Symbiosis and Normal Flora

• In a normal state, a fetus is microbe-free in utero.
• At birth, a newborn gets exposed to microbes that colonize its intestine.

Symbiosis

• Close relationship between two different species of organisms in a community.
• Mutualism: Both organisms benefit (e.g., E. coli in the human GI tract).
• Commensalism: One organism benefits, and the other is unaffected (e.g., some mycobacteria inhabiting the ear and living on secretions/dead cells).
• Parasitism: One organism benefits, and the other is harmed (e.g., tuberculosis, helminths & protozoa).
• Amensalism: One organism hampers the growth/survival of another, without being affected by the other organism (e.g., penicillium).

Normal Flora (Microbiota)

• Resident flora: Normal flora throughout life (e.g., S. epidermidis & E. coli).
• Transient flora: Flora that remain for a few hours, days, or months before disappearing (e.g. Bacillus Laterosporus sometimes lives in the intestine to limit growth of Candida).
• Normal flora are usually protective and do not cause disease in their normal habitat in a healthy person.
• When balance is interrupted, normal flora can become opportunistic pathogens.

Portal of Entry

• Exogenous: From outside the body.
• Endogenous: From inside the body.
• The majority of pathogens have a preferred portal.
• If a pathogen enters the "wrong" portal, infection might not occur.
• Some agents can enter through multiple portals (e.g., Streptococcus and Staphylococcus).

Portals of Entry

• Skin.
• Mucous membranes.
• Placenta: Some microbes can cross the placenta, leading to spontaneous abortions, birth defects, or premature births (e.g., HIV, Rubivirus, Cytomegalovirus, Parvovirus B-19, Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii).

Virulence

• Virulence is the degree of pathogenicity or disease-provoking power of a microbe.
• Virulence factors are factors that determine power, and can include:
  • Adhesion, the first step of infection, achieved by pili & cell membrane proteins.
  • Colonization of tissues in contact with the external environment such as the urogenital, digestive, and respiratory tracts, and the conjunctiva.
  • Invasion, which disrupts host cell membranes & barriers via invasins.
  • Evasion of Host Defense by avoiding contact with phagocytes, inhibition of phagocytic engulfment, survival inside phagocytes, or production of products that kill or damage phagocytes.
  • Toxins (major virulence factor).
• Toxigenesis is the ability of an organism to produce toxins.
• Bacterial toxins can act on sites remote from the original site of infection.

Endotoxin

• Lipopolysaccharides of gram-negative cell wall.
• Released during cell lysis (by host defense or by action of antibiotics).
• Less potent and less specific than exotoxins.
• Heat-stable.
• Can be affected by certain oxidizing agents.
• Example: Shiga toxin.

Exotoxins

• Proteins released by bacterium during the exponential growth phase.
• More potent & more specific than endotoxins.
• Heat-labile.
• Can also be affected by acids & proteolytic enzymes.
• Examples: enterotoxin, neurotoxin, leukocidin, hemolysin (named according to their target tissue).

Portal of Exit

• Site where a pathogen leaves an infected person.
• Often the same as the portal of entry.
• Pathogens can also exit via defecation, blood, nasal secretions, saliva, sputum, respiratory droplets, tears, and earwax.
• Etiology of infectious disease: The study of the cause of disease.

Patterns of Infection

• Local infections: Organism enters the body and stays confined to a specific tissue.
• Focal infections: Pathogen spreads from a local infection to other tissues.
• Systemic infections: Infection spreads to several sites and tissues, usually via the circulatory system.
  • Bacteremia: Presence of bacteria in the blood.
  • Septicemia: Systemic infection caused by the multiplication of pathogens in the blood.
  • Toxemia: Presence of toxins in the blood.
  • Viremia: Presence of viruses in the blood.
• Incubation period: Time from initial contact with the infectious agent (at the portal of entry) to the appearance of the first symptoms.
• Prodromal stage: Earliest, nonspecific symptoms of infection (discomfort, weakness, headache, muscle pain, upset stomach).
• Convalescence: Recovery period.
• Rehabilitation: Maximizing function of diseased tissue.
• Mixed infection: Several infectious agents concurrently establish themselves at the same site.
• Acute infection: Appears rapidly, with severe & sharp symptoms, vanishes rapidly.
• Chronic infection: Usually less severe symptoms but persists for long periods of time.
• Primary infection: Initial infection.
• Secondary infection: Follows the primary infection.
• Subclinical infection: No apparent symptoms and can persist for long periods.

Epidemiology and Public Health

• Epidemiology: Study of the distribution and cause of disease in populations.
• Considers the number of people affected, location, and disease outcome (recovery, death, disability, etc.).
• CDC (Centers for Disease Control and Prevention) is a central source of epidemiological information
  • Releases data on morbidity, mortality & incidence of specific notifiable diseases.
  • Morbidity: Number of patients with a disease within a group.
  • Mortality: Number of deaths resulting from a particular disease.
  • Incidence: Number of new cases in a given population within a specified time period.
  • Prevalence: Number of new and old or existing cases in a specific population within a specific time period.

Disease Categories

• Endemic: Repeatedly present in a given population or area (e.g., common cold).
• Sporadic: Breaks out only occasionally (e.g., typhoid fever in the U.S.).
• Epidemic: Occurs with greater frequency than usual in a population of a given area (e.g., influenza).
• Pandemic: Worldwide epidemic (e.g., AIDS and influenza of 1918).

Reservoirs

• Sites where pathogens are maintained and become a source of infection.
  • Animal reservoir: Pathogens that normally infect animals and can affect humans (zoonoses).
  • Human carriers: Symptom-free individuals.
  • Nonliving reservoirs: Include soil, water, food, fomites.

Modes of Transmission

• Contact Transmission
  • Direct Physical Contact: Between hosts without an intermediate object.
    • Person-to-person transmission by touching, kissing, sexual intercourse.
    • Examples: Respiratory tract infections, staphylococcal infections, measles, scarlet fever, STDs.
  • Indirect Contact:
    • Pathogen is transmitted by a fomite (nonliving object) e.g., tissues, handkerchiefs, towels, bedding, toys, clothes, diapers, eating utensils, drinking cups, medical equipment and devices.
• Droplet Transmission
  • Infectious agents transmitted via respiratory droplets.
  • Organisms travel less than a meter.
• Airborne Transmission: Organisms travel more than 1 meter.
• Water-borne & Food-borne Transmission occurs through untreated/poorly treated sewage & undercooked foods, or food prepared under unsanitary conditions (e.g., giardiasis, amebic dysentery, cholera, shigellosis, Hepatitis A & E).
• Bodily Fluid Transmission occurs through blood, urine, saliva, and other bodily fluids.
• Vector Transmission
  • Animals, especially arthropods act as vectors.
  • Biological Vectors: Biting insects, including mosquitoes, ticks, lice, fleas, blood-sucking flies.
  • Mechanical Vectors: Passively carry agents to a new host by their feet or other bodily parts.

Healthcare-Associated (Nosocomial) Infections

• Acquired in a hospital or hospital-like setting.
• HAIs are among the top 10 leading causes of death in the United States.
• About 99,000 patients die annually due to nosocomial infections in the United States.

Types of Nosocomial Infections

• Exogenous HAIs: Caused by pathogens in the healthcare environment, shed by sick people.
• Endogenous HAIs: Caused by microbes in the normal flora of the patient.
• Iatrogenic HAIs: Caused by medical procedures, such as catheters, invasive diagnostic procedures, and surgery.