Mednotes

L6 Infection and Immunity Transmission of Infection

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tagsinfectionandimmunity, lecture
aliasesL6 Infection and Immunity Transmission of Infection

13 min read

Overview

This lecture builds the “chain of infection” framework and then applies it throughout to MRSA as a worked example, before pivoting to horizontal/vertical gene transfer as the mechanism behind antimicrobial resistance and finishing on the global AMR burden and mitigation strategies.

The chain of infection

Six linked components, all of which must be present for infection to spread person to person, running in a cycle:

  • Causative agent: pathogenic organism (virus/bacteria/parasite) — determined by infectious dose and persistence
  • Reservoir/source: human, animal, fomite, food, water, or “carriers”
  • Means of exit: way out of the body — excretions, secretions, droplets; determined by number of microbes shed
  • Mode of transmission: direct/indirect contact, airborne, droplet, common vehicle, vector
  • Portal of entry: way into the body — respiratory, GI, GU, mucous membranes, skin
  • Person at risk: especially young, elderly, or immunocompromised individuals, which then feeds back to a new causative agent event

Modes of transmission

  • Direct contact: transfer by direct physical contact with an infected/colonised individual; one of the most common modes (example: herpes virus, perioral lesions)
  • Indirect contact: transfer via an object — unwashed hands, contaminated gloves, bed-space objects, medical equipment/instruments; also common (example: MRSA)
  • Droplet: large droplets (recorded on slide as ≥5 microns) from coughing/sneezing or aerosol-generating procedures (e.g. suctioning), propelled a short distance (<1 metre) into the new host’s nasal/oral mucosa (examples: pertussis, influenza). Some respiratory viruses transmitted this way also survive on nearby surfaces, giving combined droplet/contact spread. [flag: slide states droplet size “≥5 microns” for distance <1 metre — transcribed exactly as shown, not corrected]
  • Airborne: particles <5 microns, carried on dust or small particles, remain suspended and widely dispersed by air currents; can infect susceptible hosts some distance away, even in different rooms. Hardest to control — requires special ventilation (example given on slide: norovirus)
  • Common vehicle: transmission via a contaminated shared source — food, medication, IV fluid, shared equipment; can cause large-scale outbreaks (examples: Giardia, Cryptosporidium, transmitted via an oocyst cycle: oocysts ingested → shed in faeces → contaminate slurry/manure/waste water → contaminate soil, water, vegetables, crops → reach humans via unwashed produce, washed produce, shellfish, or raw meat/unpasteurised dairy → re-ingested, closing the cycle)
  • Vectorborne: transmission via animals/insects (examples: malaria, West Nile virus, dengue fever); prevented by facility construction/maintenance, screened windows, and housekeeping

Warning

MRSA as the causative agent

Staphylococcus aureus is a gram-positive, opportunistic pathogen causing disease ranging from self-limiting to life-threatening.

  • Infectious dose: at least 100,000 organisms in humans
  • Diseases caused: suppurative disease (impetigo, folliculitis), enteritis, toxic shock syndrome (TSS), postoperative pneumonia, staphylococcal scalded skin syndrome (SSSS), food poisoning
  • Key pathogenic factor: the staphylococcal chromosomal cassette mec, which confers resistance to penicillin derivatives (methicillin, oxacillin) and cephalosporins
  • Other pathogenic elements identified on the bacterial cell diagram: adhesins (fibronectin-binding protein, fibrinogen-binding protein), antibiotic resistance determinants (β-lactams, quinolone, aminoglycoside — associated genes sarA, mec, PBP1–4), cytotoxic factors (leukocidin, protease, enterotoxin, exfoliative toxin, TSST-1), plus unspecified “unknown factors”

Vertical vs horizontal gene transfer

De novo mutation is the underlying engine of genetic diversity.

  • Vertical transfer: from parent to offspring — a bacterial cell divides, each daughter cell inheriting a copy of the gene
  • Horizontal transfer: directly from one organism to another (not via reproduction), by three mechanisms:
    • Conjugation: DNA transferred via a sexual pilus, requires cell-to-cell contact between donor and recipient bacteria
    • Transformation: naturally transformable bacteria take up short fragments of naked (free-floating) DNA from the environment
    • Transduction: a bacteriophage transfers DNA from one bacterium into another by injecting it

MRSA reservoirs, carriage and survival

  • Worldwide carriage rate in healthcare workers: MSSA 23.7% (range 0–40%); MRSA 4.6% (range 0–59%); Australia/New Zealand 9.7%
  • Most common carriage sites: anterior nares, perineum (also axillae, ears, skin)
  • Survival times: carcasses/organs up to 42 days; floors <7 days; glass 46 hours; sunlight 17 hours; UV 7 hours; meat products 60 days; coins up to 7 days; skin 30 minutes to 38 days; on fabrics, days to months depending on colony size
  • Reservoirs include humans (carriers), fomites, animals, and food; many animals act as reservoirs, particularly cows with infected udders

MRSA applied across the chain of infection

  • Reservoir/source: human carriers, fomites, animals, food
  • Portal of entry: respiratory tract, mucous membranes, skin
  • Means of exit: epithelial shedding, nasal secretions
  • Mode of transmission: direct/indirect contact, and autoinfection
  • Person at risk: hospital patients and staff, elderly, children (one slide adds young women)

Carriage and spread of MRSA in hospitals

  • Transient carriage (common) vs persistent carriage (uncommon); transient carriage on hands is the major mode of MRSA transmission
  • Spread pathway network: new patients (transient) and visitors (persistent) both connect bidirectionally with the hospital patient; the hospital patient connects bidirectionally with the healthcare worker and the hospital environment; healthcare worker and hospital environment also connect bidirectionally with each other

Breaking the chain of infection in hospitals (interventions)

  1. Hand washing — the number 1 intervention, targeting the causative agent and contact-transmission links. Hand hygiene compliance recorded at 60–70% in Otago. The WHO “5 Moments for Hand Hygiene”: before touching a patient; before a clean/aseptic procedure; after body fluid exposure risk; after touching a patient; after touching patient surroundings.
    • Disposable gloves: sterile gloves protect the patient; non-sterile gloves protect the worker but are a risk to the patient. A Dunedin Hospital study found 50% of unused gloves in in-use boxes were contaminated (coagulase-negative staphylococci), and 13% carried transmissible bacterial pathogens. Gloves must be used together with hand hygiene, and a safe dispenser reduces contamination risk.
  2. Patient and staff screening and eradication — targets the causative agent and reservoir/source. Example regimens: (1) mupirocin twice daily for 5 days plus chlorhexidine body wash once daily for 5 days; (2) regimen 1 plus trimethoprim 200 mg twice daily and rifampin 600 mg once daily, both for 10 days; (3) regimen 2 plus oral gentamicin solution 80 mg three times daily for 10 days; (4) regimen 1 plus fusidic acid 500 mg three times daily and rifampin 600 mg once daily, both for 10 days.
  3. Fomite disinfection — targets the causative agent and reservoir/source (fomites). S. aureus is susceptible to 70% ethanol, chlorhexidine, 1% sodium hypochlorite, 2% glutaraldehyde, 0.25% benzalkonium chloride, and formaldehyde.

Susceptibility of microorganisms to disinfectants

Ordered from most resistant to least resistant: bacterial spores and parasite cysts (most resistant) → mycobacteria → non-enveloped viruses → fungi → bacteria → enveloped viruses (least resistant). Bacteria and enveloped viruses are susceptible to alcohol-based hand sanitisers. [flag: slide text has a typo, “eneveloped” for “enveloped” — transcribed verbatim]

Development of antibiotic resistance

Two parallel routes, mirroring the vertical/horizontal gene transfer distinction:

  • Vertical route: a proportion of the bacterial population gains resistance to an antibiotic via mutation → resistant bacteria survive the antibiotic → they multiply, passing on the resistant trait → the resistant population survives subsequent exposures
  • Horizontal route: some bacteria gain resistance by acquiring genes from external sources via transformation, transduction, or conjugation → resistant bacteria survive the antibiotic → they multiply, passing on the trait → the resistant population survives subsequent exposures

Timeline: new antibiotic classes have been introduced roughly every decade from the 1930s (starting with sulfonamides, 1935) through the 2000s (oxazolidinones 2000, lipopeptides 2003), alternating natural-product-derived and synthetic origins. Resistance to each class has historically emerged within years to a couple of decades of introduction (e.g. penicillinase 1940, methicillin resistance 1961, VRE 1986, VISA 1997, VRSA 2002), illustrating a repeating cycle of new drug followed by emergent resistance.

Global burden of antimicrobial resistance

  • A 2025 Lancet Infectious Diseases modelling study estimated undertreatment of carbapenem-resistant Gram-negative (CRGN) bacterial infections across eight low- and middle-income countries (Bangladesh, Brazil, Egypt, India, Kenya, Mexico, Pakistan, South Africa), where such infections are rarely detected and often not appropriately treated due to limited health system capacity.
  • A child born in Africa is 58 times more likely to die from a drug-resistant infection in the first 5 years of life than a child born in a high-income country.
  • Without concerted action, almost 40 million cumulative deaths from antibiotic resistance are projected by 2050.
  • Weighted case fatality rates for CRGN infections by indication: lower respiratory tract infections 39% case fatality (17% of infection burden); bloodstream infections 55% case fatality (33% of infection burden); urinary tract/intra-abdominal/other infections 14% case fatality (50% of infection burden); each contributes a weighted average of 32% overall.
  • The proposed care cascade (≈1.45 million estimated CRGN infections in the eight countries, 2019) shows large data gaps: the numbers accessing care, receiving timely diagnosis, and achieving clinical cure are all unknown, with only the initial infection count and a small bar for those treated with an appropriate antibiotic quantified. [flag: bar chart intermediate values for “accessing care,” “timely diagnosis,” and “clinical cure” are marked unknown on the original slide, and the “treated” bar has no numeric label]

Actionable recommendations to slow AMR

  • Educate the public and train professionals on proper antibiotic use
  • Reinforce global surveillance and hygiene recommendations in healthcare institutions
  • Promote ongoing critical debate among experts/practitioners as knowledge evolves rapidly but is slow to change clinical practice
  • Promote collection of clinical data into unified, public databases
  • Provide right incentives for drug companies, including continued support for public-private partnerships (e.g. the EU’s Innovative Medicines Initiative, IMI-ENABLE)
  • Ban antibiotics as an animal feed additive where still permitted
  • Address global inequality, including a focus on sanitation in areas where poor conditions and unregulated antibiotic use favour resistance spread

Self-test

  1. Name and describe, in order, the six components of the chain of infection.
  2. Distinguish direct contact, indirect contact, droplet, and airborne transmission from each other.
  3. Give one example organism/disease for each of the six modes of transmission covered.
  4. Describe the cycle by which Cryptosporidium and Giardia spread via the common vehicle route.
  5. What is the infectious dose of Staphylococcus aureus, and which genetic element is key to its resistance to methicillin and related antibiotics?
  6. List the diseases caused by S. aureus mentioned in the lecture.
  7. Distinguish vertical from horizontal gene transfer.
  8. Describe the three mechanisms of horizontal gene transfer in bacteria.
  9. What are the worldwide carriage rates of MSSA and MRSA in healthcare workers, and what are the most common carriage sites?
  10. Apply the chain of infection specifically to MRSA: state the reservoir, portal of entry, means of exit, and mode of transmission.
  11. Distinguish transient from persistent MRSA carriage, and explain which is the major mode of MRSA transmission.
  12. Describe the WHO’s 5 Moments for Hand Hygiene.
  13. A ward is found to have poor glove practice: staff use non-sterile gloves without hand hygiene. Explain the risk this poses to patients, referencing the Dunedin Hospital glove contamination study.
  14. List the four MRSA screening/eradication regimens described and identify which two agents are common to all of them.
  15. Which agents is S. aureus susceptible to for fomite disinfection?
  16. Order the following from most to least resistant to disinfectants: bacteria, bacterial spores, enveloped viruses, mycobacteria, non-enveloped viruses, fungi.
  17. Describe the vertical and horizontal routes by which antibiotic resistance develops in a bacterial population.
  18. What projected global death toll from antimicrobial resistance is cited for 2050, and what disparity is cited between children born in Africa versus high-income countries?
  19. Integrative: explain how the same distinction between vertical and horizontal gene transfer underlies both general bacterial genetic diversity and the specific development of antibiotic resistance.

Answers

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