Question

In the simulation you did, the disease was transmitted every time an infected person met an uninfected person who was not immune. In the real world, these people may not have become sick. Why not? State as many reasons as you can.

Answer 1

Good point — real-world transmission is not deterministic. Whether an exposed person becomes infected (or becomes sick) depends on many interacting factors. Briefly, here are many reasons why an encounter between an infected and an uninfected/non-immune person might not produce infection or illness.

Pathogen-related factors
- Infectious dose too low: the exposed person may not receive the minimum number of viable organisms needed to establish infection.
- Low shedding by the infected person: some people emit few infectious particles (not all infected are high shedders).
- Short-lived/fragile pathogen: the virus/bacterium may be inactivated quickly (by drying, heat, UV, etc.) before it reaches the susceptible tissues.
- Route mismatch: the pathogen may require a specific entry route (inhalation vs ingestion vs breaks in skin) that didn’t occur.
- Low virulence or attenuated strain: some strains are less able to invade or replicate.
- Need for specific receptors: the pathogen may require receptors that the exposed person’s cells don’t express.

Host-related factors
- Innate immune defenses: mucociliary clearance, saliva, stomach acid, antimicrobial peptides, interferons and macrophages can clear or block invaders before infection is established.
- Adaptive immunity (even if “not immune” clinically): cross-reactive antibodies or T cells from prior related infections or vaccines can reduce infection probability.
- Pre-existing antibodies (maternal antibodies, prior exposure, partial vaccination) reduce risk.
- Genetic resistance: genetic variants can make people less susceptible (e.g., CCR5-delta32 for HIV; blood-group differences for norovirus).
- Mucosal immunity: local IgA can neutralize pathogens at the entry site even if systemic titers are low.
- Microbiome competition: resident microbes can block colonization by pathogens.
- Barrier integrity: intact skin and mucosa prevent entry; injuries increase risk.
- Age and health status: young healthy immune systems may clear exposures quicker; comorbidities work the other way.
- Medications or immunomodulators: some drugs can reduce susceptibility; others increase it (but the point is this alters outcomes).
- Chance/stochastic cell-level events: infection requires successful replication in early cells — this is probabilistic.

Exposure-related factors
- Short or distant contact: brief or distant interactions reduce exposure dose and thus probability.
- Masking and barrier measures: masks, face shields, gloves reduce delivered dose.
- Hand hygiene and surface cleaning: remove or inactivate pathogens before transfer to mucosal surfaces.
- Environmental ventilation and air mixing: well-ventilated spaces dilute aerosols and lower transmission risk.
- Humidity and temperature: some pathogens survive poorly in certain conditions.
- Timing relative to infectious period: the infected person may not have been infectious yet or may have passed peak infectiousness.
- Behaviour during contact: not facing each other, not talking/shouting/singing reduces expelled particles.

Interventions and prevention
- Vaccination: most vaccines reduce the probability of infection and severity even if they don’t give sterilizing immunity.
- Post-exposure prophylaxis or antivirals: medicines given after exposure can prevent establishment of infection.
- Prior treatment of the infected person (antivirals, antibiotics) reducing shedding.

Biological outcomes vs observed disease
- Infection without disease: an exposed person may be infected but remain asymptomatic (subclinical infection) — so “didn’t become sick” but may be infected.
- Transient colonization: pathogen might colonize but be cleared without replication to disease-causing levels.
- Detection limits and timing: tests can miss low-level or transient infections, or be done outside the detection window.

Population-level variation
- Heterogeneity in transmission: a few “superspreaders” cause many infections; most infected people transmit rarely.
- Waning/partial immunity in population: reduces but does not eliminate risk; protection levels vary individually.

Ecological and coinfection effects
- Coinfections or immune activation by another pathogen can suppress or enhance susceptibility to a second pathogen (interference).
- Nutritional status and microbiome ecology influence susceptibility.

Fundamental randomness
- Transmission is probabilistic: many biological processes (attachment, entry, replication, evasion of immune response) must succeed sequentially — failure at any step prevents infection.

In short: transmission requires that the right dose of viable pathogen reaches susceptible target cells at the right time and route, and then overcomes host defenses — any break in that chain (environmental, behavioral, pathogen, or host) can prevent infection or disease. If you want, I can expand on any of the points above or give examples (measles vs influenza vs HIV vs norovirus) to illustrate how these factors differ by disease.