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PLAGUE
– Acute febrile zoonotic disease caused by infection by
Yersinia pestis
– Although human cases are infrequent and curable by
antibiotics, plague remains one of the most virulent &
lethal infections known
– Plague bacteria occurs in widely scattered foci in Asia,
Africa and the Americas where its usual hosts are wild &
peridomestic animals
– Transmit by flea bite and less commonly by direct contact
with infected animal tissues or by airborne droplets
– Principle Clinical Forms
○ Bubonic
○ Septicemic
○ Pneumonic
– Most cases are sporadic although the potential for
epidemic spread still exists in some countries
ETIOLOGY
• Yersinia pestis is Gram –ve coccobacillus
• Family : Enterobacteriaceae
• Microaerophilic
• Non-motile
• Non-spore forming
• Oxidase & urease –ve
• Biochemically unreactive
• Grows well on routinely used microbiologic media (e.g. :
sheep blood agar, brain heart infusion broth & MacConkey
agar
• Multiply w/in wide range of temp from below 0-45⁰C n pH
varies from 5-9.6
• Optimal growth : 28 C
• When incubated on agar plates ,colonies of pin-point size
grows at 24hours and 1-2mm at 48h
• Colonies are grey-white with irregular surfaces
• They have hammered-metal appearance when viewed
microscopically
• When stained with polychromatic stain, YP exhibits a
characteristic bipolar appearance often resembling closed
safety pins
• Bacteria is non-enveloped but when grown at 30 C,
produces immunogenic cell-surface envelope glycoprotein
Fraction 1
EPIDEMIOLOGY
 Dt its pandemic history, plague remains one of the 3
quarantinable diseases
 YP is maintained in enzootic cycles involving relatively
resistant wild rodents & their fleas in mostly removed lightly
populated areas of Asia, Africa & the Americas and in limited
rural foci in extreme South East Europe near the Caspian
Sea
 Humans & other non-rodent mammals are incidental hosts
 Enzootic transmission places humans at low risk
 Epizootic transmission involve susceptible rodents & flea,
resulting in local or even widespread in population of
susceptible rodents and poses more serious threat to
humans than enzootic transmission
 YP can multiply to enormous numbers in the foregut
(proventriculus) of flea, resulting in bolus of organism &
clotted blood that block passage of subsequent blood meals
 Regurgitation by blocked flea while it feeds facilitate
transmission of plague bacilli to new host
 Person to person transmission of plague during & since the
3rd Pandemic has occurred sporadically & has been limited
to clusters of close contact of Pneumonic Plague patient
(household members & caregivers)
 Plague can be transmitted during the skinning/handling of
carcasses of wild animals, such as
○ Rabbits
○ Hares
○ Coyotes
○ Wild cats
 Such direct inoculation of mammal-adapted organism
associated with 1° septicemia & high mortality rate
 Oropharyngeal plague results due to ingestion of
undercooked contaminated meat or manual transfer of
infected fluids to the mouth during handling of infected
animal tissue
PATHOGENESIS
– YP is most invasive bacteria known
– Mechanism is not completely understood but oth
chromosome and plasmid encodes are involved
– Free plasmids encode for a variety of known virulence
factors
○ F1 envelope Ag which confers bacteria
resistance
○ Murine exotoxin
○ V Ag – essential for virulence, may
immunecompromise host by blocking synthesis
of IFN, TNF
○ Pesticin – bactericidal protein
○ Protease – cn activate plasminogen & degrade
serum complement, plays a role in
dissemination of YP from peripheral sites of
infection
○ Coagulase
○ Fibrinolysis
– YP organism inoculated through the skin or mucous
membrane usually invade cutaneous lymphatic vessels &
reach regional LN although direct blood stream inoculation
may take place
– Mononuclear phagocytes which can phagocytose YP
organism w/o destroying them may play a role in
dissemination of infection to distant sites
– Plague can involve almost any organ and untreated
plague generally results in widespread & massive tissue
destruction
– In early stages infected LN or buboes are characterized
by edema & congestion without inflammatory infiltrates or
apparent vascular injury
– Fully developed buboes contain huge numbers of infected
plague organism & show distorted or obliterated LN
architecture w/o vascular destruction & hemorrhage,
serosanguineous effusion, necrosis & mild neutrophilic
infiltration
– At this stage, effusion often involve perinodal tissues
– If several adjacent LN are involved, a boggy edematous
mass can result
– 1° septicemic plague result from direct inoculation of
infected fluids/tissues or from an infected flea bite in the
apparent absence of bubo
– 2° SP occurs when lymphatic and other host defenses are
breached & plague bacillus multiply in blood stream
– In either primary or secondary SP, renal glomeruli often
have fibrin thrombi, multifocal necrosis of liver & diffuse
hemorrhagic splenic necrosis
– PP arises from 1° esposure to infected resp droplets from
a person or cat with resp plague or 2° through
hematogenous spread in pt with BP or SP.
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– PP result from accidental inhalation of YP in the lab  Develops most rapidly

– Primary PP generally begins as lobular process and then  Most frequently fatal
extends by confluence becoming lobar & multilobar  IP : 1- 4 days
– Plague organism mostly in alveoli  Onset is sudden
– Secondary PP begins more diffusedly with organism more ○ Chills
numerous in intersititium. In untreated cases, PP results in ○ Fever
diffuse hemorrhage, necrosis & scant neutrophilic ○ HA
infiltration ○ Myalgia
○ Weakness
CLINICAL PICTURE
○ Dizziness
 Pulmonary symptoms 2nd day of illness, mb
Bubonic Plague (BP) associated with
○ Cough
○ Sputum production hemoptysis, ↑
 Bubonic plague is the most common respiratory distress,
 IP = 2-6 days ○ CP
cardiopulmonary
 Typically patient experience ○ Tachypnea insufficiency, & circ
○ Chills ○ Dyspnea collapse
○ Fever (T rise within hours to38 C or >)
○ Myalgia
○ Athralgia  1° PP, the sputum is most often watery or blood-tinged,
○ HA may become frankly bloody
○ Weakness  Pulmonary symptoms  may indicate involvement of 1
 Within 24hours, patient notices tenderness & pain in 1 or lobe in early stage or rapidly developing segmental
more regional LN proximal to site of inoculation consolidation before bronchopneumonia spread to other
 Because fleas often bite the legs, femoral & inguinal LN lobes of same/opposite lung
are more commonly involved.  2° PP manifests 1st diffused interstitial pneumonitis in
 Then axillar LN and cervical LN which sputum production is scant
 Enlarged bubo become more tender and painful  Since sputum > likely to be inspissated & tenacious in
 There is guarding during palpation and limits of character, than the sputum in 1° pneumonia
movement, pressure & stretch around bubo  Rare cases
 Tissue become edematous ○ Meningitis
 Overlying skin is  Complication of BP
○ Erythematous  During 1st- 2nd weeks of antibiotic
○ Warm treatment for BP, affected patient
○ Tense present with fever, HA, meningismus
 Inspection of skin surrounding or distal to bubo reveal  & pleocytosis
flea bite marked by pustule, ulcer ○ Pharyngitis
 If present of ulcer = cutaneous Bubonic Plague  Fever, sore throat, cervical
 Treated in uncomplicated state with appropriate lymphadenitis & indistinguishable
antibiotics, BP responds quickly with T and other Sx ↓ clinically from other etiology
after 2-5days
 Bubos enlarged and tender for 1 week or more after LAB DIAGNOSIS
initiation of treatment and can become fluctuant
– When diagnosis of plague is considered, closed
 If untreated, disease results in 2° SP with DIC & organ
failure communication between the clinicians, laboratory and
qualified reference lab is essential
Septicemic Plague (SP) – When Plague is suspected, specimen should be taken
promptly
 Progressive bacterial infection – CXR should be obtained
 1° septicemia develop w/o regional lymphadenitis which – Specific anti-microbial treatment should be started
makes diagnosis difficult, sometimes only proven by pending confirmation
positive blood culture – Appropriate diagnosis specimen for smear & culture
 Patient often present with GI symptoms include
○ N+V ○ Saturated or heparinized whole blood
○ Diarrhea ○ Bubo expirate
○ Abdominal pain ○ Sputum samples
○ CSF
 Petechiae, ecchymoses & bleeding from puncture wounds
– Each specimen should be examined immediately with
as well as gangrene of upper parts are indicative of DIC
Giemsa & Wayson stains and at least one with Gram
Syndrome
staining
 Refractory HPT
– Smear should also be submitted for direct
 Renal shutdown
immunofluorescence study
 Shock symptoms are pre-terminal events
– Acute phase serum specimen should be tested for Ab to
YP
– Convalescent phase serum should also be tested
– When pt dies & plague is suspected, appropriate
Pneumonic Plague (PP)
specimens should be sent for fluorescent Ab study (bubo,
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all solid organs including liver, spleen, lung and also bone – Anti-microbial therapy continued for 10days or for at least
marrow) _______ has been afebrile & made clinical recovery
– If culture of these specimen are to be attempted, must – Pt with initial IV therapy may be changed to PO upon
sent to the lab either fresh specimen or frozen on dry ice clinical improvement
– Buboes may persist for days to weeks, it requires surgical
TREATMENT drainage
– Abscessed nodes can cause recurrent fever in patient
– Drug of choice for treatment is who have apparently recovered
– Viable YP organism have been isolated from affected
Gentamicin 5mg/kg IM/IV 1x/daily
nodes 1-2 weeks after clinical recovery
2mg/kg loading dose then 1.75mg/kg IM/IV tid

Other drugs

Doxycyline 100mg IV bid

200 mg IV mid

Ciprofloxacin 400mg IV bid

Chloramphenicol 25mg/kg IV qid

- indicated for Plague meningitis, pleuritis, ophtalmitis, myocarditis dt
its superior tissue penetration
- alone or with Streptomycin

Treatment of Patients with Pneumonic Plague in the Contained and Mass Casualty Settings and for Post-exposure prophylaxis

Patient Category Recommended Therapy

Contained Casualty Setting

Adults Preferred choices

– Streptomycin 1g IM bid
– Gentamycin 5mg/kg IM or IV once daily or 2mg/kg loading
dose followed by 1.7mg/kg IM or IV 3 times daily

Alternative Choices

– Doxycycline 100mg IV twice daily or 200mg IV once daily

– Ciprofloxacin 400mg IV twice daily
– Chloramphenicol 25mg/kg IV 4 times a day

Children Preferred choices

– Streptomycin15mg/kg IM twice daily (maximum daily dose

2g)
– Gentamicin 2.5 mg/kg IM or IV 3 times daily

Alternative choices

– Doxycycline
If ≥ 45kg, give adult dosage
If <45kg give 2.2mg/kg IV twice daily (max 200mg/d)
– Ciprofloxacin 15mg/kg IV twice daily
– Chloramphenicol 25mg/kg IV 4 times daily
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Pregnant women Preferred choices

– Gentamycin 5mg/kg IM or IV once daily or 2mg/kg loading

dose followed by 1.7mg/kg IM or IV 3 times daily

Alternative Choices

– Doxycycline 100mg IV twice daily or 200mg IV once daily

– Ciprofloxacin 400mg IV twice daily
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