Otitis Media/Externa Pathogenesis, Epidemiology And Treatment PDF

OTITIS MEDIA/EXTERNA PAT H O G E N E S I S , E P I D E M I O LO G Y A N D T R E AT M E N T Prepared by: BMS 150 Nick Inglis, Ph.D. Feb 12, 2023 OTITIS MEDIA (OM) ACUTE OTITIS MEDIA (AOM) ACUTE OTITIS MEDIA (AOM): COMPLICATIONS Suppurative complications of AOM - Acute ma...

OTITIS MEDIA/EXTERNA PAT H O G E N E S I S , E P I D E M I O LO G Y A N D T R E AT M E N T Prepared by: BMS 150 Nick Inglis, Ph.D. Feb 12, 2023 OTITIS MEDIA (OM) ACUTE OTITIS MEDIA (AOM) ACUTE OTITIS MEDIA (AOM): COMPLICATIONS Suppurative complications of AOM - Acute mastoiditis - Meningitis - Brain abscesses 21000 deaths from AOM per year 30 per 10,000 individuals: hearing loss Perforation of tympanic membrane OTITIS MEDIA WITH EFFUSION (OME) CHRONIC SUPPURATIVE OTITIS MEDIA (COM/CSOM) ACUTE OTITIS MEDIA (AOM) - EPIDEMIOLOGY OTITIS MEDIA WITH EFFUSION (OME) - EPIDEMIOLOGY Incidence and prevalence have been difficult to establish CHRONIC SUPPURATIVE OTITIS MEDIA - EPIDEMIOLOGY CAUSAL PAT H WAY S F O R OT I T I S M E D I A EUSTACHIAN TUBE ANATOMY THE COMMON OTOPATHOGENS Streptococcus pneumoniae (Pneumococcal conjugate vaccine?) Haemophilus influenzae Moraxella catarrhalis Pseudomonas aeruginosa HAEMOPHILUS INFLUENZA X Factor (Hemin) V Factor (NAD+) H. influenzae HAEMOPHILUS INFLUENZAE: VIRULENCE FACTORS Adhesins Polysaccharide capsule Lipid A chains/lipooligosaccharides Fimbriae IgA protease Biofilms MORAXELLA CATARRHALIS Gram –ve, diplococcus, aerobic bacteria Common for URT, middle ear, eye infections Commonly resistant to beta lactam drugs Part of normal microbiota of ~3% of people. (children more) Variable rates of colonizations in communities. MORAXELLA CATARRHALIS: VIRULENCE FACTORS Antiobiotic resistance (b-lactamase resistance) Outer Membrane Proteins - uspA1-A2, Pili Iron-Regulated Proteins - Transferrin-Binding proteins - Lactoferrin-binding proteins Lipid A chains/lipooligosaccharides STREPTOCOCCUS PNEUMONIAE: VIRULENCE FACTORS Polysaccharide capsule Fimbriae Surface proteins that inhibit activation of complement PSEUDOMONAS INFECTIONS Caused by Pseudomonas aeruginosa – an opportunistic pathogen that becomes an infectious agent following the burning away of skin; can also cause otitis externa PSEUDOMONAS AERUGINOSA: VIRULENCE FACTORS Fimbriae and adhesins to improve attachment Formation of biofilms Produce enzymes like elastase, which breaks down elastic fibres, degrades complement system, cleaves IgG and IgA antibodies Pyocyanin with triggers free radical accumulation (this is what causes tissue damage) PSEUDOMONAS AERUGINOSA: EPIDEMIOLOGY P. aeruginosa is found mostly in soil; not a component of regular microbiota Cannot penetrate epidermal layer independently – good news! Common nosocomial infection agent (10% of hospital infections) STAPHYLOCOCCUS AUREUS Salt tolerant, facultative anaerobe, resistant to dessication, UV radiation and heat Along with Staphylococcus epidermidis, make up ~90% of microbiota of skin. Common cause of otitis externa VIRULENCE FACTORS STAPHYLOCOCCUS AUREUS: 1. ENZYMES Coagulase, Hyaluronidase, Staphylokinase Hyaluronidase and collagenase Coagulase and kinase Bacterium Hyaluronidase Bacterium Coagulase Clot Clotting Kinase protein Epithelial cells Collagenase Collagen layer Invasive bacteria Bacteria produce Bacteria invade deeper Bacteria produce Clot forms. Bacteria later produce reach epithelial hyaluronidase and tissues. coagulase. kinase, dissolving clot surface. collagenase. and releasing bacteria. Extracellular enzymes VIRULENCE FACTORS STAPHYLOCOCCUS AUREUS: 1. ENZYMES Lipase, beta-lactamase Lactam ring b-lactamase (penicillinase) Penicillin breaks this bond Inactive penicillin VIRULENCE FACTORS STAPHYLOCOCCUS AUREUS: 2. STRUCTURAL DEFENSES Capsule/slime layer glycocalyx Phagocytosis blocked by capsule Incomplete phagocytosis Capsule around Capsule around Bacteria bacterium bacterium reproduce Phagocytic vesicle Phagocyte Lysosome Antiphagocytic factors VIRULENCE FACTORS STAPHYLOCOCCUS AUREUS: 2. STRUCTURAL DEFENSES Binding IgG antibody stem regions Pseudopod of phagocyte Fc receptor protein Prevention of Opsonization VIRULENCE FACTORS STAPHYLOCOCCUS AUREUS 3. TOXINS Cytolytic toxins to disrupt membranes of a large number of cell types Leukocydin – kills leukocytes (another means of avoiding phagocytosis) Epidermal Cell Differentiation Inhibitors – produces large holes in the lining of blood vessels Exfoliative toxins (Toxic Shock Syndrome Toxin) SOME OTHER DISEASES CAUSED BY STAPHYLOCOCCUS AUREUS Skin diseases Reproductive system diseases lecture Systemic infections/ cardiovascular Respiratory system diseases Gastrointesstinal system diseases THANKS! H AV E A G R E AT D AY ! ! ! KEY SOURCE : S CHIDLE R ET AL. (2016). OTITIS MEDIA N AT. R E V. D I S. P R I M 2 ( 1 ) ; H T T P S : / / W W W. N C B I. N L M. N I H. G O V / P M C / A R T I C L E S / P MC7097351/ MICROBIAL DISORDERS OF THE NERVOUS SYSTEM M E N I N G I T I S TO P O L I O Prepared by: BMS 150 Nick Inglis, Ph.D. BACTERIAL MENINGITIS Inflammatory bacterial infections of the meninges (particularly the two internal ones, the pia and arachnoid mater) Induces meningial swelling, restricting CSF flow and putting pressure on the organs, causing nausea, pain, vomiting, reduced brain function BACTERIAL MENINGITIS If the infection is in the spinal cord, muscles of the neck will become stiff and motor control will be reduced If the infection is in the brain (encephalitis), sensory perceptions are decreased, behavioural changes occur, and coma or death may result TESTING FOR BACTERIAL MENINGITIS Cloudy CSF; Positive meningitis test Lumbar puncture (aka spinal tap) Clear CSF; Negative meningitis test MANY BACTERIA CAN CAUSE BACTERIAL MENINGITIS: Opportunistic members of normal microbiota Staphylococcus aureus Steptococcus pyogenes Klebsiella pneumoniae Regular disease causing bacteria Streptococcus pneumoniae Haemophilus influenzae Constitute ~90% of cases Listeria monocytogenes of bacterial meningitis Neisseria meningitidis NEISSERIA MENINGITIDIS Causes meningicoccal meningitis Virulence factors include: fimbriae and polysaccharide capsules, Lipooligosaccharide (with Lipid A/Endotoxin), and various factors to prevent digestion in phagocytes BLEBBING OF N. MENINGITIDIS STREPTOCOCCUS PNEUMONIAE Leading cause of meningitis Virulence factors: capsule, secretory IgA protease, pneumolysin (inactivator of lysosomal enzymes) Primary virulence factor: phosporylcholine (attachment to cells of lungs, meninges, blood vessels – and triggers endocytosis) LISTERIA MONOCYTOGENES Gram +ve coccobacillus found in soil, water, and many animals (no endospores) Obtained through contaminated food/drink Causes meningitis in immunocompromised individuals, but only mild flu in healthy adults. Avoids immune system detection by dividing inside macrophages and epithelial cells Phagocytosis Listeria Newly infected cell Listeria Originally infected cell Pseudopod of cell 1 Pseudopod of cell 2 Phagocytosis Actin “tail” PATHOGENESIS OF BACTERIAL MENINGITIS N. meningitidis, H. influenzae, S. pneumoniae – inhaled in respiratory droplets Listeria – unpasteurized milk, cheese, meat Bacteria usually spreads to meninges from infections of lungs, sinuses, or inner ear Head or neck trauma may expose meninges directly Bacteria ferment glucose in CSF for energy PREVENTION Susceptible individuals should avoid undercooked veggies, unpasteurized milk, undercooked meat and all soft cheese People living in dormitories should receive vaccinations HANSEN’S DISEASE (LEPROSY) Causative Agent: Mycobacterium leprae Optimal growth – 30°C – so in the chilly parts of your body (peripheral nerve endings, earlobes, nose, tips of fingers and toes. Signs of disease may not be present for 10-30 years, but when the population becomes big enough, your immune system will aggressively attack them WHEN YOUR IMMUNE SYSTEM ATTACKS Not shown: nerve damage BOTULISM Causative agent: Clostridium botulinum toxin (note: NOT an infection) 3 types of botulism: foodborne, infant, and wound Foodborne/Wound Botulism symptoms: paralysis of all voluntary muscles, blurred vision, nausea (death from respiratory paralysis Infant botulism: not ingested, but C. botulinum can infect GI tract due to absence of microbiota HOW BOTULISM TOXIN ACTS AT A NEUROMUSCULAR JUNCTION TETANUS Causative agent: Clostridium tetani Portal of entry: endospores enter through breaks in skin Signs/symptoms: tightening of jaw and neck muscles, difficulty swallowing, fever, spasms Treatment: aggressive treatment of wound, antibiotics Prevention: Vaccination  Stimulating neuron Inhibitory neuron Inhibitory neurotransmitter counteracts the effect of stimulatory neurotransmitter Muscle not Stimulatory contracted neurotransmitter (relaxed) Nerve impulse inhibited Motor neuron Normal action of inhibitory neurotransmitter TETANUS TOXIN (TETANOSPASMIN)  Tetanospasmin Muscles fully contracted, cannot relax Ach Nerve impulse Tetanospasmin (tetanus toxin) blocks release of inhibitory neurotransmitter TETANUS TOXIN (TETANOSPASMIN) WEST NILE FEVER WEST NILE FEVER Absent from N. America until 1999! New York isolate identical to Israeli goose Virus infects 100s of bird, 37 mosquito, 18 other vertebrate (including humans/horses) species WEST NILE VIRUS TRANSMISSION CYCLE WNV - PATHOGENESIS Transmitted by mosquito bite Incubation period of 3-14 days 20-30% get flu-like illness called West Nile Fever 80% - NO symptoms 1/150 EXPERIENCE NEUROINVASION Headache Ocular manifestations Muscle weakness Cognitive impairment Polio-like flaccid paralysis 10% mortality WNV REPLICATIVE CYCLE IN HUMANS EPIDEMIOLOGY – US CASES EPIDEMIOLOGY – CASE FATALITY RATE WNV PREVENTION POLIOMYELITIS - POLIOVIRUS POLIOVIRUS PATHOGENESIS CD155 TRANSGENIC MICE POLIO STAINING IN MOUSE SPINAL CORD POLIO TIMECOURSE PATHOGENESIS OF POLIOMYELITIS Humans are the only known reservoir Spread by fecal-oral transmission Peaks during warm months in temperate climates Complication: post-polio syndrome 30-40 year interval 25-40% Not an infectious process POLIO EPIDEMIOLOGY EMERGENCE OF POLIO AS AN EPIDEMIC IN THE 1900S Polio has only minor symptoms for infants and adults (seems like a mild cold) Early in the 1900s, white, wealthy children starting getting paralytic polio Connection to modern plumbing, sewer systems, etc. POLIO EPIDEMIOLOGYZ 1988: 350000 cases; 2000s: ~1000 cases/year Americas/Europe: now “polio-free” THANK YOU! S E E YO U N E X T T I M E !