Legionella and Coxiella Plague and other bacterial zoonotic diseases (3/6/18) Flashcards
when was legionnaires disease was found
legionnaires conveion in 1979 and 130 got sick and 25 died with similar sympotms
morphology of legionella pneumophila
gram neg
aerobic
small pleomorphic bacilli
non capsule
catalase response to legionella
positive
where is legionella pneumophila found
in water and in soil
what is infected by legionella pneumophila
facultative intraceullar bacteria(infects protozoa_
opportunistic pathogen
how does legionella pneumophila infect protozoa
requires special media to isolate (buffered charcoal yeast extract (CYE)
how is legionella pneumophila opportunistic pathogen
only smoked and immunocompromised hosts with bad cell mediated immunity
what does legionella pneumophila
atypical pneumonia due to aerosols by humidifies and cooling systems
legionella pneumophila virulence factor
Pili (fimbriae Flagella LPS type 4 secretion (Icm/Dot) legionell-containing vacuole in macrophages low metabolic state
LPS of legionella pneumophila toxicity
less toxic than other gram-neg
how does legionella pneumophila enter a low metabolic state
biofilm-imbedded cells resist stress
what happens because legionella pneumophila is a Facultative intraceullar bacteria
can multiply inside free-living amoebas, other protozoa and alveolar macrophages
pathogenisis of legionella pneumophila
aerosolized drops breathed in
grow in macrophages, causing inflammation, producing necrotizing multifocal pneumonia
action of legionella-containg vacuole
made by mitochondiea, ribosomes, and ER proteins make the LCV to block the lysosomes and bacteria replicate inside of them
how does legionella pneumophila resist immunity
intracellular multiplcation
immunity against legionella pneumophila
innate and adpative mechanism
TLR in macrophages and dendritic cells recognize Legionella LPS
Th1 adaptive immune response: INF-gamma, Il-2, and Il-18 are produced and activate macrophages and intracellular killing
little use of antibodies
cases of legionellosis
5000 in US
25000 in world
how does legionellosis transmit
not person to person but via large complex manmade water systems (Hotel, hospitals, nursing homes, cruise ships)
forms of legionellosis
Legionannaires disease: sever - pneumonia
Pontiac fever: mild self-limited form with flu-like symptoms (no pneumonia
how are both forms of legionellosis spread
both by water and pontiac fever by sontaminiated soil
why do we have an increase in legionellosis
climate change
aging US pop
Aging plumbing
increase of at risk patients
leionnaires disease affects who
5% exposed mostly middle age or elderly smokers, and with chronic diseases of immunosuppression
legionnaires disease leads to
shock, respiratory failure or both
mortality rate of legionnaires disease
15%, and higher with health-care association (46%)
symptomes of legionnaires disease
myalgia and headach rising high fever dry cough on 2nd/3rd day and chest pain chills vomiting diarrhea confusion and delirium hepatic dysfunction
time between exposure and legionnaires disease
2-10 days
diagnosis of legionnaires disease
difficult:
direct fluorescent antibody with culture of infected tissue
PCR
how direct fluorescent antibodies are used to diagnose legionnaires disease
L. pneumophila- specific monoclonal antibodies that recognize all serogroups
use high-quality specimes (recognizes 25-50% o culture-proven cases
gram staining for legionnaires disease
bad staining
culturing for legionnaires disease
Buffered Charcoal est extract agar with vitamin, L-cystein, ferric pyrophasphate
treating legionnaires disease
Fluoroquinolone or axithromycin are preferred
erythromycin can treat infection
not penicillin: most legionella produce beta-lactamases)
how to prevent legionnaires
minimize aerosole in public places from contaminated water
why is preventing legionnaires complicated
resist chlorine and head
forms biofilms
how to prevent legionnaires
dont use tap water in aerosolizing water
infection in humans acquired by direct or indirect contact with animals
Zoonoses
types of Zoonoses
Coxiella burnetii- Q-fever
Yersina pestis: Bubonic Plague
Brucella: undulant fever
Fancisella: Tularemia (similar to plague)
Pasteurella Multocida: soft tissue infection
how to get coxiella burnetii
inhalatino of soil and dust contaminated after birth of infected animals
how to get yersina pestis
exposure to flease from infected rodents
how to get brucella
direct contact with animal infected
ingested of contaminated diary
how to get Fancisella
direct contact with infected mammal
inhalation
bite of infected tick
how to get paseurella multocida
cat or dog bite
what was Coxiella first seen as
a new type of Rickettsia
what is Coxiella related to
LEgionella
Morphology of Coxiella burnetti
gram-
small coccobacilli
pathogen as Coxiella burnetii
obligate intracellular pathogen (macrophages and phagocytic cells)
where does coxiella burnetii grow well
placental tissues contaiminating soil after birth
who is most at risk for coxiella burnetii
vets, famers, slaughter house workers, animal researchers
infectious dose foc coxiella burnetii
1-10 organisms cuase disease in 50% (id50=1)
Virulence factors for coxiella
LPS Type IV secretion (Dot/Icm) Resistant to low pH and enzymes of phagolysomes Coxiella-contain vacuole Biphasic life cycle
what happens to coxiella when phagosome and lysosome fuse
continues to multiple
a phagolysosome-like compartment where Coxiella replicates
Coxiella-containing Vacuole
The lifecycle of Coxiella
Small Cel variants: not metabolically active (like spore)
Large cell variant: metabolically active- switches to this when enters into host cell
how does Coxiella become a pathogen
Aerosol transmission- Inhaled into lungs
• Binds to alveolar macrophages and is passively taken up hrough phagocytosis
• Affinity for reticuloendothelial system (macrophages and monocytes)
• Can also invade non-phagocytic cells - epithelial and endothelial cells
intracellular trafficking of Coxiella burnetii
Once in a phagosomelysosomal
fusion occurs normally, creating a phagolysosome (pH 5.4)
• Then Coxiella expands the compartment size creating the Coxiella containing vacuole (CCV),
• Transitions to the metabolically active LCV and begins to replicate –ntakes up to 6 days
when symptomes of Q-fever occur
about 20 days after inhalation
symptoms of Q-fever
flu like-abrupt fever, chills, muscle aches and headache
Stomach pain, nausea, vomiting and diarrhea
non-productive cough
Hepatosplenomegaly and abnormal liver function common
symptoms of severe cases of !-fever
Pneumonia or hepatitis
comlications due to Q-fever
myocarditis, pericarditis, encephalitis (rare)
chronic infects of Q-fever are associtated with
endocarditiis
how to treat Q-fever
recover without antibiotcs
maybe 2 week with doxycycline
how did the plague occure
non-immune rats lead to bacteremia
fleas feed on rats and get Y pestis
bacteria block intestines so fleas vomit up Y pestis into a bite wound
when did the black plauge occure the most
high rat population and rat mortality
when flease leae an infected rodent and pass the infection to other in the population, not to humans
sylvatic cycle
masses of rats in close contact with humans, infected with flease-that bite huam
Urban cycle
how did pneumonic plague occure
when humans infected Y. Pestis develop bacteremia, infecting the lungs leading to person to person spread (No fleas needed)
exististance of sylvatic plauge
most continents
common in south east asian
not in western europe or australia
15 cases in the US
morphology of Yersinia pestis
Gram-neg
bacillus (pleomorphic)
non-motile
Enterobacteriaceae family
what part of yersinia pestis is needed for pathogenesis
virulence plasmids
how does Y pestis turn on and off virulence factors
regulatory systems that sense temp, calcium, and otehr envirnomental triggers
how does Y petsis multiply in flea foregun
low temp virulence factors
phospholipase D- resists antibacterail factors in flea midgut
who does Y pestis blocause vomitting by the flea
Coagulase
Polysaccharide biofilm
flea bite does what to Y pestis
temp shift shows new envirnoment so virulence changes
virulence of Y pestis upon biting
Differ LOPS
F1 capsule
Plasminogen activator (Pla)
Yops
LPS of Y. pestis upon flea bite
not recognized by TLR (immune evation
F1 capsule of Y pestis
gel like capsule antiphagocytic
role of plasminogen activator in Y pestis
spread through tissues - enzymatic and adhesion to matrix proteins
Roll of Yops
destroy host cell
deisrutpt host cell
how does yops secreted by type III secretion affect professional phagocytes onces inside
disrupt signalling path, estroy cytoskeleton structures, trigger apoptosis, inhibit cytokine production and acidifiaction of phagosome
what does Y pestis do when it enters the blood stream
reaches regional lymph nodes, lyses ost cell, multiply’s rapidly and produces bubo
what is bubo
hemorrhagic suppurative lymphadenitis
Bacteremia of Y pestis leads to
Toxic shoeck - LPS endotoxin, yops, proteases, and aextracellular products
incubation of bubonic plauge
2-7 days after flea bite
what does bubonic plauge do
fever and painful bubo in groin or axilla
50-70% process to bacteremia and may die from gram-negative septic shock (hours to days after dubo)
5% develop pneumonic plauge, mucoid or bloody sputum
Incubation period of pneumonic plauge
2-3 days after exposion
what does Pneumonic play do to you
fever, malaise, tighten chest
cough,sputum, dyspnea (trouble breathing), and cyanosis(blue lips) later
death on 2-3rd day
no one survives without antibiotics within 24hurs
diagnosis of Plague
gram-stained smears of aspirates from bubo show bipolar-staining gram-negative bacilli
Immunofluroescence techniquie in public heath labs
how to isolte Plague
blood agar or MacConkey agar (takes a while though so patient may die)
treating plague
Gentamicin or strptomycin withor without doxycycline
Also ciprofloxacin or Chloramphenicol if meningitisis presently
if treat plague early, what is the mortality
less than 10%
morphology of Brucella abortus
Gram negative rods
small coccobacili
non-motile
Aerobe
Brucella abortus tests positive to
catalse, oxidase, and urease
can brucella abortus ferment sugar
no
envelope of brucella abortus
unusual, phosphatidylcholine like eukaryotic cells
growth rate of brucella abortus
slow (2-3 days to culture
where does Brucellosis occur
persist for life in animals reproductive organs
what does Brucellosis cause
abortion, sterility, decreased milk production in cattle, goats and hogs
how does Brucellosis spread
direct contact with infected tissues and ingestion of contaminated feed
not person to person
how to control brucellosis
systematic control: vaccination, eradication of infected animals
how many people get brucellosis
100/year
how do humans get brucellosis
consumption of unpasteurized dairy and health products from mexico
cuts in skin, mucous membrean, inhalation ingestion
occupational exposures to brucellosis
Vets, livestock, slaughterhouse owkres, lab workers
what kind of pathogen is brucella
Facultative intracellular parasite of epithelial cells and phagocytes
waht can brucella evade once past skin or mucous membran
evade innate immunity, specifically TLR because outer membrane looks like eukaryotes
where doe Brucella multiply
macrophages in liver sinusoids, spleen, bone marrow, and reticuloendothelial systemto orm granulomes
how does brucela live within a cell
inhibit myeloperoxidase system, phagosome-lysosome fusion and apoptosis of host cell
what secretion system does Brucella have
type 4 like legionella
what in cows, sheep,pigs, and goats stimulates brucella growth
erythritol (because human placents don’t have this, Brucella can’t infect human placentas
immunity to brucella
antibodies formed, not protective
T-cell mediated immune response critical using TH1-type response with cytokines to clean Brucela from macrophages
symptoems of brcellosis (undulandt fever)
7-21 days after infection
malaise, chills, fever, headache, weight loss
periodic denching night sweats
how long does brucellosis occure
weeks-to 1-2 years
physical findings of brucellosis and localizing signs
few : less than 25 % show detectable englagement of lymph nodes
spelenomegaly most common but also lymphadenopathy and hepatomegaly
diagnosiing brucella
isolate from blood of biopsy of liver,bone marrow or lymph nodes
slow to grow in plates, but modern tech speeds it up
serological test are available, but may not indicated current disease
treating brucella
Doxycycline in combo with rifampin or gentamicin
no vaccine
effectiveness of brucella treatment
2-7 days for fever to break
10% relase within 3 months
Morphology of Francisella tularensis
GRam-negative
non-motile
Coccobacilli - small rod
Aerobic
whay is needed for francisella tularensis to grow
cystein
what kind of parasite is francisella tularensis
facultative intraceullular parsite of macrophages
what does francisella tularensis cause
Tularemia ie rabbit fever
why is francisella tularensis classified as a tier 1 select again
low dose
ease of spread
high virulence
Virulence of F. tularensis
lipid rich capsule
unusual LPS
LPS immune response of F. tularensis
induce protective antibodies
but not stimulate innate immunity (not recognized by TLR)
natural infections of F. tularensis results in what for immunity
long lasting immunity as antibody titers remain high for years
how is Tularemia spread
contact with infected mammal of blood feeding arthropod (tick bite)
rabbits, squirrels, muskrats, beaver, and deer can be infected without symptons
minor skin abrasion
inhalation
Cases of Tularemia in the us
100-200 cases with high tick and rabiit associated strains
where is tularemia not found
british isles, africa, S. america or australia
how long does tularemia grow
unimpeded until phagocytes are enountered
where do lessions occure for tularemia
near site of infection with ulceration
what happens to tularemia upon macrophages ingestion
reside in phagosome, resists lysomome fusion and escape from host cytoplasm
where can tularemia multiply
hepatocytes, kidneys, and alveolar epithelial cells
a type of inflammation due to a college of immune cells ie macrophages found in many disease
Granuloma
when does Granuloma occur
when the body attempts to wall off a foreing substance that it cannot eliminate
incubation of tularemia
2-5 days
what does tularemia progression depend on
site of inoculation and extendt of spread
how does tularemia begin
acute onset of high fever (grater than 104 degrees F), chills, and malaise
most common tularemia
ulceroglandular due to tick bite or infected animal
ulceroglandular form of tularemia results in
ulcer and swollen lymph nodes
Oculoglandular form of tularemia
inoculation through the ye, when butchering an infected animal
oropharyngeal form of tularemia
ingestion of large dose (> 10^8) rsulting in sore thraot, mouth ulcer, tonsillitis, and swelling of lymph glands
most serious Tularemia
Pneumonic form
Pneumonic form of Tularemia reuslts in
inhalation of dust or aerosols result in pneumonic tularemia or infection like typhoidal from
what can tularemi pneumonia develop hrough
bacteremia or inhalation
typhoidal form of tularemia
combination of genreal symptoms without locatlizing or other syndroms
diagnosisng tularemia
diffisult because symptoms like other more common illnesses
use pateint history (tick, der fly bites, sick/dead animal contact)
serologic tests used: agglutinating antibodies usually present by week 2 of illness
how to culture tularemia
hard to grow and must use choclate agar and sulfhydryl compounds
treating tularemia
antibioics: gentamicin and streptomycin
also doxycycline and ciprofloxacin, but may relapse
who gets vaccine for tularemia
high risk population gets live attenuated vaccine
Morphology of pasteurela multocida
small coccbacillary
gram-
facultative anaerobe
why is pasteurella multocida a facultative anaerobe
oxidase positive
what can pasteurella multocida ferment
variety of carbs
penicillin susceptibility of pasteurella multocida
is, unline most gram-negaive rods
where is pasteurella multocida found
normal respiratory flora of domstic mammals (Dogs an cats)
most common cuas of infected dog or cat bite
pasteurella multocida
when does pasteurella mutlocida occure
24 hrs of animalbite or scratch
what does pasteurella mutlocida cause
diffuse cellulties with a well defined erythematous border
