Transcript Application to Malaria Transmission

Malaria Population Genetics
From sarah volkman, harvard – unpublished
panamania data
• Population genetics approach to understanding changing
malaria transmission dynamics.
• Evidence for clonal expansion and epidemic propagation of
malaria in low transmission settings.
• Application of population genetics to assess intervention
impact.
• Fingerprint parasites to identify sources of new infection and
asymptomatic reservoirs.
Molecular barcode to fingerprint parasites
Molecular barcode tool consists of 24 neutral,
unlinked SNPs that are of a high minor allele
frequency among the global parasite population
Daniels et al, Malaria Journal 2008, 7:223
Plasmodium Life Cycle
Mosquito Cycle Takes ~ 10 Days
Uninfected COI = 1 COI = 2 COI = 3
Xinzhuan Su, Karen Hayton & Thomas E. Wellems
Nature Reviews Genetics 8, 497-506 (July 2007)
Consequence of outcrossing—multiple barcodes—heterogenomic
COI = 3
Outcrossing
Consequence of inbreeding—single barcode—homogenomic
COI = 1
Inbreeding
Panama: Low genetic diversity & population differentiation
Columbia
Guna Yala
Panama
Darien
Guna Yala
Nicanor Obaldia, Nicholas Baro
Panama: two clonal populations
Panama and Darien
Guna Yala
Colombia
K=5
•
•
Panama parasites clusters into two clonal
populations.
Addition of Columbia parasites results in
five populations
K=2
Genotyping and transmission dynamics
Outcrossing
Inbreeding
COI
EIR
High
High
Low
Medium
1
Low
Using population genetics to detect changing transmission
• Leverage malaria population genetics to monitor changes in
parasite population dynamics as transmission changes—
concept of surveillance markers.
• Genotyping creates “fingerprint” to track parasites, monitor
drug resistance, identify reservoirs of new infections, and
monitor intervention impact.
• Genomic tools inform operationally important decisions and
guide implementation strategies toward malaria elimination.
• Tools that detect changes in population genetic parameters can
infer changes in malaria transmission and provide a powerful
means of monitoring the effectiveness of interventions, and
informing best operational strategies toward malaria elimination.
From Sarah Volkman, Harvard
Diagnostic
s for
Malaria
Elimination
Toward
Eradication
Photo: © 2012 Diana Mrazikova/Networks/Senegal, Courtesy of Photoshare
BMGF meeting: Partnering for Elimination Dx Impact
January 24, 2014
Next steps
Next gen dx?? Lots of opinions
….results suggest
community-wide MDA
instead of screen and
treat strategies (2013 pub)
So much effort has
gone into scale-up of
the RDT format that
any new technology
should follow that
format (stakeholder)
Nothing will work without good
case management and vector
control, and the basics (stockouts, information systems,
training), though boring, are still
frequently unaddressed. (heard
at WHO/ERG meeting)
PCR samples should start
with 1 ml blood to get to
enable the lowest LOD
possible (0.002p/ul) (heard
at WHO/ERG meeting)
DNA-based
detection of parasites
is needed to provide
adequate sensitivity
in hotspots. (2013
pub)
Use-scenario taxonomy and framework
Use-scenario framework mapped to TPPs