Pathogenesis and Aetiology of Mastitis Flashcards
1
Q
Disease Process Involving the Mammary Gland
A
- Mastitis
- Neoplasia of Mammary Gland
- Diseases of the SKin of teats and mammary gland–> Gangrene (Wet/Dry)
- Trauma (and subsequent mastitis)
- Teat Blockage (mastitis or loss of function)
- Pathogen Transmission to young
2
Q
Mastitis
A
- Considered one of the big 3 diseases of dairy cattle
- Very Expensive as there is an issue with loss of function, treatment, cost of culling, etc.
- Has a significant impact on animal welfare: can die overnight from toxic mastitis and is it also very painful!
- Can often prevent this though which is good and do something about it
3
Q
Big Disease Processes in Dairy Cattle
(3 main)
A
- Mastitis
- Lameness
- Fertility Decrease
4
Q
Mycoplasma Bovus in the Herd
A
- Clotting/curtled appearance often associated with the pathogen Mycoplasma bovus
- If it persists it can cause persistent mastitis within the herd and lead to mass culling
- can also see lameness in these cows
- Big issue when in the herd
- causes significant issues
5
Q
Mammary Gland Structure
A
- Its like an apocrine gland of the skin
- milk producing alveoli –> leading into glandular ducts –> leading into lactiferous sinus–> then into the papillary duct and through the teat
- majority of disease entry will be through the teat
- Galactophoresis refers to all the ducts
- where as mastitis then refers also to the tissues and alveoli affected
- will spread along the sinuses and then the ducts before reaching the alveoli and affecting the milk producing tissue (if the pathogen enters from an external source)
6
Q
Mammary Gland Histo
A
- Immature gland or inactive (not induced to grow by prolactin or estrogen)
- Lactating can see the milk within the alveoli being produced
7
Q
Entry of Microorganisms into the Mammary Gland
A
- galactogenic or ascending infection - organisms somehow gain entry via the teat canal (most common)
- or bloodstream going directly into alveoli (where major blood supply is)- often diseases where we don’t see the mycoplasma associated with it
- trauma can result in damage in the teat and pathogens getting directly into the papillary duct
8
Q
Defence Against Mastitis
A
- Try to control pathogen entry and pathogen proliferation
- Whether these cases will present as mastitis - depend on host immunity, pathogen itself and env’tal conditions
9
Q
Resistance to Infection
A
- How does the mammary gland protect itself? (fight or prevent infectious disease from manifesting itself)
- Keratin block from epithelium - the teat itself prevents infection itself. Need to try and keep the teat in good function and health to act as main protection. whole of the teat is basically anitbacterial
- Main mode of protection is the teat itself so often don’t get infection - protecting the teat is a major factor. If they bypass the teat and get into the lactiferous sinus, there will be an infection no matter what
- Furstenberg Rosette - prevent the entry of bacteria, mucosal folds with a lot of blood supply so it gets a lot of plasma cells there helping with the immunity
- these are physical factors that are part of the innate immunity, but also… milking them out can be really helpful!
10
Q
Resistance to Infection
(innate Immunity)
A
- there are soluble and cellular factors to this innate immunity as well
- If you get bacteria in there, you will get neutrophils in there very very quickly
- Unfortunately, neutrophils are much more efficient in the blood than in the milk (in the milk they often don’t manage to kill the bacteria fully)
- You tend to get this inverse cycling of high numbers of neutrophils and then the neutrophils kill other neutrophils and you seen get high numbers of bacteria and low neutrophil count and keeps on going
- hard to control
- followed on by macrophages
11
Q
Resistance to Infection
(adaptive)
A
- In particular IgA on the immunoglobulin side has been the local Ig
12
Q
Mammary Tissue Damage
A
- damage/issues is therefore not only caused by the pathogens but by the inflammation
- neutrophils die off and release cytokines, host proteases that can all dmage the tissue and result in longer term damage and shorter term as well
- even repair can damage- fibrosis
13
Q
Categorization of Mastitis by “time”
A
- Traditional way of separating mastitis is: contagious and environmental, but this is a way to identify by timing
- If acute isn’t treated and hasnt reached complete resolution, then you could end up with chronic mastitis
- Chronic mastitis can lead to progressive loss of secretory ability, which can often lead to eventual culling - and the chronic is usally following subclinical infections or acute infections
- Type of Pathogen does not define this: Staph Aureus could cause all of them (peracute, acute, chronic)
- Type of mastitis is not pathogen dependent
- Do not forget subclinical mastitis as it is the most common
14
Q
Peracute Mastitis/Severe Necrotising
A
- Usually associated with systemic disease and a lot of fertility disease
- severe necrotizing
- turns cold and blue
- Tends to be caused by S.aureus - alpha toxin causing vasoconstriction and ischemia
- but can also have a more severe ‘toxic mastitis”- due to coliform bacteria, E.Coli–> endotoxin release. Get severe vascular leakage and that can be seen by marked edema (gelatinous appearance) in the subcutaneous tissue. Often it is very watery fluid
- In severe cases, if they go recumbent, part of the udder can just slough off bc its blood supply has been cut off and it becomes gangrenous and they just lose it- but they can survive this!
- But the toxemia is the major problem
15
Q
Acute Mastitis
A
- much less toxin production/release and damage to the tissue
- much more local effects: oedema, fibrin, neutrophilic inflitration (when you are milking a cow and you see the clots come out- that is usually a sign of acute mastitis)
- when you look histologically: lots of neutrophils, edema, fibroplasia
- if you dont get under control at this point and get fully rid of it, may progress to chronic mastitis
16
Q
Chronic Mastitis
A
- If the acute mastitis doesn’t clear up, you may get local fibrosis around the milk ducts and there may be a block on the milk coming from healthy areas
- may get involution (temporary loss of secretorial function due to an obstruction) of the glands - can recover in the next lactation and come back into function
- permanent loss would then be fibrosis- the tissue will not be replaces, it can not be regenerated so the tissue is lost
17
Q
Acute Localised Clinical Mastitis - Initial Flare Up
A
- Get acute infection and then travels up the ducts to settle somewhere in the mammary gland
- starting to cause some lesion and then neutrophils will come in to repair
- get some fibrosis (obviously due to tissue being damaged somewhat, get necrosis replaced by fibroplasia) - not that big a deal, normally affects this little acinoid only
- but the neutrophils aren’t very good and effective (particularly in the periparturient period - they don’t migrate as well into the mammary gland)
- thus, may get a further infection/ flare up just adjacent to it, and the same immune/repair processes occur, but then that fibrosis may block up that whole area and there is blockage - when you get repair then by fibrosis of this, the whole area connot drain anymore
- may get involution or fibrosis of this area depending on how much it spreads around
18
Q
Subclinical Mastitis
A
- Much more common than clinical
- You don’t see clots, you don’t see watery appearance - looks pretty normal, feels pretty normal
- how do we know there is mastitis then? - CELL COUNT WILL INCREASE
- CMT will be your best estimate: will detect neutrophil cells and will result in the more viscous appearance of fluid (Note: will need to know how to do these for the OSCE’s)
- from a disease development of subclinical mastitis, it develops almost identically to acute mastitis and then into chronic mastitis (still get pathogen entry, but just doesn’t cause as much local damage or disease to result in obvious or systemic changes)
- Still need to interfere and treat even though it is a lower pathogenesis
- SCC should be less than 200,000 cells/ml of milk (can input for each quarter)
- can then make sure there is no inflammation going on
- Neutrophil numbers already rise quickly in infections, so you should be able to detect them early on
19
Q
Take Home Messasges on Mastitis
A
- This is not only an issue in dairy cows! - See it in sheep (gangrenous mastitis leading to early culls)
- most of your efforts will be based on preventing galactogenic entry
- immune response has a big effect (emphasis) on the clinical presentation of mastitis
20
Q
Bovine Mastitis
A
- Divide type of Mastitis and Pathogens
- Tend to divide mastitis based on timing of clinical presentation and if it was from a contagious or env’tal source
- but the difference b/w env’t and contagious pathogens has been blurred a bit bc pathogens themselves that are important to mastitis have changed
- the spectrum of contagious and env’tal pathogens is continuous, can’t just group them together
21
Q
Causes of Clinical Mastitis in the U.K. in Dairy Cattle
(lactating Bovine Mastitis)
A
- biggest cause S. uberis
- 2nd: E.Coli (gram negative rod, derived from the gut)
- CNS: coagulase-negative staphylococci
- also 11%: coagulase positive staphylococci (S. aureus)
- Green: mixed cultures
- Coryne bacteria: small gram positive rod
- Streptococcus dysgalactiae: very small bit (only 2%), USED to be a really important pathogen in dairy cattle in the UK. Has largely been removed from the herd, as has another, Streptococcus agalactiae
22
Q
Causes of Subclinical Mastitis
(lactating Bovine Mastitis)
A
- Slightly different pattern to that of Clincial mastitis chart
- The is stil a lot of Streptococcus uberis causing disease (arguably, is it disease since it is subclinical?)
- Subclinical mastitis just means an increased somatic cell count and we can’t see it as overt clinical disease, but there is still a disease process going on there
- Also, subclinical mastitis can be defined on the high bacterial cell count you get in the milk
- Inflammation of the udder IS what mastitis is - whether it is being caused by something subclinically (can’t see until you do the tests) or whether it is acute
- CNS: coagulase- negative staphylococci (derived from skin originally) is the biggest player here!
- S. Aureus: suprisingly (nasty, aggressive pathogen) can cause disease processes in the udder that are very chronic and low grade (can’t see it is happening!)
- Coryne bacteria also appears much more in subclinical cases
- These stats are from about 10 yrs ago
23
Q
Primary Agents in Lactating Mastitis
A
- S. aureus- derived from mucus membranes (nasal, perineal, repro tract - gets into udder by ascending route)
- E.Coli - from feces, gets in ascending route as well
- S. uberis tends to be in the environment of cattle but we dont really know where it sources from to get into the udder (perhaps it is on the skin, carried in the gut)
Then there are the other pathogens, less on importance in farm animal practice, but more for completion
- S. agalactiae used to be the cause of contagious mastitis (and where the use of contagious mastitis really came from v. environmental) and used to be a huge problem –> would be transferred from cow to cow by hands or milking equipment. Truly contagious, but so host adapted to living in the udder (living around the milk). We were able to rid of it out of the national herd - now we rarely see it. (also called GBS by medics)
- GBS- Lancefield (group B streptococcus). Lancefield group is based on the carbohydrate antigen in the cell wall - same thing that oyu hear about causing reproductive problems in humans and leading to death of very young neonates as the infection is transferred from birth canal to babies
- S. dysgalactiae- comes up as about 2% of cases (used to be much bigger and is cause of more acute form of mastitis. agalactiae tended to cause chronic disease as it was so host adaptive)
- Mycoplasma bovis: Mycoplasma bacteria (NOT the same as mycobacterium) have no cell wall/peptidoglycan (so cannot treat with B-lactam AB’s (penicillins, cephalosporins- which is what is used often in mastitis) - innately and completely resistant
- C. bovis –> noted cause of mastitis on farms
- Some nasty ones that are resistant at time on farms (not that they cause more sever or acute disease) : (Pseudomonas - always AB resisitant to a wide reange of drugs, Klebsiella - enterobacteria like E.Coli but much more resistant to AB’s, and sometimes Yeasts! - fungi are not sensitive to antibacterial AB’s) –> if the mastitis tube isnt working, need to think of these being a possibility
24
Q
Staphylococcus aureus
A
- Natural habitat is skin (damaged skin particularly) and mucus membranes
- If there is damage to the udder or on the teat, the A. aureus can hone in on that colonize it very nicely
- binds to fibronectin and fibrinogen very well (scabs on the body) and will grow & invade tissue
- Enter through teat canal and go all the way from subclinical mastitis through to peracute (the full range) and over different periods of time
- 70% of the strains are resistant to B-lactam drugs (producers of penicillinase/B lactamase)
- MRSA is also ressitant to the AB’s we would use for those B-lactamase producers
- Cloxacyllin (orbenin) is used quite widely in mastitis (B-lactamase stable penicillin), but an MRSA will not be sensitive to this
- S.aureus can be an intracellular organism (usually epithelial cells or macrophages) and evade immune response and survive for long periods of time- this is likely why you get recurrence (flare-up where the infection comes back when you think you got rid of it. it is survivng in the host cells)
- Not easy to get rid of easily!
26
Q
Hypersensitivity
A
- Can get IgE attached to mast cells in the tissues and these will react and respond to the Staphylococcus even if is not invading and cause further inflammation
- organsims need to just be adherent to the internal duct of the sinus epithelium and then the mast cells will degranulate and cause inflammation there
27
Q
S. Aureus
(pathogenicity factors)
A
- alpha toxin is a nasty, awful, potent, nectrotizing protein- even small tiny amount of alpha toxin will cause necrosis and a lot of other effects that we see
- staphylococcal TSST-1 : toxic shock syndrome toxin
- produce other factors and enzymes that allow them to stick and allow them to degrade the tissues that they find around them so that they can grow
- there is no vaccine against Staphylococcal disease
28
Q
Antimicrobial Resistance in S. aureus
A
- Antimicrobial resistance in Staphylococcus is quite wide spread
- not just to B-lactams (most of the drugs on this MIC plate are B-lactams), but actually to a lot of other drugs as well
29
Q
Streptococcus agalactiae
A
- In the UK, it is largely almost gone!
- host adapted to that site and likes to cause slow progressive disease that doesnt cause much inflammation
- there is no vaccine
- in the western world, we probably no longer need a vaccine
30
Q
Streptococcus dysgalactiae
A
- causes a more acute mastitis
- Not really host adapted - natural habitat is outside the teat
- requires some sort of trauma or wound to allow it to get into the udder and into the teat canal
- Immune response (bc it is not host adapted) cuases the infections to be self limiting
- you will get fibrosis but because it is acute you will get rid of it with immune response
- again no vaccine available
31
Q
Streptococcus uberis
A
- Commonest pathogen we are seeing according to actual figures of diagnosed cases
- likely sourced from feces?
- also, requires trauma to the teat/udder to infect - some minor abrasion to allow it to get into the teat
- No Lancefield group - bacteriologically we have to do other tests to be able to distinguish it
- there are no current vaccines, efforts are the but currently not efficient enough or $$$ to use on farms
32
Q
Escherichia coli
A
- E.Coli is ubiquitous in a barn because there is shit everywhereeee
- Almost any E.coli can cause mastitis -E.Coli’s don’t need to be particularly special to cause disease
- cause of acute mastitis and can be antimicrobial resistant - some people and clinicians will say you don’t need to treat E.Coli mastitis and will rid on its own (Treat this approach with interest though! –> Toxaemia is a big concern!)
- endotoxin is LPS (its that the body responds to the LPS with cytokines like IL-1 and TNF- alpha) - lead to fever and cause damage in the body - this is the the same toxemia that causes septic shock
- but they do have pathogenicity factors - and most strains do have a combination of these virulence factors
- Fe-acquisition is huge for these pathogens
- Lactoferrin is a good protective bacteriostatic agent in the udder for pathogens, but these pathogens can overcome it!
- CNF-1 (cytotoxic necrotizing factor)
- K-types: potential capsule types
- adhesive factors in E. Coli as well (pili)
33
Q
Vaccine - killed J5
A
- there have been attempts to make vaccines for E.Coli infection and there has indeed been a vaccine that has been released on the market
- mutant lacking O- antigen (killed strain of E.Coli)
- unique core antigen technology - but really just a mutant that doesnt have an O-antigen and exposes a deeper part of the LPS
- host will make ab that wil hopefully be helpful against pathogen
34
Q
Multi-resistant E. Coli
A
- can be multi-resistant (on farms and SA clinics alike)
- they don’t always respond tothe drugs that we would expect them to respond to
- Such things as (on this plate): amoxycillin and clavulanic acid, gentamicin, streptomycin, beytril
- this strain on the plate is resistant to all those!- what do you treat it with?
35
Q
Mycoplasma Bovis
A
- widespread and important in causing mastitis and joint disease as well as respiratory disease in calves
- can’t test for it very well, but its there and animals are becoming more susceptible
- can’t easily culture for it or test for it
- colonies: look like tits in space
36
Q
Dry Cow Mastitis
A
- Primary agents in this are different for this than Lactating mastitis
- T. pyogenes - small, gram positive rod, that produces nasty toxin.
- S. dygalactiae - same as the one of Lancefield group C that causes clinical mastitis
- P. indolicus - strictly anaerobic coccus
37
Q
Trueperella pyogenes
A
- minute haemolyic colonies that are slow to grow
- been given different names! - people will mention Corynebacterium pyogenes - not the same as the corynebacterium as mentioned in lactating
- can go by any of these names that you will hear
38
Q
Mastitis in Ewes
A
- yet again slightly different pathogens causing mastitis
- M. haemolytica - little negative rod pasteurellaci
- if you go outside of UK - M. agalactiae is a concern! nasty pathogen that we do not want to import!! - if it is discovered, IT IS NOTIFIABLE
41
Q
A
- Peracute (gangrenous) mastitis
- How there is dry gangrenous tissue and the acuteness of the ring of hemorrhagic material around it
42
Q
Acute Localised Clinical Mastitis - repair by fibrosis
A
43
Q
Acute Localised Clinical Mastitis - further flare ups
A
44
Q
Acute Localised Clinical Mastitis - progressive fibrosis
A
46
Q
A
T. pyogenes - minute - haemolytic colonies - 48 hours + grow
48
Q
A
- Acute, Pre- gangrenous mammary infection
- caused by S. aureus
49
Q
A
