Bug parade part 3 Flashcards
What is the difference between category A and category B bioterror and catery Cagents, according to CDC ranking?
Category A: can be easily disseminated or transmitted from person to person, result in high mortality rates, have potential to cause panic and social breakdown, and require special action.
Category B agents, on the other hand, are only moderately easy to disseminate and result in moderate or low mortality rates.
cutaneous anthrax:
how do you get it? what happens?
how: contact with infected tissues of animal or contaminated hair/wool/etc. spores germinate and vegetative cells grow. gelatinous edema progresses to a papule progresses to a necrotic ulcer. mortality occurs in 20% of cases, usually with septicemia
gastrointestinal anthrax: how do you get it? what happens?
results from ingestion of contaminated uncooked meat. Highly lethal. mucosal lesion spreads to lymphatics and blood.
pulmonary anthrax.
inhalation of spores and lung infection leads to pulmonary anthrax. rapid onset with high fever and chest pain. prgresses to systemic hemorrhage and has a 60% case fatality rate.
what drugs can be used to treat anthrax?
penicillin, doxycycline, and ciprofloxacin
What are important virulence factors for B. anthracis?
capsular polypeptide with D glutamic acid that interferes with phagocytosis and anthrax toxins
Francisella tularensis: gram, characteristics, motility, growth, oxygen,
encapsulated pale gram-negative rod. grows on chocolate agar and is a facultative intracellular bacterium, lipid rich capsule, strict aerobe, non-motile
F. tularensis: what disease does it cause? What forms cause the disease? How is it transmitted? reservoir? Prevention?
disease: tularemia
caused by type a and type b strains, but type a more virulent (less than 10 bacteria can cause disease)
transmitted by rabbits and deer flies, or contact with infected animals or ingestion of contamiated food or water, or inhalation of aerosolized organisms.
reservoir: rodents and rabbits
prevention: yes, vaccine is possible: LVS vaccine for at risk personnel
What are the main clinical manifestation of tularemia? What are the five types? and incubation time?
acute, febrile disease
ulceroglandular tularemia: predominant form that occurs via infection of skin/mucus membranes. focal ulcers,and enlarged lymph nodes. incubation period of 21 days.
respiratory tularemia: more severe; occurs from inhalation. high fever, chills, malaise, pneumonia, cough.
oculoglandular tularemia: direct contact of bacteria
GI tularemia possible
typhoidal tularemai: systemic symptoms w/o regional ulcerations or swollen lymph nodes
What is one clinical sign of respiratory tularemia?
pulse temp dissociation: no rise in pulse rate with fever
What makes Francisella tularensis pathogenic?
bacteria can replicate in many different host cell types, but especially macrophages. entry is mediated by phagocytosis, followed by replication and alteration of phagosome maturation.
How do you diagnose and treat tularemia?
Diagnosis is very hard: bacteria must be grown on chocolate agar for several days. ID is confirmed with special antisera. Careful, because tularemia can look like other diseases (strep, staphy, mono, plague, etc.).
if recognized early, responds very well to streptomycin.
What disease is caused by yersinia pestis?
PLAGUE
How does the bubonic PLAGUE present?
caused by Yersinia pestis. presents 2-10 days following exposure.
symptoms: swollen and very tender lymph gland (“bubo”) and pain. Often seen in the femoral, inguinal or axillary regions. Bubos are filled with bacteria
How does septicemic plague present?
untreated bubonic plague invades the bloodstream: severe and usually fatal endotoxic shock.
Pneumonic plague presentation
severe respiratory illness. high fever, chills, cough, resp. difficulty, bloody sputum. Human-human transmission possible. Incubation of 3 days, followed by death about 3 days later if untreated
How do you treat plague?
gentamycin or doxycycline
Yersinia pestis: gram, morphology, ox needs, motility, shape.
pleiomorphic bacillus gram negative, BIPOLAR gram staining facultative aerobe nonmotile facultative intracellular pathogen
How does yersinia pestis cause disease?
- non-encapsulated form enters during the feeding of an infected flea.
- some non-encapsulated organisms are taken up by histiocytes, and capsule is resynthesized.
- Encapsulated organisms rapidly proliferate and then get released.
- bacteria replicate extracellularly and the infection spreads. Often leads to a fatal inflammatory disease.
What are some of the virulence factors associated with yersinia pestis?
V and W proteins (associated with septicemia)
Yops:
envelope F1 antigen
coagulase/plasminogen (attenuate phagocytosis)
Brucella abortus: reservoir, how it is spread
many zoonotic reservoirs: cattle, sheep, goats, pigs, dogs
Spread: consumption of unpasteurized dairy products, inhalation of aerosolized bacteria, abrasions in the skin. human to human spread is very rare, but is possible. inhalation is also possible (rare for naturally occurring disease but could be a bioterror concern). Very low infectious dose- less than 10 organisms needed.
Brucella characteristics: gram, motility, shape, growth, ox needs
gram negative non-motile coccobacillus strict aerobes very slow growing: up to 6 wks!
Brucellosis: symptoms
aka undulant fever
affects organs rich in erythritol: breast, uterus, epididymuis.
can lead to late-term abortion
can occur acutely or with undulant fevers that cycle with the time of day- peaks in evening and normalizes by morning (chronic form). chronic form is accompanied by severe depression, osteoarticular disease, hepatomegaly, and splenomegaly. caused by persistence in phagocytic cells and low levels of bacteria.
What are some characteristics of the clostridium species? Gram stain, shape, ox needs,
gram positive, spore forming, obligate anaerobes
most species are saprophytes
Clostridium botulinum: food posing form. where/how is this seen? symptoms?
spores can contaminate lots of different things, esp. in moist, low acid foods (meats, veggies, canned foods) with less than 2% O2. Symptoms: weakness, dizziness, dry mout 8-36 hrs after ingestion. followed by nausea, vomiting, and neuological symptoms like blurred vision, dysphagia (difficulty swallowing), difficulty speaking, paralysis
NO FEVER
infant botulism: what happens? symptoms?
toxingenic infections in infant GI systems. follows ingestion of the spores.
This is why babies under 18 mo. CAN’T EAT RAW HONEY.
symptoms relatively similar: constipation, then muscle weakness and paralysis. trouble controlling head
Wound botulism: symptoms. who is most susceptible?
symptoms: double vision, dry mouth, difficulty speaking, weakness or fatigue, wound pain.
usually seen only in IV drug users, esp. those who inject heroin right into tissue instead of veins. No GI symptoms.
How does the C. botulinum toxin work?
It prevents ACh release at the neuromuscular junction: no contraction can occur and you see flaccid paralysis.
How do you treat botulism? What serotype of botulism is most common?
administer antitoxin
type A is the most common toxin.
Describe the pathogenesis of C. dificile (steps)
- an event occurs: prolonged antibiotic use, surgery, etc.
- spores germinate and cells multiply
- c. diff aderes to mucus and erythrocytes
- c diff makes toxins
What are some major symptoms of C. difficile disease?
very broad spectrum of symptoms:
mild-moderate watery diarrhea, cramps. may begin after the completion of antibiotic therapy.
colitis: characterized by low grade fever, leukocytosis, and colonic abnormalities
pseudomembraneous colites: systemic, high fever, severe diarrhea with blood, elevated WBC, and raised yellow plaques on colorectal mucosa.
How is C. difficile diagnosed and treated?
diagnosed by looking for toxins in the stool: TcdA or TcdB. Or by using PCR. This is better than culture of stool sample, since culture doesn’t distinguish between pathogenic and non-pathogenic strains very well.
treatment: 10 day course of metronidiazole or vancomycin. relapses are common. or fecal transplant
Clostridium perfringens: what are important diseases?
gas gangrene and food poisoning
C. perfringens gastroenteritis: symptoms, pathogenisis, how do you get it?
acquired after consuming contaminated food
Then, C. perfringens produces heat-resistant enterotoxins and you get sever abdominal cramping, pain, diarrhea and severe flatulence. You might see fever/chills, esp. in very young and very old.
Gas gangrene: what is it? What causes it? Treatment?
C. perfringens is the cause.
symptoms: rapid onset of high fever, brown pus, gas bubbles under the skin, skin discoloration, and foul odor. tachycardia, shock, kidney failure, and coma.
treatment: debridement and excision, amputation. antibiotics ineffective: they don’t get to the ischemic necrotic tissue.
Clostridium tetani: what is the disease? what are the characteristics?
tetanus
characteristic symptoms: lockjaw, severe painful spasms, rigidity, respiratory involvement that can lead to death
How do you treat tetanus?
immediate administration of immune globulin and some antibiotics, like metronidazole
bacteriodes fragilis: characteristics (gram, shape, ox needs)
gram NEG, anaerobic, bacilli. usually this is a commensal organism
Bacteroides fragilis infection: what happens?
opportunistic infection: intestinal species introduced to abdominal cavity through surgery, malignancy, or appendicitis
2 stages of infection: first, aerobic bacteria proliferate and begin to destroy tissue and use up oxygen
2. then, B. fragilis can grow (it can tolerate a tiny bit of O2 while it waits for the aerobic bacteria to do their thing). it has a capsule that evades phagocytosis nad and form abscesses or disseminate
rickettsioses characteristics (gram, size, ox requirements, mobility, etc)
small gram negative aerobic coccobacilli
OBLIGATE intracellular parasites of eukaryotic cells. no flagella
they have leaky membranes, so they have to have intracellular environment to take care of them
what happens during rickettsiae pathogenesis (steps)
- rickettsiae get into the skin via a tick bite or through damaged skin contact with the feces of fleas/lice
- bacteria infects the blood and gets to the endothelium (among other cells: receptors are almost ubiquitous). Induces endocytosis
- Rickettsiae enter the cytoplasm and start to multiplythen,
Rickettsiae type then has an impact on what happens next: - typhus groups released via lysis
- spotted fever groups don’t lyse host cells, but rather propel themselves through the cytoplasm and into tips of membranous extrusions, and escape that way. infected cells display some membrane damage.
Rocky mountain spotted fever:
cause
symptoms, onset
pearl
cause: tick bites (ixodid tick)
signs: 2-14 days (onset)
fever, headach, pain, rash (usually, but only 3-5 days after onset of illness). rash is on ankles and wrists- “spots” faint pink macules
nausea, vomiting, diarrhea, cough may also be present
frequently fatal, esp. if diagnosed late
history critical: colorado mountains, mountains of north carolina
Diagnosis, treatment
epidemiologic and clinical clues
may confirm diagnosis after you start treatment with IFA (immunofluorescence assay)
treatment: doxycycline before the 5th day of symptoms.
typhus
cause, sings and symptoms, treatment
cause: rickettsia prowazekii from rat, lice, or conditions of crowding and poor sanitation
onset: fever, chills, headache, and myalgia largy macules on trunk, then extremities. you can also see people who appear to be cured but then have a re-emergence
treat with doxycycline
murine typhis: causative agent
Rickettsia typhi. generally causes discomfort but not death
ehrlichiosis
caused by ehrlichia chaffeensis transmited by the lone star tick
resembles rocky mountain spotted fever but without the rash (usually).
treat with doxycycline
bartonella henselae: gram, reservoir, growth
gram-neg, facultative intracellular pathogens (can live within erythrocytes)
reservori: many different animals, but cats and fleas are most frequent carriers
leads to fever and pustule formation and painful lymph nodes at the scratch site
How does ehrlichia survive and grow in the body?
inside of phagocytes: it can grow, multiply, and lyse the phagosomes
What are bacillary angiomatosis?
common infection of HIV/AIDS caused by Bartonella henselae and bartonella quintana. charachterized by vasoproliferative tumors that can lead to endocarditis and neurological symptoms
treat with antibiotics (doxycycline or azithromycin)
bartonella quintana: disease caused, disease, transmission
causes trench fever. mild relapsing fever with a maculopapular rast accompanied by joint pain, malaise, dizziness. recurring fever ever 5 days with diminishing intesnity
transmitted by body louse
bartonella bacilliformis: disease, symptoms, transmission, regions
disease: Carrion, oroya
infectious anemia from RBC destruction
damage to liver and spleen
transmitted by sandfly in Andes region of South America.
what is the difference between an exotoxin and an endotoxin?
exotoxin: excreted from the bacteria cell
endotoxin: embedded in the bacterial cell surface
What is a super antigen?
superantigen is an exotoxin that binds to macrophages and T cells in a promiscuous way. this leads to the activation of huge numbers of T-cell populations, which can lead to shock.
What are examples of super antigens?
toxic shock toxins of S aureus and Streptococcus pyogenes
can cause toxic shock syndrome, scarlet fever, food poisoning, and scalded skin syndrome
What are the two kinds of membrane-disrupting toxins?
channel forming kind (uses a lot of alpha helices
and phospholipid-hydrolyzing kind of membrane disrupting toxin. this kind removes polar head groups from phospholipids, wich leads to destabilization of the membrane.
What is an example of an alpha helix pore forming toxin?
diphtheria toxin, exotoxin a from P. aeruginosa
What is an example of a beta barrel pore forming toxin?
alpha-hemolysin
What are the cholesterol-dependent cytolysins? What effect do they have on host cell physiology?
many examples, but esp. Perfringolysin O/theta toxin from clostridium perfringens
at lower concentrations, we see induced expression of pro-inflammatory platelet activating factors in endothelial cells. at high expressions, we see cell death and cell lysis.
what is an example of a phospholipase toxin?
phospholipase C from Listeria monocytogenes
What is an example of ADP-ribosylation toxins?
diphtheria toxin, pseudomonas aeruginosa exotoxin A, and some endotoxins, like the cholera toxin
How does diphtheria toxin work (biochemically)?
AB toxin.
B portion binds to the cell membrane (binds the heparin-binding epidermal growth factor, which is found on MANY cell types)
Then, the A subuint dissociates and catalyzes the transfer of adenosine diphosphate ribose (ADP-ribose) to EF-2. THIS STOPS PROTEIN SYNTHESIS IRREVERSIBLY.
What is the process for diphtheria toxin binding, uptake, and translocation?
B fragment binds heparin binding epidermal growth factor (HB-EGF)
toxin is endocytosed
chand in pH changes the conformation and allows the toxin to access the vesicle membrane
The A fragment is released and goes on to cause ADP-ribosylation of EF-2.
How does botulinum toxin work?
synthesizes as an inactive polypeptide that must be cleaved. Then, botulism toxin interacts with the nerve terminal membrane, is internalized, and cleaves the proteins involved in synaptic vesicle membrane fusion. This inhibits the release of Acetocholine at the neuromuscular junction
can lead to irreversible damage, especially since the antitoxin can’t counter the effects of toxin that has already been internalized.
How does the tetanus toxin work?
Retrograde axonal transport to the CNS leading to the blockage of the release of inhibitory neurotransmitters. therefore, there is nothing to check nervous impulses and we see generalized muscular spasms
What is one major example of an organism that has a type III secretion system?
Yersinia
What is the difference between the e. coli enterotoxins?
Heat labile: resembles cholera toxin
heat stabile causes accumulation of fluid on the lumen of the small bowel via guanylate cyclase
what are three superantigens?
staphylococcal enterotoxin, streptococcal erythrogenic toxin
What are some characteristics of M. tuberculosis (shape, gram, grwoth considerations)
rod-shaped
obligate aerobe (can survive but not replicated in anaerobic envrionments)
very slow growing
gram positive, but very strange gram positive: mycobacterial cell evelope is rich in lipids and has less peptidoglycan than is typical of gram positive organisms. Also hasarabinogalactan polysaccharide on the inside of the envelope
(layers, inside to outside: cell membrane, peptidoglycan, arabinogalactan polysaccharide, mycolic acids and glycolipids)
What are some important points about non-tuberculous mycobacteria? (4 diseases/bacteria)
- M. avium: pulmonary infections in immunocompromised ppl, esp. AIDS pts
- M. ulcerans: Buruli ulcer
- M. marinum: cutaneous lesions, esp. of ppl who deal with the water
- M. leprae: causes leprosy. obligate pathogen- no lab culture- but is contatious thuman to human. MDT stops transmission.
How does antimicrobial resistance arise in M. tuberculosis?
ALWAYS by random chromosomal mutation.
Isoniazid and ethionamide and pyrazinamide are all prodrugs that are activated by the TB organism. Mutations that prevent the organism from activating the prodrugs represent a common way in which the bacteria gets resistance
What is the standard frontline course of treatment for M. tuberculosis? How do they work?
isoniazid and rifampicin and pyrazinamide and ethambutol for 6-9 months.
These drugs work by: inhibiting cell wall synthesis, (isoniazid and ethambutol), inhibiting RNA synthesis (rifampin), and disrupting plasma membrane (pyrazinamide)
Where do we see most primary lesions of tuberculosis?
lower lobes of the lungs
What is the difference between multidrug resistant TB and extensively drug resistant TB?
MDR-TB: resistant to 2 or more frontline TB therapies
XDR: two front-line drugs, rifampin and isoniazid, PLUS one fluoroquinolone and one injectable aminoglycoside (amikacin)
Why is the BCG vaccine so variable in its efficacy?
- different vaccine stocks from M. bovis
- exposure to environmental mycobacteria may induce some immunity to the vaccine itself (remember, this is a live attenuated vaccine)
- immunity to M. tuberculosis from exposure to environmental mycobacteria may mask any enhancement of immunity from BCG vaccination, esp. near the equator
What are some symptoms of pulmonary TB?
positive PPD, coughing, night sweats, fever, weight loss
What characterizes TB entry into macrophages?
no definitive adhesins
entria via complement or mannose receptors
cholesterol is essential
What characterizes M. tuburculosis replication in vivo?
inside non-activated macrophages
preferentially uses fatty acids for energy
