Epidemiology

Infection, Infectious Diseases, and Epidemiology

Symbiotic Relationships

  • Symbiosis is the relationship between normal microbiota and the host.
  • Types of symbiosis:
    • Commensalism: One organism benefits, and the other is unaffected.
    • Mutualism: Both organisms benefit.
    • Parasitism: One organism benefits at the expense of the other.
  • Some normal microbiota can act as opportunistic pathogens under certain conditions.

Normal Microbiota and the Host

  • Normal microbiota permanently colonize the host but typically do not cause disease under normal circumstances.
    • Microbial antagonism: Competition between microbes, providing protection by:
      • Occupying niches, preventing pathogens from colonizing.
      • Producing acids, which can inhibit pathogen growth.
      • Producing bacteriocins, antimicrobial peptides detrimental to other bacteria.
  • Transient microbiota: Microbes that are present only temporarily.
  • Probiotics: Live microbes applied to or ingested into the body, intended to exert a beneficial effect on the host.

Acquisition of Normal Microbiota

  • Development in the womb is generally free of microorganisms (axenic environment).
  • Microbiota begin to develop significantly during the birthing process.
  • Much of an individual's resident microbiota is established during the first months of life.

Reservoirs of Infection

  • Most pathogens cannot survive for long periods outside of their host.
  • Reservoirs of infection are sites where pathogens are maintained as a source of infection.
  • Three main types of reservoirs:
    • Animal reservoirs
    • Human carriers
    • Nonliving reservoirs
Animal Reservoirs
  • Zoonoses: Diseases naturally spread from animal hosts to humans.
  • Humans can acquire zoonoses through various routes:
    • Direct contact with an animal or its waste.
    • Eating infected animals or animal products.
    • Through bites of bloodsucking arthropods (vectors).
  • Humans are typically considered dead-end hosts for zoonotic pathogens, meaning they usually do not transmit the disease back to animals or further to other humans (though there are exceptions).
Human Carriers
  • Human carriers: Infected individuals who are asymptomatic but capable of transmitting the infection to others.
  • Common in latent diseases where symptoms may not be present.
  • Some carriers eventually develop symptoms of the illness, while others may never get sick.
  • Healthy carriers often possess defensive systems that protect them from symptomatic disease while still harboring and transmitting the pathogen.
  • Diseases commonly spread by human carriers include AIDS and gonorrhea.
Nonliving Reservoirs
  • Soil, water, and food can serve as reservoirs of infection.
  • The presence of microorganisms in these nonliving reservoirs is frequently due to contamination by feces or urine.
  • Examples of diseases originating from nonliving reservoirs include botulism, tetanus (soil), and cholera (water).

Exposure to Microbes

  • Contamination: The mere presence of microbes in or on the body.
  • Infection: Occurs when pathogenic microorganisms successfully colonize or invade the body.
  • Disease: A condition that arises when an infection causes a change from the normal state of health.
  • Pathology: The scientific study of disease, focusing on its causes, development, and effects.
  • Etiology: The specific study of the cause of a disease.
  • Pathogenesis: The step-by-step development and progression of a disease.

Portals of Entry: How Pathogens Get You!

  • Pathogens enter the body through specific sites called portals of entry.
  • Major pathways:
    • Skin
    • Mucous membranes
    • Placenta
    • Parenteral route
  • Pathogenicity: The general ability of a microorganism to cause disease.
  • Virulence: The degree of pathogenicity, indicating how harmful a pathogen is.
Placenta
  • The placenta typically forms an effective barrier against pathogens.
  • However, some pathogens can cross the placenta (e.g., Toxoplasma gondii, Treponema pallidum, HIV, Listeria monocytogenes, cytomegalovirus, enterovirus, rubella virus), potentially infecting the fetus.
  • Fetal infection can lead to spontaneous abortion, birth defects, or premature birth.
Skin
  • Microorganisms can enter through natural openings in the skin, such as hair follicles and sweat glands.
  • Some pathogens, like hookworm larvae (Necator americanus), can actively bore through intact skin.
  • Certain fungi grow on the keratin in the skin (e.g., dermatophytes) or directly infect the skin itself.
Mucous Membranes: Respiratory Tract
  • The respiratory tract is the easiest and most frequent portal of entry, as it is constantly exposed to the external environment.
  • Pathogens are typically inhaled in airborne droplets or dust particles.
  • Includes common cold, tuberculosis, pneumonia, influenza, and measles.
Mucous Membranes: Gastrointestinal Tract
  • Pathogens enter the gastrointestinal tract through contaminated food, water, or unwashed fingers.
  • Most microbes entering this route are destroyed by the acidic stomach environment and various digestive enzymes.
  • Those that survive and colonize can cause diseases such as polio, hepatitis A, typhoid fever, amoebic dysentery, and cholera.
Mucous Membranes: Genitourinary Tract and Conjunctiva
  • Genitourinary tract: Primarily a portal for sexually transmitted diseases (STDs).
    • Examples: HIV, warts, herpes, syphilis, and gonorrhea.
  • Conjunctiva: The mucous membrane covering the eye surface and inner eyelids.
    • Example: Conjunctivitis (pink eye).
Parenteral Route
  • The parenteral route involves the direct deposition of microorganisms into tissues beneath the skin or mucous membranes.
  • This bypasses the body's primary surface barriers.
  • Entry can occur through punctures, injections, bites, cuts, wounds, surgery, or even splitting skin due to swelling or drying.

Portals and Numbers of Microbes

  • Not all microbes cause disease, and the specific portal of entry can be a critical factor.
    • Salmonella typhi causes disease when ingested but typically not when applied to the skin.
    • Streptococcus species cause pneumonia when inhaled but generally not when ingested.
  • Yersinia pestis (causing plague) is an example of a pathogen that can successfully enter through more than one portal of entry, demonstrating variable pathogenicity based on entry route.
Yersinia pestis (Bubonic Plague)
  • A Gram-negative rod.
  • Transmitted by fleas that feed on infected hosts (e.g., rodents).
  • An infected flea bites a new host, infecting them.
  • If the new host dies, the flea needs a new host to feed on, continuing the cycle.

Numbers of Invading Microbes

  • The number of invading microbes (infectious dose) significantly influences the onset and severity of disease.
  • The virulence or potency of toxins is often expressed using these metrics:
    • LD50\text{LD}_{50}: Lethal dose for 50% of the test population; the amount of a toxin that kills half of the host population.
    • ID50\text{ID}_{50}: Infectious dose for 50% of the test population; the number of microbes required to cause infection in half of the host population.

Role of Adhesion in Infection

  • Most pathogens possess specific methods to attach to host cells, which is a necessary step in pathogenicity.
  • Attachment involves the binding of adhesins (surface molecules on the pathogen) to complementary receptors (surface molecules on host tissues).
    • Receptors: Host cell surface molecules, often glycoproteins or glycolipids.
    • Adhesins/ligands: Pathogen surface molecules, typically proteins or polysaccharides.
  • Examples of adhesion structures:
    • Glycocalyx: A sticky extracellular polysaccharide layer, like in Streptococcus mutans (important for dental plaque).
    • Fimbriae: Hair-like protein appendages, such as in Escherichia coli (for urinary tract infections).
    • M protein: A heat- and acid-resistant protein found on the surface of Streptococcus pyogenes.
  • Many pathogens can form biofilms, complex communities of microbes encased in an extracellular matrix, which enhance adhesion and protection.

The Nature of Infectious Diseases

  • Symptom: A subjective change in body function that is felt by a patient as a result of disease (e.g., pain, fatigue, nausea).
  • Sign: An objective change in a body that can be measured or observed by a healthcare professional as a result of disease (e.g., fever, rash, swelling, altered lab values).
  • Syndrome: A specific group of signs and symptoms that consistently accompany a particular disease (e.g., impetigo, AIDS).

Etiology: Causation of Disease

  • Germ theory of disease: The fundamental concept that infectious diseases are caused by infections of pathogenic microorganisms.
  • Koch's Postulates: A set of criteria developed by Robert Koch to prove the cause of an infectious disease.
    1. The same pathogen must be present in every case of the disease.
    2. The pathogen must be isolated from the diseased host and grown in pure culture.
    3. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal.
    4. The pathogen must be re-isolated from the inoculated animal and must be shown to be the original pathogen.
Exceptions and Difficulties in Satisfying Koch's Postulates
  • Some pathogens cannot be cultured in the laboratory (e.g., Treponema pallidum for syphilis, many viruses).
  • Some diseases are caused by a combination of pathogens or by pathogens acting with other cofactors.
  • Some pathogens cause disease only in humans, making animal models difficult or unethical to use.
  • Some pathogens can cause several different disease conditions (e.g., Streptococcus pyogenes causing pharyngitis, scarlet fever, and impetigo).

Virulence Factors of Infectious Agents

  • Pathogenicity: The ability of a microorganism to cause disease.
  • Virulence: The degree of pathogenicity, influenced by specific virulence factors.
  • Virulence factors contribute to a pathogen's ability to infect and cause harm:
    • Adhesion factors
    • Biofilms
    • Extracellular enzymes
    • Toxins
    • Antiphagocytic factors
Relative Virulence
  • Microbes exhibit a range of virulence:
    • More virulent: Francisella tularensis (rabbit fever), Yersinia pestis (plague), Bordetella pertussis (whooping cough).
    • Less virulent: Pseudomonas aeruginosa (infections of burns), Clostridium difficile (antibiotic-induced colitis), Candida albicans (vaginitis, thrush).
    • Generally non-virulent (normal microbiota): Lactobacilli, diphtheroids.
Enzymes and Increased Virulence (Exoenzymes)
  • Some extracellular enzymes (exoenzymes) produced by bacteria are ejected from the cell and enhance virulence.
  • Leukocidins: Destroy neutrophils and leukocytes (white blood cells) active in phagocytosis. Produced by Staphylococci and Streptococci.
  • Hemolysins: Cause the lysis of erythrocytes (red blood cells). Found in Staphylococci, Clostridium perfringens, and Streptococci.
    • Streptolysins: Hemolysins specifically produced by streptococci.
      • Streptolysin O is inactivated by oxygen.
      • Streptolysin S has an affinity for albumin.
  • Coagulase: Coagulates fibrinogen in the blood, forming a fibrin clot.
    • Clotting may protect bacteria from phagocytosis.
    • May be involved in