Parasite strain turnover and mosquito infectivity in untreated subpatent malaria.

BACKGROUND: In settings where malaria transmission has declined, subpatent malaria due to low density P. falciparum infection remains prevalent. Low density parasitemia persisting over time may represent dynamic turnover of parasite genetic variants. METHODS: We performed targeted parasite sequencing in 330 persons with asymptomatic malaria in Bagamoyo, Tanzania from 2018-2021. A subset of 286 with subpatent parasitemia (RDT-negative, PCR-positive) were followed over 4 weeks to examine outcomes and parasite genetic make-up within individuals in the absence of treatment. Infectiousness to mosquitoes was assessed using direct skin feeding assays. RESULTS: Parasite diversity based on microhaplotypes at four hypervariable markers (CSP, AMA-1, SERA2, TRAP) was high, with a mean of 1.7 (range 1-8) unique microhaplotypes per sampling. While roughly half of RDT-negative parasitemias were transient, in those with persistent subpatent carriage, parasite strain turnover was frequent, with 91% of those sampled three times showing new microhaplotypes at subsequent visits. Among the 28% (79/286) of subpatent carriers who developed RDT-positivity within 4 weeks, 94% (15/16 with paired genotyping) were associated with turnover in the major haplotype in at least one marker, whereas persistence of the major haplotype was more common in those with persistent subpatent carriage. Infectiousness appeared to increase in those who developed patent malaria but not in those with persistent carriage. CONCLUSIONS: In coastal Tanzania, subpatent malaria is often transient while persistent carriage involves dynamically changing parasite variants and low-level infectivity to mosquitoes. Patent malaria with higher transmission potential develops in the setting of newly inoculated or ascendant genotypes.