Infection, Infectious Diseases, and Epidemiology: Core Concepts and Mechanisms

Symbiotic Relationships Between Microbes and Their Hosts

Types of Symbiosis

Symbiosis refers to the close association between two different biological species. In microbiology, humans maintain various symbiotic relationships with microorganisms, which can be classified as follows:

• Mutualism: Both organisms benefit from the relationship. Example: Bacteria in the human colon synthesize vitamins beneficial to the host and receive nutrients in return.

• Commensalism: One organism benefits, while the other is neither helped nor harmed. Example: Mites living in human hair follicles.

• Amensalism: One organism is harmed, while the other is unaffected. Example: Fungus secreting antibiotics that inhibit nearby bacteria.

• Parasitism: One organism benefits at the expense of the other. Example: Mycobacterium tuberculosis in the human lung.

Type	Organism 1	Organism 2	Example
Mutualism	Benefits	Benefits	Bacteria in human colon
Commensalism	Benefits	Neither benefits nor is harmed	Mites in hair follicles
Amensalism	Neither benefits nor is harmed	Is harmed	Fungus secreting antibiotic
Parasitism	Benefits	Is harmed	Tuberculosis bacteria in lung

Normal Microbiota of Humans

The microbiome consists of all microorganisms that colonize the body's surfaces without causing disease under normal conditions. These are also called normal microbiota, normal flora, or indigenous microbiota. There are two main types:

• Resident microbiota: Remain throughout life, mostly commensal.

• Transient microbiota: Present for short periods; eliminated by competition, body defenses, or changes in the body.

Distribution of Resident Microbiota

Resident microbiota inhabit various body regions, each with characteristic genera and ecological notes:

Body Site	Genera	Notes
Upper Respiratory Tract	Fusobacterium, Haemophilus, Lactobacillus, Moraxella, Staphylococcus, Streptococcus, Candida (fungus)	Microbiota of trachea/bronchi sparse; lungs nearly sterile.
Upper Digestive Tract	Actinomyces, Bacteroides, Corynebacterium, Haemophilus, Lactobacillus, Neisseria, Staphylococcus, Streptococcus, Treponema, Candida (fungus)	Colonize teeth, gingiva, lining of cheeks, pharynx, and saliva.
Lower Digestive Tract	Bacteroides, Bifidobacterium, Clostridium, Enterococcus, Escherichia, Lactobacillus, Proteus, Candida (fungus)	Mostly strict anaerobes; some facultative anaerobes.
Female Urinary/Reproductive	Bacteroides, Clostridium, Lactobacillus, Staphylococcus, Streptococcus, Candida (fungus), Trichomonas (protozoan)	Microbiota change with menstrual cycle; urine flow prevents colonization.
Male Urinary/Reproductive	Bacteroides, Lactobacillus, Mycobacterium, Pseudomonas, Staphylococcus, Streptococcus	Urine flow prevents colonization.
Skin/Eyes	Corynebacterium, Micrococcus, Propionibacterium, Staphylococcus, Candida (fungus), Malassezia (fungus)	Microbes on outer dead skin; deeper layers are sterile.

Acquisition and Changes in the Microbiome

• Humans are sterile in the womb; microbiome develops during birth and early life.

• Resident microbiota are established in the first months of life.

• Transient microbiota are present temporarily and eliminated by competition, immune defenses, or body changes.

Opportunistic Pathogens

Normal microbiota can become opportunistic pathogens under certain conditions, such as:

• Introduction into unusual body sites

• Immune suppression

• Changes in the normal microbiota (e.g., antibiotics)

• Stressful conditions

Reservoirs of Infectious Diseases

Types of Reservoirs

Reservoirs are sites where pathogens are maintained as sources of infection. There are three main types:

• Animal reservoirs: Zoonoses are diseases naturally spread from animals to humans (e.g., rabies, malaria).

• Human carriers: Asymptomatic individuals can transmit pathogens; some never develop illness.

• Nonliving reservoirs: Soil, water, and food contaminated with pathogens (e.g., Clostridium in soil).

Common Zoonoses

Disease	Causative Agent	Animal Reservoir	Mode of Transmission
Rabies	Lyssavirus sp.	Bats, skunks, foxes, dogs	Bite of infected animal
Malaria	Plasmodium spp.	Monkeys	Bite of Anopheles mosquito
Ringworm	Trichophyton spp.	Domestic animals	Direct contact
Anthrax	Bacillus anthracis	Domestic livestock	Direct contact, inhalation
Lyme disease	Borrelia burgdorferi	Deer	Tick bites

The Invasion and Establishment of Microbes in Hosts: Infection

Contamination vs. Infection

• Contamination: Presence of microbes on or in the body.

• Infection: Microbes evade defenses, multiply, and establish in the body.

Portals of Entry

Pathogens enter the body through specific portals:

• Skin: Entry through cuts, openings, or by burrowing/digesting outer layers.

• Mucous membranes: Line body cavities open to the environment; respiratory tract is most common entry site.

• Placenta: Usually a barrier, but some pathogens can cross and infect the fetus.

• Parenteral route: Circumvents usual portals; pathogens deposited directly into tissues (e.g., via puncture).

Pathogens Crossing the Placenta

Pathogen	Condition in Adult	Effect on Embryo/Fetus
Toxoplasma gondii	Toxoplasmosis	Abortion, epilepsy, blindness, etc.
Treponema pallidum	Syphilis	Abortion, birth defects
Listeria monocytogenes	Listeriosis	Granulomatosis infantiseptica, death
Cytomegalovirus	Usually asymptomatic	Deafness, microcephaly
Rubivirus	German measles	Severe birth defects or death

The Role of Adhesion in Infection

Adhesion is the process by which microorganisms attach to host cells, a critical step for colonization and infection. This involves:

• Adhesion factors (specialized structures or attachment molecules)

• Attachment proteins (ligands) binding to host cell receptors

• Formation of biofilms by some bacteria

The Nature of Infectious Disease

Manifestations of Disease

• Symptoms: Subjective characteristics felt only by the patient (e.g., pain, nausea).

• Signs: Objective manifestations observed or measured by others (e.g., fever, rash).

• Syndrome: Group of symptoms and signs that characterize a disease.

• Asymptomatic (subclinical): Infections without symptoms but with detectable signs.

Symptoms	Signs
Pain, nausea, headache, chills, fatigue, malaise, itching, abdominal cramps	Swelling, rash, vomiting, diarrhea, fever, pus, anemia, leukocytosis/leukopenia, bubo, tachycardia/bradycardia

Etiology: Causation of Disease

• Etiology: Study of the cause of disease.

• Diseases can be hereditary, congenital, degenerative, nutritional, endocrine, mental, immunological, neoplastic, infectious, iatrogenic, idiopathic, or healthcare-associated.

Koch’s Postulates

Robert Koch established criteria to prove that a specific pathogen causes a specific disease:

1. The suspected agent must be present in every case of the disease.

2. The agent must be isolated and grown in pure culture.

3. The cultured agent must cause the disease when inoculated into a healthy host.

4. The same agent must be reisolated from the diseased experimental host.

Virulence Factors of Infectious Agents

• Pathogenicity: Ability to cause disease.

• Virulence: Degree of pathogenicity, determined by virulence factors such as adhesion factors, biofilms, extracellular enzymes, toxins, and antiphagocytic factors.

Extracellular Enzymes

• Secreted by pathogens to dissolve host chemicals, aiding invasion and evasion of defenses.

• Mutants lacking these enzymes are often avirulent.

Toxins

• Toxins: Chemicals that harm tissues or trigger damaging immune responses.

• Toxemia: Presence of toxins in the bloodstream.

• Two main types: Exotoxins (secreted proteins) and endotoxins (lipid A of LPS in Gram-negative bacteria).

Feature	Exotoxins	Endotoxins
Source	Gram-positive and Gram-negative bacteria	Gram-negative bacteria
Chemical Nature	Protein/peptide	Lipid A of LPS
Toxicity	High	Low (may be fatal in high doses)
Heat Stability	Unstable (>60°C)	Stable (up to 121°C)
Fever Producing?	No	Yes
Antigenicity	Strong	Weak
Toxoid Formation	Possible	Not feasible
Representative Diseases	Botulism, tetanus, cholera	Typhoid fever, endotoxic shock

Antiphagocytic Factors

• Prevent phagocytosis by host cells, allowing pathogens to persist.

• Bacterial capsules are slippery and not recognized as foreign.

• Antiphagocytic chemicals prevent lysosome fusion or destroy phagocytes (leukocidins).

Stages of Infectious Disease

Infectious diseases typically progress through five stages:

1. Incubation period: No signs or symptoms.

2. Prodromal period: Vague, general symptoms.

3. Illness: Most severe signs and symptoms.

4. Decline: Declining signs and symptoms.

5. Convalescence: No signs or symptoms.

The Movement of Pathogens Out of Hosts: Portals of Exit

Pathogens exit the host through portals often shared with entry points, such as the respiratory tract, gastrointestinal tract, and urogenital tract. They are commonly shed in secretions or excretions.

Modes of Infectious Disease Transmission

Transmission Groups

• Contact transmission: Direct (person-to-person), indirect (via fomites), or droplet (mucus droplets).

• Vehicle transmission: Airborne (aerosols), waterborne (fecal-oral), foodborne, or via bodily fluids.

• Vector transmission: Biological (arthropods as hosts) or mechanical (passive transfer by insects).

Selected Arthropod Vectors

Vector	Disease	Causative Agent
Mosquitoes	Malaria, Yellow fever, Dengue	Plasmodium spp., Flavivirus sp.
Ticks	Lyme disease, Rocky Mountain spotted fever	Borrelia burgdorferi, Rickettsia rickettsii
Fleas	Bubonic plague, Endemic typhus	Yersinia pestis, Rickettsia typhi
Lice	Epidemic typhus	Rickettsia prowazekii
Houseflies/Cockroaches	Foodborne infections	Shigella spp., Salmonella spp., E. coli

Classification of Infectious Diseases

Term	Definition
Acute disease	Symptoms develop rapidly, runs course quickly
Chronic disease	Mild symptoms, develop slowly, last long
Subacute disease	Symptoms/time course between acute and chronic
Latent disease	Appears long after infection
Communicable disease	Transmitted from host to host
Contagious disease	Easily spread communicable disease
Noncommunicable disease	Not passed person to person
Local infection	Confined to small region
Systemic infection	Widespread in many systems
Focal infection	Site serves as source for other infections
Primary infection	Initial infection in a patient
Secondary infection	Follows a primary infection, often by opportunists

Epidemiology of Infectious Diseases

Frequency of Disease

• Incidence: Number of new cases in a given area and time.

• Prevalence: Total number of cases in a given area and time.

Epidemiological Studies

• Descriptive epidemiology: Tabulation of data, identification of index case.

• Analytical epidemiology: Determines probable cause, mode of transmission, and prevention; often retrospective.

• Experimental epidemiology: Tests hypotheses, applies Koch’s postulates.

Healthcare-Associated (Nosocomial) Infections

• Exogenous: Acquired from healthcare environment.

• Endogenous: Arise from normal microbiota within patient.

• Iatrogenic: Result from medical procedures.

• Superinfections: Result from antimicrobial drugs inhibiting resident microbiota.

• Prevention: Handwashing is most effective.

Public Health and Disease Control

• Data sharing among local, national, and global agencies (e.g., CDC, WHO).

• Enforcement of cleanliness, immunization, vector control, isolation, and quarantine.

• Public education campaigns to limit disease transmission.