Pneumococcal-Pneumonia.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Pneumococcal Pneumonia,Symptoms&signs of pneumococcal pneumonia,Sudden onsets of chills,fever 40C and malaise,Cough,tachypnea,dyspnea and chest pain,Bloody sputum,Auscultation&percussion loss of vesicular sound(normal sound heard over the lung field),crackling,loss of resonance,egophony(increased resonance),Day 5-10 of illness,crisis,sudden drop in fever and improvement or fatal infection(development of,opsonizing antibodies),Pathology:phases of red and white(or grey)hepatization.,Progression of pneumococcal pneumonia,“,Red Hepatization,”,Hyperemia and Edema,Progression of pneumococcal pneumonia,“,Grey Hepatization,”,“,Yellow Hepatization,”,Envelope Structure of,Streptococcus pneumoniae,Polysaccharide Capsule,The single most important virulence factor,antiphagocytic properties,prevents complement deposition,more than 100 serotypes,Capsular,“,Opsonizing antibodies,”,lysis after crisis of pneumococcal pneumonia.,Therapy and prevention of,S.pneumoniae,infections,Penicillin,-lactams if successful,Increasing drug resistance,-lactam resistant,S.pneumonia,can be resistant to other antimicrobials,15-20%overall resistance(CDC Surveillance),PCV13,(,Prevnar-13,Pfizer,:13 capsular polysaccharide conjugate vaccine):all,children 65,high risk individuals(sickle cell anemia,CSF leak,cochlear implant,asplenia,malignancy etc)as primary,immunization series,PPSV23,(,Pneumovax,Merck,:23 purified capsular polysaccharide vaccine,non-conjugated)together with PCV13:,asplenia,spenic dysfunction(sickle cell anemia),hematological malignancies,heart-lung-disease,alcoholism),AIDS and other immunodeficiencies,Renal and other transplants,Serotype replacement following PCV vaccination,Carriage rate and temporal prevalence of PCV(pneumococcal conjugate vaccine)VT(vaccine types)and NVT(non-vaccine types)following introduction of PCV7(2000)and PCV13(2006)in the UK,PCV7 serotype replacement was near complete 5 years after PCV7 introduction.,S.pneumoniae,carriage rate remained stable throughout the 5 year period.,Serotypes unique to PCV13 significantly decreased by 2011.,Clonal expansion of existing genotypes was primarily responsible for replacement.,Continued surveillance is needed to monitor replacement until equilibrium is reached.,Bacterial Pathogenesis&Immunity,Virulent(Smooth)and Avirulent(Rough)Pneumococci,The transforming principle,DNA for capsule biosynthesis,Pneumococcal capsule,synthesis genes,Bacterial genomes,multi-locus sequence typing(MLST)and genome sequencing,tools to unravel the epidemiology of bacterial diseases,Bacterial genome sequencing,recombination events in 173 isolates of post-PCV7 vaccine escape mutants detect serotype switches and changes in antibiotic resistance,Uses of bacterial genome sequencing,DNA,sequencing is cheap,analysis and long term data storage are expensive,Epidemiology:follow the evolution and the spread of a pathogen and analyze changes in carriers and patients,Evolution of antibiotic resistance in commensals and pathogens colonizing or infecting humans and their animals,Consequences of bacterial vaccines on the carriage rate and disease rates of isolates from a specific pathogen,Determine the source of infectious disease outbreaks and identify individuals responsible for transmission and the route of transmission,Characterize,inventory and follow microbiota surrounding humans for their impact on health and disease,Epidemiology of bacterial disease:,S.pneumoniae,drivers:disease susceptibility,mortality,immunity,single(variable)virulence trait,transformation&recombination to generate capsule diversity,Vaccines against bacterial disease:,S.pneumoniae,drivers:vaccine serotypes,immunity,transformation&recombination to generate new(capsule)serotypes,Epidemiology of bacterial disease:,C.diphtheriae,drivers:disease susceptibility,mortality,immunity,toxin=virulence,toxoid=immunity,monomorphic clone,Bacterial conjugation-Josh Lederberg,Lysogenic or Lytic Bacteriophage Infections-Lwoff,Lysogenic,Lytic,Bacteriophage transduction-Norton Zinder,Rules of thumb for bacterial pathogens,If you want to invade a host-,stick to it,If you dont want to get killed-,bring your weapons and fight,If you want to invade another host-,get out if you can,If you want to get all of it done-,bring your proteins out,Bacterial Pathogen Rule#1,If you want to invade a host-stick to it,Listeria attachment to epithelial cells leads to invasion and dissemination,Bacterial Pathogen Rule#2,If you dont want to get killed-bring your weapons and fight,S.aureus,adenosine and deoxyadenosine synthesis,Vibrio cholera,pathogenesis secretion of cholera toxin,an AB type toxin,Bacterial Pathogen Rule#3,The goal is to invade another host,bacteria must get out,Physical contact,Diarrhea,oral uptake,Runny nose,respiratory droplets,Purulent exsudate,Insect(vector)borne transmission(mosquitoes,fleas,lice,ticks,mites),Sexual intercourse,IVDA,needle sharing,Bacterial Pathogen Rule#4,If you want to get all of it done-,bring your proteins out,Secretion Pathways of Bacterial PathogensProtein Translocation by the Sec Pathway,Secretion pathways of Gram-negative bacteria,Autotransporter:secretion into the periplasm,insertion into outer membrane,self-catalyzed cleavage and transport into the extracellular medium,Secretion pathways of Gram-negative bacteria,Type I secretion:ATP fueled,single transport step from the cytoplasm across the entire envelope into the extracellular medium,Secretion pathways of Gram-negative bacteria,Type II secretion:secretion into the periplasm,then secretin-mediated transport across the outer membrane into the extracellular medium,Secretion pathways of Gram-negative bacteria,Type III secretion:transport from the bacterial cytoplasm through a needle complex directly into host cells,Yersinia pestis,injects type III effector Yops into immune cells,Secretion pathways of Gram-negative bacteria,Type IV secretion:transport from the bacterial cytoplasm through a secretion machine into the cytoplasm of host cells,Agrobacterial type IV secretion of T-DNA,Iron(Fe)limitation during bacterial infection,LTF=lactoferrin,NGAL=lipocalin,TF=transferrin,HP=haptoglobin,HPX=haemopexin,Iron acquisition during bacterial infection,Similarities and differences between Gram-negative and Gram-positive bacteria,Host molecules counteracting siderophores,Lipocalins(siderocalins)sequester siderophores,Glucosylation of siderophores(enterobactin)prevents sequestration by lipocalin,The human microbiome,Interindividual variation among fecal samples from 648 individuals,The human microbiome,Intraindividual variation among fecal samples from 2 individuals,The human microbiome,Intraindividual variation among vaginal samples from 2 individuals,The human microbiome,Factors influencing the human microbiome,The human microbiome,Hypotheses on how to perturb the interactions between microbiota,host and pathogen,