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

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

6. MICROBIOLOGY•STAINING
•GRAM NEGATIVE
COCCOBACILLUS
•GIEMSA, WRIGHT,
WAYSON STAINS –
BIPOLAR “SAFETY
PIN” STAINING Image courtesy of CDC

8. 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

9. 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

10. 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

11. 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

12. HOW THE PLAGUE SPREADS

13. PATHOGENESIS
•INTRACELLULAR ORGANISM
• SURVIVES IN MONOCYTES/MACROPHAGES
•INHALATION (PNEUMONIC FORM)
• DEPOSITION INTO ALVEOLI
• CLASSIC LOBULAR PNEUMONIA
•RESULTING MANIFESTATION
• LIQUEFACTION NECROSIS, RESIDUAL SCARRING

14. CLINICAL FEATURES
•THREE TYPES
OF DISEASE
•BUBONIC
•SEPTIC EMIC
•PNEUMONIC

15. 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

16. 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

17. 17
Bubonic
Septicaemic
Pneumonic

18. 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.

19. SEPTICEMIC PLAGUE
CAN LEAD TO TERMINAL
EVENT
• MENINGITIS
INVOLVEMENT
• DIC MAY LEAD TO
GANGRENE OF SKIN,
FINGERS, AND PENIS

20. 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

21. MAJOR MANIFESTATIONS IN PLAGUE

22. 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

23. PNEUMONIC PLAGUE
• GET BY DROPLET
INFECTION,
HEMORRHAGIC
PNEUMONIA
• CYANOSIS A MAJOR
MANIFESTATION
• ON EXAMINATION OF
SPUTUM SHOWS MANY
BACTERIA

24. CLINICAL FEATURES
•OTHER
COMPLICATIONS
• MENINGITIS
• CUTANEOUS DISEASE
• PHARYNGEAL DISEASE
• ENTERIC DISEASE
• SUSTAINED OCCULT FEVER
FROM ABSCESSED

25. 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

26. EPIDEMIOLOGY
• ZOONOTIC DISEASE
• RODENTS – RAT FLEAS
SPREAD
• BACILLI MULTIPLY IN
STOMACH OF FLEA
• BLOCK PROVENTRCULARIS
• 2 WEEKS EXTRINSIC
INCUBATION
• BITE IF INFECTIVE,

28. 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

29. 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

30. BACTERIOLOGICAL DIAGNOSIS IS GOLD
STANDARD

31. 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

32. 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,

33. 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

34. 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)

35. 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

36. 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)

37. 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

38. 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

39. BIOWEAPON POTENTIAL
• DELIVERY MECHANISM
• AEROSOL
• BIOWEAPONS PROGRAMS
DEVELOPED TECHNIQUES
TO AEROSOLIZE PLAGUE
DIRECTLY
• PNEUMONIC FORM WOULD
BE EXPECTED
• PROVEN INFECTIVITY OF

40. 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

41. 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

42. INFECTION CONTROL
•NATIONAL CONTROL
PROGRAMS
• SURVEILLANCE
• EARLY
DIAGNOSIS, TREATMENT
& ISOLATION OF CASES
• ENVIRONMENTAL
SANITATION &
EXPOSURE AVOIDANCE
• PUBLIC EDUCATION
• NON-ERADICABLE

43. 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.

44. • PROGRAMME CREATED BY DR.T.V.RAO
MD FOR MEDICAL AND PARAMEDICAL
STUDENTS IN THE DEVELOPING WORLD
•EMAIL
•DOCTORTVRAO@GMAIL.COM