Tracking the flow of malaria parasites and drug resistance within the DRC and across its borders

ABSTRACT Malaria? ?remains? ?endemic? ?in? ?sub-Saharan? ?Africa? ?in? ?large? ?part? ?due? ?to? ?continued? ?evolution? ?and? ?spread? ?of? ?drug resistance? ?which? ?undermines? ?ongoing? ?large-scale? ?control? ?and? ?elimination? ?efforts.? ?We? ?will? ?leverage high-throughput? ?genotyping? ?of? ?parasites? ?using? ?a? ?state-of-the-art? ?panel? ?of? ?molecular? ?inversion? ?probes? ?(MIPs)? ?for targeted? ?sequencing? ?of? ?thousands? ?of? ?resistance? ?and? ?neutral? ?loci? ?across? ?thousands? ?of? ?infections? ?covering? ?the entire? ?Democratic? ?Republic? ?of? ?Congo? ?(DRC)? ?and? ?select? ?areas? ?in? ?bordering? ?countries.? ?This? ?will? ?provide? ?us? ?a? ?map with? ?an? ?unprecedented? ?scale? ?and? ?resolution? ?to? ?define? ?the? ?evolution? ?and? ?spread? ?of? ?antimalarial? ?resistance mutations.? ?In? ?this? ?project,? ?we? ?will? ?first? ?develop? ?our? ?genotyping? ?panel? ?which? ?should? ?provide? ?a? ?high-resolution? ?tool for? ?studying? ?all? ?known? ?drug? ?resistance? ?loci? ?and? ?general? ?parasite? ?population? ?structure? ?in? ?this? ?and? ?other? ?settings.

Applying? ?this? ?to? ?well? ?annotated? ?samples? ?from? ?across? ?the? ?DRC? ?and? ?bordering? ?countries,? ?we? ?will? ?define? ?the prevalence? ?of? ?drug? ?resistance? ?mutations? ?and? ?define? ?them? ?based? ?on? ?their? ?genetic? ?haplotypes? ?which? ?act? ?as? ?a unique? ?fingerprints.? ?We? ?will? ?then? ?map? ?these? ?drug? ?resistance? ?haplotypes? ?and? ?study? ?their? ?spread? ?and? ?spatial associations? ?and? ?further? ?examine? ?their? ?epidemiologic? ?associations? ?and? ?interactions.? ?Onto? ?this? ?detailed? ?spatial map,? ?we? ?will? ?? ?examine? ?specific? ?locales? ?of? ?interest? ?for? ?temporal? ?changes.? ?? ?These? ?focal? ?regions? ?in? ?the? ?DRC represent? ?diverse? ?ecologic? ?and? ?demographic? ?features? ?that? ?likely? ?impact? ?resistance? ?spread? ?and? ?evolution including? ?areas? ?with? ?minimal? ?health? ?care? ?infrastructure? ?and? ?ongoing? ?regions? ?of? ?conflict.? ?Our? ?final? ?work? ?will? ?be? ?to apply? ?more? ?sophisticated? ?models? ?to? ?the? ?rich? ?sequence? ?data? ?in? ?order? ?to? ?estimate? ?the? ?flow? ?of? ?parasites? ?and resistance? ?mutations? ?within? ?and? ?between? ?the? ?DRC.? ?This? ?includes? ?the? ?development? ?of? ?new? ?? ?population? ?structure models? ?(MALECOT)? ?incorporating? ?parasite? ?infections? ?that? ?have? ?multiple? ?strains? ?allowing? ?for? ?a? ?better understanding? ?of? ?the? ?full? ?dataset? ?as? ?in? ?polyclonal? ?infections? ?are? ?often? ?the? ?majority? ?in? ?endemic? ?African? ?countries.

This? ?model? ?should? ?be? ?broadly? ?applicable? ?to? ?other? ?studies? ?of? ?malaria? ?or? ?infections? ?with? ?mixed? ?strains.? ?We? ?will also? ?leverage? ?? ?spatially? ?explicit? ?models? ?to? ?define? ?general? ?parasite? ?flow? ?in? ?both? ?relative? ?and? ?absolute? ?terms comparing? ?and? ?contrasting? ?to? ?the? ?flow? ?of? ?resistant? ?parasites.? ?This? ?work? ?will? ?provide? ?the? ?patterns? ?of? ?general? ?gene flow? ?and? ?barriers? ?on? ?the? ?spread? ?of? ?specific? ?drug? ?resistance? ?alleles? ?and? ?haplotypes.? ?In? ?summary,? ?not? ?only? ?will this? ?project? ?enhance? ?our? ?understanding? ?of? ?malaria? ?landscape? ?genetics? ?and? ?the? ?evolution? ?and? ?spread? ?of antimalarial? ?resistance,? ?it? ?will? ?provide? ?tools? ?and? ?analysis? ?framework? ?for? ?improving? ?public? ?health? ?interventions that? ?will? ?directly? ?inform? ?the? ?DRC? ?National? ?Malaria? ?Control? ?Program.