• 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Malaria Population GeneticsFrom sarah volkman, harvard – unpublished panamania data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