Transcript Timeliness of intervention in epidemic outbreaks

Threshold, Amory Faulkner, oil on canvas
The prospects of
elimination of HIV with
test and treat strategy
Mirjam Kretzschmar 1,2
Maarten Schim van der Loeff
Daniela de Angelis 4
Roel Coutinho 1,2
26July 2012
AIDS conference
1
Washington
DC
1
2
3
4
3
Centre for Infectious Disease Control, RIVM
University Medical Centre Utrecht, NL
Municipal Health Service, Amsterdam, NL
MRC Biostatistics Unit, Cambridge, UK
Test and treat strategy
Treatment and infectivity
Cohen et al. NEJM 2011
Elimination possible?
From Granich et al. Lancet 2009
Aims of our study:
• Modify and generalize the model to include knowledge on natural history
• Derive and analyze under what conditions elimination is possible
Generalized model structure
• Variable number of compartments with variable duration
• Variable infectivity
-> better description of natural history including variable infectivity
Epidemic dynamics
Epidemic growth and elimination are threshold phenomena => linear analysis
Transient dynamics
Exponential
growth
Elimination
Exponential growth at the start of the epidemic, growth rate
determined by R0
Exponential decay at elimination, decay rate determined by Re
Analysis
•
•
•
•
•
•
•
Determine explicit expressions for R0 and Re from model equations
Estimate disease progression parameters from data (CASCADE
collaboration)
Use information about distribution of infectivity (Hollingsworth et
al. JID 2008)
Relate infectivity to epidemic growth rate r and R0 via generation
interval distribution (Wallinga & Lipsitch 2007)
Estimate r from incidence or doubling time at onset of epidemic
From R0 determine transmission parameter λ
Elimination threshold is determined as function of coverage and
adherence to treatment
Assumption: populations and behaviors driving HIV
transmission during growth phase also determine
transmission dynamics during elimination .
•
•
•
•
3 infection stages
Progression rates from CASCADE
Infectivity from Hollingsworth 2008
Relationship r and R0:
Elimination threshold






Elimination threshold Re as
function of transmission and
intervention parameters
Elimination possible if Re < 1
From incidence or doubling
time during exponential
growth phase estimate r
From r compute R0
Determine elimination
threshold for given R0
If more recent estimates of R0
are available these can be
used (e.g. from genetic data)
Elimination threshold
6.0
 For R0 > 6 elimination not
possible
 Elimination possible for low
risk populations
 For the coverage and drop
out rate assumed by
Granich elimination is
feasible if R0<5
4.6
4.2
3.9
3.5
3.0
2.5
R0=1.5
Estimates from literature
Population
r (1/yr)
South Africa
R0
d (yrs)
7.0
1.25
Data type
Ref
incidence
Granich 2009
France
1.15
3.65
incidence
Nishiura 2010
West Germany
2.15
4.08
incidence
Nishiura 2010
UK
1.21
3.67
incidence
Nishiura 2010
SSAC
0.273
2.536
genetic
Walker 2005
High income
countries
0.479
1.446
genetic
Walker 2005
genetic
Salemi 2008
incidence
Gran 2008
genetic
Bello 2007
incidence
Bezemer 2008
Albania
England &
Wales
Brazil
MSM
Netherlands
0.69
8.0
0.9049
10.05
0.55
1.25
2.39
Conclusions
 Elimination is a threshold phenomenon. Information about possible
elimination can be obtained from epidemic growth rate and
generation interval distribution.
 Elimination is only feasible for populations with low basic
reproduction numbers or if the reproduction number is lowered
significantly as a result of other additional interventions.
 High infectivity during primary infection significantly increases the
elimination threshold.
 If reliable estimates for R0 could be obtained from phylogenetic
analysis prospects of elimination could be quantified more reliably.
Acknowledgements
Co-authors:
Maarten Schim van der Loeff
Infectious Disease Unit, Municipal Health Service Amsterdam,
The Netherlands
Daniela de Angelis
MRC Biostatistics Unit, Cambridge UK
Roel Coutinho
Center for Infectious Disease Control, RIVM and
University Medical Center Utrecht, The Netherlands
CASCADE Collaboration
Paul Birrell, MRC Biostatistics Unit, Cambridge UK