Ch8-Infectious diseases.ppt

INFECTIOUS DISEASES  Vandaag Categorieen infectieuze agens Diagnostische methoden Entrée route, methode Spreiding microben Infectie mechanismen Type ontstekings respons op infectie CATEGORIES Prions Viruses Bacteria Fungi Protozoa H...

INFECTIOUS DISEASES  Vandaag Categorieen infectieuze agens Diagnostische methoden Entrée route, methode Spreiding microben Infectie mechanismen Type ontstekings respons op infectie CATEGORIES Prions Viruses Bacteria Fungi Protozoa Helminths  T8-1 Classes of Human Pathogens and Their Lifestyles Site of Taxonomic Size Propagation Examples Disease Prions 30-50kD Intracellular Prion protein Creutzfeld-Jacob disease Viruses 20–300 nm Obligate intracellular* Poliovirus Poliomyelitis Bacteria 0.2–15 µm Obligate intracellular Chlamydia trachomatis Trachoma, urethritis Extracellular Streptococcus pneumoniae Pneumonia Facultative intracellular* Mycobacterium tuberculosis Tuberculosis Fungi 2–200 µm Extracellular Candida albicans Trush Facultative intracellular Histoplasma capsulatum Histoplasmosis Protozoa 1–50 µm Extracellular Trypanosoma gambiense Sleeping sickness Facultative intracellular Trypanosoma cruzi Chagas disease Obligate intracellular Leishmania donovani Kala-azar Helminths 3 mm–10 m Extracellular Wuchereria bancrofti Filariasis Intracellular Trichinella spiralis Trichinosis *Obligate intracellular= growth only inside host cells *Facultative intracellular= survive & replicate either outside or inside hostcells PRIONS = PRO-teinaceous IN-fectious particle abn. forms host protein or PrP sc (prion proteins) Pathogenesis: accumulation PrPsc  PRIONS Clinically: “Bovine Spongiform Encephalitis” (Cows), “CJD”, Kuru (Humans)  VIRUSES Less than ½ micron, usually MUCH less DNA/RNA “CORE” (genome) Protein coat “CAPSID” Sometimes lipid membrane “ENVELOPE”  BACTERIA GRAM staining with CRYSTAL VIOLET – POSITIVE: THICK wall, ONE phospholipid layer – NEGATIVE: THIN wall, TWO phospholipid layers SHAPE – COCCI (balls) – BACILLI (rods) OXYGEN requirements – AEROBIC (NEED O2) – ANAEROBIC (do NOT NEED O2) Gram + bacilli (rods) Gram - cocci  FUNGI GROWTH: YEASTS, HYPHAE (SEPTATE/ASEPTATE) CANDIDA MOST PREVALENT INFECTION: – SUPERFICIAL i.e. skin = DERMATOPHYTES, (“tinea” pedis , capitis) – DEEP FUNGI (GRANULOMAS) HISTOPLASMOSIS BLASTOMYCOSIS COCCIDIOMYCOSIS – OPPORTUNISTIC CANDIDA, ASPERGILLUS, MUCOR & CRYPTOCOCCUS SEPTATE HYPHAE  PROTOZOA INTESTINAL or BLOOD PLASMODIUM (MALARIA) LEISHMANIA TRYPANOSOMA TOXOPLASMA ENTAMOEBA GIARDIA  HELMINTHS (ROUND[nematode]), TAPE[cestode]) Roundworms, Tapeworms Complex Life Cycles: sexual, asexual ROUNDWORMS (nematodes): ASCARIS, TOXOCARA (VLM), STRONGYLOIDES, ENTEROBIUS TAPE(FLAT)WORMS (cestodes): TAENIA (solium vs. saginata), DIPHYLLOBOTHRIUM, Hymenolepsis  DIAGNOSTIC TECNIQUES HEMATOXYLIN AND EOSIN (HE) SPECIAL STAINS (GRAM+/- , ACID-FAST, SILVER, GIEMSA) SERUM (PATHOGEN SPECIFC ANTIBODIES) MOLECULAR DIAGNOSTICS (DETECTION AND QUANTIFYING) – POLYMERASE CHAIN REACTION  AGENTS OF BIOTERRORISM 3 CATEGORIES – A. = HIGHEST RISK – B. = MODERATE – C. = EMERGING  EMERGING INFECTIOUS DISEASES SARS (2003) SWINE FLU (MEXICAN FLU) (2009) Ebola (2014) Chikungunya (2014) Zika (2015)  EMERGING INFECTIOUS DISEASES COVID-19 disease Virus : severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)  ENTRY ROUTES MICROBES – SKIN – GI TRACT – RESPIRATORY TRACT – UROGENITALIS TRACT  ENTRY METHOD –INHALATION –INGESTION –SEX. TRANSMISSION –INSECT / ANIMAL BITES –INJECTION  SKIN – OPPORTUNISTS (S.EPIDERMIS & C.ALBICANS) – PENETRATE UNBROKEN SKIN (SCHISTOSOMA) – PENETRATE THROUGH SKIN BREAKS ( FUNGUS, WOUNDS: STAPH. , BURN WOUND: P.AERUGINOSA, PRESSURE (Diab Mell) : MULTIBACT – INSECT / ANIMAL BITE (ARBOVIRUS: GELEKOORTS, BACT:LYME DISEASE, PROTOZOA : MALARIA, LEISHMANIA HELMINTEN:FILARIASIS) – INJECTION ( HBC, HCV & hiov)  G.I. TRACT BACTERIA –ENTEROTOXINS (STAPHYLOCOCCEN) –MULTIPLY IN MUCUS (V. CHOLERA EN TOXISCH E. COLI) –INVASION & DESTRUCTION of MUCOSA (SHIGELLA, SALMONELLE & CAMPYLOBACTER)  G.I. TRACT (2) FUNGUS – IMMUNE COMPROMISED. (CANDIDA OESOFAGITIS) PROTOZOA – ATTACH TO BRUSH BORDER (G. LAMBLIA) – ENTRY IN ENTEROCYTES (CRYPTOSPORIDIA) – CONTACT MEDIATED CYTOLYSE (E. HISTOLYTICA), TRAC. RESPIRATORIUS –IMPAIR CILIAR ACTIVITY (H.INFLUENZA & B. PERTUSSIS) –ESCAPE KILLING (M.TUBERCULOSIS) –OPPORTUNISTS (SCHIMMELS) –CILIOSTATIC (M.PNEUMONIAE)  TR. UROGENITALIS URINARY TRACT –ALWAYS FROM EXTERIOR, URETHRA –♀ 10X INFECTIONS, SHORT URETHRA –URINE OBSTRUCTION/REFLUX  TR. UROGENITALIS (2) GENITAL TRACT –AB kills LACTOBACILLEN –MUCOSA BREAKS (SOA:HIV, HPV, T,PALLIDUM) SPREAD & DISSEMINATION MICROBES LOCAL PROLIFERATION LYMPH VESSELS BLOOD NERVOUS TISSUE FIGURE 8-4 Routes of entry and dissemination of microbes.  RELEASE MICROBES FROM BODY SKIN SHEDDING COUGHING/SNEEZING URINE FAECES BLOOD VECTORS EX. InsectS “zoonose” SOA (Sexueel Overdraagbare Aandoeningen) STD (2)  NOSOCOMIAL HOSPITAL ASSOCIATED INFECTIONS  IMMUNITY INNATE – EXISTING – PHYSICAL BARRIERS – PHAGOCYT. CELLS – NK CELLS – PLASMA PROTEINS ADAPTIEVE – AFTER MICROBE EXPOSURE – T & B CELLS  INFECTION MECHANISMS CELL CONTACT / ENTRY TOXINS NECROSIS ACTIV. IMMUNE RESPONS TISSUE DAMAGE MECHANISM VIRAL INJURY BINDING /TROPISME INTREDEN TRANSCRIPTIE TRANSLATIE  MECHANISM BACTERIAL INJURY DAMAGE DEPENDS ON: – ADHERENCE – CELL INVASION BACT.VIRULENCE – TOXINS  BACT. ADHERENCE –ADHESINS (SURFACE MOLECULES) –PILI (SURFACE FILAMENTOUS PROTEINEN) BACTERIAL TOXINS –ENDO (COMPONENT BACT CELL ex. LIPOPOLYSACCHARIDE) –EXO (SECRETED BACT. PROTEINS) ENZYMS (PR0TEASES, HYALURONIDASE, COAGULASE, FIBRINOLYSINE) INTRACELL SIGNALS NEUROTOXINS (C.BOTULINUM & C.TETANI) SUPERANTIGENS (S.AUREUS & S.PYOGENES) TISSUE DAMAGE DUE TO IMMUNITY –DIRECT TISSUE DAMAGE (VB. HBV/HCV) –CROSS REACTION (S.PYOGENES, RHEUMAT HARTZIEKTE/ POSTSTREPTOCOCCEN GLOMERULONEFRITIS) IMMUUN EVASION INACCESSIBLE ANTIGENIC VARIATION RESIST. INNATE IMMUNITY INHIB. T-CEL RESPONS IMMUUN EVASION INACCESSIBLE ANTIGENIC VARIATION RESIST. INNATE IMMUNITY INHIB. T-CEL RESPONS  INACCESSIBLE MULTIPLY IN SITE (C.DIIFICILE) FAST CELINVASION (MALARIA) DENSE CAPSULE IMMUUN EVASION INACCESSIBLE ANTIGENIC VARIATION RESIST. INNATE IMMUNITY INHIB. T-CEL RESPONS  ANTIGENIC VARIATION T 8-6 IMMUUN EVASION INACCESSIBLE ANTIGENIC VARIATION RESIST. INNATE IMMUNITY INHIB. T-CEL RESPONS  RESISTANCE AGAINST INNATE IMMUNITY RESIST. AGAINST ANTIMICROB. PEPTIDES (ex. DEFENSINEN,CATHELICIDINEN & THROMBOCIDINEN) SHIELDING BACT. ANTIGENS WITH CARBOHYDRATE CAPSULE KILL PHAGOCYTES THROUGH TOX. PROTEINS MODIFY LPS (SALMONELLA) REPLICATE IN PHAGOCYTES (MYCOBACT, CRYPTOC.NEOFORMANS, LEISHMANIA, TOXOPLASMOSIS IMMUUN EVASION INACCESSIBLE ANTIGENIC VARIATION RESIST. INNATE IMMUNITY INHIB. T-CEL RESPONS  INHIB. T-CELL RESPONS DECREASE RECOGNITION INFECTED CELLS INFLAMMATION RESPONSES TO INFECTION ABSCESS CHRONIC “MONONUCLEAR” INFLAMMATION GRANULOMA HSV infected cells contain large pink to purple intranuclear inclusions (Cowdry type A), consist of intact and disrupted virions Tissue necrosis  Councilman VIRAL HEPATITIS  THE BIG 4 VIRUSES BACTERIA FUNGI PARASITES  VIRAL TRANSIENT, ACUTE, (Measles, Mumps, Polio, West Nile, Viral hemorrhagic fevers) CHRONIC LATENT (HERPES FAMILY: Herpes Simplex Virus, CytoMegaloVirus, Varicella Zoster Virus) CHRONIC productive (HEPATITIS B, HIV) “TRANSFORMING” -> causation of cancer (Epstein-Barr V, Human Papilloma V, Hepatitis B V, Human T- Lymphotropic Virus- type I )  VIRAL TRANSIENT, ACUTE – Measles: Skin, Lung, GI, Cornea, Brain – Mumps: Parotitis, Orchitis, Pancreas, CNS – Polio: Myelitis (Anterior horn motor neurons) – West Nile (arbo-): Meningoencephalitis – Viral hemorrhagic fevers (dengue): fever, headache, myalgia, thromobocytopenia, shock  Measles Single stranded RNA Paramyxovirus family  Clinically: – Croup – Pneumonia – Diarrhea with protein losing enteropathy – Keratitis with scarring& blindness – Encephalitis – Hemorrh rashes Diagnosis: – Clinically – Serology – Detection viral antigen in nasal exudate & urinary sediment Measles “giant” cell in measles pneumonia = WARTHIN FINKELDEY CELL. Croup Measles  Mumps Paramyxovirus family Respiratory droplets → enters upper respiratory tract → lnn →virus replication in T-cells → trough blood to salivary glands → infection → pain & swelling Mumps can spread to CNS, testis & ovary Complication: aseptic meningitis  orchitis. Mumps  Polio virus Uncapsulated RNA virus Entero virus Fecal-oral transmission Infects first oropharynx→ secretion in saliva → swallowed → multiplies intestinal mucosa & lnn Most infection asymtomatic Diagnosis 1 of 100 infected CNS - viral culture of throat secretions or stool - serology infection → replication in motor neurons in spinal Prevention by vaccination cord 1. destruction of neurons 2. INFLAMMATORY infiltrate 3. microglial nodules 4. perivascular cuffing  Viral hemorrhagic fevers Enveloped RNA viruses Arena, filo, bunya and Hemorrhagic manifections due to thrombocytopenia or severe platelet or flavi virus endothelial dysfunction Depend on animal or insect host for survival or transmission Clinically spectrum range from mild acute (fever, headache, myalgia, rash, neutropenia & trombocytopenia ) life threatening (sudden hemodynamic deterioration & shock) aedes aegypti  VIRAL CHRONIC LATENT (HERPES FAMILY) : – Herpes Simplex Virus – Varicella-Zoster Virus – Cyto Megalo Virus  HSV Gingivostomatitis (HSV1) / koorts blaasjes  HSV Genital herpes (HSV2> 1) HSV replicate in skin & mucous membrane at entry site (Port d ‘entree), causes vesicular lesions of epidermis  HSV CLINICALLY – Self limiting cold sores (KOORTS BLAASJES), recurrent – Gingivostomatitis (HSV1) – Disseminated visceral infections – Encephalitis – Genital herpes (HSV2> 1) – Corneal lesions (epitheliale & stromale keratitis)  HSV HSV infected cells contain large pink to purple intranuclear inclusions (Cowdry type A), consist of intact and disrupted virions VZV  VZV CLINICALLY – 2 conditions Chickenpox : acute infection Shingles (roos): reactivation latente VZV (herpes zoster) less recurrent than HSV – Infects : muc.membrane, skin and neurons – Evades im.respons – Latent infection in dorsal root ganglia – Multiple recurrence: im.suppresed / elderly  CMV Infects: monocytes, bone marrow progenitors Reactivation due to depressed cell.immunity Sx: – Asx / mononucleosis like – Im.compromised: systemic infection Transmission: – Transplacental – Neonatal: cervical/vaginal secretions, breast milk – Saliva – Venereal / respiratory / fecal-oral – Iatrogenic: organ transplants/blood transfusions CONGENITAL IMMUNOSUPPRESSED BASOPHILIC INCLUSION CLEAR HALO CMV pneumonia  VIRAL CHRONIC INFECTIONS, Hep. B  HEPATITIS B VIRUS ACUTE & CHRONIC TRANSMISSION: – PERCUTANEOUSLY(I.V. DRUGS/BLOOD TRANSFUSION) – PERINATALLY – SEXUALLY INFECTS HEPATOCYTES INJURY DUE TO IM.RESPONSE (CTL-RESPONS) RECURRENT INJURY ►CIRRHOSIS►↑RISK HCC NORMAL LIVER  Councilman ACUTE VIRAL HEPATITIS  VIRAL “TRANSFORMING” Epstein-Barr, EBV, lymphoma Human Papilloma, HPV, cervical cancer (squamous cell) EBV  EBV CAUSES INFECTIOUS MONONUCLEOSIS (pfeiffer) ASSOCIATION: – LYMPHOMAS – NASO-PHARYNGEAL CARCINOMA TRANSMISSION: – SALIVA (KISSING DISEASE)  EBV PATHOGENESIS: FIG8-16  ATYP LYMPHOCYTES MONONUCLEOSIS, caused by EBV Emerging disease : COVID-19 Dec 2019 Wuhan End march 2020 worldwide pandemic Coronavirus : SARS- CoV-2 Left: healthy lungs, captured in a CT scan; right: the lungs of someone infected with COVID-19.  BACTERIAL Gram+ Gram- MYCO-bacteria SPIROCHETES ANAEROBIC “OBLIGATE” INTRACELLULAR  BACTERIAL Gram+ (Staph, Strep) Gram- (rods) MYCO-bacteria (TB) SPIROCHETES (SYPHILIS) ANAEROBIC (ABSCESSES) “OBLIGATE” INTRACELLULAR  GRAM POSITIVE BACTERIAL INFECTION Gram+ cocci (Staph, Strptcc) SKIN RESPIRATORY TRACT S T A P H S. AUREUS INFECTION VIRULENCE FACTORS: – SURFACE PROTEINS (ADHERENCE) – SECRETED ENZYMES DEGRADE PROTEINS – TOXINS DAMAGE HOST CELLS MORPHOLOGY: – PURULENT INFLAMMATION ANTIBIOTIC RESISTANCE – METHICILLIN RESIST. S. AUREUS (MRSA) STREP: GR+ COCCI SKIN (ERYSIPELAS) RESPIRATORY HART OROPHARYNX (PHARYNGITIS) ERISIPELAS  STREPTOCOCCAL INFECTION POST INFECTIOUS SYNDROMES – RHEUMATIC FEVER (ANTI-STREP M PROTEIN ANTIBODIES) – IM COMPLEX GLOMERULONEFRITIS – ERYTHEMA NODOSUM  GRAM POSITIVE RODS DIPTHERIA LISTERIA ANTHRAX------ NOCARDIA  GRAM POSITIVE RODS DIPTHERIA (CORYNEBACTERIUM DIPTHERIAE ) LISTERIOSIS (LISTERIA MONOCYTOGENES) ANTHRAX (BACILLUS ANTHRACIS) NOCARDIA GRAM NEGATIVE COCCI Neisseria (diplococ) –GONORRHEA ( –MENINGITIDIS (bact meningitis) GRAM NEGATIVE RODS Bordetella pertussis (Whooping cough) Pseudomonas aeruginosa Klebsiella granulomatis) (granuloma inguinale /Aerobacter Yersinia pestis (plague) Hemophilus ducreyi (chancroid) E. COLI  A: M. tuberculose / M. avium CASUS Afb 3 In plaats van een granulomateuze ontstekings infiltraat wordt nu in het lymfklier excisie biopt overwegend een infiltraat gezien opgebouwd uit macrofagen met intra-cytoplasmatisch gelegen micro-organismen. In de GROCOTT kleuringen worden sporen vormen (3-5um) gezien. Wat is uw diagnose (hint zie t 6-14)  CASUS (hint zie t 6-14)  A: M. tuberculose / M. avium CASUS Afb 3 In plaats van een granulomateuze ontstekings infiltraat wordt nu in het lymfklier excisie biopt overwegend een infiltraat gezien opgebouwd uit macrofagen met intra-cytoplasmatisch gelegen micro-organismen. In de GROCOTT kleuringen worden sporen vormen (3-5um) gezien. Wat is uw diagnose (hint zie t 6-14) A: Histoplasmosis  MYCOBACTERIA (acid fast) Tuberculosis “Atypical” mycobacteria, the most important of which is MAC (Mycobacterium Avium Intercellulare Complex, in HIV patients) Leprae  Tuberculosis 1.7 billion worldwide 8,7 million new cases 1.4 million deaths each year 10 million HIV & TB Risk factors: – AIDS – Diabetes mellitus – Hodgkin lymphoma – Chronic lung disease – Chronic renal failure – Malnutrition – Alcoholism – immunosuppression Tuberculosis, pathogenesis  Tuberculosis, CLINICAL PRIMARY TB – PREVIOUS UNEXPOSED – ELDERLY & IM SUPPRESED – Sx: Resemble acute bact infection Hilar lnn pathie Pleural effusion Cavitation = rare Lymphohematogenous dissemination (TB meningitis / miliary TB) Tuberculosis, MORPHOLOGY  Tuberculosis, CLINICAL SECONDARY TB – SENSITIZED HOST – YEARS AFTER INITIAL INFECTION – Sx: Apical disease with cavitation Malaise, anorexia, weight↓, fever, night sweats Sputum Hemoptysis Pleuritic pain Extrapulmonary manifestations Tuberculosis  Tuberculosis, DIAGNOSIS PHYSICAL EXAM X-CHEST (CONSOLIDATION / CAVITATION LUNG APEX) ACID FAST SMEARS SPUTUM CULTURES OF SPUTUM (10.000ORG)`-> gold standard due to drug susceptibility testing PCR (10 ORG)  Tuberculosis, HIV+ CD4 >300 CELLS/MM3 = SECOND TB CD4 < 200 CELLS/MM3 = PRIM TB FALSE – MANTOUX FALSE – SPUTUM SMEARS ( ↓T-CELL ► LESS CAVITATION & BRONCHIAL WALL ►↓ BACILLI EXCRETION) CULTURES OF SPUTUM (10.000ORG) PCR (10 ORG) Tuberculosis, MORPHOLOGY Tuberculosis, MORPHOLOGY Tuberculosis, MORPHOLOGY ISOLATED INFECTION – MENINGES = TB MENINGITIS – KIDNEYS= RENAL TB – ADRENAL – BONES (OSTEOMYELITIS)= POTTS DISEASES – FALLOPIAN TUBES = TB SALPINGITIS Tuberculosis, MORPHOLOGY  MYCOBACTERIUM LEPRAE EFFECTS SKIN & PERIPH NERVES TRANSM: AEROSOLS OBLIGATE INTRACELL ORG. CELL MEDIAT. IMMUNITY CLINICALLY: – TUBERCULOID LEPROSY – LEPROMATOUS LEPROSY – BORDERLINE LEPROSY  MYCOBACTERIUM LEPRAE MORPHOLOGY: – TUBERCULOID LEPROSY GRANULOMATOUS INFILTRATE NERVE DESTRUCTION DUE TO INFLAMMATION NO/FEW BACILLI =“PAUCI BACILLARY” – LEPROMATOUS LEPROSY AGGREGATES LIPID LADEN MΦ MASSES OF BACILLI = “MULTIBACILLARY” PERIPH NERVES MINIMAL INFLAMMATION  Vandaag BACTERIA vervolg SPIROCHETEN ANAEROBEN OBLIGATE INTRACELL BACTERIA : CHLAMYDIA FUNGI PARASITES SPIROCHETES SYPHILIS (Treponema pallidum) RELAPSING FEVER (Borrelia recurrentis) LYME DISEASE (Borrelia burgdorferi)  SPIROCHETES Gram negative bacteria Slender corkscrew shaped Covered by membrane “ outer sheath” -> mask bacterial antigens from immune respons  SYPHILIS AE: TREPONEMA PALLIDUM SUBSP. PALLIDUM GR- CORKSCREW SHAPED BACTERIA DX: – SEROLOGY, – PCR – SILVER STAINS – DARK-FIELD EXAM – IMMUNOFLUORESCENCE TRANSM: SEX. CONTACT / TRANSPLACENTAL STAGES: – PRIMARY – SECONDARY – TERTIARY SYPHILIS FIGURE 8-37 Protean manifestations of syphilis.