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Plague

• The first pandemic was believed to have started in Africa and killed 100 million people over a span of 60 years. plague killed approximately one fourth of Europe's population.

• The pandemic that began in China in the 1860s spread to Hong Kong in the 1890s and was subsequently spread by rats transported on ships to Africa, Asia, California, and port cities of South America.

Background .

Background

• In the early twentieth century, plague epidemics accounted for about 10 million deaths in India.

• Plague is worldwide in distribution, with most of the human cases reported from developing countries.

Epidemiology

• A vector is an organism that does not cause disease itself but that transmits infection by conveying pathogens from one host to another,[1] serving as a route of transmission.

• Natural reservoir, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal.

Causative organism.

• Non motile, non–spore-forming, pleomorphic, gram-negative cocco-bacillus.

• The bacteria elaborate a lipopolysaccharide endotoxin, coagulase, and a fibrinolysin, which are the principal factors in the pathogenesis of this disease.

Yersinia pestis :

Yersinia pestis : Yesinia is named in

honor of Alexander Yersin, who successfully isolated the bacteria in 1894 during the pandemic that began in China in the 1860s.

Reservoirs :

• urban rats :• are the most important

reservoirs for the plague bacillus,

• but field mice, cats, camels, chipmunks, prairie dogs, rabbits, and squirrels can be important animal reservoirs as well.

vector for transmission .

• It is the rat flea, which is he most important vector for transmission of plague .

• Ticks and human lice have been identified

Xenopsylla cheopis.

Pathophysiology • When a rat flea ingests a

blood meal from an animal infected with Y pestis, the coagulase of the bacteria causes the blood to clot. The bacilli multiply in the blood clot,

• the flea inoculates thousands of these bacilli into a host's skin during subsequent blood meals.

• The bacilli migrate to the regional lymph nodes, are phagocytosed by the polymorphonuclear cells and mononuclear phagocytes, and multiply intracellularly.

Pathophysiology

•Involved lymph nodes show dense concentrations of plague bacilli,

• destruction of the normal architecture, and medullary necrosis. With subsequent lysis of the phagocytes,

• bacteremia can occur and may lead to invasion of distant organs in the absence of

specific therapy .

Clinical

• History :

• Travel to endemic areas.

• history of a flea bite,

• close contact with a potential host,

• exposure to dead rodents or rabbits should heighten consideration of a plague diagnosis.

History :Bubonic plague

• Patients most commonly present with this form of plague.

• The incubation period varies but usually lasts 2-6 days.

• Patients have a sudden onset of high fever, chills, and headache.

• Patients also experience body aches, extreme exhaustion, weakness, abdominal pain, and/or diarrhea.

• Painful, swollen lymph glands (buboes) arise, usually in the groin, axilla, or neck.

History. Meningeal plague

• Fever, headache, and nuchal rigidity

• Buboes are common with meningeal plague.

• Axillary buboes are associated with an increased incidence of the meningeal form.

History. Pharyngeal plague

• Pharyngeal plague results from ingestion of the plague bacilli.

• Patients experience sore throat, fever, and painful cervical lymph nodes.

History. Pneumonic plague

• Pneumonic plague is highly contagious and transmitted by aerosol droplets.

• Patients have an abrupt onset of fever and chills, accompanied by cough, chest pain, dyspnea, purulent sputum, or hemoptysis.

• Buboes may or may not appear in pneumonic plague.

History. Septicemic plague

• Septicemic plague is observed in elderly patients and causes a rapid onset of symptoms.

• Patients experience nausea, vomiting, abdominal pain, and diarrhea. (Diarrhea may be the predominant symptom.)

• Patients exhibit a toxic appearance and soon become moribund.

• Buboes are not observed with septicemic plague.• This form of plague is associated with a high

mortality rate.

Physical :Bubonic plague

• Vesicles may be observed at the site of the infected flea bite.

• With advanced disease pustules, carbuncles, or papules may be observed in areas of the skin drained by the involved lymph nodes.

• A generalized papular rash of the hands and feet may be observed.

Physical :Bubonic plague

• Buboes are unilateral, oval, extremely tender lymph nodes and can vary from 2-10 cm in size. Femoral lymph nodes are most commonly involved.

• Hepatomegaly and splenomegaly often occur, causing tenderness.

Physical

• Pharyngeal plague :

• causes pharyngeal erythema and painful and tender anterior cervical nodes.

• Pneumonic plague :

• causes fever, lymphadenopathy, productive sputum, or hemoptysis.

Physical• Septicemic plague• toxic appearance tachycardia,

tachypnea, and hypotension. Hypothermia is common.

• Generalized purpura may be observed and can progress to necrosis and gangrene of the distal extremities.

• No evidence of lymphadenitis or bubo formation is apparent. Patients may die from a high level of bacteremia.

Septicemic plague

•necrosis and

gangrene of the distal

extremities.

Risk factors • Flea bite.• Contact with a patient or a potential host.• Contact with sick animals or rodents.• Residing in endemic areas of plague (eg,

southwestern United States).• Presence of a food source for rodents in the

immediate vicinity of the home.• Camping, hiking, hunting, or fishing.• Occupational exposure (eg, researchers,

veterinarians)• Direct handling or inhalation of contaminated

tissues or tissue fluids.

Differential Diagnoses • Acute Renal Failure

Pharyngitis, BacterialAnthraxPneumonia, BacterialBrucellosisCatscratch DiseaseRocky Mountain Spotted FeverCellulitisSepsis, BacterialChancroidSeptic ShockDengue Fever

• SyphilisDisseminated Intravascular CoagulationLymphogranuloma Venereum (LGV)

•TularemiaLymphoma, B-CellTyphusMalaria

Laboratory Studies

• Leucocytosis with a predominance of neutrophils is observed, Leukemoid reactions may be observed, more commonly in children.

• Peripheral blood smear shows toxic granulations and Dohle bodies.

• Thrombocytopenia is common, and levels of fibrin degradation products may be elevated.

• Serum transaminase and bilirubin levels may be elevated.

• Proteinuria may be present, and renal function test findings may be abnormal.

• Hypoglycemia may be observed.

Laboratory Studies

• Blood culture results are often positive for Y pestis in patients with bubonic plague and septicemic plague. Y pestis may be observed on a peripheral blood smear.

• Lymph node aspirates often demonstrate Y pestis. In patients with pharyngeal plague, Y pestis is cultured from throat swabs.

• Cerebrospinal fluid (CSF) analysis in meningeal plague may show pleocytosis with a predominance of polymorphonuclear leukocytes. Gram stain of CSF may show plague bacilli. Limulus test of CSF demonstrates the presence of endotoxin.

• Gram stain of sputum often reveals Y pestis.

Imaging Studies

• On chest x-ray films, patchy infiltrates, consolidation, or a persistent cavity is observed in patients with pneumonic plague.

• ECG reveals sinus tachycardia and ST-T changes.

• Obtain a CT scan of the head in a patient with altered mental status.

• Nuclear imaging may help in localizing areas of lymphadenitis and meningeal inflammation.

Other Tests

• Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis.

• A passive hemagglutination test (performed on serum from a patient in acute or convalescent stages) with a 4-fold or greater increase in titer suggests plague infection.

Procedures

• Aspiration of lymph node (bubo)– Inject 1 mL of sterile saline into the bubo with a 20-gauge

needle; after withdrawing several times, aspirate the fluid. Gram stain of the aspirate reveals gram-negative coccobacilli and polymorphonuclear leucocytes.

– Wayson stain of the aspirate shows plague bacilli as light-blue bacilli with dark-blue polar bodies.

– Examination of the aspirate of the fluid from the inguinal lymph nodes shows a characteristic bipolar appearance that resembles a closed safety pin.

• Lumbar puncture for CSF analysis

Treatment

• Medical Care :• Precautions.

– Place all patients thought to have plague and signs of pneumonia in strict respiratory isolation for 48-72 hours after starting antibiotic therapy.

– Report patients thought to have plague to the local health department and to the World Health Organization.

– Alert laboratory personnel to the possibility of the diagnosis of plague. All fluid specimens must be handled with gloves and mask to prevent aerosolization of the infected fluids.

Treatment

• Medical Care :• Supportive therapy

– Hemodynamic monitoring and ventilatory support are performed as appropriate.

– Intravenous fluids, epinephrine, and dopamine are necessary for correction of dehydration and hypotension.

Treatment.

• Surgical Care• Enlarging or fluctuant buboes require

incision and drainage.• Consultations• Infectious disease specialists• Pulmonary and critical care specialists• General surgeons• Neurologists

Medication :

• Streptomycin sulfate :• is the preferred drug of choice to treat

plague.• Dosing:• 30 mg/kg/day (up to a total of 2 g/day) in

divided doses given IM, for a full course of 10 days of therapy or until 3 days after the temperature has returned to normal .

Medication :

• Doxycycline:• Inhibits protein synthesis and thus

bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

• Dosing

• Adult 100 mg PO/IV q12h• Pediatric• <8 years: Not recommended

>8 years: 2-5 mg/kg/d PO/IV qd or divided bid; not to exceed 200 mg/d

Medication :

• Chloramphenicol :• Binds to 50S bacterial ribosomal subunits

and inhibits bacterial growth by inhibiting protein synthesis. Effective against gram-negative and gram-positive bacteria.

• Dosing• Adult• 500 mg PO/IV q6h• Pediatric• 50-75 mg/kg/d PO/IV divided q6h

Medication :

• Aminoglycoside antibiotic recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.

• Gentamicin :• Dosing• Adult• 2 mg/kg IV loading dose with normal renal

function; then, 1.7 mg/kg IV q8h for 10 d.

Medication :

Fluoroquinolones :

such as ciprofloxacin, have been shown to have good effect against Y. pestis in both in vitro and animal studies. Ciprofloxacin is bacteriocidal and has broad spectrum activity against most Gram-negative aerobic bacteria,

Medication :

• Sulfonamides :

• The combination drug trimethoprim-sulfamethoxazole has been used both in treatment and prevention of plague.

Prevention .

• Prophylactic antibiotic therapy.• The CDC recommends administering

prophylactic antibiotics for a short time to :• people who have been exposed to the bites

of potentially infected rodent fleas during a plague outbreak.

• persons who have handled an animal known to be infected with the plague bacterium.

• persons who have had close exposure to a person or an animal thought to have pneumonic plague.

Prevention .

• Preferred antibiotics for prophylaxis against plague are :

• Doxycycline 100 mg PO q12h for 14-21 days (for patients > 8 y) and trimethoprim 160 mg/ sulfamethoxazole 800 mg PO q12h for 14-21 days.

Prevention .

• Plague vaccine• Vaccination is of limited use and is not

mandatory for entry into any country.• The vaccine is not effective against the

pneumonic form of plague.• Plague vaccine is recommended for field

workers in areas endemic for plague and for scientists and laboratory personnel who routinely work with the plague bacterium.

Prevention .

• Environmental sanitation• Remove food sources used by rodents.

• Make homes, buildings, or warehouses "rodent-proof."

• Trained professionals should apply chemicals to kill fleas and rodents.

• Trained professionals should fumigate cargo areas of ships and docks.

Complications.

• Acute respiratory distress syndrome.

• Chronic lymphedema from lymphatic scarring.

• Disseminated intravascular coagulation

• Septic shock.

• Super infections of the buboes by Staphylococcus and Pseudomonas

species

Prognosis

• Untreated patients with plague have a mortality rate of approximately 50%; however, with appropriate therapy, the mortality rate drops to approximately 5%.

• Wayson stain showing the characteristic "safety pin" appearance of Yersinia pestis, the plague bacillus

• Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis, the plague bacillus.

• Histopathology of lung in fatal human plague–fibrinopurulent pneumonia.

• Histopathology of lung showing pneumonia with many Yersinia pestis organisms (the plague bacillus) on a Giemsa stain.

• Histopathology of spleen in fatal human plague

• Histopathology of lymph node showing medullary necrosis and Yersinia pestis, the plague bacillus

• Histopathology of liver in fatal human plague .

• Focal hemorrhages in islet of Langerhans in fatal human plague.

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