--- module: 036-01 language: en chapter: 36 title: "Transmission, Virulence, Host Defence, and Diagnostic Microbiology" module_title: "Foundations" source_sha256: 0cf2141590ebc966d5940534608ff1aa93f0751733dec61575ff7c6a660f318f --- # Foundations of infection and diagnostic microbiology ## Infection chain and transmission ### Exposure does not guarantee colonisation #### Colonisation does not guarantee disease #### Detection does not guarantee causation ### Reservoirs: humans, animals, soil, water, food, equipment ### Routes: contact, droplet, aerosol, faecal-oral, blood, vertical #### Droplets short range; aerosols stay suspended ### Incubation ends with symptoms; latency with infectiousness #### Communicability may precede symptoms or outlast recovery ## Colonisation and invasion ### Adhesion via pili, surface proteins, capsules ### Tropism: receptors, temperature, nutrients, oxygen ### Resist mucus, cilia, flow, coughing, peristalsis ### Invasion via cells, phagocytes, lymph, blood, nerves ### Intracellular survival #### Block phagolysosome fusion or escape to cytosol ### Dose and portal shape presentation #### Devices, breached skin, aspiration create new niches ## Toxins and tissue injury ### Exotoxins: secreted proteins with specific targets #### A-B toxins: binding part plus enzymatic part #### Superantigens activate many T cells ### Endotoxin: Gram-negative lipopolysaccharide #### Lipid A activates innate sensors ##### Fever, vasodilation, capillary leak, shock ### Virulence is relative and context-dependent #### Opportunists exploit altered host defences #### Damage from too little or excessive response ## Innate barriers and recognition ### Skin, mucus, acid, urine flow, microbiota ### Pattern-recognition receptors detect conserved structures #### Activate inflammasomes, interferons, cell death ### Complement: classical, lectin, alternative routes #### Opsonises, recruits inflammation, forms attack complexes #### Regulatory proteins protect host surfaces ### Neutrophils: phagocytosis, oxidants, extracellular traps ### Macrophages: ingest, present antigen, organise repair ### Natural killer cells kill stressed cells ## Adaptive defence ### B cells become plasma or memory cells #### Immunoglobulin M appears early #### Immunoglobulin G: systemic memory, crosses placenta #### Immunoglobulin A protects mucosa and milk ### T-cell help enables class switching #### Conjugate vaccines build memory to capsules ### CD-four cells coordinate responses by subtype ### CD-eight cells kill cells presenting class one peptide ### Vaccine protection varies and can wane ## Immune evasion and immunodeficiency ### Evasion strategies #### Capsules, antigenic variation, latency ### Defect type predicts infection #### Neutropenia: invasive bacteria and fungi, muted pus #### T-cell deficiency: opportunists, intracellular organisms #### Antibody deficiency: sinopulmonary, encapsulated #### Terminal complement defects: Neisseria #### Absent splenic function: encapsulated organisms ### Secondary impairment more common than primary #### Fever may be absent; act on subtle decline ## Choosing and collecting specimens ### Sample involved site, not colonised surface ### Collect before antimicrobials if no delay ### Aseptic, adequate volume, rapid transport ### Rejecting a poor specimen can be safer ## Microscopy, culture, identification ### Gram stain: wall class and morphology #### Sensitivity depends on burden and specimen ### Culture shows viability, enables susceptibility #### Negative after treatment, poor sampling, slow growth ### Identify by biochemistry, antigen, mass spec, sequence ### Flora significant at sterile site, expected on skin ## Antigen, nucleic acid, serology ### Nucleic-acid amplification multiplexes and quantifies #### May detect colonisation or non-viable material #### Gene present does not guarantee expression ### Serology detects antibody or antigen #### Immunoglobulin M may persist or cross-react #### Seroconversion or rising titre is stronger #### Absent early or with immune deficiency ## Susceptibility and interpretation ### Exposure-informed breakpoints #### Minimum inhibitory concentrations cannot rank drugs ### Penetration, dose, source control decide success ### Pretest probability frames results #### Predictive value changes with prevalence ### One-set skin organism may be contamination #### Devices or immune impairment make it real ### Repeated low-value testing yields incidental positives