q12hr (max 200mg) kids <45kg Better absorption, distribution, half-life than TCN 1 st choice po therapy for mass casualties tetracycline 500 mg po qid adults 6.25-12.5 mg/kg po qid kids >9yo

34. Treatment 2 nd choices Fluor quinolones–better in vitro, no human data ciprofloxacin 400 mg iv q12hr adults 15 mg/kg iv q12hr kids (max 1g/day) Levofloxacin Ofloxacin Chloramphenicol 1 st choice for meningitis +/- aminoglycoside Crosses blood-brain barrier 25mg/kg iv q6hr adults & kids, keep level 5-20 μg /ml Avoid in kids <2 yo (grey baby syndrome)

35. Prevention Vaccination - Bubonic only Killed virulent strain – used in U.S. Formalin-fixed, no longer commercially available Future production and licensure unknown Series 3 primary (1.0cc, 0.2 cc at 1-3 mo and 5-6 mo later) 2 boosters 0.2cc at 6 mo intervals then q1-2yrs

36. Prevention Vaccination Indications Lab workers with fully virulent strains Military personnel stationed in endemic areas Efficacy Based on WWII (0 cases) and Vietnam (3 cases) troops Protects vs. bubonic only, not pneumonic Adverse effects Significant number have mild reactions May be severe

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

38. Infection Control Mechanism for person-person spread Not completely understood Respiratory droplets most likely, not droplet nuclei Historically prevented by masks Respiratory Droplet Precautions Wear mask, gown, gloves, eye protection Suspected cases - isolate Immediately respiratory (even for bubonic) Avoid unnecessary close contact 1 st 48 hrs of abx Duration 2 days after initiating antibiotics and clinically improved After sputum cultures negative

39. Infection Control Respiratory Droplet Precautions Mask during transport Can cohort if not enough room Contacts – consider isolation Recommended for those receiving PEP during1 st 48 hrs of Rx Not recommended for those refusing PEP but still observe 7 days Image: National Library of Medicine

40. Infection Control National control programs Surveillance Early diagnosis, treatment & isolation of cases Environmental sanitation & exposure avoidance Public education Non-eradicable

41. Never forget plague can occur anywhere do minimal evaluations to diagnose Sudden, severe pneumonia in previous healthy Hemoptysis GI symptoms Pneumonia on CXR Bipolar staining gram- rod in sputum, blood Pneumonic person-to-person transmission 3 rd gen cephalosporins ineffective – use aminoglycoside Report suspected cases to Health Depts.

42. programme created by Dr.T.V.Rao MD for medical and paramedical students in the Developing world Email [email protected]