Differential Diagnosis Inhalation anthrax
Viral Pneumonia Influenza, Hantavirus, RSV, CMV
Other Bacterial Pneumonia
Q Fever Meningococcemia
Septicemia caused by other Gram-Negative BacteriaPneumonic PlagueSepticemic Plague
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)
DiagnosisSuspected Plague Both of the following conditions are met:
DiagnosisPresumptive Plague*Agglutination testing must be shown to be specific to Y. pestis F1 antigen by hemagglutination inhibition.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.*
DiagnosisConfirmed Plague1. 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.* One of the following conditions is met:*Agglutination testing must be shown to be specific to Y. pestis F1 antigen by hemagglutination inhibition.
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.
For a minimum of 10 days (or 3-4 days after clinical recovery)Treatment
*Preferred Treatment (others are alternatives)Antibiotic Therapy
Antibiotics Mechanism of Action
Prognosis1 Pneumonic Plague progresses the most rapidly
Prevention Education on modes of transmission
Control Rat & Flea Populations ( traps, insecticides) Integrated Vector Management (surveillance of animal reservoirs)San Jose, CA; 1991
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 Prevention
PreventionExisting Vaccines None Available for Use!
PreventionImproved Vaccines In Development
PreventionProphylactic 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)
Caution: Drug Resistant Strains in Patients
Weaponization of the Plague
History of WeaponizationMongols 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.
CDC Classification of PlaguePlague 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 personresult in high mortality rates and have the potential for major public health impactmight cause public panic and social disruptionrequire special action for public health preparedness
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
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 didnt 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.
In The Event of An AttackEarly treatment with antibiotics (gentamicin, streptomycin, tetracycline, fluoroquinoline)
Use of surgical masks to prevent further transmission.
The Bad NewsResistanceSequence 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.
The Good NewsRequires 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.
Culture isolates will be forwarded to a reference laboratory for definitive identification, which may involve antigen detection, IgM enzyme immunoassay, or polymerase chain reaction. Antibiotic susceptibility testing of Y. pestis is also undertaken at reference laboratories, which are better equipped for this purpose than most hospital laboratories.Numerous other ways for detection, confirmation and characterization (ELISA, PCR, mouse inoculation, IHC, Dipstick Assay, Bacteriological culture, gram stain)Smears should be sent to a reference lab for fluorescent antibody microscopy.Test can be done in < 2hrs but F1 expressed at 37C, so refrigerated samples or samples from cultures that have been incubated at lower temps would test negative2. Smaller elevations are considered a presumptive diagnosis.These techniques are slowY Pestis grows slowly in culture & antibodies can take a number of days or weeks after disease onset to devt usually good for a retrospective confirmation of plague
b/c tests take so long, treatment should begin as soon as plague is suspected isolation 72 hours after starting antibiotic therapy.If treated with antibiotics, buboes typically recede in 10 to 14 days and do not require drainage. Strep FDA approved but limited use in usa, so small supply
Aminoglycosides (Streptomycin, Gentamycin); Tetracyclines (Doxycycline); Quinolones (Ciprofloxacin); Chloramphenicol; Pt should have f/uPeople continue to die of plague, not because the bacilli have become resistant but, most often, because physicians do not include plague in their differential Diagnosis (in the United States) or because treatment is absent or delayed (in underdeveloped countries). Pneumonic plague is the most rapidly fatal form of plague, and most victims will die if they do not receive antibiotics within the first 18 hours after symptoms begin. Bubonic: most deaths occurring from sepsis in 3 to 5 days. Primary or secondary septicemic plague (infection active in the bloodstream and the victim has symptoms of shock) has a 40% death rate, even when treated.
Insecticide application must always precede rodent controlRodent control (by trapping, gassing or poisoning) must be undertaken with caution overkill make lead to new reservoirs
Used in US military during Vietnam war only 8 cases of immunized servicemen reported. but severe inflammatory reactions are frequent. Primary IM injection followed by boosters at 3-5 mos then another booster at 5-6 mos then 3 more booster shots at 6 mos intervals followed by 1-2 year intervals until not needed. Prevent it from developing into a disease; Recommendations are for mass casualty setting where number of pts. too great for all to receive IV antibioticsRare point out adenylylation vs. phosphorylation; 150kb vs 40kb
Where:? Contact with gut bacteria in dead human host, contact with microorganisms in flea midgutWe need to find:molecular and genetic basis origins and evolution of the resistancepotential for the spread of resistant Y. pestis in its natural cycle