FACTORS OF PATOGENICITY AND VIRULENCE Based upon lectures of doc. Woznicova

Patogenicity and virulence Contagiosity Contagiosity - transfer between hosts Invasivity entrance to host multiply in host = overrule spreading defence Toxicity Toxicity - ability damage the host

Contagiosity Depend on: transfer type – type of elimination, amount of eliminated microbes, entrance gate tenacity of microbe – resistance against outer environment minimum infectious dose – amount of microbes beginning an infection host behaviour

1. Elimination Due to respiratory secrets, diarrhea stool/other biological materials Amount of eliminated microbes: 10 2 virions/1 infected respiratory epitelium → 10 9 virions/ml secret Entrance gate: infection better penetrate through mucous membrane than through skin (tick born encephalitis as laboratory respiratory infection)

2. Tenacity of microbes (stability in environment) Resistant – bacterial spores (Clostridium tetani), cysts of protozoa (Giardia lamblia), eggs of helmints (Taenia saginata) Vulnerable - direct transmission (sexual transmission – gonococci, treponema), biologic vectors (borrelia), through water (leptospires)

3. Infectious dose high: V. cholerae salmonela – cca agens multiplies in vehiculum – salad cream, sauce, yolk in sweets low: shigela 10 2 – dirty hand disease – contaminated objects (door handle - WC etc.) gonococci, M. tuberculosis 10 1, Coxiella burnetii (Q-fever)

4. Host behaviour Misuse of defence reflexes: cough, sneezing, diarrhea Specific behaviour change: Toxoplasma gondii - „inhibits“ reaction of rat, inficated rat loose fear from cats – predator easier kill them Yersinia pestis - flea (Xenopsylla cheopis) is suckling angry, because Yersinia blocks its digestive tract

Invasivity – Entrance into a host Most often through the mucous membrane If there is previous colonization = overcoming concurence of commensales Ability to: adhere to epitelium by the help of various adherence factors penetrate through epitelium by the force of barrier factors

Penetration to internal environment – I Direct Fissure in skin (S. aureus, S. pyogenes, B. anthracis) Fissure in mucous membrane (T. pallidum, HBV, HIV) Bite (rabies, P. multocida) Arthropod sting (borrelia, plasmodia) With help of ensymes (penetrate factors) lecithinase (C. perfringens) hyaluronidase (S. pyogenes): intercellular cement

Penetration to internal environment – II Forced phagocytosis Change of cellular skeleton with help of invasines Ipa (shigela) internalin (L. monocytogeses) YadA (Y. enterocolitica) Surface undulation (ruffling) of epitelia (salmonela) Unknown mechanism (legionella, chlamydia)

Reproduction in vivo Intracellular reproduction Intracellular reproduction better - nutrients, save before immunity - intracellular parasites (mycobacteria, rickettsia, chlamydia, listeria) Extracellular reproduction Extracellular reproduction – in plasm exist antibacterial substances (complement, lysozym, antibodies), less free Fe - bacteria form siderofores, hemolysines

Dissemination in organism Local infection (running nose) Systemic infection (grip, meningitis) Generalizate infection (morbilli, abdominal typhus, rare also local/systemic infection) Way of dissemination: lymph blood per continuitatem along nerves

Toxicity Direct damage of infectious agens Cellular death - lysis due to toxins, viruses, immune lymphocytes, apoptosis (HSV, shigella) Metabolic damage – exotoxins Mechanic damage (pablanes in diphteria ) Death cause → septic shock due to endotoxins G – → lipopolysaccharide G + → teichoic acid + peptidoglycan

Bacterial exotoxins Penetration factors (DN-ase, elastase, kolagenase) Cytolysins (lecithinase, sfingomyelinase, hemolysins) Inhibitors of proteosynthesis (diphteric toxin) Pharmacological effective toxins (choleragen, termolab. enterotoxin E. coli, pertussis t.) Neurotoxins (tetanotoxin, botulotoxin) Superantigens (staf. enterotoxin+exfoliatin, streptococcus pyrogen toxin)

Case 71 years old woman bitted by dog - many wounds penetrating to fascia on left leg and left hand, ambulant revision 48 hrs later: diarrhea, vomitting, pain in wounds. Surgical revision, expansion of hematomas, hospitalization rejected 72 hrs later – pain in LDL, vomitting, vertigo. LDL edema, any secret, shock - intubation

Microbiology Hemocultures - 2x Streptococcus pyogenes Sputum and stool – normal flora Urine - negative Streptococcus pyogenes and Staphylococcus aureus (TSST–1 and enterotoxine A producer) Wound - Streptococcus pyogenes and Staphylococcus aureus (TSST–1 and enterotoxine A producer) ATB susceptibility: S. pyogenes - penicilin, erytromycin, linkomycin, chloramphenicol, ofloxacin S. aureus - oxacilin, cotrimoxazol, erytromycin, linkomycin, tetracyclin

Case - end Development of hemorrhagic bulls, serous liquid from wounds, punctate from bulls – microscopic streptococcus Therapy: Penicilin, ciprofloxacin 12 h after hospitalization - surgical revision-myonecrosis leading to high amputation S. pyogenes strain S. aureus with production of toxic shock syndrom toxine (TSST-1) and enterotoxine A 47 hrs after hospitalization - death because of sepsis caused by invasive S. pyogenes strain complicated with toxic shock syndrome caused by S. aureus with production of toxic shock syndrom toxine (TSST-1) and enterotoxine A

Toxicity Damage caused due to defence reaction inflamatory reaction (calor, rubor, tumor, dolor, functio laesa a) Damage cause via inflamatory reaction (calor, rubor, tumor, dolor, functio laesa = typic inflamatory signs) edema: encephalitis, epiglottitis inflamatory infiltrate: pneumonia purulence: gonococci caused blenorrhoea neonatorum formation of fibrous tissue

Damage as result defence reaction b) Damage via specific immune reaction IgE, anafylaxis I. type: IgE, anafylaxis - helmintosis cytotoxicity II. type: cytotoxicity - hepatitis B imunocomplexes III. type: imunocomplexes - poststreptococcal renal inflamation, systemic septic reaction later, cellular IV. type: later, cellular - tbc

Ability overrule defence A) Overrule congenital immunity: 1. resist complement inhibition of complement activation surface protection 2. resist phagocytosis not letting absorb alive inside phagocyte 3. Interfere with cytokine function

1. Resist complement Inhibition of complement activation - - capsule (meningococci, pneumococci) - inhibitors of activation (S. pyogenes and P. aeruginosa - ensymes cleaving C3b and C5a) Surface protection (flagella of salmonela, proteus) Ability withstand C → seroresistence

2. Resistance to phagocytosis Not letting absorb Not letting absorb - - inhibitors of chemotaxis (bordetela, vaginal anaerobes, pseudomonades) - leukocidins and lecithinase (staphylococci, streptococci, pseudomonades, clostridia) - capsules production – N. meningitidis, H. influenzae, S. pneumoniae, E. coli, K. pneumoniae

Resistance to phagocytosis – II Alive inside phagocyte - - blocade of phagolysosome (chlamydia, mycobacteria, legionella, toxoplasma) - escape from phagosome (rickettsia, shigella, listeria, leishmania, trypanosoma) - antioxidants production (staphylococci, gonococci, meningococci) - high tenacity (coxiella, ehrlichia) phagocytosis

Ability overrule defence B) Overrule acquired immunity: - get round AB, or imunne lymphocytes - quickly multiply (respiratory viruses, agents causing diarrhea, malaric plasmodia) - bluff immune system 1. hide themselves 3. change their antigens 2. evoke tolerance - *suppress immune reaction

Ability bluff imunne system 1. Hide - in - in ganglias (HSV, VZV) - on intracellular membranes (HIV, adenovirus) - in inf. reservoirs (M. tbc, echinococcus) - in privileg. places (T. gondii in eye) 2. Evoke tolerance (CMV, rubella, leishmania, cryptococcus) 3. Antigen changes - - mimicry (S. pyogenes, T. pallidum) - - camouflage (schistosoma – blood proteins, staphylococci – protein A) - - variation (trypanosoma, borrelia, gonococci, influenza)

B) Overrule acquired immunity - end * Suppress immune reaction invasion to immune system (HIV, measless) intervention to cytokine formation (M. leprae, protozoa) superantigens production (staphylococci, streptococci) protease production (meningococci, gonococci, pneumococci) attachment of Fc-fragment IgG (staf./str., HSV) ? (influenza, HBV, EBV)