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Transcript
Pathogenesis of Infectious Diseases BY Prof. DR. Zainalabideen A. Abdulla, DTM&H., MRCPI, Ph.D., FRCPath. (U.K.) Learning Objectives Infection versus Infectious Diseases • Patho from path = Disease • Pathogenicity = Ability to cause a disease • Pathogenesis = Steps/mechanisms involved in development of a disease • Infection = Colonization by a pathogen, but NOT necessary to have infectious disease (WHY?) Why infection does not always occur • Microbes are unable to multiply e.g. respiratory microbes on the skin • Lack of a specific tissue receptor for microbes • Antibacterial factors, e.g. Lysozymes • Indigenous microbiota, e.g. Bacteriocins • Overall health status • Immunity and vaccination • Phagocytosis: In blood and tissues Periods/Phases of infectious diseases 1. Incubation Period Pathogen arrival Symptoms Onset 2. Prodromal Period: Out of sort/No symptoms 3. Period of illness: Symptoms/Communicable 4. Convalescent: Recovery; may be long or with tissue damage Localized vs systemic infections • Localized infections, e.g. boils, abscesses • Systemic infection: Localized Spread by blood, lymph or phagocytes (wondering) e.g. Mycobacterium tuberculosis spread to internal organs is called military tuberculosis (disseminated) Acute, Subacute, and Chronic diseases Acute disease: Rapid onset; Rapid recovery e.g. Measles, mumps Chronic disease: Slow onset; Lasts a long time e.g. Tuberculosis, Leprosy Subacute disease: More sudden that chronic, less than acute e.g. Subacute endocarditis (SAE) Symptoms vs Signs of a disease Symptoms: Subjective evidence experienced or perceived by patients, pain, itching, nausea, etc Symptomatic disease: Clinical disease “with” Asymptomatic disease: Subclinical “unaware” Example: N. gonorrheae: Male: Symptomatic Female: Asymptomatic Trichomonas vaginalis: Reverse Signs: Objective evidence of a disease detected by clinicians, e.g. hepatomegaly, heart rate, etc Latent infection • Latent = Lie hidden • Latent disease: Dormant (Not currently manifest) Symptomatic Asymptomatic Symptomatic Examples: - Human Herpes Virus (HHV) type 1 Cold Sore or HHV type 2 Genital - HHV type 3 (Chickenpox Shingles) - Syphilis (Spirochete: Treponema pallidum) Primary vs Secondary Infections • One infectious disease follows another • First: Primary infection Second: Secondary infection • Example: Primary: Mild viral respiratory infection (damage respiratory ciliated epithelium) Secondary: Pneumonia; due to inhaled: • Streptococcus pneumonia • Haemophilus influenzae Steps in pathogenesis of infectious disease 1. Entry (different routes) 2. Attachment 3. Multiplication (Local or systemic) 4. Invasion or spread 5. Evasion (avoid) of host defenses 6. Damage to host tissue (s) N.B.: Not always ALL steps involved Virulence • Synonym to Pathogenic (Virulent) Disease Nonpathogenic (Avirulent) NOT • Toxigenic (virulent), e.g. C. diphtheria • Encapsulated (virulent), e.g. S. pneumoniae • Some pathogens are more virulent than others e.g. Shigella > Salmonella • Strains more pathogenic than others of the same pathogen, e.g. S. pyogenes producing erythrogenic toxin (causes scarlet fever) Virulence Factors Attachment: • Receptors (integrin) on tissues: - Glycoprotein - S. pyogenes: Adhesin (Protein F) - HIV: CD4 receptor • Adhesin (Ligand) on pathogens: - HIV: Glycoprotein gp 120 CD4 Bacterial Fimbriae (Pili) • Hairlike, flexible projections • Proteins (Pilin) • Attach to surfaces • Example: N. gonorrheae: To Urethra E.coli: Bladder S. pyogenes M protein: - Adhere to pharyngeal epithelium - Anti-phagocytic Obligate intracellular pathogens • G- : Rickettsia (endothelial cells) Chlamydia (Respiratory/genital epith. Eye conjunctiva) • Malaria: Plasmodium (RBC) Facultative intracellular pathogens • Extracellular and intracellular existance e.g. in phagocytes & on culture media Intracellular survival mechanisms • Phagocytes: Macrophages & neutrophils e.g. M. tuberculosis: Wax (protect m.o. from destruction inside phagocytic cells); Table Capsules • Anti-phagocytic (unable to engulf) e.g. Streptococcus pneumoniae Haemophilus influenzae Klebsiella pneumoniae Flagella • Motile bacteria: So invade aqueous areas • Anti-phagocytic Exoenzymes • Necrotizing enzymes, coagulase, kinases, hyaluronidase, collagenase, hemolysins and lecithinase • Some pathogens produce also toxins e.g. S. pyogenes Necrotizing enzymes • Destroy tissues - Clostridium perfringens causes gas gangrene (myonecrosis) by proteases and lipases - S. pyogenes (flesh-eating strain) causes necrotizing fasciitis Coagulase • Staphylococcus aureus feature • Binds prothrombin Staphylothrombin Clot plasma Protect themselves by fibrin coat against Ab and phagocytosis Kinases • Fibrinolysins (vs coagulase) • Example: - Streptokinase of Streptococci (used to treat coronary thrombosis) - Staphylokinase of Staphylococci Hyaluronidase • Spreading factor • Breaks hyaluronic acid of connective tissue • Staphylococcus, Streptococcus, Clostridium Collagenase • Breaks collagen (tendon, cartilage, bones) • Example: C. perfringens Hemolysins • Destroy RBC Iron to pathogens • Types of hemolysis (alpha, beta, gamma) Lecithinase • Breaks phospholipids (Lecithin) as of RBC • Example: C. perfringens Toxins 1. Endotoxin 2. Exotoxins Endotoxin • Septicemia (sepsis) • G- cell wall (Lipid A of Lipopolysaccharides) • Fever (caused by pyrogens) •• Septic shock: Inadequate blood supply to vital organs Exotoxin • Poisonous proteins • Neurotoxins, enterotoxins, cytotoxins, exfoliative toxin, erythrogenic toxin, diphtheria toxin cont./… exotoxins Neurotoxins • Affect CNS • Clostridium tetani (Tetanospasmin effect: spastic, rigid paralysis); Figure Clostridium botulinum (generalized flaccid paralysis) Enterotoxins • Cause diarrhea and vomiting • E. coli, Shigella, Salmonella, C. perfringens C. difficile (Toxin A and B) Toxic Shock syndrome: 1. Staphylococcus aureus (common cause) TSST-1 affects integrity of capillary wall 2. Streptococcus pyogenes (less common) Exfoliative (epidermolytic) toxin • S. aureus Scaled Skin Syndrome Erythrogenic toxin • S. pyogenes Scarlet fever Leukocidin • Destroy leukocytes (WBC)/the phagocytes • Staphylococci, Streptococci, Clostridia Diphtheria toxin • Corynebacterium diphtheria • Inhibits protein synthesis Kills mucosal epithelial cells & phagocytes Affects heart and nervous system Coded for by bacteriophage gene (infected)