Infection and Disease Study Notes on Disease

Nature of the Host-Microbe Relationship

• In Utero Status: Under normal circumstances, humans are free of microbes while in utero.

• Birth and Colonization: During the process of birth, a newborn is exposed to microbes. These microorganisms begin to colonize the infant’s intestine.

• Establishment of Symbiosis: Humans and microbes begin to establish a symbiotic relationship from birth.

Symbiosis and Ecological Interactions

Symbiosis describes a close relationship between two different types of organisms living within a community. There are four primary types described:

• Mutualism: A relationship where both members benefit from the interaction.

• Commensalism: A relationship where one organism benefits, while the other is neither harmed nor helped.

• Parasitism: A relationship where one organism benefits while the other is harmed slightly or may even be killed.

  • Pathogen: A specific type of parasite that causes disease.

• Amensalism: A relationship where one organism can hamper or prevent the growth or survival of another organism without being affected by that second organism.

Normal Flora

Normal flora refers to the microbes that colonize the human body without normally causing disease.

• Establishment of Flora:

  • The newborn's first contact with microbes occurs in the birth canal.

  • This is followed by microbes introduced through breathing.

  • Further colonization occurs during feeding.

  • Throughout life, microbes establish residency in mucous membranes that are open to the external environment.

• Resident Flora: These microbes remain part of the normal flora throughout the entire life of a person.

• Transient Flora: These are found in the same locations as resident microbes but remain for only a few hours, days, or months before they vanish.

Opportunistic Pathogens

While a balance is usually maintained between the normal flora and the human host, certain conditions can turn normal flora into opportunistic pathogens.

• Pathogen Definition: A microorganism capable of causing disease.

• Conditions for Opportunism:

  • Compromised Immune System: A weakened host defense allows normally benign microbes to cause illness.

  • Changes in Normal Flora: Normal flora is usually protective; when competition between microbes no longer exists (e.g., due to antibiotic use), certain species may overgrow.

  • Displacement: Entrance of the normal flora into areas of the body where they are not present under normal conditions.

• Nature of Organisms: These organisms do not cause disease in their normal habitat in a healthy, balanced person.

Stages of Infection and Portals of Entry

There is a distinct difference between the presence of a microbe and the development of an infection:

• Contamination: The mere presence of microbes in or on the body.

• Infection: Occurs when the microorganism gains entry into the host and its tissue. An infection does not necessarily result in disease.

• Source of Infection:

  • Exogenous: Pathogens originating from outside the body.

  • Endogenous: Organisms already present in the body, such as normal flora.

• Portals of Entry: Sites where pathogens enter the body. These are generally the same areas that support normal flora.

• Specificity: Most pathogens have a preferred portal of entry. If a pathogen enters through the "wrong" portal, infection will typically not occur. However, some agents can enter via more than one portal.

Specific Portals of Entry

Skin

• Consists of a thick layer of keratinized dead cells.

• Pathogens enter through natural openings like hair follicles and sweat glands.

• Damage to the skin—including abrasions, cuts, punctures, scrapes, and stabs—opens the skin and allows microbe entry.

Mucous Membranes

• Respiratory Tract: The most frequently used portal of entry. Pathogens enter via air, dust particles, moisture, and respiratory droplets. Examples include pathogens causing sore throat, meningitis, diphtheria, whooping cough, common cold, influenza, measles, mumps, rubella, and chickenpox.

• Gastrointestinal (GI) Tract: Portal for pathogens in food, liquid, and ingested substances.

  • Enteric Bacteria: Salmonella, Shigella, Vibrio, and certain strains of E. coli.

  • Viruses: Poliovirus, Hepatitis A, Echovirus, and Rotavirus.

  • Protozoans: Entamoeba histolytica and Giardia lamblia.

  • Helminths: Trematodes, cestodes, and nematodes.

• Urogenital Tract: Usually contracted via sexual contact.

  • Girls and women not sexually active are susceptible to lower urinary tract infections due to the close proximity of the anus to the urethra.

  • Examples: Opportunistic infections by E. coli and vaginal yeast infections caused by an overgrowth of Candida albicans.

• Conjunctiva: Generally a good barrier, though some bacteria can attach to this membrane easily.

Placenta

• Usually an effective barrier against microorganisms.

• Some microbes can cross the placenta and infect the embryo or fetus, potentially causing spontaneous abortions, birth defects, or premature births.

Parenteral Route

• Not technically a portal of entry, but a means by which portals are evaded.

• Pathogens are introduced directly into subcutaneous tissue.

• Examples: Punctures by nails, thorns, or contaminated needles; cuts, bites, stab wounds, deep abrasions, and surgery.

Virulence and Pathogenicity

• Pathogenicity: Related to several factors including the number of microorganisms, the portal of entry, host defenses, intrinsic characteristics of the organism, and specific virulence factors.

• Virulence: The degree of pathogenicity or the disease-provoking power of a specific microbe.

Mechanics of Infection

1. Adhesion: The first and most crucial step. Without binding, organisms are removed by ciliary motion, sneezing, coughing, swallowing, urine flow, tears, or intestinal peristalsis. Bacteria bind via pili, fimbriae, or specific membrane receptor sites. Adhesion can be specific or nonspecific.

2. Colonization: Pathogens typically colonize tissues in contact with the external environment, such as the respiratory, digestive, and urogenital tracts, or the conjunctiva.

3. Invasion: Often aided by invasins (extracellular substances) that disrupt host cell membranes and break down primary and secondary barriers.

4. Evasion of Host Defense: Pathogens may avoid contact with phagocytes, inhibit phagocytic engulfment, survive inside phagocytes, or produce products that kill/damage phagocytes before or after ingestion.

Toxigenicity

A toxigenic organism is one that produces toxins, which are the underlying mechanisms for producing disease.

• Exotoxins:

  • Proteins released by bacteria during the exponential growth phase.

  • Can act at sites remote from the original location of infection.

  • Often species-specific and associated with particular diseases.

• Endotoxins:

  • Lipopolysaccharides (LPS) of the Gram-negative cell wall.

  • Released during lysis caused by host defenses or antibiotics.

  • Less potent and less specific than exotoxins.

Portal of Exit

• The site where a pathogen leaves the infected person.

• Often the same as the portal of entry.

• Pathogens also leave the host via excretion or secretion.

Etiology and Koch's Postulates

Etiology is the study of the cause of disease.

Koch’s Postulates

1. The suspected 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 inoculated into a healthy, susceptible experimental host.

4. The same pathogen must be isolated from the experimental host and shown to be identical to the original pathogen.

Exceptions to the Postulates

• Some pathogens cannot be cultured in a laboratory.

• Many infectious diseases can be caused by several different pathogens.

• A single pathogen can cause different diseases depending on the portal of entry.

• Some diseases are caused by combinations of pathogens.

• Ethical considerations prevent human inoculation of exclusively human pathogens when animal models are unavailable.

Epidemiology and Disease Patterns

Epidemiology is the study of the distribution and cause of disease in populations. It provides the foundation for public health interventions and preventive medicine.

Patterns of Infection

• Local: Confined to a specific tissue.

• Focal: Spreads from a local site to other tissues.

• Systemic: Spreads to several sites and tissue fluids, usually via the circulatory system (e.g., septicemia, bacteremia, toxemia, viremia).

• Mixed: Several agents concurrently established at the same site.

• Acute: Appears rapidly with severe symptoms and vanishes rapidly.

• Chronic: Less severe symptoms that persist for long periods.

• Primary: The initial infection.

• Secondary: Follows a primary infection.

• Subclinical: Does not cause apparent symptoms; can be carried for long periods.

Types of Epidemiology

• Descriptive: Collecting data (age, gender, occupation, etc.) regarding the affected individuals, location, and time period. Includes identifying the index case.

• Analytical: Demonstrates cause-and-effect. Can be retrospective (after an epidemic) or prospective (during an epidemic).

• Experimental: Testing hypotheses through designed studies.

Public Health Statistics

• CDC (Centers for Disease Control and Prevention): The central source of epidemiological information in the U.S. It publishes the Morbidity and Mortality Weekly Report (www.cdc.gov).

• Prevalence: Total number of existing cases in the entire population.

• Incidence: Number of new cases over a certain period compared with the healthy population.

Classification of Disease Frequency

• Endemic: Repeatedly present in a specific population or geographical area.

• Sporadic: Breaks out only occasionally.

• Epidemic: Occurs with greater frequency than usual in a population.

• Pandemic: A worldwide epidemic.

Reservoirs and Modes of Transmission

Reservoirs of Infection

• Animal Reservoirs: Cause zoonoses (diseases transmitted from animals to humans). Routes include direct contact, waste, contaminated food/water, dust from hides/feathers, or insect vectors.

• Human Carriers: The human body is the main reservoir. "Carriers" are infected individuals who do not show symptoms.

• Nonliving Reservoirs: Soil, water, and food.

Transmission Modes

• Contact:

  • Direct: Touching, kissing, sexual intercourse (e.g., STDs, measles).

  • Indirect: Via a fomite (nonliving object like tissues, toys, or medical equipment).

  • Droplet: Respiratory droplets released by sneezing (most effective), coughing, or exhaling.

• Vehicle:

  • Airborne: Via aerosol or dust; must travel more than $1\,\text{meter}$.

  • Waterborne: Fecal-oral route through untreated sewage (e.g., cholera, giardiasis).

  • Foodborne: Undercooked or unsanitary food.

  • Bodily Fluids: Blood, urine, and saliva.

• Vector:

  • Biological: Animals (arthropods) that serve as hosts for part of the pathogen's life cycle (e.g., mosquitoes, ticks).

  • Mechanical: Passively carry agents on feet or body parts.

Healthcare-Associated (Nosocomial) Infections (HAIs)

HAIs are acquired during treatment in a hospital or similar setting and are secondary to the patient's original condition. They are among the top $10$ leading causes of death in the United States.

Types of HAIs

• Exogenous: Caused by pathogens in the healthcare environment shed by sick people.

• Endogenous: Caused by the patient's own normal flora becoming pathogenic due to immune decline, antimicrobial drugs, or superinfections.

• Iatrogenic: Result from medical procedures such as catheters, surgery, or invasive diagnostics.

Transmission and Control

• Transmission Routes: Staff to patient contact, patient to patient via staff activities, fomites, and ventilation systems.

• Antimicrobial Resistance: More than $70\%$ of bacteria causing HAIs are resistant to at least one drug commonly used to treat them.

• Control: safety programs, blood-borne pathogen training, proper hand washing, and hospital infection control committees.