General Goal: To know the cause of this disease, the most common modes of transmission, the major manifestations, and the major complications of this disease.
Specific Educational Objectives: The student should be able to:
1. identify the cause of this disease (hint: safety pin appearance).
2. recite the common means of transmission and identify the major disease manifestations.
3. identify what type of pathogen this bacterium is [ex. extracellular, intracellular (what cell does it dwell in)].
4. tell what groups of people and occupations are more likely to get this disease and how to avoid getting infected with this pathogen.
Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 6th Edition. pp. 310-311.
Lecture: Dr. Neal R. Chamberlain
References:
Simonet, M, B. Riot, N. Fortineau, P. Berche. 1996. Invasin production by Yersinia pestis is abolished by insertion of an IS200-like element within the inv gene. Infect. Immun. 64(1):375-9.
K.A. Fields, M.L. Nilles, C. Cowan, S.C. Straley. 1999. Virulence Role of V antigen of Yersinia pestis at the bacterial surface. Infect. Immun. 67(10):5395-5408.
Heath, D. G., . Immun. 64G. W. Anderson, Jr., J. M. Mauro, S. L. Welkos, G. P. Andrews,
J. Adamovicz, and A. M. Friedlander. 1998. Protection against experimental
bubonic and pneumonic plague by a recombinant capsular F1-V antigen
fusion protein vaccine. Vaccine 16:1131–1137.
OVERVIEW
In 2002 two residents of New York City acquired plague from New Mexico.
It is also on the list of possible agents that could be
used by terrorists. Especially since transmission by aerosols results in a very
deadly form of this disease that then can spread from person to person.
Human to human transmission: By droplets (pneumonic) or by fleas. Pneumonic plague has not been reported in the U.S. since 1925.
Sylvatic cycle: almost all cases of plague since 1925. Incidents are on the rise, but are limited to the western U.S.
Plague is endemic in the U.S. Here is a picture
of the endemic regions. This figure also demonstrates
where plague is endemic in the
world.
Epizootic plague. Sensitive or moderately-resistant
hosts are infected by fleas or by ingestion, resulting in a highly visible
die-off, e.g., rats, prairie dogs, rock squirrels.
Some Y. pestis in the flea are then regurgitated
when the flea gets its next blood meal thus transferring the infection
to a new host. While growing in the flea, Y. pestis loses its capsular
layer. Most of the organisms are phagocytosed and killed by the polymorphonuclear
leukocytes in the human host. A few bacilli are taken up by tissue macrophages.
The macrophages are unable to kill
Y. pestis and provide a protected
environment for the organisms to synthesize their virulence factors.
The organisms then kill the macrophage
and are released into the extracellular environment, where they resist
phagocytosis (YopH and YopE; Yersinia outer membrane protein) by the polymorphs. The Y. pestis quickly spread to
the draining lymph nodes, which become hot, swollen, tender, and hemorrhagic.
This gives rise to the characteristic black buboes
responsible for the name of this disease.
Within hours of the initial flea bite, the infection
spills out into the bloodstream, leading to involvement of the liver, spleen,
and lungs. The patient develops a severe bacterial pneumonia, exhaling
large numbers of viable organisms into the air during coughing fits. 50
to 60 percent of untreated patients w out into the bloodstream, leading to involvement of the liver, spleen,
and lungs. The patient develops a severe bacterial pneumonia, exhaling
largeill die if untreated. As the epidemic
of bubonic plague develops (especially under conditions of severe overcrowding,
malnutrition, and heavy flea infestation), it eventually shifts into a
predominately pneumonic form, which is far more difficult to control and
which has 100 percent mortality.
Important virulence factors include proteins encoded
by three different plasmids:
Septicemia with regional lymph node involvement
(bubonic plague, 85-90% of the cases)
Septicemia without lymph node involvement (primary
septicemic plague, 10-15% of the cases); depends on level of lymph node
inflammatory response.
Complications: The most common complication
of bubonic and septicemic plague is disseminated intravascular coagulation
(DIC), pneumonia and meningitis.
Death: The patient usually dies of endotoxic
shock.">Complications: The most common compl
General malaise
High fever (hyperpyrexia)
Pain or tenderness at the regional lymph nodes,
which may enlarge to be called buboes (pic
2).
Septicemia is intermittent at first but rapidly
becomes constant.
DIC
Convulsions
Shock
Diffuse, hemorrhagic changes in the skin plus
cyanosis from the necrotizing pneumonia produce the dark skin at the extremities
giving rise to the term "black death."
Excruciatingly painful, inflamed regional lymph
nodes.
Fever, prostration, headache.
Exposure to rodents, rabbits, or fleas in the
western U.S.
Blood and bubo aspiragly painful, inflamed regional lymph
nodes.
Fever, prostration, headache.
Exposure tes and sputum should be
Giemsa stained. Smears typically show the bacillus to have a bipolar
or "safety pin" appearance.
Send smears to a reference lab for fluorescent
antibody microscopy.
Most Gram-negative bacteria produce colonies within
24 h; F. tularensis and Y. pestis do not.
Yersinia pestis poses a serious infectious
hazard for nursing and laboratory personnel. Protective clothing and a
full face respirator should always be worn when working with this organism.
Cultivation and virulence testing of this organism should be attempted
only in P-3 containment facilities by staff who have been immunized recently
with live attenuated vaccine. Without treatment, fatality rates: up to 90% for
bubonic plague, 100% for septicemic or pneumonic plague.
Treatment, fatality rate= (5-20%). Rapid treatment
is critical to improved survival.
Gentamicin or streptomycin can be used. ß-lactams
are not useful.
Isolate patients in case pneumonia devt, fatality rate= (5-20%). Rapid treatment
is critical to improved survival.
Gentamicin or streptomycin can be used.elops. By
law, patients with pneumonic plague must be isolated. Patients who survive
severe septic shock may show a marked necrosis or dry gangrene of the tissues
on extremities, i.e., the black death. Doxycycline can be used for post-exposure prophylaxis. Eliminate urban plague with sanitation measures.
A formalin-inactivated vaccine is available for
adults (18-61yrs old) at high risk, 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. This vaccine is protective against the bubonic form of plague however, it does not protect against the more lethal pneumonic form of this disease.
Other investigators are
experimenting with a recombinant fusion protein vaccine consisting of the Yersinia
pestis F1 (capsular protein) and V antigens. So far experiments in murine
models of plague infection have shown great promise in protecting animals against bubonic and pneumonic plague infections. Human safety studies have begun and if all goes well the company producing the vaccine (Dynport Vaccine Company) plans to ask for FDA approval sometime in 2015.
Revised 2/11/10
TYPES OF PLAGUE
Incubation period of 1-3 days (pneumonic) or 2-6
days (bubonic).
Send comments and mail to Dr. Neal R. Chamberlain, nchamberlain@atsu.edu
©2010 Neal R. Chamberlain, Ph.D., All rights reserved.