Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava COURSE AND FORMS OF INFECTION – I The 10th lecture for the 2nd-year students, April 20th, 2015 What is the pathogenesis? – revision •Pathogenesis explains the origin and development of pathological symptoms •What does the pathogenesis of infection include? •The way the agent spreads through the macroorganism •Mechanisms of defence against it •Actual causes of symptoms: • a) either the infectious agent itself, • b) or the reaction of macroorganism to it Spreading by means of lymph – revision •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 Spreading by means of blood – revision •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 •Sometimes agents of other systemic and local infections: during meningitis, pyelonephritis (urosepsis), suppurating wounds and suchlike • Spreading per continuitatem – revision •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 Spreading along nerves – revision •Either axonally (within nerve fibres) •or by progressive infection of Schwann sheath • •HSV, VZV, B-virus, rabies virus •Mycobacterium leprae •Naegleria fowleri •tetanic toxin Elimination of agent from the body – revision •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 – revision • • 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 – revision •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 – revision •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 – revision • •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 – revision •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 •… Infection •Definition: •Infection = a relation between the pathogenic microbe and the macroorganism (= ecological point of view) •Infection × colonization: •Infection = situation when an etiological agent 1)penetrates into an organism and multiplies in it, or 2)it settles on bodily surfaces (skin or mucosae) and unfavourably affects them •× Colonization = situation when 1)a non-pathogenic microbe settles on a bodily surface, or 2)a pathogen located there does not cause pathological symptoms Relationship between the microbe and the host – revision •The relationship is a dynamic one and influenced by the environment: • microbe host • • environment •Illness is not a rule – peaceful coexistence is usually better for the parasite •In spite of that the host tries to get rid of the parasite – to destroy, remove or at least to keep it in one spot • Course of infection – I •Four components can be distinguished during the course of infection: • •Incubation time •Prodromes •Typical syndrome (= complex of symptoms) of the infectious disease •Convalescence Course of infection – II •Incubation time salmonellosis ½–1 day, influenza 1–2 days, tbc 2–8 weeks, hepatitis B 90–100 days •Prodromes not always; nonspecific (  T, headache, feeling ill etc.), several hours to days •Typical syndrome of infectious disease as described in textbooks •Convalescence from subsiding troubles till normalization of laboratory results (except antibodies!) Course of infection – III •Relapse the same agent, infection comes on again during the convalescence •Recurrence the agent remains in the body, infection comes on again only after recovery (Brill-Zinsser disease = recurrence of epidemic typhus) •Reinfection new infection by the same agent from outside •Superinfection infection by another agent before recovery from the first infection • • Forms of infection •Inapparent infection (without symptoms) sole consequence: development of immunity (usually by means of antibodies) •Manifest infection (with symptoms) • subclinical: non-characteristic signs only • abortive: only some symptoms or slightly manifested ones • clinical: typical signs as in textbooks • foudroyant, fulminant: very abrupt, with dramatic symptoms • Duration of infection •Acute: days (common cold, salmonellosis) to weeks (majority of infections) •Subacute: months – either as a complication of any infection, or as the rule (some kinds of hepatitis, warts, sepsis lenta) •Chronic: years (tbc, lepra, dermatomycoses, parasitic infections) •Fulminant, foudroyant: very rapid course – hours (meningococcal sepsis) • Extent of infection •Local: portal of entry & regional nodes, or a specific organ (common cold, ringworm, warts, uncomplicated gonorrhoea, abscessus in an organ) •Systemic: whole organ system (influenza, lung tbc, meningitis, extensive pyodermia, pyelonephritis, pelvic inflammatory disease) •Generalized: regularly (exanthematic viroses, typhoid fever, exanthematic typhus), or as a complication (sepsis after injury, during cystitis or cholecystitis, salmonellosis in a newborn) Focal infection – I •Focal infection theory: chronic infection limited to a certain focus can result in a systemic illness with symptoms in quite a different site •Concept of focal infection used to be very fashionable formerly in diverse medical branches •In the name of so-called sanation of focuses thousands of patients were bona fide subjected to tooth extractions, tonsillectomies, cholecystectomies and other surgical interventions without proving the usefulness of these procedures by controlled studies Focal infection – II •The connection between systemic disease and a local infection has been proved only in •rheumatic fever – inflammation of heart, kidneys and joints after tonsillar infection by Streptococcus pyogenes •Reiter’s syndrome – reactive arthritis after 1. sexually transmitted urogenital infection by Chlamydia trachomatis serotypes D-K, 2. intestinal infection caused by pathogens from genus Salmonella, Shigella, Yersinia or Campylobacter •hemolytic-uremic syndrome after intestinal infection by Escherichia coli serotype O157:H7 •sterile mykids e.g. on palms during tinea pedis Special types of chronic infections • •Inapparent chronic infections can be clasified as •1. latent: agent hides in a non-infectious form, or it escapes from the infected cell after an activation of infection only • HSV and VZV: nerve ganglia cells, CMV: kidney and salivary glands cells, EBV: lymphocytes •2. persistent: agent can be detected by routine methods, because it is present mostly in an infectious form •Both types are markers of failing immunity •Both types can be activated Examples of persistent infections • •Bacterial: Rickettsia prowazekii (activation of exanthematic typhus = m. Brill-Zinsser), Salmonella Typhi (carriers), Mycob. tbc (lymphatic nodes) •Viral: HBV (hepatocytes), adenoviruses (adenoids), JCV and BKV (kidneys), congenital infections by CMV and rubella virus •Parasitary: hypnozoites of Plasmodium ovale and P. vivax (liver), Toxoplasma gondii bradyzoites (nodes, muscles, brain) •… 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 •Hans Zinsser: Rats, Lice, and History •Michael Crichton: Andromeda Strain •Albert Camus: Peste •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 • •