PLAGUE

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PLAGUE
CASE DEFINITION

Clinical case description:
Disease characterized by rapid onset of fever, chills, headache, severe malaise, prostration
with
• Bubonic form: extreme painful swelling of lymph nodes (buboes)
• Pneumonic form: cough with blood-stained sputum, chest pain, difficult breathing
• Septicemia form: toxic changes in the patient.

Laboratory criteria for diagnosis:
• Giemsa smear should be positive
• Direct fluorescent antibody testing of smears (for anti-F1 antibody)
• PCR test
• 4 fold increase in antibody titres against F1 antigen (by PHA tests)
• Isolation of the bacteria by culture and phage lysis

Case classification
Suspect case: A case that meets the clinical case definition.
Probable case: A suspect case with
• Y.pestis F1 antigen detected in clinical materials by direct fluorescent
antibody testing or by some other standardized antigen detection method,
or
• Isolate from a clinical specimen demonstrates biochemical reactions
consistent with Y.pestis or PCR positivity, or
• A single serum specimen is found positive for diagnostic levels of antibodies
to Y.pestis F1 antigen, not explainable on the basis of prior infection or
immunization
• Epidemiological link with a confirmed case.
Confirmed case: a suspected or probable case that is lab-confirmed
• Isolate identified as Y. pestis by phage lysis or cultures; or
• A significant (4-fold) change in antibody titre to the F1 antigen in paired
serum specimens.

EPIDEMIOLOGY (see Fig 1)
Agent: The agent is a gram-negative cocco-bacilli – Yersinia pestis; which has a bipolar
(safety pin) appearance on aniline staining. Sunlight, high temperatures and desiccation
have a destructive effect, and ordinary disinfectants such as Lysol and preparations
containing chlorine kill it within 1 to 10 minutes.

Reservoir: Wild rodents are the natural reservoirs. In India the reservoirs are mainly the
wild rats – Bandicoota bengalensis, Tatera indica etc. They are susceptible to infection but

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not the disease. Others like wild squirrels, rabbits and wild carnivores may also be a
source of infection. Plague remains in the wild due to various factors – e.g. rat – flea –rat
cycle; survival of fleas in rat burrows for long periods of time; survival of plague bacilli in
the rat burrows, eating of infected rodents by carnivore, etc.

Fig 1 – Epidemiology of plague

DOMESTIC CYCLE SYLVATIC CYCLE

Wild
Bioterrorism Uninfected rodent
host (man)

Flea Flea
Domestic / Peri-
domestic rodent
Wild
Handling infected rodent
tissues
Infected host
(man)
Droplet
infection

Diseased host

Pneumonic Bubonic Septicemic
plague plague plague

Recovery Death

7
Vector: The main vector is the Oriental rat flea – Xenopsylla cheopis

Transmission: 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

Host: All ages and both sexes are susceptible. People with occupations like hunting and
grazing are more susceptible. There is no natural immunity and one can contract the
disease even after previous illness.

Environment: Plague in North India is seasonal – higher chances in the winter. In the
south, there are no definite seasonal trends. Any environmental condition that disturbs the
rodent’s natural environment e.g. floods and causes the overlap between the wild rodents
and the peridomestic rodents is a potential source for plague in humans.

Incubation period: For Bubonic and septicemic plague – 2 to 6 days; for pneumonic
plague – 1 to 3 days. The person is not infective during this period.

SIGNS AND SYMPTOMS:
Bubonic plague: Fever, chills, headache, prostration and painful lymphadenitis (inguinal
nodes are involved in 90% of the cases). The nodes swollen, inflamed and may
suppurate. Specific treatment leads to resolution of the fever and general symptoms but
the bubo remains painful and tender for weeks. If untreated, 50 – 60% die.
Pneumonic plague: It may be primary or secondary. In primary, the host acquires it from
another patient with pneumonic plague, while in the secondary form, the host acquires it
secondary to a bubonic / septicemic plague. The symptoms in primary plague are onset of
fever, chills, headache, prostration and cough 1 to 3 days after exposure to a case of
pneumonic plague. Increasing chest pain, dyspnoea and hemoptysis become prominent
as the disease rapidly progresses. In secondary pneumonic plague, the patient already
has symptoms of either bubonic plague or septicemic plague and is already moribund
before developing the signs and symptoms. The disease is fatal if the patients with
pneumonic plague are untreated in the initial 18 – 24 hours.
Common Symptoms/Syndromes of Human Plague

Primary
List of Symptoms Bubonic Septicaemic
Pneumonic
Sudden onset + + +
High Fever + + +
Bubo + + - -
Cough with blood - - +
stained sputum

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Septicemic plague: This is a rapidly progressive infection resulting in endotoxic shock,
DIC, multi organ failure, ARDS etc. It leads to metastatic infection of other organ systems.
Others: Other forms of plague are pharyngeal plague (symptomatic or asymptomatic
colonization of the pharynx) and Meningeal plague (fever, headache, stiff neck, delirium
and coma).

DIFFERENTIAL DIAGNOSIS:
Bubonic plague: Strep / Staph lymphadenitis, lymphatic filariasis, infectious
mononucleosis etc
Septicemic plague: Any gram-negative septicemia
Pneumonic plague: Any pneumonia

LABORATORY SPECIMENS
When plague is suspected, clinical specimens should be collected urgently, and specific
antimicrobial treatment begun without waiting for the laboratory report. The specimen to
be collected depends on the type of plague. The details are given below. All specimens
should be collected under aseptic conditions, put in sterile containers and transported by
maintaining cold chain. Cary Blair media can be used as a transport media for any
material that is to be cultured.

A brief summary of specimens required is shown in table
Clinical Presentation Specimen
Bubonic Bubo fluid / aspirate
Blood
Serum
Pneumonic Bronchial/tracheal washing
Sputum
Blood
Serum
Septicaemic Blood
Post-mortem Biopsy from
Lymph nodes
Lungs
Bone marrow

Precautions in Handling Specimens
As these specimens are known or thought likely to contain infectious substances, the
following precautions should be applied:
• Strict aseptic technique (gowns, gloves, masks)
• Wash hands before and after the collection of material
• Place the specimen aseptically in an appropriate sterile container
• Tightly close the container
• Label and date the container
All handling specimens should be put on chemoprophylaxis.
Packaging/Transportation of Specimen

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In accordance with currently accepted biosafety norms, Y.pestis is listed under Biosafety 2
level. The details are given at the end of this chapter. Samples should be sent to the
following laboratory with prior intimation.
NICD
22, Shamnath Marg,
New Delhi – 110054
Tel: 011 3913148 / 3971272 / 3971344
Fax: 011 3922677 / 3946893
Email: dirnicd@bol.net.in; dirnicd@del3.vsnl.net.in

As plague is a public health emergency, the specimen should be sent by air to NICD.
Either a special messenger should carry the specimen or it should be sent by air cargo
after informing NICD officials about the details so that there is somebody at Delhi to
receive the same.

CASE MANAGEMENT:
Inj Streptomicin (30 mg/kg/day - up to a total of 2 g/day) im Q12H for 10 days.

or
Cap. Chloramphenicol (50mg/kg/day) Q6H for 10 days.

or
Cap Tetracycline (50mg / kg / day) Q6H for 10 days

or
Cap Doxycycline 200mg / day Q12H for 10 days.

or
Tab. Cotrimoxazole (10mg/kg/day) Q12H for 10 days

Penicillins, Cephalosporins, Macrolides - These classes of antibiotics should not be
used for the treatment of plague.

Treatment of plague during pregnancy and in children
The preferred antibiotic for treating plague in pregnancy is
Gentamycin given intravenously (IV) or intramuscularly (IM).

Other supportive measures maybe instituted to the hospitalized patients.
Adequate isolation measures should be instituted. In the event of pneumonic or
septicaemic plague, intravenous antibiotics should be given.

PREVENTION
Chemoprophylaxis
• To those people who are entering an area that has a known outbreak of plague or
those health care personnel who would be handling plague material.
• To those who have come in contact with plague patients, especially pneumonic
plague.

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• Ideally the drugs for chemoprophylaxis should be given for 5 – 7 days from date of
last exposure
• The drugs to be used for chemoprophylaxis are given below. Doxycycline has been
the drug of choice for chemoprophylaxis.

Immunisation during an outbreak has negligible value as the bacteria spreads very fast.
Moreover, it is not fully protective, especially in pneumonic plague and finally the chances
of adverse reactions are high.

Anti flea measures – personal protection with repellants, dusting with Malathion (5%) or
synthetic pyrethroids in rat burrows / houses (junction of floor and wall).

Anti rodent measures – only during inter epidemic period. Sanitation and proper disposal
of garbage, poisons (anticoagulants, aluminium phosphide, fumigants)

Plague Prophylaxis Guidelines
Drug Dosage Interval (hrs) Route of
Administration
Tetracycline
Adults 1-2g/day 6 PO
Children 9 25-50mg/kg/day 6 PO
years
Doxycycline
Adults 200mg/day 12 PO
Children 9 200mg/day 12 PO
years
Sulfamethosazole/
Trimethoprim
Adults 1.6g/day* 12 PO
Children 2 40mg/kg/day* 12 PO
years

SURVEILLANCE
Plague surveillance is mainly laboratory based active surveillance. The various
components of surveillance are:
• Rodent surveillance
• Flea surveillance
• Sero surveillance among wild rodents and dogs
• Clinical surveillance

Details of this are given in the WHO Plague manual and are usually carried out by
specialized plague surveillance units. What is important is to recognize the trigger events
that are the precursors of a potential outbreak. These trigger events are:
• Rat fall – more than one dead rat in a house, or more than one house with dead
rats1

1
Where it has been ascertained that the deaths among the rats have not been due to poisoning.

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• Flea index more than one
• Positive serology in rodents / canines
• A suspected case of human plague.

If any one of the trigger events is positive, then a potential outbreak should be suspected
and appropriate authorities, including NICD should be informed immediately.

OUTBREAK INVESTIGATION AND MANAGEMENT
In the event of an outbreak, it should be considered as a Public Health Emergency and a
clear cut drill should be followed as given in Annex 2 under the guidance of an expert
team from the State / NICD. The main steps are:

• Verification of the outbreak immediately
• Notification to the higher authorities
• Institution of containment measures
• Confirmation of the outbreak

To summarize
• Report suspected case to the next level and NICD. Also verify the case diagnosis by a
clinician.
• Collect clinical samples (before starting antibiotics) for confirming the outbreak. Send
the material to the state as per guidelines given above. Collect also samples of rodents
and fleas.
• Do an epidemiological investigation
o Active search for cases of plague – identify all cases by age, sex and history of
contact or exposure. Also date of onset of illness and complications if any. Get
the support of the community for this search.
o Draw the epidemic curve and understand the dynamics of the outbreak,
including the index case, the transmission and direction of spread and the
susceptible population.
o Analyse the data by time, place and person.
o Calculate the attack rate and the case fatality ratio.
• Simultaneously institute control mechanism
o Case management of individual suspect cases
o Hospitalise all suspect cases in isolation wards.
o Avoid transportation of suspect pneumonic plague in public vehicles.
o Institute standard precautions for bubonic / septicemic plague and droplet
precautions for pneumonic plague.
o Disinfection of all contaminated material

For patients with pneumonic plague, strict isolation with precautions against
airborne droplet spread is required (see…) until a period of at least 48 hours after
completion of appropriate antibiotic therapy (usually ten days + 48 hours) and there
is evidence of satisfactory clinical response

o Chemoprophylaxis to all contacts
o Minimise movement of people into and out of the village.

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o Anti flea measures especially in bubonic plague e.g. dusting of rodent burrows,
disinsectation of clothes, dwelling etc. Not important if the outbreak is due to
primary pneumonic plague.
o Anti rodent measures minimised to sanitation and rat proofing the houses.
Important in the case of bubonic plague outbreak. Not so with primary
pneumonic plague outbreak. DO NOT KILL RATS DURING AN EPIDEMIC.
o Educate the community about “dos and don’ts” – example is given below.
o Keep the higher authorities informed through daily updates and then a final
report at the end of the outbreak (20 days after last case)

CONCLUSIONS
Plague is a rare disease in our country and outbreaks occurs periodically. However, an
outbreak of plague has various implications, its high case fatality ratio attracts
considerable fear among the public; its epidemic potential is a health manager’s
nightmare and its economic implications makes it politically sensitive. And of late, it has
been considered as an agent for biological warfare.

Keeping in mind all these implications, an outbreak of plague has to be handled very
sensitively and vigorously.

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ANNEX 1
Packaging/Transportation of Specimen
In accordance with currently accepted biosafety norms, Y.pestis is listed under
Biosafety 2 level. Therefore, the regulations of the WHO as contained in its publication
(WHO/EMC/97.3) “Guidelines for the Safe Transport of Infectious Substances and
Diagnostic Specimens” for shipping dangerous good (should) apply when the specimens
are to be shipped via air transport either domestic or international.
The requirements, in brief, are:
• A watertight primary receptacle
• A watertight secondary receptacle
• An absorbent material, which must be placed between the primary receptacle and
the secondary packaging. The absorbing material must be adequate to absorb the
entire contents of all primary receptacles.
• Must be at least 100 mm in the smallest overall external dimension
• Itemized list of contents must be enclosed.
• Receptacles must withstand, without leakage, internal pressure difference of not
less than 95 kPa (0.09 bar, 13.8 lb/in2) and temperature range of –40oC to +55oC.
• Outside package must be marked with identification of the infectious substance,
volume of contents, name, and telephone number of shipper.

All materials should be double-packaged in crush-proof and leak-proof containers.
Infectious agents, serum or cultures vessels should be labelled with alcohol-resistant,
permanent ink marker as to the contents and dated. The materials should be sealed with
Para film or tape to prevent inadvertent leakage and then wrapped with several layers of
absorbent material. The absorbent-wrapped materials are placed in a leak-proof bag,
soaked with disinfectant (quaternary ammonium or phenolic solutions) and sealed. The
sealed bag is then placed in the first of two crush-proof containers, sealed and placed into
the second crush-proof container. Depending on the specimen and the destination, the
double container is sent in a sealed box with or without coolant.

Do not use wet ice for packaging because it melts and leaks. Cool packs (plastic bags
containing frozen foam/refrigerant) are acceptable but must be placed in the box so that,
upon thawing they do not permit movement of materials within the box. Containers must
be especially well sealed if they are being shipped under dry ice conditions. Dry ice
evaporates, thus when packing, this must be taken into consideration.

Important parts of shipping are the proper labelling of the container and the inclusion of
the paper work that identifies the specimen(s), the clinical history or the epidemiologic
information, the sender’s identification and address, the purpose of which the specimen is
sent and the import/export licenses if necessary. The outside of the container must be
labelled with all the proper identification and biohazard warnings. If shipping with dry
ice, the box must be identified with the correct label.

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ANNEX 2
OUTBREAK RESPONSE
Suspected case of plague
(bubonic / septicemic / pneumonic)

Immediate Verification by the MO
(based on history of exposure, clinical signs and symptoms)

Suspected plague

Immediate notification Immediate institution of
to District authorities containment measures

Notify State and 1. Send RRT 1. Case management –
National immediately for appropriate antibiotic for 10
authorities conducting days
immediately epidemiological / 2. Hospitalize all suspect cases
clinical / laboratory 3. Active surveillance for new
investigation cases
2. Activate Epidemic 4. Chemoprophylaxis to all
control committee contacts
3. Set up a control room. 5. Flea control and sanitation
4. Mobilize drugs, measures in the event of
vehicles, manpower, bubonic plague.
finances
5. Send lab specimens
to State / NICD

Lab reports

Positive Negative

• National authorities to Investigate further to find out
notify to WHO cause of outbreak
• Intensify containment
measures further
• IEC

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ANNEX 3
Hospital precautions
Standard patient-care precautions should be applied to management of all suspected
plague patients, and standard droplet precautions for those with suspect or presumptive
or confirmed pneumonic plague.

5.3 Standard Precautions
Use Standard Precautions for the equivalent, for the care of all suspect
plague patients.
A. Handwashing
(1) Wash hands after touching blood, body fluids, secretions, excretions, and
contaminated items, whether or not gloves are worn. Wash hands immediately
after gloves are removed, between patient contacts, and when otherwise
indicated to avoid transfer of microorganisms to other patients or
environments. It may be necessary to wash hands between tasks and
procedures on the same patient to prevent cross-contamination of different
body sites.
(2) Use a plain (non-antimicrobial) soap for routine hand washing.
(3) Use an antimicrobial agent or a waterless antiseptic agent for specific
circumstances (e.g., control of outbreaks or hyperendemic infections), as
defined by the infection control program.
B. Gloves
Wear gloves (clean, nonsterile gloves are adequate) when touching blood,
body fluids, secretions, excretions, and contaminated items. Put on clean
gloves just before touching mucous membranes and nonintact skin. Change
gloves between tasks and procedures on the same patient after contact with
material that may contain a high concentration of micro organisms. Remove
gloves promptly after use, before touching noncontaminated items and
environmental surfaces, and before going to another patient, and wash hands
immediately to avoid transfer of microorganisms to other patients or
environments.
C. Mask, Eye Protection, Face Shield

Wear a mask and eye protection or a face shield to protect mucous membranes
of the eyes, nose, and mouth during procedures and patient-care activities that
are likely to generate splashes or sprays of blood, body fluids, secretions, and
excretions.
D. Gown
Wear a gown (a clean, nonsterile gown is adequate) to protect skin and to
prevent soiling of clothing during procedures and patient-care activities that
are likely to generate splashes or sprays of blood, body fluids, secretions, or
excretions. Select a gown that is appropriate for the activity and amount of
fluid likely to be encountered. Remove a soiled gown as promptly as possible,
and wash hands to avoid transfer of microorganisms to other patients or

16
environments.
E. Patient-Care Equipment
Handle used patient-care equipment soiled with blood, body fluids, secretions,
and excretions in a manner that prevents skin and mucous membrane
exposures, contamination of clothing, and transfer of micro-organisms to other
patients and environments. Ensure that reusable equipment is not used for the
care of another patient until it has been cleaned and reprocessed appropriately.
Ensure that single-use items are discarded properly.
F. Environmental Control
Ensure that the hospital has adequate procedures for the routine care, cleaning,
and disinfection of environmental surfaces, beds, bedrails, bedside equipment,
and other frequently touched surfaces, and ensure that these procedures are
being followed.
G. Linen
Handle, transport, and process used linen soiled with blood, body fluids,
secretions, and excretions in a manner that prevents skin and mucous
membrane exposures and contamination of clothing, and that avoids transfer
of microorganisms to other patients and environments.
H. Occupational Health and Blood-borne Pathogens
(1) Take care to prevent injuries when using needles, scalpels, and other sharp
instruments or devices; when handling sharp instruments after procedures;
when cleaning used instruments; and when disposing of used needles. Never
recap used needles, or otherwise manipulate them using both hands, or use
any other technique that involves directing the point of a needle toward any
part of the body; rather, use either a one-handed "scoop" technique or a
mechanical device designed for holding the needle sheath. Do not remove
used needles from disposable syringes by hand, and do not bend, break, or
otherwise manipulate used needles by hand. Place used disposable syringes
and needles, scalpel blades, and other sharp items in appropriate puncture-
resistant containers, which are located as close as practical to the area in which
the items were used, and place reusable syringes and needles in a puncture-
resistant container for transport to the reprocessing area.
(2) Use mouthpieces, resuscitation bags, or other ventilation devices as an
alternative to mouth-to-mouth resuscitation methods in areas where the need
for resuscitation is predictable.
I. Patient Placement
Place a patient who contaminates the environment or who does not (or cannot
be expected to) assist in maintaining appropriate hygiene or environmental
control in a separate individual room. If a separate room is not available,
consult with infection control professionals regarding patient placement or
other alternatives.

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5.4 Droplet Precautions

In addition to Standard Precautions, use Droplet Precautions, or the
equivalent, for a pneumonic plague patient known or suspected to be infected
with micro organisms transmitted by droplets (large-particle droplets [larger
than 5 µm in size] that can be generated by the patient during coughing,
sneezing, talking, or the performance of procedures).
A. Patient Placement
Place the patient in an individual room. If an individual room is not available,
place the patients of the same cluster cohorts together in a room (same
symptoms, same date of onset) When a separate individual room is not
available and cohorting is not achievable, maintain spatial separation of at least
two (2) metres between the infected patient and other patients and visitors.
Special air handling and ventilation are not necessary, and the door may
remain open.
B. Mask
In addition to wearing a mask as outlined under Standard Precautions, wear a
mask when working within 2 metres of the patient. (Logistically, some
hospitals may want to implement the wearing of a mask to enter the room.)
C. Patient Transport
Restrict the movement and transport of the patient. If transport or
movement is necessary, minimize patient dispersal of droplets by masking the
patient.