philena the philly some help?people.upei.ca/bdespres/streptococcus_pei-10_handout_b_w.pdf · 6 next...
TRANSCRIPT
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First Case Phil’s Friendly Filly: Philena
Quarter horse
One-year-old
Owner’s complaint: Yucky yellow-green
stuff running out if its nose…………. (aka nasal discharge)
Not eating well
Acting “sick”
Philena the Philly
Physical exam: Fever
Nasal discharge
Swelling behind the mandible: right side
Tip: This is abnormal 24 hour BAP culture
Some Help?
Gram’s stain of exudate
What’s Your Diagnosis? Diagnosis? (disease common name)
A. Strangles
B. Lymphadenitis
C. Mastitis
D. Runny nose
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What is the cause?
A. Streptococcus suis
B. Streptococcus agalactiae
C. Streptococcus equi
D. None of the above
What is the most probable source of the infection?
A. Soil
B. Feed
C. Normal bacterial flora in the nose
D. Another infected horse
Which of the following are important to the pathogenesis?
A. M protein on Strep. equi
B. Age of the horse
C. Acute inflammatory response: PMNs
D. Localization in regional lymph nodes
E. All of the above
Source = infected horse; another foal or adult carrierExposure history, e.g.. horse showHost immunologically vulnerable; age / naïveCritical time between end of passive immunity and beginning of active immunity
Inhalation or ingestion: infection starts at tonsilsInvasion – inflammation (PMN) – dissemination S. equi factors:resists phagocytosis: M proteinkills phagocytes: leukotoxinimpairs host attempt to wall off: fibrinolysinDNAase: thin runny pus
Key Elements of the Story
More Key Story Elements
Swelling = pain, abscessation = dead PMNs
Dissemination = bastard strangles
Antibiotic resistance not a problem: penicillin
To treat or not to treat………THAT is the question
Diagnosis by culture
Prevention by vaccination
Lymph node infection – more inflammation
Human version of the story
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What if The Foal Was Vaccinated?
Strep equi vaccine
IM
2 doses
2 weeks apart
Vaccines Sometime Fail..why?
Dratt!
Vaccines Sometime Fail..why?
D ose; too low, not often enough or inactive (dashboard)
R oute; antibodies not at site of infection
A gent wrong; by genus, species or strain (antigenic type)what else causes strangles?
A ge; too young or too old
T iming; too soon before challenge or too long ago
T ype; killed – shorter immunity, live – longer immunity
Next Case
Marvin’s MistakeI expanded my herd by 200 cows last month. Now I’ve got some serious cases of mastitis.
Millie's Mammary
Holstein
4 years-old
Ten days post-calving
One quarter hot and inflamed
Don’t you DARE touch me!
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Milk abnormal -High somatic cell count (SCC)
Clotted, stringy, cellular
Additional information
BAP at 24 hours
Gram stain
CAMP Test
Strep unknown
Staph. aureus (dbl zone)
Synergistic hemolysis
What’s Your Diagnosis?
MastitisStreptococcus agalactiae
(a Group B Streptococcus)
What was the primary source of infection?
A. Infected purchased cattle
B. Skin of the milker’s hands
C. Cow’s environment
D. Normal microflora of the udder
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Source = infected cowOBLIGATE pathogenCan be eradicated from herd
Prevention by pre-purchase testingSpreads at milking - - HYGIENEAscending infectionAcute inflammation; neutrophilsAntibiotic resistance not a problemDiagnosis: culture, cow or bulk tankCAMP test = definitive
Key Elements of the Story Culture, treat, and follow-up when eradicating Strep ag
1. Culture ALL cows – not just high SCC.
2. Use commercial intramammary drugs. Use aseptic good technique when treating
3. Recheck all treated cows 10 days later.
4. Cull cows that did not cure.
What is an SCC?How do you measure the SCC?
Mastitis Measures SCC = somatic (animal) cell
count; primarily inflammatory cells (PMNs) most common measure of milk quality; farmers paid a premium for milk with lower SCC.
DHI labs –automated cell counters.
Cow-side – CMTCalifornia Mastitis Test rough estimate of SCC.
SPC = Standard Plate Count; counts of bacteria
Clumping = positive: grade 0, 1, 2
SCC: How High is Too High?
High quality milk has SCC < 200,000/ml
Strep ag in a large herdFour important lessons………
1. Use a reliable lab close to home.
2. Culture all cows early.3. Culture again shortly
after treatment.4. It is possible to culture
thousands of cows and eliminate the problem.
From Pharmacia & Upjohn excerpted From Dairy Health Solutions.
Don’t Buy ProblemsJim Dickrell, Dairy Today, October 1999.
Herd A – bought 110 cows no mastitis screening: Cost of mastitis* = $48,131
Herd B – bought 450 cows cultured all cows first: Cost of prevention = $7,485
* Due to Strep agPrevention Pays !!!
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Next Case Katie’s Kittens Katie loves cats: she owns 12.
One of Katie’s queens, Kathleen, had her first litter of kittens last week: 5 born live and 1 born dead.
Katie says a kitten (no name yet)
died yesterday and the some of the other kittens are very lethargic and not nursing well.
Kitten’s Clinical Exam
Three kittens have a fever.
Most are weak.
Several have a moist, red, swollen umbilicus.
You start the kittens on antibiotics and submit blood for culture.
Blood Culture Result
BAP at 24 hours
Gram stain
Clear zone of hemolysis around small translucent colony.
What’s Your Diagnosis?
SepticemiaStrep canis
aka Group G Streptococcus
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What is the most probable source of infection?
A. Contaminated litter box
B. Skin of human owner
C. Vagina of the queen
D. Mouth of the tom cat?
Source = vagina of queen 50% or more cats <2 yr old are carriers
Opportunistic pathogenInvasion of neonate via umbilicusRapid dissemination septicemia / bacteremiaPrevention: disinfect umbilicus2% tincture of iodine
Kittens of immune dams get antibodies via colostrumThus, kitten septicemia due to Strep. less frequent in older queens
Diagnosis: cultureAntibiotic resistance not a problemPenicillin or ampicillin 1st drug of choice
Key Elements of the Story
What Strep Has Similar Epidemiology in Humans?
50% case fatality rate in 1970s
10% - 30% of pregnant women are colonized with GBS.
What Does Group G Mean?
Schematic from: http://www.bact.wisc.edu/bact330/lecturespyo
Strains of Strep. can be distinguished based on cell wall carbohydrates, known as Lancefield antigens. Commercial agglutination tests allow for rapid identification of Strep. GROUPS.
Next Case Case: Rita’s Wrist
Adult human
Infected wound
Rapid progression
Extensive tissue destruction
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24 hour BAP culture
Culture results What’s Your Diagnosis?
Necrotizing fasciitis Streptococcus pyogenes
Group A Strep
NNFF = true stories
Source = exogenous or endogenousInoculation: wound, surgery, burn, virus. Host immunologically vulnerableInvasion – inflammation (PMN) – dissemination S. pyogenes exceptionally virulent strain
– named by the press “Flesh Eating Bacteria”resists phagocytosis: M proteinkills phagocytes: leukotoxinPyrogenic exotoxins A, B, C… = Superantigens
Key Elements of the Story
Superantigens trigger cytokine release Bind MHC-II on antigen presenting cell
(APC) to Vβ region of T cell receptors nonspecifically causing massive activation and cytokine release:
IL-1,IL-6, TNF, IFN tissue destruction & leaky capillaries hypotension hypotension shock death
Story - continuedSuperantigen Binding Site Outside Typical Receptor
Activates only“primed” T-cells
Activation ofALL T-cells
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Flesh Eating BacteriaA well-deserved name
Summary: Strep Virulence Factorsnot all factors are present in all species or strains of Strep.
M-proteins Block phagocytosis Bind fibronectin to covers C’ binding sites Adherence to host cells
Capsule Low immunogenicity
Hyaluronic acid (like host tissue) Polysaccharide
Hydrophilic Impairs phagocytosis
Blocks complement (C’) activation by covering C’ binding sites
Other cell wall proteins Bind Fc portion of antibodies covering
Strep cell with host IgG decreasing C’binding and phagocytosis
Lipoteichoic acid Host cell binding
C5a peptidase Cleaves C5a (chemotaxin) preventing
recruitment of PMNs.
Exoenzymes Streptolysin S
β hemolysin; creates pores in cell membrane Fibrinolysin - fibrin lysis enhances spread of Strep
into deeper tissues
Hyaluronidase DNAases
Superantigens Toxic shock-like toxins
Immunomodulatory; triggers nonspecifc T cell stimulation and cytokine release serious negative affects on multiple organ systems leading to shock and death.
Leukocidin Kills leukocytes
Cell-associated Secreted
Multiple redundant virulence factors make streptococci very common and successful pathogens.
Immune-Mediated Sequelae Rheumatic fever – after Strep pharyngitis
Heart tissue damage caused by…. Cross reactive antigens: myosin & M-protein Genetic susceptibility of host Immune complex deposition
Acute glomerulonephritis – after skin infections Kidney damage - theories
Immune complex deposition Cross reactive antigens Alteration of glomerular tissues by Strep Complement activation by Strep in glomeruli
Purpura hemmorhagica in horses? Some experts think this is also a immune-mediated disease
triggered by strep infections.
Hemorrhages on mucosa
Edema
Other Strep Infections
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Streptococcus pneumoniaeLobar pneumonia in humans and primates.
The polysaccharide capsule is a critical virulence factor.
77 H1N1 cases evaluated
22 had bacterial pneumonia 10 Strep. pneumoniae
6 Strep. pyogenes
7 Staph. aureus – most MRSA
2 Strep. mitis
Vegetative endocarditisMultiple species of streptococci can cause this condition.
Damaged tissues predisposed to infection.
EnterococcusStrep-like morphology; differentiated by lab tests
Normal flora skin & gut
Opportunistic infections Cystitis, mastitis, endocarditis
Pathogenesis poorly understood
Difficult to treat
Emerging problem Antibiotic resistance acquired in animals can be
transferred to human strains of Enterococcus.
The End