1 2 3 High-resolution micro-epidemiology of parasite spatial and temporal dynamics in a high 4 malaria transmission setting in Kenya 5 6 7 Cody S.
Abstract WC: 149 (150 max) 24Main Text WC: 4,830 (5,000 max) 25Methods WC: 2,450 (3,000 max) 26
ABSTRACT 27Novel interventions that leverage the heterogeneity of parasite transmission are needed to push 28 malaria further towards elimination. To better understand spatial and temporal dynamics of 29 transmission, we applied amplicon NGS of two polymorphic gene regions (csp and ama1) to a 30 cohort identified via reactive case detection in a high-transmission setting in western Kenya. From 31 4/2013-6/2014, we enrolled 442 symptomatic children with malaria, 442 matched controls, and 32 all household members of both groups. We evaluated genetic similarity between infected 33 individuals using three novel indices: sharing of parasite haplotypes on binary and proportional 34 scales and the L1 norm. Symptomatic children more commonly shared haplotypes with their own 35 household members. Furthermore, we identified robust temporal structuring of parasite genetic 36 similarity that we exploited to identify the molecular signature of an outbreak. These findings of 37 both micro-and macro-scale organization of parasite populations might be harnessed to inform 38 next-generation malaria control measures. 39
RESULTS 94Haplotype metrics and read coverage. 95Of 5,353 total study participants from across the study area (Fig. 1), 1,050 were RDT+ for 96 P. falciparum. A total of 966 RDT+ infections were submitted for amplicon NGS of csp and ama1 97 loci (Fig. 1). After haplotype assignment 17 and quality filtering of reads, we identified 120 unique 98 csp haplotypes across 655 participants and 180 ama1 haplotypes across 667 participants ( Fig. 99