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A SEMINAR
ON
PLAGUE
(Epidemiology and control)

BY-
BY-
Dr. RAJESH KUMAR
M.V.Sc. 1st YEAR
ROLL No-
No-4786
m m
‡ Plague is an acute, highly infectious, zoonotic disease caused
by O  

‡ Plague also known as the black death, the great pestilence, and
the bubonic plague.

‡ Disease transmitted to humans and animals by the bite of rat


flea.

‡ O   was first isolated by Alexandre Yersin in 1894


in Hong Kong.

‡ Between 1987 and 2001, 36876 cases of plague with 2847


deaths were reported to WHO.
ISTORY
‡ Plague has produced at least three great pandemics and
multiple epidemics throughout history.
Three great Pandemics
1. 542-
542-556 B.C. - Plague of Justinian
2. 1346-
1346-1350 - µBlack Death¶
3. 1894 - Modern Pandemic

‡ The first pandemic known as the Justinian plague in


543--542 B.C. was believed to have started in Egypt
543
spreading into the Middle East and Mediterranean.
‡ killing 100 million people over 60 years.


‡ The second pandemic known as the Black Death began in 1347,


The Black Death had killed approximately

‡ One
One--forth of Europe population and

‡ One thirds of the worlds populations

‡ About 30 million people death.

‡ The third pandemic began in China in 1860s spreading to Hong


Kong in 1890s. Plague was spread by rats transported on ship to
Africa, Asia, California, and South America

‡ Foci of infection established in wild rodents in rural areas.


‡ About 20 million dead in India alone between 1889 and
1950
Major plague outbreaks
Years Country Deaths
740--744
740 Turkey 200,000
1672 Italy 400,000
1711 Germany, Austria 500,000
1792 Egypt 800,000
1898--1908
1898 China, India 3 million
1909-1918
1909- China, India 1,335,000
1920 India 2 million
1994 India (Surat) 56 (WHO)
2002 Shimla ( H.P.) 4 (WHO)
Huma ague ma ura  
‡ In 1994
1994,, total 693 suspected bubonic or pneumonic plague
cases were reported to WHO by Government of India.
India.

‡ The outbreak of suspected plague disease lasted from August


26, 1994 to October 18, 1994, that resulted in 56 deaths
deaths..

‡ These cases were from STATE Cases reported


Maharashtra 488
Gujarat 77
Karnataka 46
CDC. Human plague - India, Uttar Pradesh 10
1994. MMWR 1994;43:689-
1994;43:689-91.
Madhya Pradesh 4
New Delhi 68
Discovery of causative agent
‡ 1894: Hong Kong pandemic

‡ Dr. Alexandre Yersin first


isolated and described in detail,
m
  ,
, the old term
used for O  .
.
‡ Gram negative
‡ Bacillus

‡ In 1896, Yersin developed an


antiserum that saved the life of
an 18 year old Chinese student.
÷AUSATIVE AGENT

O   
‡ Family Enterobacteriaceae
‡ Gram negative, coccobacillus,
pleomorphic.

‡ Aerobic, facultative anaerobic, CDC/ Courtesy of Larry Stauffer,


and facultative intracellular.

‡ Several plasmids and virulence


factors
± F1, murine exotoxin, LPS
endotoxin, coagulase, pesticin,
plasminogen activator
O  
‡ Giemsa, Wright, Wayson
stains ± bipolar ³safety
³safety pin"
pin"
staining
‡ Destroyed by
‡ Sunlight
‡ Desiccation
‡ Survival
‡ 1 hour in air
‡ Briefly in soil
‡ 1 week in soft tissue Source: Centers for Disease Control and
Prevention, Division of Vector-Borne
‡ Years when frozen Infectious Diseases, Fort Collins, CO
a ma m

‡ Geographical distribution
‡ Reservoir
‡ Vector
‡ Incidental host
‡ Epidemiological Cycles of Plague
‡ Mode of Transmission
Geographic distribution
‡ Natural foci of infection persist on nearly on all continents, they
do not exist in Australia, New Zealand, and Japan (OIE 2004)
‡ Worldwide
The WHO document between 1000
1000--3000 cases per year
‡ 18,739 cases from 1980±
1980±1994
‡ 2,603 cases in 1999 from 14 countries and 181 deaths

‡ 2118 cases in 2003 from 9 countries and 182 deaths


‡ More than 76% of cases and deaths were reported from
Africa.

‡ There have been recent outbreaks of plague in India in 2002 and


Algeria in 2003.
uman plague cases : countries having notified to WO 2004
Asa
Most cases of plague worldwide were reported from Asia from 1954-80¶s.
There were outbreaks in Tanzania and Madagascar in the 1990s.
Outbreaks occurred in India in 1954, 1963, and then again 30 years later in 1994.
The plague outbreak in India in 1994 is a result of the earthquake in September
1993 that disturbed the equilibrium density of domestic rodents and their fleas.


 

H.P
Gujarat
Maharashtra
A.P.
Karnataka
T.N.

NICD DELHI PLAGUE ENDEMIC STATES ± 6


aam
‡ Wild and domestic rats ‡ Gerbils
‡ Ground squirrels ‡ Voles
‡ Rock squirrels ‡ Chipmunks
‡ Prairie dogs ‡ Marmots
‡ Deer mice ‡ Guinea pigs
‡ Field mice ‡ Kangaroo rats
«over 200 identified reservoirs species
a

v 

  The oriental rat flea; nearly worldwide


in moderate climates

?

  United States


„

   Nearly worldwide in temperate climates


v 

 
  Africa, India, South America

v 

  Indonesia and Southeast Asia


v 

  
 Pacific Islands

~30 identified flea vectors


m ma A H

‡ Humans ‡ Coyotes
‡ Domestic and feral ‡ Camels
cats ‡ Goats
‡ Dogs ‡ Deer
‡ Lagomorphs (rabbits ‡ Antelope
and hares)
aem ga  es  ague
‡ Ô    m 


‡ Reservoir (foci) = wild rodents (prairie dogs, rabbits, mice,
dogs)
‡ Vector = wild rodent flea
‡    m 

‡ Reservoir = domestic (urban) black rat
‡ Vector = oriental rat flea ((
    )
)

‡ 
 m 


‡ Bubonic plague acquired from contact with either sylvatic
or urban reservoirs or arthropod vector bite and further
transmitted in human population by spread of pneumonic
plague.
A  mm

‡ Bites from flea vectors (78%)


‡ Direct animal contact (20%)
‡ With infectious body fluids, tissues, scratches, bites while
handling an infected animal (which can be dead or alive)

‡ Enters through break in skin

‡ Ingestion of raw or uncooked meat from an infected


animal (marmots, prairie dogs, goats, camel)

‡ Inhalation of infectious droplets, aerosol (2%)


e  rasmss
There are at least 6 potential modes of transmission:

1. Wild rodent Flea Peridomestic rodents


Flea Domestic rodent Flea Humans

2. Human with pneumonic plague droplet


infection Humans

3. Wild rodents Flea Humans (when


humans enter the forests etc where the sylvatic
cycle is maintained)


4. Handling infected rodent tissue (wild / domestic)


or any other infected material e.g. pus from
buboes

5. Domestic cats eat infected rodents develop


pneumonic plague Droplet infection
Humans

6. Plague bacilli Bioterrorism Humans


!! m A  mm

‡ Bites from flea vectors

‡ Bites or scratches from infected animals, such as


cats

‡ Direct contact with infected animal carcasses, such


as rodents (especially marmots), rabbits, hares,
carnivores (eg, wild cats, coyotes), and goats
a ma m A  mm

‡ Bites from flea vectors where O  is inserted


directly into bloodstream
± no discernible bubo present

‡ Develops as a complication of bubonic or 1º


pneumonic plague
± When O  enters the bloodstream

‡ Neither bubonic plague nor septicemic plague


spreads directly from person to person
a  m A  mm

‡ Inhalation of respiratory droplets from infected animals such


as cats.

‡ Inhalation of respiratory droplets from a person with primary


or secondary pneumonic plague.

‡ Handling O  cultures in the laboratory.

‡ Bubonic and 11°° septicemic spread plague bacilli


hematogenously to the lungs.

‡ The ability to cause infection by aerosol and the serious


nature of pneumonic plague make O a
a potential
biological weapon.
aer    eas rasm  ague



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  

3 Forms of the disease
1. Bubonic Plague. 80
80--95%
Painful lymph node swellings, buboes

2. Septicemic Plague. 10
10--20%
Also called ³blood
³blood poisoning´,
poisoning´, attacked the
blood system

3. Pneumonic Plague. rarest


Attacked the respiratory system
! 

‡ Incubation: 2-
2-6 days
‡ Clinical signs
± Fever, chills, malaise, muscle aches, headache
± Regional lymphadenitis (buboes)
1. Swollen, very painful lymph nodes
2. Typically inguinal (most common),
femoral, axillary, or cervical
3. Swellings expanding until they burst Ô death following
soon after
- ° vomiting, abdominal pain, nausea, petechiae
‡ Mortality (untreated): 30 -75 %
Cont«

‡ Painful lymph node


swelling, called buboes

‡ Dark blotches = acral


necrosis Ô Black Death!

Source: CDC NVBID


Ô  

½ Systemic spread (Blood
(Blood-- Poisoning)

½    
   

1. Similar to bubonic, plus Prostration, circulatory collapse,
septic shock, organ failure, hemorrhage,
2. Skin turns dark purple, almost black = The Black Death.
Death.
due to DIC (disseminated intravascular coagulation)

3. Necrosis of extremities

4. Microthrombi blocking capillaries

5. Victims died the same day symptoms appeared.


Cont«
½ It is most deadly form
½ Mortality (untreated): 100%
½ No treatment even today
Hemorrhagic changes in skin
called ³purpuric lesions´

‡ Extremity gangrene
 

‡ Incubation: 11--6 days (usually 2-
2-4 days)
‡ Primary - O   inhaled
‡ Secondary ± septicemic or bubonic form spreads and Infected
the lungs.

‡ Clinical signs
1. Acute onset of fever with cough, dyspnea, and chest pain

2. Hemoptysis characteristic; watery or purulent sputum also


possible (Slimy sputum tinted with blood)

3. Prominent GI symptoms may be present, including nausea,


vomiting, diarrhea, and abdominal pain
Cont«
‡ Only pneumonic form of plague is spread person-
person-to
to--
person

‡ Mortality Rate (untreated) : 90


90--95%

Radiography ± usually patchy


bilateral infiltrates, consolidation

Photograph by Ken Gage, Ph.D., Centers of Disease Control and Prevention, Fort Collins, CO.
    
½ Many found serologically positive
Bears, bobcats, badgers, fox, ringtails, skunks, deer,
Mountain lion, African elephant, African buffalo, camel,
coyote, more «
½ Rodents
‡ Most rodent die readily from infection
½ Farm animals and dogs
‡ Very resistant to disease
‡ May be incubating at time of slaughter
‡ Human risk
÷ats and Plague
‡ No human cases from cats prior to 1977
‡ In 1998, 23 cases reported among - 5 fatal
‡ Cats develop severe illness
Signs mimic human illness
Bubonic, septicemic, pneumonic and die

‡ Can transfer disease to humans


± Owners, veterinarians or staff
± Pneumonic, fleas, bite, scratch
‡ Hundreds of cases of domestic cats reported with plague.

‡ In U.S cats have been sours of infection for about 5% case of


plague in man
Dogs and Plague
‡ Rarely show signs
± Fever, lethargy, oral lesions,
lymph node lesions

‡ May seroconvert
‡ May carry infected fleas

‡ Cats and dogs are now recognized as sources of


infection for humans.
Laboratory diagnosis
‡ The appropriate specimens for diagnosis of bubonic, pneumonic,
and septicaemic plague are, bubo aspirate,
aspirate, sputum,
sputum, and blood
respectively.

‡ Giemsa smear ((bipolar


bipolar staining) with
Gram¶s stain ((gram
gram--negative)

‡ A characteristic growth is seen in


nutrient broth such as brain-
brain-heart
heart--infusion

Y pestis culture at 48 h in
brain-
brain-heart
heart--infusion broth at 26
26JJC
Cont«
‡ Yersinia-
Yersinia-specific CIN agar can be
useful for culture of contaminated
specimens, such as sputum

‡ Rapid diagnosis is possible by detection of


Y.pestis F1 antigen by Immunofluorescence

‡ PCR test http://www.cdc.gov/ncidod/dvbid/plague/p4.htm

‡ 4 fold increase in antibody titres against F1 antigen


(by PHA tests)

‡ Isolation of the bacteria by culture and phage lysis.


ague 
ague  rea me
‡ Isolation :-
:-
± Patients Isolation for the first 48 hours after the initiation of
treatment.
± Patients with pneumonia must be isolated at least 4 days of
antibiotic therapy.
‡ Antibiotic Therapy:-
Therapy:-
± Streptomycin (drug of choice)
choice)--15
15--30 mg/kg IM bid x 10 days
± Gentamicin - 2 mg/kg IV then 1.0-
1.0-1.5 mg/kg q8h or 5 mg/kg IV
q24h x 10 days
± Doxycycline - 200 mg IV then 100 mg bid x 10-
10-14 days
± Ciprofloxacin - 400 mg IV q12h x 10 days
± Chloramphenicol
Chloramphenicol-- 25 mg/kg IV q6h (Max. 4 Gm/day)
Avoid in children < 2 year old
‡ Avoid streptomycin in pregnant women
reve  a  r
‡ Two things that could limit the spread of disease:-
disease:-
1. Epidemic plague is best prevented by controlling rat population
in rural and urban areas.
2. Close surveillance of human plague associated with plague in
rodents and use of effective insecticide for controlling rodents
flea.

‡ Some other measures taken to control plague are:-


are:-
1. Prophylactic antibiotic therapy as recommended by CDC for
people who have been exposed to to--
‡ Plague outbreak/flea bites
‡ Handled infected animal
‡ Close contact with plague case
÷ont«
Preferred post
post--exposure prophylaxis:
‡ Doxycycline 100 mg PO BID
‡ Ciprofloxacin 500 mg PO BID
‡ Duration of prophylaxis: 7 days
2. Plague Vaccine
± Live and killed vaccine developed
Killed vaccine prevents bubonic plague
‡ Primary vaccination: 0, 1-
1-3, & 5-
5-6 months
‡ Boosters: 12, 18, & 24 mo., then every 1-
1-2 years
Vaccination is of limited use and is ineffective against
pneumonic form of plague.


3. Environmental sanitation
‡ Removing food sources used by rodents.
‡ Rodents proofing homes, buildings.

‡ Eliminate rodent habitat around home


‡ Applying chemicals to kill flea and rodents.

4. Treatment pets
‡ Such as dogs and cats for proper flea control.
5. Public health education
‡ Risks, transmission, prevention.


6Personal
Personal protection

Surgical mask, gloves, eye protection, gowns,


and goggles should be worn at all times

7. Safe disposal of the bodies of the persons who have died due to
plague

8. Report of rat fall / cases of fever with painful lymphadenitis


Immediately
To -
‡ State health authorities
‡ NICD, Delhi
‡ Plague Surveillance Unit of NICD, Bangalore
Vaccines

‡ The killed-
killed-whole
whole--cell vaccine did not protect against
primary pneumonic plague.

‡ The live vaccines were ill


ill--defined and retained
enough virulence to be unsuitable for current use.

‡ A subunit vaccine protects mice against respiratory


infection with O is
is in clinical trials.

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