Lecture 25: Control and Intervention Strategies

Aims of Control and Intervention

  • Control:
    • Maintain the parasite (pathogen) population at an acceptable level.
    • Acceptable level can vary based on the specific scenario, parasite, and host population.
  • Elimination:
    • Achieve zero incidence (new cases per unit time).
    • Limited to a defined geographical area (e.g., country or continent).
    • Geographical factors influence feasibility (e.g., island nations like the UK may aim for national elimination).
  • Eradication:
    • Achieve zero incidence worldwide.
    • Historically achieved for only one human infection (smallpox) and one animal infection.
    • Extremely complicated and difficult to achieve.
  • Extinction:
    • Complete absence of the pathogen, even in labs.
    • May not always be the primary goal, as lab samples can be valuable for research.
    • Concerns exist about potential use as a biological weapon (e.g., smallpox).

Intervention Options

  • Preventing Transmission:
    • Targeted Vaccination:
      • Mass vaccination campaigns (e.g., smallpox eradication).
      • Targeting specific risk groups (e.g., children for measles, mumps, rubella (MMR)).
      • Spatial targeting (e.g., ring vaccination).
    • Reduction in Contact:
      • Handwashing.
      • Condom use.
      • Environmental sanitation.
      • These measures are often the first public health recommendations due to their relatively low cost.
      • Requires marketing and logistical considerations.
      • Adherence can be a challenge.
  • Intervening After Transmission:
    • Contact Tracing:
      • Identify and isolate individuals who have been in contact with infected persons.
    • Isolation:
      • Separate infected individuals to prevent further transmission.
    • Culling:
      • Used in animal populations to control outbreaks.
    • Examples:
      • SARS (2003) was contained through contact tracing and isolation.
      • Animal diseases: foot and mouth, bovine spongiform encephalopathy (BSE), avian influenza.

Factors for Pathogen Persistence & Intervention Logic

  • Effective R (Reproductive Rate):
    • R_e > 1: Pathogen persists in the population.
    • R_e < 1: Pathogen declines.
    • Re=S⋅C⋅P⋅DR_e = S \cdot C \cdot P \cdot D
      • S = Proportion of susceptible individuals.
      • C = Frequency of contacts.
      • P = Probability of transmission per contact.
      • D = Duration of infectiousness.
      • R0=C⋅P⋅DR_0 = C \cdot P \cdot D
  • Targeting Components of Effective R:
    • Reduce Susceptibles (S):
      • Vaccination: Increases immunity and reduces the proportion of susceptible individuals.
    • Reduce Duration of Infectiousness (D):
      • Treatment: Speeds recovery and shortens the infectious period.
      • Contact tracing and isolation: Reduces the time an individual is infectious in the population.
    • Reduce Effective Contact Rate (C x P):
      • Public health measures: Sanitation and behavioral changes to reduce contact or transmission probability.

Vaccination Strategies

  • Moving Susceptibles to Immune Group (R):
    • Vaccination aims to reduce the number of susceptible individuals (S) and move them into the recovered/immune group (R).
    • Compartmental models (SIR) are fundamental in understanding the dynamics of control.
  • Continuous Replenishment of Susceptibles:
    • Births continuously add new susceptible individuals to the population.
    • Requires continuous vaccination programs to maintain immunity.
    • Short outbreaks might not require sustained vaccination.

Vaccination Coverage: How Much Is Enough?

  • Goal: Achieve R_0 < 1 to stop outbreaks.
  • Endemic Equilibrium:
    • Proportion of susceptible individuals: S=1R0S = \frac{1}{R_0}
  • Critical Immunization Threshold (PC):
    • PC=1−1R0PC = 1 - \frac{1}{R_0}
    • The proportion of the population that needs to be immune to prevent outbreaks.
    • Achieved through vaccination to reach the required threshold.
  • Example: Polio (R0 ≈ 4):
    • PC=1−14=0.75PC = 1 - \frac{1}{4} = 0.75
    • 75% of the population needs to be immune to prevent polio outbreaks.

Herd Immunity

  • Concept: Not everyone needs to be immune; a sufficient proportion of immune individuals protects the susceptible.
  • The pathogen cannot effectively transmit through a population with high immunity.
  • Misconceptions during COVID-19 pandemic: Letting the virus spread unchecked does not lead to effective herd immunity.

Factors Affecting Vaccination Threshold

  • R0 is the Sole Determinant:
    • PC is directly related to R0.
  • Graph of PC vs. R0:
    • Lower R0 values require less vaccination.
    • Higher R0 values require significantly higher vaccination rates.
    • Smallpox (R0 ≈ 6): Requires 83% vaccination.
    • Measles (R0 ≈ 18): Requires 94% vaccination, making eradication very difficult.

Herd Immunity Requires Intervention

  • Active Immunization:
    • Vaccination campaigns are essential to increase immunity beyond natural infection rates.
    • Pathogens that infect everyone will exhaust their hosts and disappear, which is not evolutionarily advantageous for the pathogen.
  • Partial Immunity:
    • Population Level: A proportion of the population is immune.
    • Individual Level: The host's immune system provides some protection, reducing the severity of infection.

Historical Context: Edward Jenner and Smallpox

  • Jenner's Observation:
    • Milkmaids who contracted cowpox were immune to smallpox.
  • Jenner's Experiment:
    • Inoculated his gardener's son with cowpox pus.
    • The boy developed immunity and did not contract smallpox after multiple challenges with smallpox.
  • First Vaccine:
    • Jenner's cowpox inoculation was the world's first vaccine.
  • Vaccination Terminology:
    • "Vaccination" originates from "vaccinia," meaning "derived from a cow."
    • Initially, "vaccine" referred only to the smallpox vaccine.

Smallpox: A Case Study in Eradication

  • Two Viruses:
    • Variola major (more deadly, 90% of cases).
    • Variola minor.
  • Transmission:
    • Prolonged face-to-face contact (droplets).
    • Contagious scabs and pus.
  • Mortality Rates:
    • Variola major: Significantly higher mortality.
  • 20th Century Impact:
    • 300-500 million deaths.
  • 1950s:
    • Estimated 50 million new cases per year.
  • Late 1960s:
    • Despite healthcare improvements, smallpox remained a major threat, prompting eradication efforts.

Smallpox Eradication Program

  • 1959:
    • Global mass vaccination program initiated.
    • 80% coverage achieved.
  • 1969:
    • Eliminated in all but one country in Africa.
  • 1971:
    • The UK and USA ceased vaccination programs.
  • 1972:
    • Only 12 countries remained endemic.
  • Major Epidemics:
    • Despite progress, major epidemics persisted in India, Pakistan, and Bangladesh.
  • Surveillance and Containment:
    • Intensive monitoring and control measures implemented.
  • 1980:
    • Smallpox declared eradicated, the first human infectious disease to achieve this milestone.

Smallpox: An Imperfect Success

  • Last Natural Case: 1975
  • Lab Cases:
    • Cases occurred in Birmingham due to laboratory research.
    • A technician died after contracting smallpox in a lab.
  • Eradicated, Not Extinct:
    • The virus still exists in laboratories.

Demographic Factors and Vaccination Effectiveness

  • Africa vs. India:
    • Mass vaccination achieved 80% coverage but had different outcomes.
  • Average Age of Infection:
    • Africa: 17 years.
    • India: 13 years.
  • Life Expectancy:
    • Africa: 45 years.
    • India: 60 years.
  • A/L Ratio:
    • The ratio of the average age of infection (A) to life expectancy (L).
    • Africa: 37% of life before infection means 37% uninfected.
    • India: Only 21% of life before infection.
  • Alternative R0 Calculation:
    • R0=1+LAR_0 = 1 + \frac{L}{A}
    • Using this: African R0 = 3.7; Indian R0 = 5.7
  • Implications:
    • Different R0 values mean different herd immunity thresholds.
    • Africa: PC = 73% vaccination needed.
    • India: PC = 82% vaccination needed.

The Importance of R0 & Vaccination Thresholds

  • Same Strategy, Different Outcomes:
    • The same vaccination strategy had different results due to demographic factors.
    • In India, susceptible individuals replenished, leading to later outbreaks.
  • Damaged Trust:
    • Initial success followed by significant outbreaks damages public trust in public health strategies.

Control vs. Eradication: Measles Example

  • Measles:
    • Locally eliminated but frequently reintroduced.
  • Similarities to Smallpox:
    • No animal reservoir.
    • Cheap, safe, effective vaccine.
    • High morbidity and mortality.
  • Differences from Smallpox:
    • Measles transmits more readily (higher R0).
    • Measles is highly infectious but less virulent (less deadly), impacting public perception.

Measles Cases in England and Wales (1940-2007)

  • Pre-Vaccine Era:
    • Oscillating between 150,000 and 750,000 cases per year.
  • Vaccine Introduction (1968):
    • Cases significantly reduced.
  • MMR Vaccine (1988):
    • Dramatic decrease in cases, close to zero.

The Wakefield Paper and Anti-Vax Movement

  • Successful Campaigns Undermined:
    • Idiots aka Anti-vaxxers.
  • 1996:
    • Only 100 UK cases of measles.
  • Vaccination Rates:
    • Were not meeting herd immunity percentage.
  • Wakefield Paper:
    • Published in 1998, claimed MMR vaccine caused autism.
    • Results in huge media explosion, pre social media era.
    • Caused a significant decline in vaccination rates (from >90% to 80%).
  • Consequences:
    • Measles cases rose again into the thousands.
    • Outbreak in Samoa due to social media influencers and anti-vax sentiment.

Further Intervention: Infectiousness Curtailment

  • After Transmission Methods:
    • Surveillance to identify cases.
    • Contact tracing to find secondary cases.
    • Isolation of infected individuals.
  • Tracing and Containment:
    • Focus on potential secondary and tertiary cases.
  • Ring Vaccination:
    • Vaccinating contacts of infected individuals.
  • Ring Culling:
    • Culling animals in a defined area around infected farms (used in animal outbreaks).

Ring Culling: Avian Influenza Example

  • Avian Influenza Outbreak:
    • Estimated R0 of 5.8.
    • 30 million birds slaughtered in the Netherlands and Belgium.
  • Strategy:
    • Establish a ring (e.g., 1 km radius) around infected farms.
    • Cull all farms within the ring, and movement restrictions.
  • Impact:
    • 1145 farms culled, but only 255 were positive for the infection.
    • Significant economic and ethical considerations.

Summary: Part 1

  • Vaccination and herd immunity are essential for infectious disease prevention.
  • Age of onset and lifespan impact R0.
  • Contact tracing and ring containment are other methods.