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