Differential Diagnosis

1. Differential Diagnosis Pneumonic Plague Septicemic Plague ■ Inhalation anthrax ■ Tularemia ■ Viral Pneumonia Influenza, Hantavirus, RSV, CMV ■ Other Bacterial Pneumonia ■ Q Fever ■ Meningococcemia ■ Septicemia caused by other Gram-Negative Bacteria

2. Diagnosis Suspected Plague Both of the following conditions are met: 1. Clinical symptoms of Plague in person who resides in or has recently traveled to a plague-endemic region 2. Smear* taken from affected tissues shows small gram-negative and/or bipolar-staining coccobacilli (Polychromic stains: Wright, Giemsa, or Wayson stain ) * Sample taken from Bubo (bubonic plague), Blood (septicemic plague), or Tracheal/lung aspirate (pneumonic plague)

3. Diagnosis Presumptive Plague One or both of the following conditions are met: 1. Immunofluorescence stain of smear +ve for the presence of Yersinia pestis F1 antigen. 2. Only a single serum specimen is tested & the anti-F1 antigen titer by agglutination is >1:10.* *Agglutination testing must be shown to be specific to Y. pestis F1 antigen by hemagglutination inhibition.

4. Diagnosis Confirmed Plague One of the following conditions is met: 1. Isolated culture lysed by specific bacteriophage. 2. 2 serum specimens demonstrate a 4 fold anti-F1 antigen titer difference by agglutination testing.* 3. Single serum specimen tested by agglutination has a titer of >1:128 and the patient has no known previous plague exposure or vaccination history.* *Agglutination testing must be shown to be specific to Y. pestis F1 antigen by hemagglutination inhibition.

5. Treatment Isolation: ■ For the first 48 hours following treatment, in case pneumonia develops ■ By law, patients with pneumonic plague must be isolated ■ If patients have no pneumonia or draining lesions at 48 hours, they may be taken out of strict isolation. Antibiotics: ■ For a minimum of 10 days (or 3-4 days after clinical recovery)

6. Antibiotic Therapy *Preferred Treatment (others are alternatives)

7. Antibiotics – Mechanism of Action

8. Prognosis  1 Pneumonic Plague progresses the most rapidly

9. Prevention ■Integrated Vector Management (surveillance of animal reservoirs) ■ Education on modes of transmission ■ Control Rat & Flea Populations ( traps, insecticides) San Jose, CA; 1991

10. Prevention Personal Sanitation Measures ■ Veterinary workers in endemic areas: gloves, eye protection, surgical masks when treating suspect cats ■ Hunters and Outdoorsmen: avoid rodent nests, use insect repellents/insecticides, wear gloves when handling potentially infected animals ■ In the Lab: - Standard Control: when handling Y. Pestis organisms - Biosafety Level 2: when processing clinical specimens & cultures - Biosafety Level 3: with large amounts of bacteria or with potential for aerosolization

11. Prevention Existing Vaccines – None Available for Use!

12. Prevention Improved Vaccines – In Development

13. Prevention Prophylactic Antibiotics ■ only following high-risk exposure to pneumonic plague *Preferred Treatment (others are alternatives) ■ treat for 10 days (if fever/cough develops during prophylactic treatment, then follow standard therapy for Y. Pestis)

14. Caution: Drug Resistant Strains in Patients

15. Weaponization of the Plague

16. History of Weaponization • Mongols throw plague infected bodies over the walls of the besieged city of Kaffa in 1346 • In WWII, Japanese army dropped Plague-infected fleas packed into bombs over Manchuria and infected their water supply resulting in an outbreak. • During The Cold War, the U.S. and Soviet Union developed methods of aerosolizing Plague-thereby eliminating the flea vector.

17. CDC Classification of Plague • Plague is in Category A, it is a high-priority organism • High-priority agents include organisms that pose a risk to national security because: • can be easily disseminated or transmitted from person to person • result in high mortality rates and have the potential for major public health impact • might cause public panic and social disruption • require special action for public health preparedness

18. Plague is a Suitable Pathogen For Use As a Weapon Because… • It is accessible, simple to reproduce, economical and efficient. • It can be delivered in aerosol form • Pneumonic plague causes serious illness with a high case fatality rate • Pneumonic plague is communicable • 100-500 bacteria are enough to cause pneumonic plague, whereas it takes between 1,000-10,000 spores to cause pulmonary anthrax

19. Are We Prepared? • A 1970 WHO report estimated that an aerosol release of 50kg of Y.Pestis over a city of 5 million people would produce 150,000 illnesses and up to 36,000 deaths. (This report didn’t take into account the secondary cases that would occur through person-to-person contact. • A simulated bioterror attack (TOPOFF) involving aerosolization of the plague was carried out in May 2001, in Colorado. By the end of the third day, 783 people had contracted pneumonic plague, by the next day the number of plague cases had risen to 1,871 and by the third day the number stood at 3,060. At the end of the exercise 950 people had “died” of pneumonic plague.

20. In The Event of An Attack… • Early treatment with antibiotics (gentamicin, streptomycin, tetracycline, fluoroquinoline) • Use of surgical masks to prevent further transmission.

21. The Bad News…Resistance • Sequence of Y.pestis could have boomerang effect, enabling terrorists to create antibiotic resistant strands. • According to Alastair Hay, the Soviet Union has already developed a form of Yersinia pestis that was resistant to 16 different antibiotics. • Right: Picture of Staphylococcus Aureus next to Y. Pestis. A transfer of antibiotic resistant genes from Staph to Y. Pestis could result in a uncontrollably lethal bacterium.

22. The Good News… • Requires a high level of knowledge to distinguish between virulent and non-virulent strain, efficiently produce the virulent strains, and aerosolize it. • Plague bacteria is a fragile organism because it is non-spore forming, so it can only remain viable for only about 1hr after aerosolization.