Plague

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PLAGUE

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Plague

  1. 1. PLAGUE DR.T.V.RAO MD
  2. 2. HISTORY •Y. PESTIS WAS DISCOVERED IN 1894 BY ALEXANDRE YERSIN, A SWISS/FRENCH PHYSICIAN AND BACTERIOLOGIST FROM THE PASTEUR INSTITUTE, DURING AN
  3. 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. 4. MICROBIOLOGY • TAXONOMY • FAMILY ENTEROBACTERIACEAE • 11 YERSINIA SPECIES – 3 HUMAN PATHOGENS • Y. PESTIS • Y. PSEUDOTUBERCULOSIS • Y. ENTEROCOLITICA Dr.T.V.Rao MD 4
  5. 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
  6. 6. MICROBIOLOGY•STAINING •GRAM NEGATIVE COCCOBACILLUS •GIEMSA, WRIGHT, WAYSON STAINS – BIPOLAR “SAFETY PIN” STAINING Image courtesy of CDC
  7. 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
  8. 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. 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. 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. 11. HOW THE PLAGUE SPREADS
  12. 12. PATHOGENESIS •INTRACELLULAR ORGANISM • SURVIVES IN MONOCYTES/MACROPHAGES •INHALATION (PNEUMONIC FORM) • DEPOSITION INTO ALVEOLI • CLASSIC LOBULAR PNEUMONIA •RESULTING MANIFESTATION • LIQUEFACTION NECROSIS, RESIDUAL SCARRING
  13. 13. CLINICAL FEATURES •THREE TYPES OF DISEASE •BUBONIC •SEPTIC EMIC •PNEUMONIC
  14. 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. 15. CLINICAL FEATURES •SEPTICEMIC • HISTORICALLY 12.6% U.S. CASES ARE 1º 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. 16. 17 Bubonic Septicaemic Pneumonic
  17. 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. 18. SEPTICEMIC PLAGUE CAN LEAD TO TERMINAL EVENT • MENINGITIS INVOLVEMENT • DIC MAY LEAD TO GANGRENE OF SKIN, FINGERS, AND PENIS
  19. 19. CLINICAL FEATURES• PNEUMONIC • NUMBERS • APPROX. 2% ALL PLAGUE IN U.S. ARE 1º PNEUMONIC • 12% ARE SECONDARY PNEUMONIC • USUALLY SMALL % OF CASES IN ENDEMIC AREAS • SECONDARY IF PRECEDING BUBONIC (MOST CASES) OR
  20. 20. MAJOR MANIFESTATIONS IN PLAGUE
  21. 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. 22. PNEUMONIC PLAGUE • GET BY DROPLET INFECTION, HEMORRHAGIC PNEUMONIA • CYANOSIS A MAJOR MANIFESTATION • ON EXAMINATION OF SPUTUM SHOWS MANY BACTERIA
  23. 23. CLINICAL FEATURES •OTHER COMPLICATIONS • MENINGITIS • CUTANEOUS DISEASE • PHARYNGEAL DISEASE • ENTERIC DISEASE • SUSTAINED OCCULT FEVER FROM ABSCESSED
  24. 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. 25. EPIDEMIOLOGY • ZOONOTIC DISEASE • RODENTS – RAT FLEAS SPREAD • BACILLI MULTIPLY IN STOMACH OF FLEA • BLOCK PROVENTRCULARIS • 2 WEEKS EXTRINSIC INCUBATION • BITE IF INFECTIVE,
  26. 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. 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. 28. BACTERIOLOGICAL DIAGNOSIS IS GOLD STANDARD
  29. 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
  30. 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,
  31. 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 • 1ST CHOICE GENTAMICIN, SAME ADULT DOSE • 2ND CHOICE DOXY, SAME ADULT DOSE • 3RD CHOICE CIPRO, SAME ADULT DOSE • BREASTFEEDING WOMEN • SAME RECOMMENDATIONS AS PREGNANT • IMMUNOSUPPRESSED – NO DIFFERENT THAN COMPETENT
  32. 32. TREATMENT • ANTIBIOTICS FOR CONTAINED CASUALTIES • (FOR MASS CASUALTIES, SAME AS PEP) • 1ST 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. 33. TREATMENT • 2ND 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 • 1ST CHOICE PO THERAPY FOR MASS CASUALTIES • TETRACYCLINE • 500 MG PO QID ADULTS
  34. 34. TREATMENT •2ND 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 • 1ST 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. 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
  36. 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
  37. 37. BIOWEAPON POTENTIAL • DELIVERY MECHANISM • AEROSOL • BIOWEAPONS PROGRAMS DEVELOPED TECHNIQUES TO AEROSOLIZE PLAGUE DIRECTLY • PNEUMONIC FORM WOULD BE EXPECTED • PROVEN INFECTIVITY OF
  38. 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 1ST 48 HRS OF ABX • DURATION • 2 DAYS AFTER INITIATING ANTIBIOTICS AND CLINICALLY IMPROVED • AFTER SPUTUM CULTURES NEGATIVE
  39. 39. INFECTION CONTROL • RESPIRATORY DROPLET PRECAUTIONS • MASK DURING TRANSPORT • CAN COHORT IF NOT ENOUGH ROOM • CONTACTS – CONSIDER ISOLATION • RECOMMENDED FOR THOSE RECEIVING PEP • DURING1ST 48 HRS OF RX • NOT RECOMMENDED FOR THOSE REFUSING PEP • BUT STILL OBSERVE 7 DAYS Image: National Library of Medicine
  40. 40. INFECTION CONTROL •NATIONAL CONTROL PROGRAMS • SURVEILLANCE • EARLY DIAGNOSIS, TREATMENT & ISOLATION OF CASES • ENVIRONMENTAL SANITATION & EXPOSURE AVOIDANCE • PUBLIC EDUCATION • NON-ERADICABLE
  41. 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 • 3RD GEN CEPHALOSPORINS INEFFECTIVE – USE AMINOGLYCOSIDE • REPORT SUSPECTED CASES TO HEALTH DEPTS.
  42. 42. • PROGRAMME CREATED BY DR.T.V.RAO MD FOR MEDICAL AND PARAMEDICAL STUDENTS IN THE DEVELOPING WORLD •EMAIL •DOCTORTVRAO@GMAIL.COM

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