--- module: 036-02 language: en chapter: 36 title: "Transmission, Virulence, Host Defence, and Diagnostic Microbiology" module_title: "Exposure chains, immune phenotypes, and microbiological inference" source_sha256: 9fccf67e0ca9c30f07c95db032072309e3035ffa8e2475c0d647db07150191b1 --- # Exposure chains, immune phenotypes, microbiological inference ## Infection as a causal chain ### Reservoir, transmission, portal, host, damage #### Breaking any link prevents disease ### Same organism: colonisation, local infection, or bacteraemia ### A positive assay is not the diagnosis #### Integrate exposure, site, host, burden, timing ## Transmission and exposure history ### Respiratory particles form a continuum #### Large wet particles settle rapidly #### Small aerosols accumulate in poor ventilation ### Surface detection does not prove the contact route ### Ask space, ventilation, time, distance, symptom interval ### Risk set by inoculum and host defence ### Choose measures that actually break the chain ## Portals and infectious dose ### Portal must match niche #### Gastric acid, cilia, urine flow, intact skin ### Acid suppression, catheters, wounds alter barriers ### Infectious dose is conditional #### Direct tissue entry lowers the dose needed ### Prior immunity reduces progression, not entry ## Virulence factors and host injury ### Virulence factors are advantageous traits #### Adhesins, capsules, secretion systems, siderophores ### Disease only in context #### Capsule valuable in blood #### Acid tolerance matters in gastric passage ### Injury microbe-driven, immune-driven, or both #### Cytotoxic lymphocytes damage the organ they protect #### Granulomas contain organisms but distort tissue #### Sepsis: dysregulated host response ### Improvement lags behind microbial killing ## Innate and adaptive immunity ### Innate response buys time and shapes adaptive #### Complement opsonises, attracts, forms attack complexes #### Excess activation injures endothelium ### Class-switched antibody usually needs T-cell help ### CD-eight cells kill cells presenting intracellular peptide ### Memory responds faster at lower antigen burden ### Vaccine correlates of protection differ #### Circulating antibody may prevent invasion #### T-cell memory chiefly prevents severe disease ## Immune phenotypes ### Neutropenia: bacteria and moulds, little pus ### T-cell deficiency: opportunists, weak granulomas ### Antibody deficiency: encapsulated respiratory bacteria ### Terminal complement deficiency: meningococcus ### Asplenia: encapsulated organisms, infected erythrocytes ### Patterns shift probability, not exclusive lists ### Secondary immunodeficiency depends on dose and duration #### Transplant timing predicts changing risks ### Record drugs, doses, dates, counts, spleen #### "Immune suppression" alone cannot express risk ### Inflammation slight for severity is a danger clue ## Specimens and collection ### A specimen samples a diagnostic hypothesis #### Sputum with saliva may show oral flora #### Ulcer swab may not represent bone ### State site, syndrome, immune status, antimicrobials ### Collect cultures before antimicrobials ### Blood culture volume beats repeated small sets #### Separate venepunctures identify contamination ### Container, temperature, oxygen, transport alter results ### Send unfixed tissue for culture at biopsy ## Laboratory methods ### Gram stain rapid but burden-dependent #### Negative cannot exclude low-density disease ### Culture misses fastidious or treated organisms ### Histology shows invasion and may prove causality ### Nucleic-acid amplification is analytically powerful #### Also detects colonisation and dead organisms #### Negative useful only with right site and time ### Serology is delayed and host-dependent #### Lifelong antibody proves exposure, not activity ## Probability and test ordering ### Predictive values depend on pretest probability #### Low-risk: false positives may outnumber true #### High-risk: negative leaves residual probability ### State pretest probability explicitly ### Decide before ordering what each result changes #### A test changing no action adds harm ## Susceptibility, stewardship, reporting ### Breakpoints integrate drug exposure and outcomes ### Site determines free drug concentration ### Test when results change management #### Formed stool or asymptomatic urine finds carriage ### Separate observation from inference #### Persistent growth with a device may be real ### Treatment plan closes the loop