Infectious Disease and Public Health

Major Types of Pathogens

• Viruses

• Bacteria

• Parasites

• Fungi

Communicable

capable of person-to-person spread (contagious)

Outbreak

infection of many people in one area over a short period of time

Epidemic

when a pathogen unexpectedly begins to infect large numbers of people in a region or community

Pandemic

when the pathogen spreads over multiple countries to affect large regions of the world

Endemic

when an outbreak remains constant and predictable within a specific population or environment (Malaria in Africa; chicken pox in low vaccination regions)

Global Mortality

• In 2000, 6 of the top 10 causes of death worldwide (55% of all mortality) were linked to communicable diseases.

• By 2019, 74% of global deaths were linked to non-communicable diseases.

• Rise of chronic illnesses

Chain of Infection

Infectious Agents:

• Microbes that can cause the disease or illness

  • Bacteria, fungi, parasites, viruses

Reservoirs:

• Places where infectious agents live, grow, and reproduce

  • Soil, water, animals, people

Portals of Exit:

• Ways that the infectious agents leave human or animal reservoirs

  • Secretions, fecal material, skin, blood

Modes of Transmission:

• Ways that infectious agents can encounter a susceptible host

  • Direct (physical contact/respiratory droplets) or indirect (air, water, surface, vector)

Portals of Entry:

• Places where infectious agents can enter a susceptible host

  • Mucus membrane, respiratory system, digestive system, broken skin

Susceptible Host:

• Characteristics that influence an individual’s susceptibility to infection

  • Health status, immune compromise, age, genetics

Transmission of Respiratory Infections

Factors affecting transmission:

• Physical composition of the pathogen

• Air flow in the area of release/exposure

• Humidity in the area of release/exposure

• Time pathogen is exposed to the environment

• Pathogen load at the time of potential transmission

Vector-borne Diseases

Mosquitoes:

• Chikungunya

• Dengue

• Yellow fever

• Malaria

• Lymphatic filariasis

Flies:

• Leishmaniasis

• Onchocerciasis

• Human African trypanomiasis

Ticks:

• Crimean-Congo haemorrhagic fever

• Lyme disease

Aquatic Snails:

• Schistosomiasis

Water Fleas:

• Dracunculiasis

Triatomine Bug:

• Chagas disease

Why are animals typically the reservoir for viruses

Viruses require host cells for their survival

Entry Points and In Vivo Microenvironments

• Most pathogens enter through mucosal surfaces (M).

• Can then remain local or spread through the body.

• Pathogens can be found in the extracellular fluid (E).

• Intracellular parasites and bacteria may be engulfed by or enter cells and remain in vesicles (V).

• Viruses fuse with the plasma membrane and enter the cytosol (C).

• Each of these locations allows access to different detection molecules (TLRs/PRRs)

Determinants of Susceptibility

Health status:

• Age

• Nutrition

• Hormones / pregnancy

Genetics:

• Species level (protein homology)

• Individual level (allelic variation can increase or decrease susceptibility)

Immune response:

• Age – declining of the immune system

• Immunodeficiency

• Vaccination status

Host Tropism

Most pathogens can infect only a narrow range of species (HIV, HC)

Tissue Tropism

The notion that a given pathogen can only replicate/survive in certain tissue (HCV and liver)

Why do Viruses Emerge?

• Globalization, rapid air travel

• Environmental changes, ‘mega-cities’, poverty

• Expanding populations

• Microbial evolution

• Altered ecosystems, climate change

• Deforestation

R₀ – Reproduction Rate

R₀ (R naught) = how contagious a virus is

• The average number of people that one virally infected individual will infect

• Calculated based on assumption of 100% susceptibility

• Can change if the virus changes, or if the target population changes, i.e., via introduction of vaccines and/or acquisition of immunity through natural infection

SARS-CoV Intermediate Species

Masked palm civets (Paguma larvata)

• SARS-like CoV with > 99 % nucleotide homology with human SARS-CoV was identified

• Civets are a delicacy in some places and are raised for food and coffee bean eating.

• Evidence suggested palm civets are not SARS reservoir

  • No widespread infection in wild or farmed civets

  • Civets have no immunity against SARS-CoV

Human Coronaviruses Timeline

• Common cold (>1980)

  • OC43

  • 229E

• SARS-CoV (2002)

  • 812 deaths

  • CFR 10%

• HKU1; Pneumonia (2004/2005)

  • NL63; Croup

• MERS-CoV (2012)

  • 866 deaths

  • CFR 34%

• SARS-CoV-2 (2019)

  • COVID-19

• >6.9M deaths

• CFR 1% (Originally 2-3%)

• Influenza: 250,000 - 500,000/yr

Potential Transmission Routes for SARS-CoV-2

Reservoir of Origin:

• SARS-Bat-CoV

Possible Intermediate Hosts:

• Wild animals

• Domestic animals

SARS-CoV-2:

• Human

COVID-19

• Human transmission

What determines how many stages a pathogen can pass?

A combination of:

• Tropism

• R₀

• Mutation rate

Virus-induced Cytokine Storms and Inflammatory Syndromes

• Cytokine Release Syndrome (CRS) or “cytokine storm” arises from unregulated or exaggerated release of inflammatory cytokines.

• Results in localized and systemic acute-phase responses mediated by hyperactivation of immune cells.

• When CRS occurs in the lungs, such as with COVID-19, patients can experience acute respiratory distress syndrome (ADRS), fluid accumulation, hypoxia, multi-organ failure

Long COVID

• Symptoms persist beyond 4 weeks from infection

• More severe infections increase risk but 90% of Long COVID sufferers had mild infection because so many more cases are mild

• Vaccination reduces the risk of Long COVID

• Reinfection increases the risk of Long COVID

• Can have cardiovascular symptoms, neurological symptoms, metabolic symptoms, viral persistence, immune dysregulation, microbiome dysbiosis, endothelial inflammation, neuronal inflammation, and mitochondrial dysfunction

Influenza and Pandemics

• The 1918 Spanish Flu influenza pandemic killed 20-50 million people.

• Orthomyxoviridae have segmented genomes and each of the 8 RNAs codes for 1 of the 8 viral proteins.

• For an influenza virus to be infectious, it needs 1 of each of its 8 genomic RNA transcripts.

• But these can be similar enough from one viral species to another to actually complement for each other.

  • i.e., they can mix and match, like 2 different decks of cards making up 1 complete deck with cards from each of the 2 decks.

Original Antigenic Sin/Imprinting

The immune response is stronger to a virus carrying an antigen that was previously recognized even if there are new antigens present

• Refers to how the immune system’s first exposure biases future responses

Antigen Drift

• Refers to the gradual accumulation of mutations in viral genes, especially those coding for surface proteins (like the spike protein in SARS-CoV-2)

• These small changes lead to variants and subvariants, which may partially evade immunity from previous infection or vaccination

Antigenic Shift

A sudden, major change (often in influenza) caused by reassortment of viral segments

Immune Interference

When one immune response affects another, not directly related to viral evolution

The numerous variants and subvariants of SARS-CoV-2 are examples of:

Antigenic drift

Polio Eradication

Problem: as pathogen prevalence gets close to zero, people stop vaccinating, then we see outbreaks again

Polio Today: Resurgence in Africa, 1 detected human case in the US in 2022 but it was detected in 30 wastewater samples, and it was detected in 2 wastewater samples in Montreal

Measles

• Highly contagious

• No treatment

• Symptoms:

  • 7-14 days after exposure - fever, cough, runny nose, watery eyes

  • 2-3 days after symptoms start - tiny white spots (Koplik spots) may appear inside the mouth

  • 3-5 days after symptoms - typical rash

• Complications: pneumonia, ear infection, diarrhea, breathing failure, death, encephalitis, blindness, deafness, intellectual disability, miscarriage, pre-term birth, low birth weight

• Subacute Sclerosing Panencephalitis: 7-10 years after recovery, fatal, risk increases if contracted measles < 2 years old

• The measles virus wipes out immunological memory so people are more susceptible to other infections (11-73% reduction in antibody repertoire)

• WAS eliminated in USA and Canada in 2000/1998 - TODAY there are outbreaks (2014 - Disneyland & 2019 - New York)

• 5463 cases of measles in Canada 2025

Persistence and Reactivation of Herpes Infections

• HSV causes cold sores by infecting epithelial cells, and spreading to local sensory neurons

• Herpes zoster (Varicella, chicken pox) causes chicken pox. Infects dorsal root ganglia - remains latent

• An effective immune response controls the infection, but the virus persists in a latent state in sensory neurons

• Sunlight, bacterial infection, aging, or hormonal changes can reactivate the infection

• Shingles is due to reactivation of the chicken pox virus

Emerging Viruses

• Hantavirus

• Nipah virus

• West Nile virus

• Dengue virus

• Ebola virus

• Chikungunya virus

• Avian influenza virus

• Zika virus

• Monkeypox

Zoonosis

Infectious diseases naturally transmitted from vertebrate animals to humans, caused by bacteria, viruses, parasites, or fungi

Bacterial Evasion

1. Ab are IgA isotype, some bacteria secrete proteases that degrade IgA (N. gonorrhoea)

2. Gram-positive bacteria, some gram-negative bacteria, resistant to complement-mediated lysis

3. Some surface structures of bacteria inhibit phagocytic cells (fibrin, M protein), some bacteria can escape phagolysosome into cytosol

Bacterial Evasion - Mycobacteria Tuberculosis

• Replicates inside cells

  • Inhibits phagolysosome formation

• Also causes formation of granuloma inside tubercle

• Release of lytic enzymes destroy healthy tissue

• Infection is contained

• Antibiotics do not penetrate granuloma very well

Protozoans (Parasitic Infections)

• Unicellular eukaryotes

• Usually live and reproduce in host cells

• Some require intermediate host

• e.g., malaria, trypanomiasis

Helminths (Parasitic Infections)

• Multicellular

• Have the ability to live and reproduce outside host

• Worms

Parasites-Host Defense

• Generalization is difficult → immune system response is specific to the stage of life cycle of the parasite and where in the body the parasite infects

• If free within the bloodstream → humoral antibody

• If grow intracellularly → cell-mediated immune reactions (NK cells, T cells)

Helminth (Worms) - Schistomsomiasis

• Worm is too big for phagocytosis

• Cells secrete lytic enzymes (complement, basic protein, ADCC)

• Ab (IgE) involved is the same one that causes an allergic response

• Contaminated water

• Free swimming larvae

• 20-years infection (induce antigen production; hide under a glycoprotein coat with ABO-blood group)

Fungal Infections

Mostly controlled by innate immune system:

• Physical barriers and commensal microorganisms

• Neutrophil phagocytosis

• Recognized by pathogen-associated patterns (PAMP) on fungus by pattern recognition receptors (PRR) on host

  • Some fungi have evolved a capsule that blocks PRR binding

Can have some acquired immunity