population genetics approach to understanding changing malaria transmission dynamics. evidence for...
DESCRIPTION
Plasmodium Life Cycle Xinzhuan Su, Karen Hayton & Thomas E. Wellems Nature Reviews Genetics 8, (July 2007) Mosquito Cycle Takes ~ 10 Days Uninfected COI = 1 COI = 2 COI = 3TRANSCRIPT
• 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.
Malaria Population GeneticsFrom sarah volkman, harvard – unpublished panamania data
Molecular barcode to fingerprint parasites
Daniels et al, Malaria Journal 2008, 7:223
Molecular barcode tool consists of 24 neutral,unlinked SNPs that are of a high minor allele frequency among the global parasite population
Plasmodium Life Cycle
Xinzhuan Su, Karen Hayton & Thomas E. Wellems Nature Reviews Genetics 8, 497-506 (July 2007)
Mosquito Cycle Takes ~ 10 DaysUninfected COI = 1 COI = 2 COI = 3
Consequence of outcrossing—multiple barcodes—heterogenomic
Outcrossing
COI = 3
Consequence of inbreeding—single barcode—homogenomic
Inbreeding
COI = 1
Panama: Low genetic diversity & population differentiation
ColumbiaGuna Yala
Panama
Darien
Guna Yala
Nicanor Obaldia, Nicholas Baro
K=2
CoastPanama and Darien Guna Yala Colombia
K=5
Panama: two clonal populations
• Panama parasites clusters into two clonal populations.
• Addition of Columbia parasites results in five populations
COI EIR
Outcrossing High High
Low Medium
Inbreeding 1 Low
Genotyping and transmission dynamics
• 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.
Using population genetics to detect changing transmission
From Sarah Volkman, Harvard
BMGF meeting: Partnering for Elimination Dx ImpactJanuary 24, 2014
Diagnostics for Malaria Elimination Toward Eradication
Photo: © 2012 Diana Mrazikova/Networks/Senegal, Courtesy of Photoshare
Next steps
Next gen dx?? Lots of opinions
….results suggest community-wide MDA instead of screen and
treat strategies (2013 pub)
DNA-baseddetection of parasites is needed to provide adequate sensitivity in hotspots. (2013 pub)
Nothing will work without good case management and vector control, and the basics (stock-outs, information systems, training), though boring, are still frequently unaddressed. (heard at WHO/ERG meeting)
So much effort has gone into scale-up of the RDT format that any new technology should follow that
format (stakeholder)
PCR samples should start with 1 ml blood to get to enable the lowest LOD
possible (0.002p/ul) (heard at WHO/ERG meeting)
Use-scenario taxonomy and framework
Use-scenario framework mapped to TPPs