Exposure to Diverse Plasmodium falciparum Genotypes Shapes the Risk of Symptomatic Malaria in Incident and Persistent Infections: A Longitudinal Molecular Epidemiologic Study in Kenya.

Journal Article (Journal Article)

BACKGROUND: Repeated exposure to malaria infections could protect against symptomatic progression as people develop adaptive immunity to infections acquired over time. METHODS: We investigated how new, recurrent, and persistent Plasmodium falciparum infections were associated with the odds of developing symptomatic compared with asymptomatic malaria. Using a 14-month longitudinal cohort in Western Kenya, we used amplicon deep sequencing of 2 polymorphic genes (pfama1 and pfcsp) to assess overlap of parasite genotypes (represented by haplotypes) acquired within an individual's successive infections. We hypothesized infections with novel haplotypes would increase the odds of symptomatic malaria. RESULTS: After excluding initial infections, we observed 534 asymptomatic and 88 symptomatic infections across 186 people. We detected 109 pfcsp haplotypes, and each infection was classified as harboring novel, recurrent, or persistent haplotypes. Incident infections with only new haplotypes had higher odds of symptomatic malaria when compared with infections with only recurrent haplotypes [odds ratio (OR): 3.24; 95% confidence interval (CI), 1.20-8.78], but infections with both new and recurrent haplotypes (OR: 0.64; 95% CI: 0.15-2.65) did not. Assessing persistent infections, those with mixed (persistent with new or recurrent) haplotypes (OR: 0.77; 95% CI: 0.21-2.75) had no association with symptomatic malaria compared with infections with only persistent haplotypes. Results were similar for pfama1. CONCLUSIONS: These results confirm that incident infections with only novel haplotypes were associated with increased odds of symptomatic malaria compared with infections with only recurrent haplotypes but this relationship was not seen when haplotypes persisted over time in consecutive infections.

Full Text

Duke Authors

Cited Authors

  • Sumner, KM; Freedman, E; Mangeni, JN; Obala, AA; Abel, L; Edwards, JK; Emch, M; Meshnick, SR; Pence, BW; Prudhomme-O'Meara, W; Taylor, SM

Published Date

  • October 5, 2021

Published In

Volume / Issue

  • 73 / 7

Start / End Page

  • 1176 - 1184

PubMed ID

  • 33904907

Pubmed Central ID

  • PMC8492207

Electronic International Standard Serial Number (EISSN)

  • 1537-6591

Digital Object Identifier (DOI)

  • 10.1093/cid/ciab357

Language

  • eng

Conference Location

  • United States