B2

The natural history of disease refers to the development or natural course of a disease process in an individual over time, in the absence of treatment or intervention.
The process begins with the appropriate exposure to or accumulation of factors sufficient for the disease process to begin in a susceptible host.
The timeline of the natural history of disease follows these specific stages:
- Stage of Susceptibility
- Exposure
- Stage of Subclinical Disease (where pathologic changes occur)
- Onset of Symptoms
- Usual Time of Diagnosis
- Stage of Clinical Disease
- Stage of Recovery, Disability, or Death

After the disease process has been triggered, pathological changes occur without the individual being aware of them. This stage is referred to as subclinical disease.
Inapparent or Asymptomatic Stage: During the subclinical stage, the disease is said to be asymptomatic (no symptoms) or inapparent.
Incubation Period: This is the duration extending from the time of exposure to the onset of disease symptoms specifically for infectious diseases.
Latency Period: This is the duration extending from the time of exposure to the onset of disease symptoms for chronic diseases. In the context of non-communicable diseases, it refers to the time to detection; in communicable diseases, it can also refer to the time to infectiousness.
Durations: The period may be as brief as seconds (for hypersensitivity and toxic reactions) to as long as decades for certain chronic diseases. Each single disease has a characteristic incubation period that exists as a range.

Saxitoxin and similar toxins from shellfish (Paralytic shellfish poisoning): Symptoms include tingling, numbness around lips and fingertips, giddiness, incoherent speech, respiratory paralysis, and sometimes death. Period: $\text{few minutes} - 30\,\text{minutes}$ .
Organophosphorus ingestion: Symptoms include nausea, vomiting, cramps, headache, nervousness, blurred vision, chest pain, confusion, twitching, and convulsions. Period: $\text{few minutes} - \text{few hours}$ .
Salmonella: Symptoms include diarrhea, often with fever and cramps. Period: usually $6-48\,\text{hours}$ .
SARS-associated coronavirus (Severe Acute Respiratory Syndrome): Period: $3-10\,\text{days}$ , usually $4-6\,\text{days}$ .
Varicella-zoster virus (Chickenpox): Period: $10-21\,\text{days}$ , usually $14-16\,\text{days}$ .
Treponema pallidum (Syphilis): Period: $10-90\,\text{days}$ , usually $3\,\text{weeks}$ .
Hepatitis A virus (Hepatitis): Period: $14-50\,\text{days}$ , average $4\,\text{weeks}$ .
Hepatitis B virus (Hepatitis): Period: $50-180\,\text{days}$ , usually $2-3\,\text{months}$ .
Human immunodeficiency virus (AIDS): Period: $<1\,\text{to } 15+\,\text{years}$ .
Atomic bomb radiation (Japan) - Leukemia: Period: $2-12\,\text{years}$ .
Atomic bomb radiation (Japan, Chernobyl) - Thyroid cancer: Period: $3-20+\,\text{years}$ .
Radium (watch dial painters) - Bone cancer: Period: $8-40\,\text{years}$ .

Spectrum of Disease: The onset of symptoms marks the transition from subclinical to clinical disease. The spectrum of disease refers to the full range of manifestations of a disease, which may range from mild to severe or fatal. In some individuals, the process may never progress to clinically apparent illness.
Clinical Stage Outcomes: The disease process ultimately ends in recovery, disability, or death.
Infectivity: The proportion of exposed persons who become infected.
Pathogenicity: The proportion of infected individuals who develop clinically apparent disease.
Virulence: The proportion of clinically apparent cases that are severe or fatal.
The Iceberg Concept: Because the spectrum of disease includes asymptomatic and mild cases, the cases diagnosed by clinicians in a community often represent only the "tip of the iceberg." Many cases may be too early to diagnose or never reach the clinical stage.
Carriers: Individuals who are infectious but have subclinical disease. These persons can transmit infection to others despite being unaware of their own infection. Carriers may include:
- Persons with incubating disease.
- Persons with inapparent infections (e.g., Measles, Hepatitis A).
- Chronic carriers who appear to have recovered but remain infectious (e.g., Hepatitis B virus).

The epidemiologic triad or triangle is the traditional model for infectious disease. It consists of three components:
- Agent: Originally referred to as an infectious microorganism or pathogen (virus, bacterium, parasite, or other microbe). It must generally be present for disease to occur, though presence alone is not always sufficient. The concept has been broadened to include chemical contaminants (e.g., L-tryptophan) and physical forces (e.g., repetitive mechanical forces).
- Host: The human who can get the disease. Factors intrinsic to the host include genetic composition, nutritional and immunologic status, anatomic structure, presence of disease or medications, age, sex, and psychological makeup.
- Environment: Extrinsic factors that affect the agent and the opportunity for exposure. These include physical factors (geology, climate), biologic factors (insects/vectors), and socioeconomic factors (crowding, sanitation, health services).

Proposed by Rothman in 1976, this model accounts for the multifactorial nature of causation, particularly for non-infectious diseases.
Component Cause: An individual factor that contributes to the cause of a disease, represented as a piece of a pie.
Sufficient Cause: The complete pie, which represents a causal pathway. After all component causes (pieces) fall into place, the pie is complete and disease occurs. A disease can have more than one sufficient cause.
Necessary Cause: A component cause that appears in every sufficient cause pie or pathway. Without this component, the disease cannot occur.
Example (Pneumocystis carinii): This organism is a necessary but not sufficient cause of pneumocystis pneumonia. It colonizes healthy persons harmlessly but causes pneumonia in those with immune systems weakened by HIV.
Example (Lung Cancer):
- Component Cause B: Smoking.
- Component Cause C: Asbestos.
- Sufficient Cause I: Includes both smoking (B) and asbestos (C).
- Sufficient Cause II: Includes smoking without asbestos.
- Sufficient Cause III: Includes asbestos without smoking.
- Since lung cancer can occur in those exposed to neither, a proper model would require at least one more sufficient cause pie excluding both B and C.
Public Health Implication: Disease prevention does not require identifying every component cause. Blocking any single component of a sufficient cause can prevent disease through that specific pathway.

List down 3 pioneers of epidemiology and identify their contributions.
In your own words and understanding, define and explain epidemiology.
What is the difference between the incubation period and the latency period?
Explain the concepts of infectivity, pathogenicity, and virulence within the spectrum of disease.
Differentiate the Epidemiologic Triad from Rothman's Causal Pies.