Module 5: The Pathology Of Infectious Disease And Population Health Flashcards
(43 cards)
Four Classes of Microbes
Bacteria
- Microscopic unicellular prokaryotes
- Contain circular double-stranded DNA
- Most have cell walls distinct from eukaryotic cells
Examples:
Mycobacterium tuberculosis (tuberculosis)
Salmonella species (food poisoning)
Viruses
- Obligate microbes requiring host cells for replication
- Have DNA- or RNA-based genomes within a protein coat
- Infect specific host cells, including bacteria, plants, and animals
Examples:
Influenza (flu)
Rhinovirus (common cold)
Measles morbillivirus (measles)
Fungi
- Unicellular or multicellular eukaryotes with thick cell walls
- Cause superficial infections or invade deeper tissues
Examples:
Dermatophyte fungi (athlete’s foot, jock itch, ringworm)
Aspergillus (respiratory tract infections)
-Candida species (thrush)
Parasites
- Eukaryotic organisms that cause disease in a host
- Include protozoa, parasitic worms (helminths), and ectoparasites
- Some ectoparasites act as disease vectors
Examples:
Plasmodium parasites (malaria)
Sarcoptes scabiei (scabies)
The Microbiome: Normal Flora
- The microbiome is the collection of microbes (bacteria, viruses, fungi, and parasites) that live symbiotically in and on the human body.
- Found mainly on the skin and mucous membranes.
Functions of the microbiome:
Aids in digestion
Prevents inflammation
Protects against infections
Produces essential vitamins
- Mucous membranes: Membranes lining body cavities and internal organ surfaces.
Microbes as Pathogens
Opportunistic Microbes (Potential Pathogens):
- Normally part of the body’s normal flora but can cause disease if an imbalance occurs.
- Example: Staphylococcus aureus – a skin bacterium that can cause infections if it enters deeper tissues.
Always Pathogenic Microbes (Pathogens):
- Not part of the normal flora and always cause disease.
- Example: Rhinovirus – causes the common cold and spreads through airborne droplets or direct contact.
Immunity and Response
Innate Immune System (Immediate, Non-Specific Response)
- First line of defense, prevents pathogen spread.
Components:
- Physical barriers: Skin, mucous membranes.
- Chemical barriers: Enzymes in saliva and tears.
- Immune cells: Cause inflammation or engulf pathogens.
Adaptive Immune System (Delayed, Specific Response)
- Takes days to activate but targets specific pathogens.
- Recognizes antigens (foreign molecules) and triggers a strong response (pus, swelling, redness, pain).
- Forms immune memory to quickly fight future infections from the same microbe.
How Pathogens Cause Infection
- Entry: Pathogen enters the body (e.g., SARS-CoV-2 enters through the oral/nasal passages into the lungs).
- Invasion & Colonization: Pathogen attaches to human cells (SARS-CoV-2 uses spike proteins to bind to ACE2 receptors in the lungs).
- Evasion of Immune Response: Pathogens use different tactics to avoid detection (SARS-CoV-2 delays the adaptive immune response).
- Infection: Pathogen replicates and spreads (SARS-CoV-2 hijacks cell machinery to reproduce and infect more cells)
Conditions for Infectious Disease
Reservoir:
- Locations where pathogens persist long-term.
- Examples: Biological (humans, bats, chickens) or environmental (soil, lakes, swamps).
Mode of Transmission:
- Pathogens spread through various means:
Direct contact: With infected organisms or surfaces.
Droplets: From sneezing or coughing.
Airborne: Spores in the air.
Vectors: Carriers like mosquitoes or fleas.
Vehicles: Contaminated water or food.
Opportunistic Conditions:
- Factors that promote infection or weaken immune defenses.
- Examples: Stress, surgery, aging.
Infectious Disease Prevention
Eliminating Reservoirs:
- Removing sources of pathogens prevents disease spread (e.g., eliminating malaria-carrying mosquitoes).
Enhancing Barriers:
- Physical measures like face masks, hand washing, and social distancing reduce transmission.
Distributing Vaccines:
- Vaccines help the immune system recognize and fight infections before exposure.
Developing Targeted Medicines:
- Drugs can treat or prevent infections (e.g., ivermectin for parasitic worms)
Chickenpox Vaccination
- Cause: Chickenpox is a highly contagious viral disease.
- Symptoms: Blister-like rash (lasting ~1 week), fever, fatigue, headache.
- Vaccine Development:
Available in Canada since 1998.
Government-subsidized starting in 2004.
Now part of routine childhood immunizations. - Impact: Over 100-fold reduction in chickenpox prevalence in Canada
Herd Immunity
- Vaccines: Most effective and cost-efficient protection against infectious diseases.
- Vulnerable Groups: Some individuals cannot get vaccinated (e.g., infants, elderly, pregnant women, immunocompromised individuals).
- Herd Immunity: When a large portion of the population is vaccinated, it indirectly protects those who cannot be vaccinated by reducing disease spread.
Infection from Colonization
Disease Introduction: European settlers brought smallpox, tuberculosis, and measles, leading to devastating epidemics among Indigenous Peoples.
Consequences:
High mortality rates wiped out entire groups.
Survivors were often too weak to sustain themselves.
Loss of oral histories due to community collapse.
Unequal Public Health Response: Colonists used quarantine and vaccines but let diseases spread in Indigenous communities.
Biological Warfare: In 1763, Jeffrey Amherst used smallpox-contaminated blankets to weaken First Nations resistance—the first documented case of biological warfare.
Eradication of Smallpox: Due to global vaccination efforts, the World Health Organization declared smallpox eradicated in 1980—the first disease eliminated by public health measures
Infections In First Nations Communities
Strep Throat Case:
- 2014: Brody Meekis, a 5-year-old from Sandy Lake First Nation, died of strep throat due to inadequate healthcare services, such as poorly staffed clinics and unreliable medical transportation.
- This highlights failures in the Canadian healthcare system, particularly for Indigenous communities, where even treatable diseases can lead to death.
Tuberculosis (TB):
- TB was introduced to Canada by European settlers, and crowded reserves, residential schools, and Indian hospitals contributed to its rapid spread among Indigenous populations.
- Mortality rates for TB were historically highest among Indigenous peoples.
Current incidence rates of TB:
0.6 per 100,000 among non-Indigenous
23.8 per 100,000 among First Nations
170.1 per 100,000 among Inuit
2.1 per 100,000 among Métis
Bacteria
Bacterial Evolution:
- Bacteria were among Earth’s first lifeforms and evolved into multicellular eukaryotes over time, including humans.
- Most bacteria in the human body are crucial for health maintenance.
Gram Positive Bacteria:
- Thick peptidoglycan wall
- Stains purple with Gram stain due to the thick cell wall.
Gram Negative Bacteria:
- Thin peptidoglycan wall surrounded by an outer membrane.
- Stains pink with Gram stain due to the outer membrane.
Gram Staining:
- The Gram stain distinguishes bacteria based on their cell wall structure.
- This staining helps determine treatment options in healthcare.
- Peptidoglycan: A mesh of amino acids and proteins surrounding the bacterial plasma membrane.
Pathogenic Bacteria and Antibiotics
Bacterial Pathogenicity:
- Some bacteria are pathogenic and can cause diseases in humans.
- Antibiotics have revolutionized healthcare by helping to combat bacterial infections.
Bacterial Cell Envelope:
- Composed of the plasma membrane and the cell wall.
- The cell wall contains peptidoglycan, which differs between Gram positive and Gram negative bacteria.
- The primary role of the cell envelope is to contain internal pressure within the bacterial cell, preventing it from bursting.
Importance in Drug Design:
- Since cell walls (with peptidoglycan) are absent in eukaryotic cells, they become an ideal target for antibiotics.
- Antibiotics can be designed to target specific components of the bacterial envelope, without harming human cells.
Antibiotics and Antimicrobials
Antimicrobials:
- Broad term for agents, natural or synthetic, that stop the growth of or kill microorganisms.
- Includes substances like antibiotics, but also includes non-antibiotic agents such as bleach.
Antibiotics:
- Antibiotics are a type of antimicrobial specifically used as medications produced by microorganisms or synthetically, designed to stop the growth of or kill microorganisms.
- All antibiotics are antimicrobials, but not all antimicrobials are antibiotics
Antibiotic Classification
How They Target Bacteria:
-Bactericidal Antibiotics:
Kill bacteria directly, without needing the host’s immune system.
Effective in treating life-threatening infections.
Bacteriostatic Antibiotics:
Inhibit bacterial growth, relying on the host’s immune system to eliminate bacteria.
Not ideal for life-threatening infections.
What They Target:
Broad-Spectrum Antibiotics:
Target a wide range of bacteria, both Gram-positive and Gram-negative.
Narrow-Spectrum Antibiotics:
Target a small group of specific bacteria.
Cell Wall Synthesis Inhibitors
- The bacterial cell wall provides structural integrity and prevents osmotic rupture.
- These antibiotics block enzymes responsible for building the peptidoglycan layer.
- Example: Penicillin, a β-lactam antibiotic, binds permanently to the enzyme that crosslinks peptidoglycan, leading to weak cell walls and bacterial death.
- Some of these antibiotics are specific to Gram-positive or Gram-negative bacteria due to differences in cell wall composition.
Metabolic Pathway Disruptors
- These antibiotics target bacterial metabolic pathways that are absent or different in humans.
- A common target is folate synthesis, which bacteria need to produce DNA and proteins, whereas humans get folate from their diet.
- Example: Cotrimoxazole combines two antibiotics that each block a different enzyme in folate synthesis. Alone, they are bacteriostatic (stop growth), but together, they become bactericidal (kill bacteria).
Protein Synthesis Inhibitors
- These antibiotics block bacterial ribosomes, preventing translation of mRNA into proteins.
- Bacteria have prokaryotic ribosomes (70S), which differ structurally from human eukaryotic ribosomes (80S), allowing selective targeting.
- Example: Doxycycline binds to bacterial ribosomes, blocking protein synthesis and preventing bacterial growth.
- This class is useful for infections like Lyme disease, where a single dose of doxycycline can prevent illness after a tick bite.
Cell Membrane Disruptors
- These antibiotics disrupt the bacterial plasma membrane, causing leaks that interfere with essential cellular functions.
- Since bacterial and human membranes are similar, these drugs tend to have stronger side effects.
- Example: Daptomycin inserts into the bacterial membrane, creating leaks that lead to cell death by disrupting protein synthesis and other critical processes.
- Despite its side effects, daptomycin is increasingly used for multi-drug-resistant infections.
Nucleic Acid Synthesis Inhibitors
- Bacteria have circular DNA that must be supercoiled to fit inside the cell.
- During replication and transcription, an enzyme called gyrase temporarily relaxes this supercoiling.
- These antibiotics block DNA gyrase, preventing proper supercoiling and leading to DNA degradation and cell death.
- Example: Fluoroquinolones selectively target bacterial DNA gyrase, disrupting replication without harming human cells (which use different enzymes).
Antibiotic Resistance Pathways
Bacteria can develop antibiotic resistance through various mechanisms:
1. Alter Targets – Mutations change the drug’s target structure or replace its function, making the antibiotic ineffective.
2. Restrict Target Access – Bacteria block antibiotic entry or use efflux pumps to remove the drug.
3. Develop Drug-Specific Enzymes – Bacteria produce enzymes that break down or modify antibiotics, neutralizing them.
These adaptations allow bacteria to evade treatment, making infections harder to cure.
Development of Antibiotic Resistance
Antibiotic resistance develops through four key steps:
1. Infection – A host is infected with bacteria, including some that are drug-resistant.
2. Treatment – Antibiotics kill susceptible bacteria, but drug-resistant ones survive.
3. Proliferation – Resistant bacteria multiply, unaffected by the antibiotic.
4. Gene Transfer – Resistant bacteria can pass their resistance genes to other bacteria, spreading resistance.
This process allows antibiotic-resistant bacteria to thrive, making infections harder to treat.
Transfer of Antibiotic Resistance
Bacteria can spread antibiotic resistance genes through both vertical (to offspring) and horizontal gene transfer (to other bacteria), resulting in faster and more widespread accumulation of resistance.
Horizontal transfer occurs in three ways:
Transformation – Bacteria absorb free DNA from their environment and integrate it into their genome.
Conjugation – Direct cell-to-cell transfer of resistance genes via plasmids.
Transduction – Bacteriophages (viruses) transfer resistance genes between bacteria.
Maintenance of Resistance
Antibiotic resistance has a metabolic cost for bacteria, as producing resistance proteins and enzymes requires extra energy.
From an evolutionary perspective, resistant bacteria lose their advantage when antibiotics are absent. Non-resistant strains, which use fewer resources, can outcompete them and grow faster.
Selective pressure ensures that resistance is maintained only if antibiotics remain in the environment. Without the drug, resistant bacteria may die off over time.
