抗生素PPT课件（英文精品）Penicillinresistant pneumococci potentials for modeling（57p）.pptVIP

Penicillin-resistant pneumococci - potentials for modeling Prof. Karl Ekdahl KI/MEB and ECDC About the bug Streptococcus pneumoniae (pneumococcus) Gram-positive, encapsulated diplococcus Capsular swelling observed when reacted with type-specific antisera (Quellung reaction) Electron micrograph of pneumococcus Polysaccharide capsule Capsular polysaccharides: hydrophilic gels on organism surface Most important virulence factor Protects against phagocytosis by granulocytes and macrophages Elicits a T-cell–independent (not boostable) immune response Pathogenesis Colonisation of mucous membranes in respiratory tracts Adhesion (bacterial adhesins) Invasion of tissues if not defeated Middle ear Sinuses Bronchi Important for modelling:Pneumococcal serotypes Based on properties of capsular polysaccharides Immunologically distinct and basis for classification 40 serogroups (e.g. group 19) 90 serotypes (e.g. types 19A, 19C, 19F) No immunologic cross-reactivity between serogroups Some cross-reactivity within some serogroups and some cross-protection Geographical and temporal variation Some more immunogenic than others IPD serotypes over time (Sweden) Important for modelling:Pneumococcal serotypes (II) Children 5 y lack ability to mount antibody response to several serotypes Such types (6B, 9V, 14, 19F, 23F) more dominating among young children = child serotypes Account for the majority of carriage and disease in children Explains high incidences of carriage and disease in the youngest Child serotypes heavily linked to antibiotic resistance Limited number of very successful international clones Pneumococcal vaccine Antibody response in young children Important for modelling:Capsular switch Pnc very “promiscous bacteria” with excellent ability to exchange genetic material Highly capable of switching serotype while retaining other properties (incl antibiotic resistance) Likely frequent event (DCC outbreaks) Survival mechanism Often switches to other “child serotypes”: 23F