Derek A.T. Cummings

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Models of New Vaccines for Measles
Derek A.T. Cummings University of Pittsburgh
Graduate School of Public Health and Johns
Hopkins Bloomberg School of Public Health
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Measles Virus

• Major cause of child morbidity and mortality
• Causes 500,000 deaths each year

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Distribution of Global Mortality
2003 282,000 183,000 57,000 8,000 530,000
Region Africa South Asia East Asia and
Pacific Other Total
1999 519,000 263,000 77,000 14,000 873,000
MMWR, 2005
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Current measles vaccine

• Current vaccine is a live attenuated vaccine
  derived from passage in chick embryo cells
• Targeted age of delivery is 9-12 months
• Induces immunity in 85 of recipients at 9 months
  of age and 90-95 of recipients at 12 months of
  age
• Immunogenicity in early infancy is limited by
  relative immaturity of the immune system and the
  presence of maternal antibodies

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Can we eliminate/eradicate measles using this
vaccine?
The experience in the Americas suggests we can
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Some of the Largest Challenges lie ahead for
Measles Control
Strebel, Nature, 2001
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Vaccine Candidates

• Several candidates are under development
• Aerosol delivered vaccines that could minimize
  interference with maternal antibody and ease
  delivery
• DNA vaccines encoding particular measles virus
  proteins with the potential to be immunogenic at
  ages as early as 2 months
• One design goal is to be able to target earlier
  ages in the EPI schedule

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Long history of work in measles on disease
dynamics
Data (red circles) and Model (blue line) of
weekly measles incidence in London, 1944-1965
Grenfell et al, 2001
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RAS model of measles transmission
Mi
Si
Ei
Ii
Ri
i denotes age cohorts
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Cohorts age together

• Schenzles approach used to reduce system of
  partial differential equations to a system of
  ordinary differential equations
• Age groups all age at the same time

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Force of Infection

• As a first step, Ive used age specific forces of
  infection from the literature estimated using age
  stratified serological data in the UK and in
  Senegal

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WAIFW Matrix
ß1 ß1 ß1 ß1 ß1 ß2 ß2 ß2 ß1
ß2 ß3 ß3 ß1 ß2 ß3 ß4
ß1 ß1 ß1 ß1 ß1 ß2 ß1 ß1 ß1
ß1 ß3 ß1 ß1 ß1 ß1 ß4




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Age Structure of the Population
Need to incorporate younger age groups than
previous models (0-1 months, 1-2 months,2-3
months, 3-4 months, 4-5 months, 5-6 months,6-9
months, 9-12 months, 1-2 years, 2-3 years, 5-10
years, 10 and older Uniformly distribute age
specific force of infection of larger age classes
to smaller age classes Used data on the age
structure of the population in Cameroon from a
Demographics and Health Survey Set derivatives
with respect to time to zero and solved for birth
rate and age specific deaths rates that would
match age distribution
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Comparing different age cohort structures
(red, 13 age classes, agregatedyellow, 7 age
classes,
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Vaccination

• Vaccination moves some portion of susceptible or
  those with maternal immunity into the removed
  class
• Vaccination is done during the age cohort
  transitions into targeted age groups
• As simplest case I assume new vaccine is
  delivered at 4th month (third dose of DPT)
• Vaccination rates are higher at 4 months than 9
  months

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Results using a vaccine given at 4 months w/ 65
efficacy (irrespective of presence of maternal
immunity compared to current vaccine delivered at
9 months with reduced efficacy in those with
maternal immunity
Equivalent vaccine efficacy is 78 With extreme
empirical estimate of increase in vaccination, 71
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Extensions

• Multiphase strategy
• Incorporate vaccine efficacy at three doses
• Incorporate empirical data on association of
  timeliness of vaccines on age of delivery
• Create analogous stochastic model to explore
  elimination

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Is the birth cohort large enough in these cities
so that the number of children not targeted by
the vaccine is greater than the critical
community size
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Monthly measles incidence in Cameroon, 1997-2001
Cummings et al, IJID, 2006
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Incidence in Northern Region
Incidence in Southern Region
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An aside one lesson from Cameroon experience

• The number of cases is not the best indicator of
  the state of population immunity. Susceptible
  fractions can slowly increase and lead to large
  outbreaks.
• Public health systems should anticipate
  post-honeymoon outbreaks

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The experience in the Americas is the standard.
Would models predict the elimination of measles
transmission in this region given the vaccination
coverage attained
The experience in the Americas suggests we can
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Estimates of transmissibility of measles from
Africa are rare
Number of reported cases of measles in the urban
community of Niamey, 1 November 2003 to 6 June
2004.
Grais, Trans. Roy. Soc. of Trop. Med. and Hyg.
(2006)
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Recent data suggest R0 is slightly lower in some
parts of Africa than historic estimates from the
UK and the US
Estimates of R0 from Niger (Grais et al)
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• Question for the audience-
• How many think the elimination campaign in
  southern Africa will maintain low numbers of
  cases?
• Do you think we can eliminate measles with the
  current vaccine?