pathogen adaptation under imperfect vaccination implications for pertussis n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Pathogen adaptation under imperfect vaccination: implications for pertussis PowerPoint Presentation
Download Presentation
Pathogen adaptation under imperfect vaccination: implications for pertussis

Loading in 2 Seconds...

play fullscreen
1 / 34

Pathogen adaptation under imperfect vaccination: implications for pertussis - PowerPoint PPT Presentation


  • 107 Views
  • Uploaded on

Pathogen adaptation under imperfect vaccination: implications for pertussis.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Pathogen adaptation under imperfect vaccination: implications for pertussis' - pandora


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
pathogen adaptation under imperfect vaccination implications for pertussis

Pathogen adaptation under imperfect vaccination: implications for pertussis

Michiel van Boven1, Frits Mooi2,3, Hester de Melker3Joop Schellekens3 & Mirjam Kretzschmar31Wageningen University/Utrecht University2Utrecht University/Academic Hospital Utrecht3National Institute of Public Health & the Environment

slide2

Pertussis, basic facts

  • gram-negative bacterium
  • first described: 1540 !
  • first isolated: 1906 by Bordet and Gengou
  • main species in the genus Bordetella: B. pertussis, B. parapertussis, and B. bronchiseptica
  • B. pertussis and B. parapertussis : mostly human
  • B. bronchiseptica : dogs, pigs, sheep
  • Bp and Bpp : limited survival outside the host
  • Bb : prolonged starvation resistance
  • Bp and Bpp infections: severe in unvaccinated infants, usually mild in adolescents and adults
slide3

Pertussis vaccination

  • before 1940: a leading cause of infant death
  • nowadays: very low mortality rates in developed countries
  • Dutch vaccination program: started in 1953
  • vaccine: killed whole-cell (Tohama)
  • vaccination coverage: ~96%
  • up to 2002: vaccination at age 3,4,5, and 11 months
  • since 2002: vaccination at age 2,3,4, and 10 months
  • since 2002: booster with subunit vaccine at 4 years
  • 2006: replacement of whole-cell vaccine by subunit vaccine
  • subunit vaccines: 1-5 components (e.g., ptx, pertactin, fha)
slide9

Questions

  • What is the contribution of circulation in unvaccinated infants to the overall circulation of pertussis?
  • How does the infection incidence depend on period of immunity after vaccination or infection?
  • How will the pathogen population evolve in response to vaccination?
slide10

S

1-p

1

p

g1h

I

V

gVh

1

V

a

1

R

I

S

a

g2h

2

2

2

Model structure

Central idea: there is a difference between infection in immunologically naïve individuals (‘primary infection’) and infection in individuals whose immune system has been primed (‘secondary infection’)

slide12

Population dynamical analysis: invasion

  • herd immunity cannot always be achieved (McLean and others)
  • the reproduction ratio increases with p if
  • for the default parameter values, Rp increases with pif secondary infections are 7% more transmissible than primary infections
slide14

Evolutionary adaptation

Adaptation of B. pertussis to vaccination occurs in two ways:(1) the pathogen population may evolve to become polymorphic(2) the pathogen may evolve higher or lower levels of virulence gene expression

slide15

Scenarios

  • B. pertussis can increase (or decrease) its efficiency in immunologically naïve individuals by increasing (decreasing) the expression of virulence genes. On the other hand, increased expression of virulence genes results in a stronger immune response in primed individuals.
  • B. pertussis can evolve to circumvent the immunity induced by vaccination. However, strains that circumvent the vaccination induced immune response have reduced fitness.
slide16

Evolutionary invasion analysis

  • fitness measure: the growth rate λ(y,x) of a mutant strain characterized by a variable y in a resident pathogen population characterized by a variable x
  • the selection gradient:
  • ESS condition:
  • maximum condition:
  • convergence condition:
slide17

1. virulence gene expression

  • In the first example, the parameters f1 and f2 are molded by selection.
  • For this scenario, the ESS condition reads
slide20

2. immune evasion

  • In this example, the parameters σV and α are supposed to be molded by selection, and the ESS condition reads
slide21

2. immune evasion

  • Suppose that a resident strain is present that cannot infect individuals in class V (gv=0)
  • The infectious period of the resident strain is days.
  • A mutant strain that is fully able to infect individuals in class V (i.e. g’v=0) can invade if its infectious period is not shorter than days.
  • If the period of protection after vaccination is ten years (instead of five), the mutant can invade the infectious period is not shorter than days.
slide22

Pathogen adaptation: summary of results

  • For realistic parameter values primary susceptibles constitute only a small fraction of the population, while secondary susceptibles abound. Consequently, pertussis circulation depends mainly on (unnoticed) infections in children, adolescents and adults.
  • The pathogen is more likely to adapt to efficiently exploit secondary susceptibles than to efficiently exploit primary susceptibles.
  • Pertussis strains that evade the immunity induced by vaccination can only invade if they incur no or a modest fitness cost.
slide23

Tests and open questions

  • How long does immunity, against infection and against disease, last after infection and vaccination?
  • Are there systematic differences between strains found in countries with high vaccination coverage and strains found in countries with low vaccination coverage?
slide24

The optimal amount of antiviral control

Michiel van Boven1, Don Klinkenberg1, Franjo Weissing2, Hans Heesterbeek1

1Faculty of Veterinary Medicine, Utrecht University

2Theoretical Biology, University of Groningen

slide25

Main question: What is the optimal amount of costly (i.e. potentially lethal) antiviral therapy when faced with a virulent pathogen that can kill the host?

slide26

Two perspectives

  • the public health officer: maximize the performance of the population
  • the individual: maximize your own performance given the actions of those around you
slide27

Objective functions

  • life expectancy, L(y,x)
  • probability to be alive after T years, L(y,x,T)
  • perceived risk, L(y, I(x), V(x))
slide28

Model structure

μ: background mortality ρ : recovery rate

γ: antivirals induced mortality ν : antiviral control rate

α : infection induced mortality σ: non-compliance rate

: force of infection

slide29

1. Life expectancy at the endemic equilibrium

  • pathogen absent:
  • no antiviral control:
  • no individual differences:
  • rare type νy in a resident population νx: