M1: Etiology

Disease Etiology

• Definition: The study of the causes of diseases.

• Question addressed: What is the cause of disease?

General Causes of Disease

1. Infectious diseases caused by microorganisms

   • Types:

     • Contagious vs. non-contagious diseases

     • Prion diseases: Caused by prions, which are misfolded proteins that induce other proteins to misfold.

2. Genetic disease

   • Caused by mutations or disease alleles in individual genes.

3. Cancer

   • Caused by mutations that lead to uncontrolled cell growth and changes in cellular behavior.

4. Dietary deficiency

   • Results from a lack of essential nutrients in the diet, leading to conditions such as scurvy, rickets, or iron deficiency anemia.

5. Injury and/or exposure to toxic substances

   • Resulting from physical trauma or exposure to harmful chemicals.

6. Autoimmune disease

   • Conditions where the immune system mistakenly attacks the body’s own cells.

Microbe-Host Relationships

• Normal Microbiota: Microorganisms that establish permanent colonies inside or on the body without producing disease.

• Transient Microbiota: Microbes that may be present for several days, weeks, or months and then disappear.

• Microbial Antagonism (Competitive Exclusion): Normal microbiota maintain a balance by competing with pathogens for nutrients, producing harmful substances (like bacteriocins), and affecting conditions such as pH and available oxygen.

• Symbiosis: The relationship between normal microbiota and the host.

  • Commensalism ($+ / 0$): One organism benefits, and the other is unaffected (e.g., Staphylococcus epidermidis on skin).

  • Mutualism ($+ / +$): Both organisms benefit (e.g., E. coli in the large intestine producing Vitamin K).

  • Parasitism ($+ / -$): One organism benefits at the expense of the other (e.g., pathogens).

Microbes & Disease: Historical Context

• Hippocrates: Suggested that disease was due to an imbalance of the four bodily humors (blood, phlegm, black bile, yellow bile).

• Spontaneous Generation & Miasma Theory: Miasma theory attributed disease to "bad air" or filth, prevailing until late $1800s$.

• Contagion Theory: Proposed in $1478$ but not widely accepted until scientific evidence emerged.

Early Microscopy

• Discovery and Importance: The invention of microscopes led to the visualization of microorganisms.

• Antony van Leeuwenhoek: Innovator of early microscopy in the $1670s$; created hand-held lenses capable of approximately $200x$ magnification and was the first to observe live microorganisms ("animalcules").

Robert Koch and Germ Theory

• Koch's Contributions: In $1876$, German physician Robert Koch linked specific microbes to specific diseases, contributing to the development of the Germ Theory.

• Koch’s Postulates:

  1. Association: The same pathogen must be present in every case of the disease.

  2. Isolation: The pathogen must be isolated from the diseased host and grown in pure culture.

  3. Inoculation: The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal.

  4. Re-isolation: The pathogen must be isolated from the inoculated animal and must be shown to be the original organism.

Classifying Infectious Diseases

• Occurrence of Disease:

  • Incidence: Number of people who develop a disease during a particular time period (measure of risk and spread).

  • Prevalence: Number of people who have a disease at a specified time, regardless of when it first appeared (takes into account both old and new cases).

• Frequency of Occurrence:

  • Sporadic Disease: Occurs only occasionally (e.g., Typhoid fever).

  • Endemic Disease: Constantly present in a population (e.g., common cold).

  • Epidemic Disease: Acquired by many people in a given area in a short time (e.g., influenza).

  • Pandemic Disease: Worldwide epidemic (e.g., COVID-19).

Severity or Duration of Disease

• Acute Disease: Symptoms develop rapidly but the disease lasts only a short time.

• Chronic Disease: Symptoms develop slowly and are likely to continue or recur for long periods (e.g., tuberculosis).

• Subacute Disease: Intermediate between acute and chronic.

• Latent Disease: Causative agent remains inactive for a time but then becomes active to produce symptoms (e.g., Shingles).

Extent of Host Involvement

• Local Infection: Pathogens are limited to a small area of the body.

• Systemic (Generalized) Infection: An infection throughout the body.

• Focal Infection: Systemic infection that began as a local infection.

• Sepsis: Toxic inflammatory condition arising from the spread of microbes.

  • Bacteremia, Septicemia, Toxemia, Viremia: Presence of bacteria, proliferation of bacteria, toxins, or viruses in the blood.

Predisposing Factors

• Conditions that make the body more susceptible to disease and may alter the course of the disease:

  • Gender (e.g., females have higher incidence of UTIs).

  • Genetic background (e.g., Sickle cell gene).

  • Climate and weather.

  • Fatigue and age.

  • Lifestyle and nutrition.

  • Chemotherapy.

Terms Used to Describe Microbial Disease

• Colonization vs. Infection: Colonization refers to microbe establishment without causing disease, while infection implies disease presence.

• Infection vs. Disease: Infection indicates the presence of pathogens, whereas disease represents the resulting signs and symptoms.

• Primary vs. Secondary Infection: Primary refers to the initial infection, while secondary follows an opportunistic infection after the body's defenses are weakened.

• Primary Pathogen vs. Opportunistic Pathogens: The former causes disease in healthy hosts, while the latter primarily affects immunocompromised individuals or occurs when microbes move to a new location in the body.

Disease Progression Stages

1. Incubation Period: Time after infection, with no noticeable signs or symptoms.

2. Prodromal Period: Short period of early, mild symptoms.

3. Period of Illness: Disease is most severe; if the immune response fails, the patient dies.

4. Period of Decline: Signs and symptoms subside.

5. Period of Convalescence: The person regains strength and the body returns to its prediseased state.

Disease Reservoirs

• Human Reservoirs: Carriers may have inapparent infections or latent diseases.

• Animal Reservoirs: Zoonoses are diseases transmitted from animals to humans.

• Nonliving Reservoirs: Soil and water (e.g., Clostridium tetani in soil).

Transmission of Infectious Diseases

1. Contact Transmission:

   • Direct Contact: Person-to-person (touching, kissing).

   • Indirect Contact: Spread by fomites (e.g., toys, needles).

   • Droplet Transmission: Airborne droplets (less than $1 ext{ meter}$).

2. Vehicle Transmission: Transmission by inanimate reservoirs (Water, Food, Air over $1 ext{ meter}$).

3. Vector Transmission: Arthropods (fleas, ticks, mosquitoes).

   • Mechanical: Passive transport on body parts.

   • Biological: Pathogen reproduces in the vector.

Nosocomial Infections (Hospital-Acquired Infections)

• Affects $5-15\%$ of hospital patients, resulting in $2 ext{ million}$ infections and $20,000$ deaths annually.

• Factors: Microorganisms in hospital environment, compromised status of the host, and chain of transmission.

• Control: Handwashing is the most effective way to prevent the spread.

Emerging Infectious Diseases (EIDs)

• Diseases that are new, increasing in incidence, or showing a potential to increase in the near future.

• Factors: Genetic recombination, evolution of new strains, inappropriate use of antibiotics, and changes in weather patterns.

Epidemiology

• Descriptive: Collection and analysis of data.

• Analytical: Comparison of a diseased group and a healthy group.

• Experimental: Controlled experiments using hypothesis testing.

• Case Reporting: Healthcare workers report specified diseases to local, state, and national offices.