Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava PATHOGENESIS OF INFECTION – II The 9th lecture for 2nd-year students cancelled because of Easter Monday 2015 What is the pathogenesis? – revision •Pathogenesis explains the origin and development of pathological symptoms •What does the pathogenesis of infection include? 1.The way the agent spreads through the macroorganism 2.Mechanisms of defence against it 3.Actual causes of symptoms: • a) either the infectious agent itself, • b) or the reaction of macroorganism to it Spread of the agent through the macroorganism – revision •→ portal of entry (skin, mucosae, placenta) •→ sites of primary multiplication: portal of entry vicinity (= primary affect) regional lymphatic nodes (+ primary affect = primary complex) •→ actual spread (dissemination of agent): by means of lymph, blood, per continuitatem, along nerves •→ target organ: typically in viral diseases •→ sites of elimination from macroorganism: may not be the same as portal of entry PORTALS OF the infectious agent’s ENTRY – revision •Mucosae • respiratory ways and lungs • alimentary tract • urogenital tract • conjunctiva and cornea •Skin and hypodermis •Placenta Respiratory tract mucosa I – revision •NOSE + NASOPHARYNX: respiratory viruses (rhinoviruses, coronaviruses, adenov.), HSV, viruses of exanthematic infections (measles, rubella, chickenpox), amoebae (Naegleria , Acantamoeba, Balamuthia) •Secondary bacterial agents: Haemophilus influenzae b, Strept. pneumoniae, Staph. aureus, Moraxella catarrhalis – the gang of 4 •Chronic infections: ditto + Klebs. pneumoniae ssp. ozaenae, Kl. pn. ssp. rhinoscleromatis Respiratory tract mucosa II – revision •TONSILS + PHARYNX: respiratory viruses, HSV, Epstein-Barr v., coxsackieviruses A; Streptococcus pyogenes, other β-hemolytic streptococci, S. pneumoniae, S. aureus, H. influenzae serotype b, Neisseria meningitidis, N. gonorrhoeae, Arcanobacterium haemolyticum, Corynebacterium diphtheriae; Candida albicans; Toxoplasma gondii •EPIGLOTTIS: Haemophilus influenzae type b • Respiratory tract mucosa III – revision •LARYNX + TRACHEA: parainfluenza viruses, influenza viruses, RSV, adenoviruses; Chlamydia pneumoniae, Mycoplasma pneumoniae, Corynebacterium diphtheriae •Secondarily: S. aureus, H. influenzae •BRONCHI: influenza v., adenoviruses, RSV, parainfluenza v., RSV; M. pneumoniae, Ch. pneumoniae, Bordetella pertussis •Sec.: S. pneumoniae, H. influenzae type b, Staph. aureus, Moraxella catarrhalis •BRONCHIOLES: RSV • Lungs – revision •BRONCHOPNEUMONIA (alveoli & bronchi): Str. pneumoniae, Staph. aureus, H. influenzae type b; Legionella pneumophila, Klebsiella pneumoniae, E. coli, Pseudomonas aeruginosa; Francisella tularensis, Yersinia pestis •ATYPICAL PNEUMONIA (intersticium): Mycopl. pneumoniae, influenza virus A, Ch. pneumoniae; Chlamydia psittaci (ornithosis), Coxiella burnetii (Q fever); Pneumocystis jirovecii, CMV, atypical mycobacteria, Nocardia asteroides •SUBACUTE & CHRONIC PNEUMONIA: - anaerobes (Bacteroides fragilis, Prevotella, Peptostreptococcus) - Mycobacterium tuberculosis Gastrointestinal tract mucosa – revision •ORAL CAVITY: HSV, Candida albicans •OESOPHAGUS: CMV, C. albicans •STOMACH: Helicobacter pylori •SMALL INTESTINE: Campylobacter jejuni, salmonellae (incl. Salmonella Typhi), ETEC, EPEC etc., Yersinia enterocolitica, Vibrio cholerae; enteroviruses (polio!), rotaviruses, noroviruses; Giardia lamblia, Cryptosporidium parvum; tapeworms, pinworms, roundworms, flukes etc. •LARGE INTESTINE + RECTUM: Shigella sonnei (bacterial dysentery), Entamoeba histolytica (amoebic dysentery) Urogenital tract mucosa – revision •CLASSIC VENEREAL INFECTIONS: Neisseria gonorrhoeae (gonorrhoea), Treponema pallidum (syphilis), Haemophilus ducreyi (chancroid), Klebsiella granulomatis (granuloma inguinale), Chlamydia trachomatis serotypes L1-L3 (lymphogranuloma venereum) •OTHER SEXUALLY TRANSMITTED DISEASES (STD): Ch. trachomatis D-K, Mycoplasma hominis, Ureaplasma urealyticum; papillomaviruses, HBV, HCV, HSV-2, HIV-1; Candida albicans; Trichomonas vaginalis Conjunctiva and cornea – revision •CONJUNCTIVA: Str. pneumoniae, S. aureus, H. influenzae, Moraxella lacunata; Chlam. trachomatis D-K, N. gonorrhoeae; adenoviruses (types 3, 8, 19), enteroviruses (type 70), HSV •CORNEA: S. aureus, Strept. pneumoniae, P. aeruginosa; Acanthamoeba castellanii; Bacillus cereus; oportunistically pathogenic moulds; HSV, VZV, adenoviruses (type 8) Skin and hypodermis I – revision •INTACT SKIN: leptospirae, larvae of hookworms (Ancylostoma duodenale, Necator americanus) and Strongyloides stercoralis, cercariae of schistosomes, bilharziellae and trichobilharziae (swimmers itch) •SMALL CRACKS IN SKIN: S. aureus, S. pyogenes, Bacillus anthracis, F. tularensis, Rickettsia prowazekii; wart viruses, milker´s nodes v., cowpox virus; dermatophytes •BITE OF ARTHROPODS: arboviruses; borreliae, ehrlichiae, rickettsiae, coxiellae, bartonellae, Yersinia pestis; malaric plasmodia, leishmaniae, trypanosomes & others) Skin and hypodermis II – revision •WOUNDS: S. aureus, S. pyogenes, Clostridium tetani, gas gangrene clostridia, coagulase negative staphylococci etc. •WOUNDS AND BITES BY ANIMALS: rabies v., Spirillum minus, Pasteurella multocida, Capnocytophaga canimorsus, S. aureus, Streptobacillus moniliformis; Erysipelothrix rhusiopathiae (erysipeloid), Burkholderia pseudomallei •BURNS: Pseudomonas aeruginosa, pyogenic cocci • • Skin and hypodermis III – revision •WOUNDS IN WATER: Pseudomonas aeruginosa, Aeromonas hydrophila; Vibrio vulnificus, V. parahaemolyticus, Mycobacterium marinum •WOUNDS IN THE TROPICS: Dermatophilus congolensis, Rhodococcus equi, Mycobacterium ulcerans, Mycob. marinum; Sporothrix schenckii and many other micromycetes Placenta – revision •Congenital infections (= infections acquired during pregnancy) •VIRAL: rubella v. (Rubivirus), parvovirus B19 (Erythrovirus), cytomegalovirus (CMV), varicella-zoster v. (VZV), herpes simplex v. (HSV) •BACTERIAL: Treponema pallidum, Listeria monocytogenes •PARASITIC: Toxoplasma gondii •… SPREAD OF INFECTION (dissemination of the agent) • •By means of • a) lymph • b) blood • c) per continuitatem • d) along nerves • a) Spreading by means of lymph •skin → regional lymphatic nodes: pyogenic cocci, F. tularensis, Y. pestis; arboviruses •oropharynx, tonsils → cervical nodes: S. pyogenes, C. diphtheriae, M. tuberculosis, anaerobes (Actinomyces israeli, Prevotella), T. gondii •lungs → hilar nodes: M. tbc, B. anthracis, other respiratory pathogens •genital mucosa → inguinal nodes: Treponema pallidum, Ch. trachomatis L1-L3, H. ducreyi •Peyer plaques → mesenteric nodes: Yersinia enterocolitica, enteric adenoviruses, enteroviruses b) Spreading by means of blood •Agents of all generalized infections: exanthematic viruses, enteroviruses, arboviruses, Treponema pallidum, Salmonella Typhi and many others •Agents of pneumonia commonly appear in blood: especially Strept. pneumoniae •As complications agents of other systemic and local infections: during meningitis, pyelonephritis (urosepsis), suppurating wounds and suchlike • c) Spreading per continuitatem •From cell to cell: HSV, RSV, listeriae, yersiniae •By means of secretion down the mucosa: agents of respiratory, enteric and urogenital infections •From the site of arthropod biting to its vicinity: arboviruses, Borrelia burgdorferi •From the wound to adjacent tissue: Streptococcus pyogenes, Clostridium perfringens •From the middle ear to meninges: S. pneumoniae, Haemophilus influenzae type b •From lungs to pleura: agents of pneumonia d) Spreading along nerves •Either axonally (within nerve fibres) •or by progressive infection of Schwann sheath • •Herpes simplex v., varicella-zoster v., B-virus, rabies virus •Mycobacterium leprae •Naegleria fowleri •tetanic toxin ELIMINATION OF AGENTS FROM THE BODY • •From the mucosa of respiratory tract and oral cavity, intestine, urogenital tract, • eye •From skin lesions •By means of urine •From blood • • Elimination from respiratory tract • • Sneezing: in particular agents of common cold (rhinoviruses, coronaviruses), from bacteria e.g. Neisseria meningitidis Coughing: other respiratory viruses (primarily influenza virus), exanthematic viruses (VZV, morbilli virus, rubella virus), Neiss. meningitidis, Bordetella pertussis, Mycob. tuberculosis, Yersinia pestis Elimination from alimentary tract •Saliva: •HSV, EBV, mumps virus, Str. pyogenes •Stool: •enteroviruses (incl. poliovirus), HAV, HEV •salmonellae incl. Salm. Typhi, shigellae, EPEC, ETEC etc., V. cholerae, C. difficile •Entamoeba histolytica, Giardia lamblia •Ascaris lumbricoides, Taenia saginata • • • • Elimination from urogenital tract •From diseased mucosae: •Agents of classic venereal infections: in Europe Neiss. gonorrhoeae, Treponema pallidum •Agents of other sexually transmitted diseases (STD): Chlamydia trachomatis serotypes D-K, papillomaviruses, HSV-2 •By means of urine: •Salmonella Typhi •Agents of congenital infections (rubella virus, CMV) •Exotic viruses of hemorrhagic fevers (Ebola) Elimination from skin lesions • •Staphylococcus aureus •Streptococcus pyogenes •Varicella-zoster virus (agent of chickenpox and shingles) •Papillomaviruses (agents of warts) •Dermatophytes (e.g. Trichophyton rubrum, Microsporum canis, Epidermophyton floccosum) •Sarcoptes scabiei (itch-mite) • • • Elimination from blood •By means of vectors: • tick-borne encephalitis virus – ticks, yellow fever virus – mosquitoes • Rickettsia prowazekii – lice, Yersinia pestis – fleas, Borrelia recurrentis – lice • Malaric plasmodia – mosquitoes • •By means of small cracks in mucosa: HBV, HIV •… Recommended reading material •Paul de Kruif: Microbe Hunters •Paul de Kruif: Men against Death •Axel Munthe: The Story of San Michele •Sinclair Lewis: Arrowsmith •André Maurois: La vie de Sir Alexander Fleming •Michael Crichton: Andromeda Strain •Albert Camus: Peste (The Plague) •Victor Heisser: An American Doctor Odyssey •Richard Preston: The Hot Zone • • • •Please mail me other suggestions at: •mvotava@med.muni.cz •Thank you for your attention • • •