DCM 3101 • LWA 1 • Sub-topic 1.2
Principles of infectious disease
Infection is the establishment of a foreign organism in or on a host. It may remain as colonisation, progress to tissue injury and clinical disease, or become an opportunistic or endogenous infection when host defences are impaired. The clinical student must understand the organism, the host response and the transmission context together.
- Classify infectious agents and relate their biology to clinical disease.
- Explain normal flora, colonisation resistance and endogenous infection.
- Describe the six links in the chain of infection.
- Explain pathogenicity, virulence factors, toxins, invasion, biofilm and intracellular survival.
- Relate innate and adaptive responses to fever, inflammation, organ dysfunction and recovery.
1. Infection is an interaction, not only the presence of an organism
Colonisation may occur without overt tissue injury. Infectious disease occurs when the interaction between pathogen and host produces damage and clinical illness. Communicable disease is transmitted between hosts; endogenous disease arises from organisms already colonising the patient. Opportunistic infection occurs when natural defence is compromised by HIV, malnutrition, malignancy, immunosuppressive medicine, invasive devices or other conditions.
2. Groups of infectious agents
| Agent | Key biology | Clinical principle |
|---|---|---|
| Prions | Abnormally folded proteins without nucleic acid; induce abnormal folding of normal host protein. | Cause transmissible spongiform encephalopathies and are not treated like bacteria or viruses. |
| Viruses | Contain DNA or RNA in a capsid, sometimes with a lipid envelope; depend on host cells for replication. | Enveloped viruses are generally less environmentally stable; non-enveloped viruses often survive better on surfaces. |
| Bacteria | Prokaryotes that can synthesise proteins and nucleic acids; Gram-positive and Gram-negative cell walls differ. | Capsules, plasmids, flagella, spores and endotoxin influence disease and treatment. |
| Fungi | Eukaryotes occurring as yeasts, moulds or dimorphic forms; membranes contain ergosterol and walls contain chitin or glucan. | Superficial, systemic and opportunistic disease differ in host risk and therapy. |
| Protozoa | Unicellular eukaryotes, often with complex life cycles or vectors. | Travel, water, food, vector and immune status guide diagnosis. |
| Helminths | Multicellular parasites including nematodes, trematodes and cestodes. | Clinical disease reflects tissue migration, adult burden, eggs and host immune response. |
3. Koch’s postulates and their limits
Classical postulates linked a microorganism to a disease by finding it in cases, isolating it, reproducing disease in a susceptible host and recovering it again. They remain historically important but do not apply fully to organisms that cannot be cultured, agents that require specific host cells, members of normal flora or diseases with multiple causes. Modern evidence also uses molecular detection, serology, epidemiology and experimental models.
4. Normal human flora and colonisation resistance
Humans carry large communities of resident and transient microorganisms. Resident flora survive and replicate at a body site; transient flora remain briefly. Normal flora can be mutualistic, commensal or parasitic depending on the interaction. They contribute vitamins, occupy attachment sites, lower local pH, produce bacteriocins and stimulate protective antibodies. Antibiotics, surgery, immune suppression and barrier damage can cause overgrowth, translocation or cross-infection.
Normal flora cause illness when they overgrow at their usual site, move into a normally sterile site, or are transferred to another susceptible person. Examples include vaginal thrush after antibiotics, urinary infection from enteric flora, dental caries and device-associated infection.
5. Pathogenicity, infectivity and virulence
- Pathogenicity is the capacity to cause disease; infectivity is the capacity to establish infection; virulence is the degree of harm.
- Primary pathogens can cause disease in healthy hosts; opportunistic pathogens generally require impaired defence.
- Virulence factors include adhesins, capsules, motility, invasins, enzymes, toxins, antigenic variation, immune evasion and mechanisms that acquire nutrients.
- Plasmids, bacteriophages, mutation, recombination and horizontal gene transfer can change pathogenicity and antimicrobial resistance.
6. How pathogens establish disease
- Adherence: adhesins bind host receptors and determine tissue tropism.
- Colonisation: the organism survives local pH, oxygen, nutrients, mucus, flow and competing flora.
- Invasion: organisms cross epithelium, enter tissue or exploit wounds, devices and injections.
- Multiplication and dissemination: pathogens spread through contiguous tissue, lymph, blood, nerves or vectors.
- Tissue injury: direct cytotoxicity, nutrient theft, obstruction, invasion, toxins or immune-mediated damage.
- Persistence: latency, intracellular survival, biofilm and antigenic change permit chronic or recurrent disease.
7. Toxins and microbial injury
Endotoxin is chiefly a component of Gram-negative outer membrane lipopolysaccharide released during bacterial damage or lysis and causes broad inflammatory effects. Exotoxins are proteins released by living bacteria and often produce specific effects on target cells. Toxin-mediated disease may be severe even when the organism is no longer present at the site of injury.
8. Intracellular pathogens and biofilm
Viruses replicate inside cells. Some bacteria, parasites and fungi survive within macrophages or other cells after phagocytosis. Biofilms are communities embedded in an extracellular matrix on teeth, prostheses, catheters and other surfaces; organisms in biofilms communicate, exchange genes and become less accessible to immune cells and antimicrobials. Device removal or source control may therefore be as important as drug choice.
9. Host defence
| Defence | Examples | Clinical importance |
|---|---|---|
| Physical and chemical barriers | Skin, mucosa, mucus, cilia, cough, gastric acid, bile, urine flow | Breaks, burns, catheters, obstruction and aspiration increase risk. |
| Normal flora | Competition, pH change, bacteriocins and immune priming | Antibiotics can remove colonisation resistance. |
| Innate immunity | Neutrophils, macrophages, complement, NK cells, pattern receptors and cytokines | Fast response; excessive activation can injure tissue. |
| Adaptive immunity | Antibodies, B cells, T cells, memory and cellular cytotoxicity | Specific protection; impaired cellular or humoral immunity changes pathogens. |
10. Host response can help and harm
Clinical manifestations reflect both microbial virulence and the host response. Cytokines and antimicrobial factors help contain infection but may damage tissue. Excess inflammation can cause fever, hypotension, capillary leak, thrombosis, acute lung injury and organ dysfunction. Immune reconstitution inflammatory syndrome illustrates how recovery of immune function can paradoxically worsen inflammation against a persisting pathogen.
11. Fever and systemic inflammation
Microbial and endogenous pyrogens stimulate monocytes and macrophages to release cytokines such as IL-1, TNF and IL-6. These alter hypothalamic thermoregulation through prostaglandin E2. Rigors occur when the body attempts to raise its core temperature. Fever should be interpreted with age, immune status, antipyretic use, perfusion and organ function; absence of fever does not exclude severe infection.
12. The six links in the chain of infection
Communicable transmission requires an agent, reservoir, portal of exit, mode of transmission, portal of entry and susceptible host. Prevention works by breaking any link. For a respiratory infection, ventilation and masks affect transmission; vaccination and prophylaxis protect the host; treatment reduces the reservoir and communicability.
- Do not equate a positive culture with disease without assessing colonisation and contamination.
- Ask whether tissue injury is caused directly by the organism, by a toxin or by the immune response.
- Consider devices, biofilm, obstruction and source control when infection persists.
- Match the suspected organism and site to the host’s immune defect and exposure history.
13. Principles at the bedside
- Identify the syndrome and severity before naming an organism.
- Obtain a good specimen before antimicrobials when safe, without delaying resuscitation.
- Use local guidance and antimicrobial stewardship; narrow, stop or change treatment when evidence returns.
- Protect the patient, staff and community with standard precautions and transmission-based measures.
- Reassess response, complications and the possibility that the diagnosis is non-infectious.
References
- SlideShare: 15 Principles of Infectious Disease
- Davidson’s Principles and Practice of Medicine.
- WHO resources on infection prevention and antimicrobial resistance.
