Topic 6: Disease challenges and strategies

6.2 The emergence and re-emergence of pathogens

• Key concepts: emergence of new pathogens; re-emergence of known pathogens in a globalised world; factors include environmental change, population growth, urbanisation, and increased mobility.
• Emerging diseases: caused by a newly identified or previously unknown agent; may have existed in other species and recently jumped to humans.
• Re-emerging diseases: known diseases that increase in incidence after a period of decline.
• Examples: HIV/AIDS, SARS, Zika, MERS, COVID-19; widespread exposure linked to global connectivity.
• Important drivers: disruption of ecosystems; travel and trade; zoonoses (pathogens from animals to humans).
• Summary point: many infectious diseases remain a public health threat despite vaccines and treatments.

6.2.1 Different types of diseases

• Disease types: non-infectious (non-communicable) vs infectious (communicable).
• Non-infectious examples: genetic, degenerative, nutritional, cancers, physiological dysfunctions.
• Infectious diseases: caused by pathogens; can be transmitted between individuals.
• Pathogen: agents that cause disease.
• Emerging vs re-emerging definitions (key terms):
  • Emerging disease: new or previously unknown agent; may have existed in animals.
  • Re-emerging disease: previously controlled disease that has increased in incidence.
• Historical note: early 20th century vaccines reduced deaths from several infectious diseases; smallpox eradicated worldwide.

6.2.2 Pathogens, pandemics and epidemics

• Pandemic: global outbreak; affects multiple world regions; to be declared a pandemic, spread must be easy and sustainable in humans in at least three countries and two WHO regions; severity is not defined by this term.
• Epidemic: widespread occurrence in a community or restricted geography at a particular time.
• Relationship: an epidemic can develop into a pandemic in an interconnected world; pandemics attract greater public attention.
• Case studies: influenza pandemics (1918, 1951, 1968, 2009); HIV/AIDS pandemic; cholera pandemics; COVID-19 (SARS-CoV-2).
• Global map and context: diseases can cross borders rapidly due to travel and trade; public health responses rely on rapid identification and control.

6.2.3 The impact of European arrival on Aboriginal and Torres Strait Islander peoples

• 1770–1788: European colonisation introduced to eastern Australia; large population declines in Aboriginal peoples due to new diseases.
• Torres Strait Islander contacts: early contacts in 1606; post-1788 contact brought several diseases with devastating effects.
• Common epidemic diseases: smallpox, chickenpox, syphilis, tuberculosis, influenza, measles.
• Reasons for large fatalities: no prior exposure and little immunity; low herd immunity; high susceptibility.
• Case study note: smallpox epidemic of 1789 caused massive mortality in Aboriginal communities.
• Key ideas: demographic changes, disease exposure, and transmission routes shaped population outcomes.

6.3 Identifying and controlling the spread of pathogens

• 6.3.1 Bringing outbreaks under control

  • Outbreaks threaten public health and economy (quarantine, lockdowns, healthcare costs).
  • Key questions during outbreaks: cause? how to treat? how to prevent spread? what prevention measures are needed?
  • Rapid response teams: Epidemic Intelligence Service (EIS, CDC); WHO; Australian Health Protection Principal Committee (AHPPC).

• 6.3.2 Identifying pathogens

  • Viruses: non-cellular; require host cells for replication; isolation and culture in suitable cell lines.
  • Identification methods: physical (size/shape by X-ray crystallography/electron microscopy); immunological (ELISA variants: direct, indirect, sandwich); molecular (nucleic acid probes, in situ hybridisation; DNA sequencing).
  • ELISA types: direct ELISA (antigen + labeled antibody), indirect ELISA (primary antibody + secondary enzyme-labeled antibody), sandwich ELISA (capture antibody + detection antibody).
  • Case example: ELISA for HIV antibodies in serum (HIV diagnostics).
  • Molecular methods: DNA/RNA sequencing, probes, and in situ hybridisation to identify viral genomes.

• 6.3.3 Identifying the host

  • Reservoirs vs hosts: reservoirs are habitats where pathogens persist (humans, animals, environment); hosts are organisms that can be infected.
  • Zoonoses: diseases that can be transmitted from animals to humans.
  • Index (patient zero): first identified case; helps track spread and pathogen origin.
  • Transmission considerations help target quarantine and prevention measures.
  • Factors affecting susceptibility: genetics, immunity, nutrition, age, sex.

• 6.3.4 Modes of pathogen transmission

  • Entry/exit: portals of entry (skin, mucous membranes); exit routes (saliva, blood, feces, etc.).
  • Direct transmission: person-to-person (e.g., kissing, sexual contact).
  • Indirect transmission: droplets, contaminated objects, food/water, biological vehicles (blood, sputum, feces).
  • Vectors: organisms (ticks, fleas, mosquitoes) that transmit pathogens between hosts; zoonoses common.
  • Incubation period: time from infection to first symptoms; asymptomatic carriers can spread disease.
  • Examples: influenza, measles, HIV, Ebola, cholera, TB.

• 6.3.5 Measuring the spread of a pathogen

  • Outbreak metrics include the basic reproduction number $R_0$, indicating average secondary cases per case in a fully susceptible population.
  • WHO pandemic alert phases (influenza case): inter-pandemic, pandemic alert, and pandemic periods; earlier intervention reduces spread.
  • Example R0 values: COVID-19 $R<em>0 = 3.5$; SARS $R</em>0 = 4$; Measles $R<em>0 = 18$; Ebola $R</em>0 = 2$; HIV $R_0 = 4$.

• 6.3.6 Controlling the spread of pathogens

  • Prevention: hygiene, safe sex, sanitation, vaccination, vector control, clean water.
  • Vaccination: long-term protection; can eradicate or greatly reduce diseases (e.g., measles, polio).
  • Medication: antibiotics for bacteria; antivirals for viruses.
  • Surveillance: global monitoring and rapid response.
  • Environmental modification: e.g., vector control strategies.
  • Infection control standards: sterilisation, isolation, hygiene practices.

6.4 Vaccination programs and herd immunity

• 6.4.1 Vaccination programs

  • Aim: reduce impact of vaccine-preventable diseases by achieving high immunisation rates.
  • Vaccines induce artificial adaptive immune response and memory:
  • live attenuated, inactivated, toxoids, subunits.
  • Booster shots may be required: killed/inactivated vaccines often require boosters due to weaker, shorter-lived responses.
  • Example: Australian National Immunisation Program Schedule (NIP) across infancy and childhood; variation by state; most vaccines given in combination.

• 6.4.2 The importance of mass vaccination

  • Mass vaccination has led to elimination of diseases (worldwide or regional) such as smallpox and polio.
  • Eradication and elimination depend on sustained high coverage and public health infrastructure.

• 6.4.3 Herd immunity

  • Direct protection via individual immunity; indirect protection of unvaccinated individuals when a high proportion of the population is immune.
  • Herd immunity threshold depends on transmissibility; commonly around a high proportion (example: ~95% target).
  • Protects vulnerable members (newborns, immunocompromised, elderly).
  • High coverage achievable through mass immunisation programs (e.g., 95% target in many populations).

• 6.4.4 Case studies and schedules

  • Mass vaccination programs have reduced incidence and sometimes eliminated diseases.
  • Poliomyelitis: large global eradication efforts; differences between Salk (inactivated) and Sabin (live attenuated) vaccines; Australia eradicated local transmission.
  • Measles: outbreak dynamics tied to vaccination rates; vaccination boosts contribute to herd immunity.

• 6.4.5 Eradication, vaccination history and schedule examples

  • Smallpox eradication achieved through global vaccination; stocks of smallpox virus remain in secure labs for research.
  • Poliovirus: polio eradication efforts; vaccine types and delivery methods influence long-term success.
  • Coverage trends and regional elimination: meningococcal disease and other vaccine-preventable diseases show declines following vaccines.

6.5 Development of immunotherapy strategies

• 6.5.1 What is immunotherapy?

  • Treatments that alter the immune response to fight diseases such as cancer and autoimmune disorders.
  • Distinguishes from chemo/radiation; aims to harness or modulate immune activity.

• 6.5.2 Monoclonal antibodies (MAbs)

  • MAbs are antibodies produced from one clone; bind to a single antigen with high specificity.
  • Production: hybridomas (B cells fused with myeloma cells) to generate continual antibody production.
  • MAbs can be naked or conjugated to drugs/radiolabels for targeted therapy.
  • Examples: therapy for cancers and autoimmune diseases; many MAbs target specific antigens (e.g., CD20, CD30, HER2).

• 6.5.3 MAbs in cancer therapy

  • Modes of action include:
  • Stop angiogenesis: block VEGF to prevent new blood vessels to tumors (e.g., Bevacizumab).
  • Mark cancer cells for immune attack: antibodies bind to cancer antigens and recruit immune cells.
  • Block growth signals: e.g., trastuzumab (Herceptin) blocks HER2 signaling.
  • Deliver cytotoxic payloads: conjugated MAbs carry chemotherapy drugs or radioisotopes to cancer cells.
  • Naked vs conjugated MAbs: naked MAbs act on targets; conjugated MAbs deliver toxins or radioisotopes.
  • Examples of MAb products and targets: Bevacizumab, Trastuzumab, Brentuximab, Rituximab, Zevalin, etc.

• 6.5.4 MAbs in autoimmune diseases

  • Some MAbs suppress the immune response to reduce autoimmune damage (e.g., anti-TNF antibodies like Infliximab/Adalimumab; IL-2 receptor blockers like Basiliximab; anti-IgE like Omalizumab; anti-CD20 like Rituximab).
  • Strategies include blocking MHC/MHC-II interactions to prevent autoimmunity; targeting specific immune pathways to reduce self-reactivity.

• 6.5.5 Practical considerations

  • MAbs enable targeted therapy with potentially fewer off-target side effects than conventional chemotherapy.
  • Use often in combination with chemotherapy/radiation or as immune-modulating therapies.

6.6 Review (highlights)

• Key ideas:
  • Pathogen identification (virus/bacteria) relies on physical, immunological, and molecular methods; host/reservoir identification aids quarantine and prevention.
  • Transmission modes include direct, indirect, droplets, vectors; incubation period and asymptomatic carriers influence spread.
  • R0 ($R_0$) helps quantify spread; higher values indicate greater transmission potential.
  • Prevention and control include hygiene, vaccination, surveillance, environmental modification, and infection-control standards.
  • Vaccination creates herd immunity; high coverage protects those who cannot be vaccinated.
  • Immunotherapy (especially monoclonal antibodies) provides targeted cancer and autoimmune disease treatments; vaccines remain a cornerstone of public health.