PLAGUE

DR.T.V.RAO MD

HISTORY
Y. PESTIS WAS
DISCOVERED IN 1894 BY ALEXANDRE YERSIN, A SWISS/FRENCH PHYSICIAN AND BACTERIOLOGIST FROM THE PASTEUR INSTITUTE, DURING AN

 IMPORTANCE

HISTORY

ONE OF THREE WHO QUARANTINABLE DISEASES ESTIMATED 200 MILLION DEATHS RECORDED JUSTINIAN 541 AD BLACK DEATH 1346 CHINA 1855

THREE PRIOR PANDEMICS

MICROBIOLOGY
TAXONOMY
FAMILY
ENTEROBACTERIACEAE

11 YERSINIA SPECIES 3 HUMAN PATHOGENS Y. PESTIS

Dr.T.V.Rao MD

Y. PSEUDOTUBERCULOSIS
Y. ENTEROCOLITICA

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 HIGHMORTALITY EPIDEMICS THROUGHOUT HUMAN HISTORY, INCLUDING THE JUSTINIANIC PLAGUE OF THE SIXTH CENTURY AND THE BLACK

MICROBIOLOGY STAINING
GRAM NEGATIVE COCCOBACILLUS GIEMSA, WRIGHT, WAYSON STAINS BIPOLAR SAFETY PIN STAINING

Image courtesy of CDC

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

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

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

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

HOW THE PLAGUE SPREADS

PATHOGENESIS
INTRACELLULAR ORGANISM
SURVIVES IN MONOCYTES/MACROPHAGES

INHALATION (PNEUMONIC FORM)

DEPOSITION INTO ALVEOLI CLASSIC LOBULAR PNEUMONIA

RESULTING MANIFESTATION
LIQUEFACTION NECROSIS, RESIDUAL SCARRING

CLINICAL FEATURES
THREE TYPES OF DISEASE
BUBONIC SEPTIC EMIC PNEUMONIC

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

CLINICAL FEATURES
SEPTICEMIC
HISTORICALLY 12.6% U.S. CASES ARE 1 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

Bubonic

Pneumonic Septicaemic

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.

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

CLINICAL FEATURES PNEUMONIC

NUMBERS
APPROX. 2% ALL PLAGUE IN U.S. ARE 1 PNEUMONIC 12% ARE SECONDARY PNEUMONIC USUALLY SMALL % OF CASES IN ENDEMIC AREAS SECONDARY IF PRECEDING BUBONIC (MOST CASES) OR

MAJOR MANIFESTATIONS IN PLAGUE

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

PNEUMONIC PLAGUE
GET BY DROPLET INFECTION, HEMORRHAGIC PNEUMONIA CYANOSIS A MAJOR MANIFESTATION

ON EXAMINATION OF SPUTUM SHOWS MANY BACTERIA

CLINICAL FEATURES
OTHER COMPLICATIONS
MENINGITIS CUTANEOUS DISEASE PHARYNGEAL DISEASE ENTERIC DISEASE

SUSTAINED OCCULT FEVER FROM ABSCESSED

EPIDEMIOLOGY
THREE FORMS OF PLAGUE
BUBONIC
SEPTICEMIC PNEUMONIC

HUMAN PLAGUE MOST COMMONLY OCCURS WHEN PLAGUE-INFECTED FLEAS BITE HUMANS ANY SUSPECTED CASE IN NONENDEMIC AREAS WITHOUT RISK FACTORS REPORT IMMEDIATELY

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

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

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

BACTERIOLOGICAL DIAGNOSIS IS GOLD STANDARD

DIAGNOSIS
CXR

INOCULATE ON/IN INFUSION BROTH, BLOOD AGAR, MCCONKEY AGAR

BIOCHEMICAL PROFILES IF AUTOMATED SYSTEM HAS CAPACITY TO DETECT STAINS GRAM AND WAYSONS OR GIEMSA DFA TESTING ACUTE SERUM FOR F1 ANTIBODY

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,

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

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)

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

TREATMENT
2ND CHOICES
FLUOR QUINOLONESBETTER IN VITRO, NO HUMAN DATA
CIPROFLOXACIN

400 MG IV Q12HR ADULTS 15 MG/KG IV Q12HR KIDS (MAX 1G/DAY)

CHLORAMPHENICOL
1ST CHOICE FOR MENINGITIS +/- AMINOGLYCOSIDE CROSSES BLOOD-BRAIN BARRIER 25MG/KG IV Q6HR ADULTS & KIDS, KEEP LEVEL 5-20 G/ML
AVOID IN KIDS <2 YO (GREY BABY SYNDROME)

LEVOFLOXACIN OFLOXACIN

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

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

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

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

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

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

 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.

NEVER FORGET PLAGUE CAN OCCUR ANYWHERE DO MINIMAL EVALUATIONS TO DIAGNOSE

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