Phil s Friendly Filly: Philena. Some Help? Philena the Philly. First Case. Tip: This is abnormal. Quarter horse One-year-old Owner s complaint:

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1 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 Some Help? Physical exam: Fever Nasal discharge Swelling behind the mandible: right side Tip: This is abnormal 24 hour BAP culture Gram s stain of exudate What s Your Diagnosis? Diagnosis? (disease common name) A. Strangles B. Lymphadenitis C. Mastitis D. Runny nose 1

2 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 Key Elements of the Story Source = infected horse; another foal or adult carrier Exposure history, e.g.. horse show Host immunologically vulnerable; age / naïve Critical time between end of passive immunity and beginning of active immunity Inhalation or ingestion: infection starts at tonsils Invasion inflammation (PMN) dissemination S. equi factors: resists phagocytosis: M protein kills phagocytes: leukotoxin impairs host attempt to wall off: fibrinolysin DNAase: thin runny pus More Key Story Elements Human version of the story 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 2

3 What if The Foal Was Vaccinated? Strep equi vaccine IM 2 doses 2 weeks apart Vaccines Sometime Fail..why? Dratt! Vaccines Sometime Fail..why? Next Case 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 Marvin s Mistake I 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 postcalving One quarter hot and inflamed Don t you DARE touch me! 3

4 Milk abnormal - High somatic cell count (SCC) Additional information Gram stain BAP at 24 hours Clotted, stringy, cellular CAMP Test What s Your Diagnosis? Staph. aureus (dbl zone) Strep unknown Synergistic hemolysis What was the primary source of infection? Mastitis Streptococcus agalactiae (a Group B Streptococcus) A. Infected purchased cattle B. Skin of the milker s hands C. Cow s environment D. Normal microflora of the udder 4

5 Key Elements of the Story Source = infected cow OBLIGATE pathogen Can be eradicated from herd Prevention by pre-purchase testing Spreads at milking - - HYGIENE Ascending infection Acute inflammation; neutrophils Antibiotic resistance not a problem Diagnosis: culture, cow or bulk tank CAMP test = definitive 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 CMT California 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 herd Four 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 Problems Jim Dickrell, Dairy Today, October 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!!! 5

6 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? Septicemia Strep canis aka Group G Streptococcus 6

7 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? Key Elements of the Story Source = vagina of queen 50% or more cats <2 yr old are carriers Opportunistic pathogen Invasion of neonate via umbilicus Rapid dissemination septicemia / bacteremia Prevention: disinfect umbilicus 2% tincture of iodine Kittens of immune dams get antibodies via colostrum Thus, kitten septicemia due to Strep. less frequent in older queens Diagnosis: culture Antibiotic resistance not a problem Penicillin or ampicillin 1 st drug of choice What Strep Has Similar Epidemiology in Humans? 50% case fatality rate in 1970s What Does Group G Mean? 10% - 30% of pregnant women are colonized with GBS. 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. Schematic from: Next Case Case: Rita s Wrist Adult human Infected wound Rapid progression Extensive tissue destruction 7

8 Culture results What s Your Diagnosis? 24 hour BAP culture Key Elements of the Story Necrotizing fasciitis Streptococcus pyogenes Group A Strep NNFF = true stories Source = exogenous or endogenous Inoculation: wound, surgery, burn, virus. Host immunologically vulnerable Invasion inflammation (PMN) dissemination S. pyogenes exceptionally virulent strain named by the press Flesh Eating Bacteria resists phagocytosis: M protein kills phagocytes: leukotoxin Pyrogenic exotoxins A, B, C = Superantigens Story - continued Superantigen Binding Site Outside Typical Receptor 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 Activates only primed T-cells Activation of ALL T-cells 8

9 Flesh Eating Bacteria A well-deserved name Summary: Strep Virulence Factors not all factors are present in all species or strains of Strep. Cell-associated 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. Secreted Leukocidin Kills leukocytes 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 9

10 Streptococcus pneumoniae Lobar pneumonia in humans and primates. The polysaccharide capsule is a critical virulence factor. Vegetative endocarditis Multiple species of streptococci can cause this condition. Damaged tissues predisposed to infection. 77 H1N1 cases evaluated 22 had bacterial pneumonia 10 Strep. pneumoniae 6 Strep. pyogenes 7 Staph. aureus most MRSA 2 Strep. mitis Enterococcus Strep-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 10