(insert screaming now) The Plague (insert screaming now) Vaughn and Tess February 4, 2008

4 Flavours of The Plague Bubonic – Fever, buboes (very swollen, painful lymph nodes that can form abscesses), 50-60% mortality *Pneumonic – coughing, sputum, crackling, dyspnea; near 100% mortality within 2-4 days *Septicaemic – Fever, GI symptoms (vomitting, diarrhea, pain), purpura, petechiae in late stages; 75% mortality within a few days, quite rare Meningeal – Fever, same as meningitis; Very rare *Can be primary or secondary plague infection

Clinical Signs of Bubonic Plague Buboes – Painful, swollen lymph nodes (axillary, inguinal, femoral or cervical) - Can supparate. Bacteria migrate to lymph nodes, resist destruction by phagocytes and multiply rapidly leading to necrosis and hemorrhage

Disease course Incubation of 1-7 days Usually starts as bubonic plague, then bacteria spread via lymph nodes through blood (sepsis) Patients die of pneumonic plague, or septicaemic plague (multi-organ failure) Necrosis and petechiae characteristic of late stage disease.

Disease Source Yersinia pestis – rod shaped, gram neg. bacteria Most are killed by neutrophils, but a few are taken up by histiocytes which can not kill them. Re-synthesize their capsule resist phagocytosismultiply rapidly

Vectors Main vector – Oriental Rat Flea (Xenopsylla cheopsis) Stomach becomes blocked from abundance of bacteria. When the flea bites it’s next victim, the bacteria are regurgitated into the blood.

Reservoirs Many wild rodents Black rat (Rattus rattus) is the main culprit Lives in close proximity to humans (homes) “Rat-fall” is common omen of an epidemic Domesticated rodents and pets

Transmission Fleas live in nests of wild rodents Disturbance (war, flood etc) cause wild rodents to migrate to urban areas. Infected fleas jump from wild rodents to domesticated rodents, pets Humans Direct infection from animals possible Human-to-human transmission via respiratory droplet (pneumonic plague)

Diagnosis Y. pestis is easily recovered from: blood (septicaemic plague), aspirates of bulboes (bubonic plague), sputum (pneumatic plague) and differentiated in the lab Capsular fraction 1 antigen basis of serological tests Note: Can be confused with Y. psuedotuberculosis in labs with little or no experience in dealing with it.

Management Requires prompt antibiotic treatment. With pneumonic or septicemic plague, must be administered within 1 day of symptoms. Treatment: Use 1 antibiotic; Streptomycin preferred; gentamicin and tetracycline group also effective Course of treatment: at least 7-10 days Resistance: Only 1 case of multi-drug resistance found in Madagascar. When given early, reduces mortality to 5-14%

Prevention Formol-killed vaccine once available for health care workers that conferred some immunity against bubonic plague, but not pneumonic plague Mass immunization not in place Not practical as immunity too slow to develop in the case of an outbreak Promise in new vaccines that are under development

Y. pestis Epidemics Recorded since biblical times, many epidemics throughout history Examples: 1st epidemic (Antiqua) – 541 AD; Mediterranean region, 50-60% of pop. 2nd epidemic (Medievalis) – 1346-1351; 1/3 of the pop. of Europe died (20-30 million) 3rd epidemic (Orientalis) – 1855-1890; started in China, spread through Asia; 10 million died in India alone

The Black Death Epidemic

The Modern Day Situation Roughly 2000 cases and 200 deaths per year (WHO) Vast majority in Africa About 13 cases a year in the US

Anatomy of the Plague

Plague Control Isolation of patients with pneumonic plague Flea and rodent control Start therapy if plague is suspected – can take too long to confirm.

Plague as a Weapon Aerosolized bacteria  Pneumonic plague Takes 48-72 hours to confirm diagnosis 50kg of Y. pestis could infect 150,000 and kill 36,000 in a city of 5 million in a worst-case scenario. Bacteria would remain viable in an aerosol for 1 hour for a distance of 10 km.

Discussion Would we be better off putting money toward vaccines or emergency response with regards to a bio-terrorist attack? Why?