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 Malaria Population Genetics From sarah volkman, harvard – unpublished panamania data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, (July 2007) Mosquito Cycle Takes ~ 10 Days Uninfected 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 Columbia Guna Yala Panama Darien Guna Yala Nicanor Obaldia, Nicholas Baro

K=2 Coast Panama and Darien Guna YalaColombia K=5 Panama: two clonal populations Panama parasites clusters into two clonal populations. Addition of Columbia parasites results in five populations

Columbia Guna Yala Panama Darien Coastal Pacific Atlantic

COIEIR OutcrossingHigh LowMedium Inbreeding1Low 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 Impact January 24, 2014 Diagnostic s 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-based detection 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